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 Serotonin is produced in the brain from the amino acid tryptophan, which is derived from foods high in protein, such as meat and dairy products. Tryptophan is transported to the brain, where it is broken down by enzymes to produce serotonin. During neurotransmission, serotonin is transferred from one nerve cell, or neuron, to another, triggering an electrical impulse that stimulates or inhibits cell activity as needed. Serotonin is then reabsorbed by the first neuron, in a process known as reuptake, where it is recycled and used again or converted into an inactive chemical form and excreted.
 While the complete picture of serotonin’s function in the body is still being investigated, many disorders are known to be associated with an imbalance of serotonin in the brain. Drugs that manipulate serotonin levels have been used to alleviate the symptoms of serotonin imbalances. Some of these drugs, known as selective serotonin reuptake inhibitors (SSRIs), block or inhibit the reuptake of serotonin into neurons, enabling serotonin to remain active in the synapses for a longer period. These medications are used to treat such psychiatric disorders as depression; Obsessive-compulsive disorder, in which repetitive and disturbing thoughts trigger bizarre, ritualistic behaviors, and impulsive aggressive behaviors. Fluoxetine (more commonly known by the brand name Prozac), is a widely prescribed SSRI used to treat depression, and more recently, obsessive-compulsive disorder.
 Drugs that affect serotonin levels may prove beneficial in the treatment of nonpsychiatric disorders as well, including diabetic neuropathy (degeneration of nerves outside the central nervous system in diabetics) and premenstrual syndrome. Recently the serotonin-releasing agent dexfenfluramine has been approved for patients who are 30 percent or more over their ideal body weight. By preventing serotonin reuptake, dexfenfluramine promotes satiety, or fullness, after eating less food.
 Other drugs serve as agonists that react with neurons to produce effects similar to those of serotonin. Serotonin agonists have been used to treat migraine headaches, in which low levels of serotonin cause arteries in the brain to swell, resulting in a headache. Sumatriptan is an agonist drug that mimics the effects of serotonin in the brain, constricting blood vessels and alleviating pain.
 Drugs known as antagonists bind with neurons to prevent serotonin neurotransmission. Some antagonists have been found effective in treating the nausea that typically accompanies radiation and chemotherapy in cancer treatment. Antagonists are also being tested to treat high blood pressure and other cardiovascular disorders by blocking serotonin’s ability to constrict blood vessels. Other antagonists may produce an effect on learning and memory in age-associated memory impairment.
 The Synapse is the signal conveying everything that human beings sense and think, and every motion they make, follows nerve pathways in the human body as waves of ions (atoms or groups of atoms that carries electric charges). Australian physiologist Sir John Eccles discovered many intricacies of this electrochemical signaling process, particularly the pivotal step in which a signal is conveyed from one nerve cell to another. He shared the 1963 Nobel Prize in physiology or medicine for this work, which he described in a 1965 Scientific American article.
 How does one nerve cell transmit the nerve impulse to another cell? Electron microscopy and other methods show that it does so by means of special extensions that deliver a squirt of transmitter substance
 The human brain is the most highly organized form of matter known, and in complexity the brains of the other higher animals are not greatly inferior. For certain purposes regarding the brain for being analogous to a machine is expedient. Even if it is so regarded, however, it is a machine of a totally different kind from those made by man. In trying to understand the workings of his own brain man meets his highest challenge. Nothing is given; There are no operating diagrams, no maker's instructions.
 The first step in trying to understand the brain is to examine its structure to discover the components from which it is built and how they are related to each another. After that one can attempt to understand the mode of operation of the simplest components. These two modes of investigation - the morphological and the physiological - have now become complementary. In studying the nervous system with today's sensitive electrical device, however, finding physiological events that cannot be correlated with any known anatomical structure is all too easy. Conversely, the electron microscope reveals many structural details whose physiological significance is obscure or unknown.
 At the close of the past century the Spanish anatomist Santiago Ramón Cajal showed how all parts of the nervous system are built up of individual nerve cells of many different shapes and sizes. Like other cells, each nerve cell has a nucleus and the surrounding cytoplasm. Its outer surface consists of many fine branches - the dendrites - that receive nerve impulses from other nerve cells, and one relatively long branch - the axon - that transmits nerve impulses. Near its end the axon divides into branches that end at the dendrites or bodies of other nerve cells. The axon can be as short as a fraction of a millimeter or if a meter, depending on its place and function. It has many properties of an electric cable and is uniquely specialized to conduct the brief electrical waves called nerve impulses. In very thin axons these impulses travel at less than one meter per second; In others, for example in the large axons of the nerve cells that activate muscles, they travel as fast as 100 meters per second.
 The electrical impulse that travels along the axon ceases abruptly when it comes to the point where the axon's terminal fibers contact another nerve cell. These junction points were given the name ‘synapses’ by Sir Charles Sherrington, who laid the foundations of what is sometimes called synaptology. If the nerve impulse is to continue beyond the synapse, it must be regenerated afresh on the other side. As recently as 15 years ago some physiologists held that transmission at the synapse was predominantly, if not exclusively, an electrical phenomenon. Now, however, there is abundant evidence that transmission is made by the release of specific chemical substances that trigger a regeneration of the impulse. In fact, the first strong evidence showing that some transmitter substance act across the synapse was provided more than 40 years ago by Sir Henry Dale and Otto Loewi.
 It has been estimated that the human central nervous system, which of course includes the spinal cord and the brain itself, consists of about 10 billion (1010) nerve cells. With rare exceptions each nerve cell receives information directly as impulses from many other nerve cells - often hundreds - and transmits information to a like number. Depending on its threshold of response, a given nerve cell may fire an impulse when stimulated by only a few incoming fibers or it may not fire until stimulated by many incoming fibers. It has long been known that this threshold can be raised or lowered by various factors. Moreover, it was supposed some 60 years ago that some incoming fibers must inhibit the firing of the receiving cell rather than excite it. The conjecture was subsequently confirmed, and the mechanism of the inhibitory effect has now been clarified. This mechanism and its equally fundamental counterpart - nerve-cell excitation - are of its topic.
 In the levels of anatomy there are some clues to show how the fine axon terminals impinging on a nerve cell can make the cell regenerate a nerve impulse of its own nerve cell and its dendrites are covered by fine branches of nerve fibers that end in knob-like structures. These structures are the synapses.
 The electron microscope has revealed structural details of synapses that fit in nicely with the view that a chemical transmitter is involved in nerve transmission. Enclosed in the synaptic knob are many vesicles, or tiny sacs, which appear to contain the transmitter substances that induce synaptic transmission. Between the synaptic knob and the synaptic membrane of the adjoining nerve cell is a remarkably uniform space of about 20 millimicrons that is termed the synaptic cleft. Many of the synaptic vesicles are concentrated adjacent to this cleft; It seems plausible that the transmitter substance is discharged from the nearest vesicles into the cleft, where it can act on the adjacent cell membrane. This hypothesis is supported by the discovery that the transmitter is released in packets of a few thousand molecules.
 The study of synaptic transmission was revolutionized in 1951 by the introduction of delicate techniques for recording electrically from the interior of single nerve cells. This is done by inserting into the nerve cell an extremely fine glass pipette with a diameter of .5 microns - about a fifty-thousandth of an inch. The pipette is filled with an electrically conducting salt solution such as concentrated potassium chloride. If the pipette is carefully inserted and held rigidly in place, the cell membrane appears to seal quickly around the glass, thus preventing the flow of a short-circuiting current through the puncture in the cell membrane. Impaled in this fashion, nerve cells can function normally for hours. Although there is no way of observing the cells during the insertion of the pipette, the insertion can be guided by using as clues the electric signals that the pipette picks up when close to active nerve cells.
 At the John Curtin School of Medical Research in Canberra first employed this technique, choosing to study the large nerve cells called motoneurons, which lie in the spinal cord whose function is to activate muscles. This was a fortunate choice: Intracellular investigations with motoneurons are easier and more rewarding than those with any other kind of mammalian nerve cell.
 Finding that when the nerve cell responds to the chemical synaptic transmitter, the response depends in part on characteristic features of ionic composition that are also concerned with the transmission of impulses in the cell and along its axon. When the nerve cell is at rest, its physiological makeup resembles that of most other cells in that the water solution inside the cell is quite different in composition from the solution in which the cell is bathed. The nerve cell can exploit this difference between external and internal composition and use it in quite different ways for generating an electrical impulse and for synaptic transmission.
 The composition of the external solution is well established because the solution is essentially the same as blood from which cells and proteins have been removed. The composition of the internal solution is known only approximately. Indirect evidence suggests that the concentrations of sodium and chloride ions outside the cell are respectively some 10 and 14 times higher than the concentrations inside the cell. In contrast, the concentration of potassium ions inside the cell is about 30 times higher than the concentration outside.
 How can one account for this remarkable state of affairs? Part of the explanation is that inside the cell is negatively charged with the respect of the cell about 70 millivolts. Since like charges repel each other, this internal negative charge tends to drive chloride ions (Cl-) outward through the cell membrane and, at the same time, to impede their inward movement. In fact, a potential difference of 70 millivolts is just sufficient to maintain the observed disparity in the concentration of chloride ions inside the cell and outside it; Chloride ions diffuse inward and outward at equal rates. A drop of 70 millivolts across the membrane therefore defines the ‘equilibrium potential’ for chloride ions.
 To obtain a concentration of potassium ions (K) that is 30 times higher inside the cell than outside would require that the interior of the cell membrane be about 90 millivolts negative with respect to the exterior. Since the actual interior is only 70 millivolts negative, it falls short of the equilibrium potential for potassium ions by 20 millivolts. Evidently the thirtyfold concentration can be achieved and maintained only if there is some auxiliary mechanism for ‘pumping’ potassium ions into the cell at a rate equal to their spontaneous net outward diffusion.
 The pumping mechanisms have fewer, but more difficult tasks of pumping sodium ions (Na) out of the cell against a potential gradient of 130 millivolts. This figure is obtained by adding the 70 millivolts of internal negative charge to the equilibrium potential for sodium ions, which is 60 millivolts of internal positive charge. If it were not for this postulated pump, the concentration of sodium ions inside and outside the cell would be almost the reverse of what is observed.
 In their classic studies of nerve-impulse transmission in the giant axon of the squid, A. L. Hodgkin, A. F. Huxley and Bernhard Katz of Britain proved that the propagation of the impulse coincides with abrupt changes in the permeability of the axon membrane. When a nerve impulse has been triggered in some way, what can be described as a gate opens and lets sodium ions pour into the axon during the advance of the impulse, making the interior of the axon locally positive. The process is self-reinforcing in that the flow of some sodium ions through the membrane opens the gate further and makes it easier for others to follow. The sharp reversal of the internal polarity of the membrane makes up the nerve impulse, which moves like a wave until it has traveled the length of the axon. In the wake of the impulse the sodium gate closes and a potassium gate opens, by that restoring the normal polarity of the membrane within a millisecond or less.
 With this understanding of the nerve impulse in hand, one is ready to follow the electrical events at the excitatory synapse. One might guess that if the nerve impulse results from an abrupt inflow of sodium ions and a rapid change in the electrical polarity of the axon's interior, something similar must happen at the body and dendrites of the nerve cell in order to generate the impulse in the first place. Indeed, the function of the excitatory synaptic terminals on the cell body and its dendrites is to depolarize the interior of the cell membrane essentially by permitting an inflow of sodium ions. When the depolarization reaches a threshold value, a nerve impulse is triggered.
 As a simple instance of this phenomenon we have recorded the depolarization that occurs in a single motoneuron activated directly by the large nerve fibers that enter the spinal cord from special stretch-receptors known as annulospiral endings. These receptors in turn are found in the same muscle that is activated by the motoneuron under study. Thus the whole system forms a typical reflex arc, such as the arc responsible for the patellar reflex, or ‘knee jerk.’
 To conduct the experiment we anesthetize an animal (most often a cat) and free by dissection a muscle nerves that contains these large nerve fibers. By applying a mild electric shock to the exposed nerve one can produce a single impulse in each of the fibers; Since the impulses travel to the spinal cord almost synchronously, they are referred to collectively as a volley. The number of impulses contained in the volley can be reduced by reducing the stimulation applied to the nerve. The volley strength is measured at a point just outside the spinal cord and is displayed on an oscilloscope. About half a millisecond after detection of a volley there is a wavelike change in the voltage inside the motoneuron that has received the volley. The change is detected by a microelectrode inserted in the motoneuron and is displayed on another oscilloscope.
 What we find is that the negative voltage inside the cell becomes progressively fewer negative as more of the fibers impinging on the cell are stimulated to fire. This observed depolarization is in fact a simple summation of the depolarization produced by each individual synapse. When the depolarization of the interior of the motoneuron reaches a critical point, a ‘spike’ suddenly appears on the second oscilloscope, showing that a nerve impulse has been generated. During the spike the voltage inside the cell changes from about 70 millivolts negative to as much as 30 millivolts positive. The spike regularly appears when the depolarization, or reduction of membrane potential, reaches a critical level, which is usually between 10 and 18 millivolts. The only effect of a further strengthening of the synaptic stimulus is to shorten the time needed for the motoneuron to reach the firing threshold. The depolarizing potentials produced in the cell membrane by excitatory synapses are called excitatory postsynaptic potentials, or EPSP's.
 Through one barrel of a double-barreled microelectrode one can apply a background current to change the resting potential of the interior of the cell membrane, either increasing it or decreasing it. When the potential is made more negative, the EPSP rises more steeply to an earlier peak. When the potential is made less negative, the EPSP rises more slowly to a lower peak. Finally, when the charge inside the cell is reversed so as to be positive with respect to the exterior, the excitatory synapses give rise to an EPSP that is actually the reverse of the normal one.
 These observations support the hypothesis that excitatory synapses produce what amounts virtually to a short circuit in the synaptic membrane potential. When this occurs, the membrane no longer acts as a barrier to the passage of ions but lets them flow through in response to the differing electric potential on the two sides of the membrane. In other words, the ions are momentarily allowed to travel freely down their electrochemical gradients, which means that the sodium ions flow into the cell and, to a lesser degree, potassium ions flow out. It is this net flow of positive ions that creates the excitatory postsynaptic potential. The flow of negative ions, such as the chloride ion, is apparently not involved. By artificially altering the potential inside the cell one can establish that there is no flow of ions, and therefore no EPSP, when the voltage drop across the membrane is zero.
 How is the synaptic membrane converted from a strong ionic barrier into an ion-permeable state? It is currently accepted that the agency of conversion is the chemical transmitter substance contained in the vesicles inside the synaptic knob. When a nerve impulse reaches the synaptic knob, some of the vesicles are caused to eject the transmitter substance into the synaptic cleft. The molecules of the substance would take only a few microseconds to diffuse across the cleft and become attached to specific receptor sites on the surface membrane of the adjacent nerve cell.
 Presumably the receptor sites are associated with fine channels in the membrane that are opened in some way by the attachment of the transmitter-substance molecules to the receptor sites. With the channels thus opened, sodium and potassium ions flow through the membrane thousands of times more readily than they normally do, by that producing the intense ionic flux that depolarizes the cell membrane and produces the EPSP. In many synapses the current flows strongly for only about a millisecond before the transmitter substance is eliminated from the synaptic cleft, either by diffusion into the surrounding regions or as a result of being destroyed by enzymes. The latter process is known to occur when the transmitter substance is acetylcholine, which is destroyed by the enzyme acetylcholinesterase.
 The substantiation of this general picture of synaptic transmission requires the solution of many fundamental problems. Since we do not know the specific transmitter substance for the vast majority of synapses in the nervous system, we do not know whether there are many different substances or only a few. The only one identified with reasonable certainty in the mammalian central nervous system is acetylcholine. We know practically nothing about the mechanism by which a presynaptic nerve impulse causes the transmitter substance to be injected into the synaptic cleft. Nor do we know how the synaptic vesicles not immediately next to the synaptic cleft follow to moved up to the firing line to replace the emptied vesicles. It is supposed that the vesicles contain the enzyme systems needed to recharge themselves. The entire process must be swift and efficient: The total amount of transmitter substance in synaptic terminals is enough for only a few minutes of synaptic activity at normal operating rates. There are also knotty problems to be solved on the other side of the synaptic cleft. What, for example, is the nature of the receptor sites? How are the ionic channels in the membrane opened?
 The second type of synapse that has been identified in the nervous system. These are the synapses that can inhibit the firing of a nerve cell even though it may be receiving a volley of excitatory impulses. When inhibitory synapses are examined in the electron microscope, they look very much like excitatory synapses. (There are probably some subtle differences, but they need not concern us here.) Microelectrode recordings of the activity of single motoneurons and other nerve cells have now shown that the inhibitory postsynaptic potential (IPSP) is virtually a mirror image of the EPSP. Moreover, individual inhibitory synapses, like excitatory synapses, have a cumulative effect. The chief difference is simply that the IPSP makes the cell's internal voltage more negative than it is normally, which is in a direction opposite to that needed for generating a spike discharge.
 By driving the internal voltage of a nerve cell in the negative direction inhibitory synapses oppose the action of excitatory synapses, which of course drive it in the positive direction. So if the potential inside a resting cell is 70 millivolts negative, a strong volley of inhibitory impulses can drive the potential to 75 or 80 millivolts depreciating count. One can easily see that if the potential is made more negative in this way the excitatory synapses find it more difficult to raise the internal voltage to the threshold point for the generation of a spike. Thus, the nerve cell responds to the algebraic sum of the internal voltage changes produced by excitatory and inhibitory synapses.
 If, as in the experiment described earlier, the internal membrane potential is altered by the flow of an electric current through one barrel of a double-barreled microelectrode, one can observe the effect of such changes on the inhibitory postsynaptic potential. When the internal potential is made less negative, the inhibitory postsynaptic potential is deepened. Conversely, when the potential is made more negative, the IPSP diminishes; it finally reverses when the internal potential is driven below minus 80 millivolts.
 One can therefore assume that inhibitory synapse’s share with excitatory synapses the ability to change the ionic permeability of the synaptic membrane. The difference is that inhibitory synapses enable ions to flow freely down an electrochemical gradient that has an equilibrium point at minus 80 millivolts rather than at zero, as is the case for excitatory synapses. This effect could be achieved by the outward flow of positively charged ions such as potassium or the inward flow of negatively charged ions such as chloride, or by a combination of negative and positive ionic flows such that the interior reaches equilibrium at minus 80 millivolts.
 If the concentration of chloride ions within the cell is increased as much as three times, the inhibitory postsynaptic potential reverses and acts as a depolarizing current; that is, it resembles an excitatory potential. On the other hand, if the cell is heavily injected with sulfate ions, which are also negatively charged, there is no such reversal. This simple test shows that under the influence of the inhibitory transmitter substance, which is still unidentified, the subsynaptic membrane becomes permeable momentarily to chloride ions but not to sulfate ions. During the generation of the IPSP the outflow of chloride ions is so rapid that it more than outweighs the flow of other ions that generate the normal inhibitory potential.
 The effect of injecting motoneurons with more than 30 kinds of negatively lunged ions. With one exception the hydrated ions (ions bound to water) to which the cell membrane is permeable under the influence of the inhibitory transmitter substance are smaller than the hydrated ions to which the membrane is impermeable. The exception is the formate ion (HCO2-), which may have an ellipsoidal shape and so be able to pass through membrane pores that block smaller spherical ions.
 Apart from the formate ion all the ions to which the membrane is permeable have a diameter not greater than 1.14 times the diameter of the potassium ion; That is, they are less than 2.9 angstrom units in diameter. Comparable investigations in other laboratories have found the same permeability effects, including the exceptional behavior of the formate ion, in fishes, toads and snails. It might be that the ionic mechanism responsible for synaptic inhibition is the same throughout the animal kingdom.
 The significance of these and other studies is that they strongly suggest that the inhibitory transmitter substance open the membrane to the flow of potassium ions but not to sodium ions. It is known that the sodium ion is somewhat larger than any of the negatively charged ions, including the formate ion, that are able to pass through the membrane during synaptic inhibition. Testing the effectiveness of potassium ions by injecting excess amounts into the cell is not possible, however, because the excess is immediately diluted by an osmotic flow of water into the cell.
 The concentration of potassium ions inside the nerve cell is about 30 times greater than the concentration outside, and to maintain this large difference in concentration without the help of some metabolic pumps inside of the membrane would have to be charged 90 millivolts negative with respect to the exterior. This implies that if the membrane were suddenly made porous to potassium ions, the resulting outflow of ions would make the inside potential of the membrane even more negative than it is in the resting state, and that is just what happens during synaptic inhibition. The membrane must not simultaneously become porous to sodium ions, because they exist in much higher concentration outside the cell than inside and their rapid inflow would more than compensate for the potassium outflow. In fact, the fundamental difference between synaptic excitation and synaptic inhibition is that the membrane freely passes sodium ions in response to the former and largely excludes the passage of sodium ions in response to the latter.
 This fine discrimination between ions that are not very different in size must be explained by any hypothesis of synaptic action. It is most unlikely that the channels through the membrane are created afresh and accurately maintained for a thousandth of a second every time a burst of transmitter substance is released into the synaptic cleft. It is more likely that channels of at least two different sizes are built directly into the membrane structure. In some way the excitatory transmitter substance would selectively unplug the larger channels and permit the free inflow of sodium ions. Potassium ions would simultaneously flow out and thus would tend to counteract the large potential change that would be produced by the massive sodium inflow. The inhibitory transmitter substance would selectively unplug the smaller channels that are large enough to pass potassium and chloride ions but not sodium ions.
 To explain certain types of inhibition other features must be added to this hypothesis of synaptic transmission. In the simple hypothesis chloride and potassium ions can flow freely through pores of all inhibitory synapses. It has been shown, however, that the inhibition of the contraction of heart muscle by the vagus nerve is due almost exclusively to potassium-ion flow. On the other hand, in the muscles of crustaceans and in nerve cells in the snail's brain synaptic inhibition is due largely to the flow of chloride ions. This selective permeability could be explained if there were fixed charges along the walls of the channels. If such charges were negative, they would repel negatively charged ions and prevent their passage; if they were positive, they would similarly prevent the passage of positively charged ions. One can now suggest that the channels opened by the excitatory transmitter are negatively charged and so do not permit the passage of the negatively charged chloride ion, even though it is small enough to move through the channel freely.
 One might wonder if a given nerve cell can have excitatory synaptic action at some of its axon terminals and inhibitory action at others. The answer is no. Two different kinds of nerve cells are needed, one for each type of transmission and synaptic transmitter substance. This can readily be shown by the effect of strychnine and tetanus toxins in the spinal cord; They specifically prevent inhibitory synaptic action and leave excitatory action unaltered. As a result the synaptic excitation of nerve cells is uncontrolled and convulsions result. The special types of cells responsible for inhibitory synaptic action are now being recognized in many parts of the central nervous system.
 This account of communication between nerve cells is necessarily oversimplified, yet it shows that some significant advances are being made at the level of individual components of the nervous system. By selecting the most favorable situations we have been able to throw light on some details of nerve-cell behavior. We can be encouraged by these limited successes. Nevertheless, the task of understanding in a comprehensive way how the human brain operates staggers its own imagination.
 Our brain begins with its portion of the central nervous system contained within the skull. The brain is the control center for movement, sleep, hunger, thirst, and virtually every other vital activity necessary to survival. All human emotions - including love, hate, fear, anger, elation, and sadness - are controlled by the brain. It also receives and interprets the countless signals that are sent to it from other parts of the body and from the external environment. The brain makes us conscious, emotional, and intelligent
 The human brain has three major structural components: the large dome-shaped cerebrum, the smaller somewhat spherical cerebellum, and the brainstem. Prominent in the brainstem are the medulla oblongata and the thalamus - between the medulla and the cerebrum. The cerebrum is responsible for intelligence and reasoning. The cerebellum helps to maintain balance and posture. The medulla is involved in maintaining involuntary functions such as respiration, and the thalamus act as a relay center for electrical impulses traveling to and from the cerebral cortex.
 The adult human brain is a 1.3-kg. (3-lb.) Mass of pinkish-gray jellylike tissue made up of approximately 100 billion nerve cells or neurons: The Neuroglia (supporting-tissue) cells, and vascular (blood-carrying) and other tissues.
 Between the brain and the cranium - the part of the skull that directly covers the brain - are three protective membranes, or meninges. The outermost membrane, the dura mater, is the toughest and thickest. Below the dura mater is a middle membrane, called the arachnoid layer. The innermost membrane, the pia mater, consists mainly of small blood vessels and follows the contours of the surface of the brain.
 A clear liquid, the cerebrospinal fluid, bathes the entire brain and fills a series of four cavities, called ventricles, near the center of the brain. The cerebrospinal fluid protects the internal portion of the brain from varying pressures and transports chemical substances within the nervous system.
 From the outside, the brain appears as three associatively distinct but connected parts, the cerebrum (the Latin word for brain) - two large, almost symmetrical hemispheres; the cerebellum ('little brain') - two smaller hemispheres located at the back of the cerebrum; and the brain stem - a central core that gradually becomes the spinal cord, exiting the skull through an opening at its base called the foramen magnum. Two other major parts of the brain, the thalamus and the hypothalamus, lie in the midline above the brain stem underneath the cerebellum.
 The brain and the spinal cord together make up the central nervous system, which communicates with the rest of the body through the peripheral nervous system. The peripheral nervous system consists of 12 pairs of cranial nerves extending from the cerebrum and brain stem; a system of other nerves branching throughout the body from the spinal cord, and the autonomic nervous system, which regulates vital functions is not very consciously of its own control, such as the activity of the heart muscle, smooth muscle (involuntary muscle found in the skin, blood vessels, and internal organs), and glands.
 Many motor and sensory functions have been ‘mapped’ to specific areas of the cerebral cortex, some of which are indicated here. In general, these areas exist in both hemispheres of the cerebrum, each serving the opposite side of the body. Fewer defined are the areas of association, located mainly in the frontal cortex, operatives in functions of thought and emotion and responsible for linking input from different senses. The areas of language are an exception: Both Wernicke’s area, concerned with the comprehension of spoken language, and Broca’s area, governing the production of speech, have been pinpointed on the cortex. 
 Most high-level brain functions take place in the cerebrum. Its two large hemispheres make up approximately 85 percent of the brain's weight. The exterior surface of the cerebrum, the cerebral cortex, is a convoluted, or folded, grayish layer of cell bodies known as the gray matter. The gray matter covers an underlying mass of fibers called the white matter. The convolutions are made up of ridgelike bulges, known as gyri, separated by small grooves called sulci and larger grooves called fissures. Approximately two-thirds of the cortical surface is hidden in the folds of the sulci. The extensive convolutions enable a very large surface area of brain cortices - roughly, 1.5 m2  (16 ft2) in an adult - to fit within the cranium. The pattern of these convolutions is similar, although not identical, in all humans.
 The two cerebral hemispheres are partially separated from each other by a deep fold known as the longitudinal fissure. Communication between the two hemispheres is through several concentrated bundles of axons, called commissures, the largest of which is the corpus callosum.
 Several major sulci divides the cortex into distinguishable regions. The central sulcus, or Rolandic fissure, runs from the middle of the top of each hemisphere downward, forwards, and toward another major sulcus, the lateral (side), or Sylvian, sulcus. These and other sulci and gyri divide the cerebrum into five lobes: The frontal, parietal, temporal, and occipital lobes and the insula.
 Although the cerebrum is symmetrical in structure, with two lobes emerging from the brain stem and matching motor and sensory areas in each, certain intellectual functions are restricted to one hemisphere. A person’s dominant hemisphere is usually occupied with language and logical operations, while the other hemisphere controls emotion and artistic and spatial skills. In nearly all right-handed and many left-handed people, the left hemisphere is dominant.
 The frontal lobe is the largest of the five and consists of all the cortices in front of the central sulcus. Broca's area, a part of the cortex related to speech, is located in the frontal lobe. The parietal lobe consists of the cortex behind the central sulcus to some sulcus near the back of the cerebrum known as the parieto-occipital sulcus. The parieto-occipital sulcus, in turn, forms the front border of the occipital lobe, which are the rearmost part of the cerebrum. The temporal lobe is to the side of and below the lateral sulcus. Wernicke's area, a part of the cortex related to the understanding of language, is located in the temporal lobe. The insula lies deep within the folds of the lateral sulcus.
 The cerebrum receives information from all the sense organs and sends motor commands (signals that results in activity in the muscles or glands) to other parts of the brain and the rest of the body. Motor commands are transmitted by the motor cortex, a strip of cerebral cortex extending from side to side across the top of the cerebrum just in front of the central sulcus. The sensory cortex, parallel strips of cerebral cortex just in back of the central sulcus, receives input from the sense organs.
 Many other areas of the cerebral cortex have also been mapped according to their specific functions, such as vision, hearing, speech, emotions, language, and other aspects of perceiving, thinking, and remembering. Cortical regions known as associative cortices are responsible for integrating multiple inputs, processing the information, and carrying out complex responses.
 The cerebellum coordinates body movements. Located at the lower back of the brain beneath the occipital lobes, the cerebellum is divided into two lateral (side-by-side) lobes connected by a fingerlike bundle of white fibers called the vermis. The outer layer, or cortex, of the cerebellum consists of fine folds called folia. As in the cerebrum, the outer layer of cortical gray matter surrounds a deeper layer of white matter and nuclei (groups of nerve cells). Three fiber bundles called cerebellar peduncles connect the cerebellum to the three parts of the brain stem - the midbrain, the pons, and the medulla oblongata.
 The cerebellum coordinates voluntary movements by fine-tuning commands from the motor cortex in the cerebrum. The cerebellum also maintains posture and balance by controlling muscle tone and sensing the position of the limbs. All motor activity, from hitting a baseball to fingering a violin, depends on the cerebellum.
 The limbic system is a group of brain structures that play a role in emotion, memory, and motivation. For example, electrical stimulation of the amygdala in laboratory animals can provoke fear, anger, and aggression. The hypothalamus regulates hunger, thirst, sleep, body temperature, sexual drive, and other functions.
 The thalamus and the hypothalamus lie underneath the cerebrum and connect it to the brain stem. The thalamus consist of two rounded masses of gray tissue lying within the middle of the brain, between the two cerebral hemispheres. The thalamus are the main relay station for incoming sensory signals to the cerebral cortex and for outgoing motor signals from it. All sensory input to the brain, except that of the sense of smell, connects to individual nuclei of the thalamus.
 The hypothalamus lies beneath the thalamus on the midline at the base of the brain. It regulates or is involved directly in the control of many of the body's vital drives and activities, such as eating, drinking, temperature regulation, sleep, emotional behavior, and sexual activity. It also controls the function of internal body organs by means of the autonomic nervous system, interacts closely with the pituitary gland, and helps coordinate activities of the brain stem.
 The brain stem, shown here in colored cross section, is the lowest part of the brain. It serves as the path for messages traveling between the upper brain and spinal cord but is also the seat of basic and vital functions such as breathing, blood pressure, and heart rates, as well as reflexes like eye movement and vomiting. The brain stem has three main parts: the medulla, pons, and midbrain. A canal runs longitudinally through these structures carrying cerebrospinal fluid. Also distributed along its length is a network of cells, referred to as the reticular formation, that governs the state of alertness.
 The brain stem is revolutionarily the most primitive part of the brain and is responsible for sustaining the basic functions of life, such as breathing and blood pressure. It includes three main structures lying between and below the two cerebral hemispheres - the midbrain, pons, and medulla oblongata.
  The topmost structure of the brain stem is the midbrain. It contains major relay stations for neurons transmitting signals to the cerebral cortex, as well as many reflex centers - pathways carrying sensory (input) information and motor (output) command. Relays and reflex centers for visual and auditory (hearing) functions are located in the top portion of the midbrain. A pair of nuclei called the superior colliculus control reflex actions of the eye, such as blinking, opening and closing the pupil, and focusing the lens. A second pair of nuclei, called the inferior colliculus, controls auditory reflexes, such as adjusting the ear to the volume of sound. At the bottom of the midbrain are reflex and relay centers relating to pain, temperature, and touch, as well as several regions associated with the control of movement, such as the red nucleus and the substantia nigra.
 Continuous with and below the midbrain and directly in front of the cerebellum is a prominent bulge in the brain stem called the pons. The pons consists of large bundles of nerve fibers that connect the two halves of the cerebellum and also connect each side of the cerebellum with the opposite-side cerebral hemisphere. The pons serves mainly as a relay station linking the cerebral cortex and the medulla oblongata.
 The long, stalklike lowermost portion of the brain stem is called the medulla oblongata. At the top, it is continuous with the pons and the midbrain; at the bottom, it makes a gradual transition into the spinal cord at the foramen magnum. Sensory and motor nerve fibers connecting the brain and the rest of the body cross over to the opposite side as they pass through the medulla. Thus, the left half of the brain communicates with the right half of the body, and the right half of the brain with the left half of the body.
 Running up the brain stem from the medulla oblongata through the pons and the midbrain is a netlike formation of nuclei known as the reticular formation. The reticular formation controls respiration, cardiovascular function, digestion, levels of alertness, and patterns of sleep. It also determines which parts of the constant flow of sensory information into the body are received by the cerebrum.
 There are two main types of brain cells, neurons and neuroglia. Neurons are responsible for the transmission and analysis of all electrochemical communication within the brain and other parts of the nervous system. Each neuron is composed of a cell body called a soma, and a major fiber called an axon, and a system of branches called dendrites. Axons, also called nerve fibers, convey electrical signals away from the soma and can be up to 1 m. (3.3 ft.) in length. Most axons are covered with a protective sheath of myelin, a substance made of fats and protein, which insulates the axon. Myelinated axons conduct neuronal signals faster than do unmyelinated axons. Dendrites convey electrical signals toward the soma, are shorter than axons, and are usually multiple and branching.
 Neuroglial cells are twice as numerous as neurons and account for half of the brain's weight. Neuroglia (from glia, Greek for 'glue') provides structural support to the neurons. Neuroglial cells also form myelin, guide developing neurons, take up chemicals involved in cell-to-cell communication, and contribute to the maintenance of the environment around neurons.
 Twelve pairs of cranial nerves arise symmetrically from the base of the brain and are numbered, from front to back, in the order in which they arise. They connect mainly with structures of the head and neck, such as the eyes, ears, nose, mouth, tongue, and throat. Some are motor nerves, controlling muscle movement; some are sensory nerves, conveying information from the sense organs; and others contain fibers for both sensory and motor impulses. The first and second pairs of cranial nerves - the olfactory (smell) nerves and the optic (vision) nerve - carry sensory information from the nose and eyes, respectively, to the undersurface of the cerebral hemispheres. The other ten pairs of cranial nerves originate in or end in the brain stem.
 The brain functions by complex neuronal, or nerve cell, circuits. Communication between neurons is both electrical and chemical and always travels from the dendrites of a neuron, through its soma, and out its axon to the dendrites of another neuron.
 Dendrites of one neuron receive signals from the axons of other neurons through chemicals known as neurotransmitters. The neurotransmitters set off electrical charges in the dendrites, which then carry the signals electrochemically to the soma. The soma integrates the information, which is then transmitted electrochemically down the axon to its tip.
 At the tip of the axon, small, bubble-like structures called vesicles’ release neurotransmitters that carries the signal across the synapse, or gap, between two neurons. There are many types of neurotransmitters, including norepinephrine, dopamine, and serotonin. Neurotransmitters can be excitatory (that is, they excite an electrochemical response in the dendrite receptors) or inhibitory (they block the response of the dendrite receptors).
 One neuron may communicate with thousands of other neurons, and many thousands of neurons are involved with even the simplest behavior. It is believed that these connections and their efficiency can be modified, or altered, by experience.
 Scientists have used two primary approaches to studying how the brain works. One approach is to study brain function after parts of the brain have been damaged. Functions that disappear or that is no longer normal after injury to specific regions of the brain can often be associated with the damaged areas. The second approach is to study the response of the brain to direct stimulation or to stimulation of various sense organs.
 Neurons are grouped by function into collections of cells called nuclei. These nuclei are connected to form sensory, motor, and other systems. Scientists can study the function of somatosensory (pain and touch), motor, olfactory, visual, auditory, language, and other systems by measuring the physiological (physical and chemical) change that occur in the brain when these senses are activated. For example, electroencephalography (EEG) measures the electrical activity of specific groups of neurons through electrodes attached to the surface of the skull. Electrodes incorporate directly into the brain can give readings of individual neurons. Changes in blood flow, glucose (sugar), or oxygen consumption in groups of active cells can also be mapped.
 Although the brain appears symmetrical, how it functions is not. Each hemisphere is specializing and dominates the other in certain functions. Research has shown that hemispheric dominance is related to whether a person is predominantly right-handed or left-handed. In most right-handed people, the left hemisphere processes arithmetic, language, and speech. The right hemisphere interprets music, complex imagery, and spatial relationships and recognizes and expresses emotion. In left-handed people, the pattern of brain organization is more variable.
 Hemispheric specialization has traditionally been studied in people who have sustained damage to the connections between the two hemispheres, as may occur with a stroke, an interruption of blood flow to an area of the brain that causes the death of nerve cells in that area. The division of functions between the two hemispheres has also been studied in people who have had to have the connection between the two hemispheres surgically cut in order to control severe epilepsy, a neurological disease characterized by convulsions and loss of consciousness.
 The visual system of humans is one of the most advanced sensory systems in the body. More information is conveyed visually than by any other means. In addition to the structures of the eye itself, several cortical regions - collectively called a primary visual and visual associative cortex - as well as the midbrain are involved in the visual system. Conscious processing of visual input occurs in the primary visual cortex, but reflexive - that is, immediate and unconscious - responses occur at the superior colliculus in the midbrain. Associative cortical regions - specialized regions that can associate, or integrate, multiple inputs - in the parietal and frontal lobes along with parts of the temporal lobe are also involved in the processing of visual information and the establishment of visual memories.
 Language involves specialized cortical regions in a complex interaction that allows the brain to comprehend and communicate abstract ideas. The motor cortex initiates impulses that travel through the brain stem to produce audible sounds. Neighboring regions of motor cortices, called the supplemental motor cortex, are involved in sequencing and coordinating sounds. Broca's area of the frontal lobe is responsible for the sequencing of language elements for output. The comprehension of language is dependent upon Wernicke's area of the temporal lobe. Other cortical circuits connect these areas.
 Memory is usually considered a diffusely stored associative process - that is, it puts together information from many different sources. Although research has failed to identify specific sites in the brain as locations of individual memories, certain brain areas are critical for memory to function. Immediate recall - the ability to repeat short series of words or numbers immediately after hearing them - is thought to be located in the auditory associative cortex. Short-term memory - the ability to retain a limited amount of information for up to an hour - is located in the deep temporal lobe. Long-term memory probably involves exchanges between the medial temporal lobe, various cortical regions, and the midbrain.
 The autonomic nervous system regulates the life support systems of the body reflexively - that is, without conscious direction. It automatically controls the muscles of the heart, digestive system, and lungs; Certain glands, and homeostasis - that is, the equilibrium of the internal environment of the body. The autonomic nervous system itself is controlled by nerve centers in the spinal cord and brain stem and is fine-tuned by regions higher in the brain, such as the midbrain and cortex. Reactions such as blushing indicate that cognitive, or thinking, centers of the brain are also involved in autonomic responses.
 The brain is guarded by several highly developed protective mechanisms. The bony cranium, the surrounding meninges, and the cerebrospinal fluid all contribute to the mechanical protection of the brain. In addition, a filtration system called the blood-brain barrier protects the brain from exposure to potentially harmful substances carried in the bloodstream.
 Brain disorders have a wide range of causes, including head injury, stroke, bacterial diseases, complex chemical imbalances, and changes associated with aging.
 Head injury can initiate a cascade of damaging events. After a blow to the head, a person may be stunned or may become unconscious for a moment. This injury, called - concussion, - usually leaves no permanent damage. If the blow is more severe and hemorrhage (excessive bleeding) and swelling occurs, however, severe headache, dizziness, paralysis, a convulsion, or temporary blindness may result, depending on the area of the brain affected. Damage to the cerebrum can also result in profound personality changes.
 Damage to Broca's area in the frontal lobe causes difficulty in speaking and writing, a problem known as Broca's aphasia. Injury to Wernicke's area in the left temporal lobe results in an inability to comprehend spoken language, called Wernicke's aphasia.
 An injury or disturbance to a part of the hypothalamus may cause a variety of different symptoms, such as loss of appetite with an extreme drop in body weight, increase in appetite leading to obesity; Extraordinary thirst with excessive urination (diabetes insipidus), failure in body-temperature control, resulting in either low temperature (hypothermia) or high temperature (fever), excessive emotionality, and uncontrolled anger or aggression. If the relationship between the hypothalamus and the pituitary gland is damaged, other vital bodily functions may be disturbed, such as sexual function, metabolism, and cardiovascular activity.
 Injury to the brain stem is even more serious because it houses the nerve centers that control breathing and heart action. Damage to the medulla oblongata usually results in immediate death.
 A stroke is damage to the brain due to an interruption in blood flow. The interruption may be caused by a blood clot, constriction of a blood vessel, or rupture of a vessel accompanied by bleeding. A pouchlike expansion of the wall of a blood vessel, called an aneurysm, may weaken and burst, for example, because of high blood pressure.
 Sufficient quantities of glucose and oxygen, transported through the bloodstream, are needed to keep nerve cells alive. When the blood supply to a small part of the brain is interrupted, the cells in that area die and the function of the area is lost. A massive stroke can cause a one-sided paralysis (hemiplegia) and sensory loss on the side of the body opposite the hemisphere damaged by the stroke.
 Some brain diseases, such as multiple sclerosis and Parkinson disease, are progressive, becoming worse over time. Multiple sclerosis damages the myelin sheath around axons in the brain and spinal cord. As a result, the affected axons cannot transmit nerve impulses properly. Parkinson disease destroys the cells of the substantia nigra in the midbrain, resulting in a deficiency in the neurotransmitter dopamine that affects motor functions.
 Cerebral palsy is a broad term for brain damage sustained close to birth that permanently affects motor function. The damage may take place either in the developing fetus, during birth, or just after birth and is the result of the faulty development or breaking down of motor pathways. Cerebral palsy is nonprogressive - that is, it does not worsen with time.
 A bacterial infection in the cerebrum or in the coverings of the brain, swelling of the brain, or an abnormal growth of healthy brain tissue can all cause an increase in intracranial pressure and result in serious damage to the brain.
 Scientists are finding that certain brain chemical imbalances are associated with mental disorders such as schizophrenia and depression. Such findings have changed scientific understanding of mental health and have resulted in new treatments that chemically correct these imbalances.
 During childhood development, the brain is particularly susceptible to damage because of the rapid growth and reorganization of nerve connections. Problems that originate in the immature brain can appear as epilepsy or other brain-function problems in adulthood.
 Several neurological problems are common in aging. Alzheimer's disease damages many areas of the brain, including the frontal, temporal, and parietal lobes. The brain tissue of people with Alzheimer's disease shows characteristic patterns of damaged neurons, known as plaques and tangles. Alzheimer's disease produces progressive dementia, characterized by symptoms such as failing attention and memory, loss of mathematical ability, irritability, and poor orientation in space and time.
 A magnetic resonance imaging (MRI) scan of the human brain reveals the contours of one of the brain’s hemispheres. The gyri, or ridges, appear in red, while the sulci, or valleys, are shown in blue. Each person has slightly different patterns of gyri and sulci, which reflect individual differences in brain development.
 Several commonly used diagnostic methods give images of the brain without invading the skull. Some portray anatomy - that is, the structure of the brain - whereas others measure brain function. Two or more methods may be used to complement each other, together providing a more complete picture than would be possible by one method alone.
 Magnetic resonance imaging (MRI), introduced in the early 1980s, beams high-frequency radio waves into the brain in a highly magnetized field that causes the protons that form the nuclei of hydrogen atoms in the brain to reemit the radio waves. The reemitted radio waves are analyzed by computer to create thin cross-sectional images of the brain. MRI provides the most detailed images of the brain and is safer than imaging methods that use X-rays. However, MRI is a lengthy process and also cannot be used with people who have pacemakers or metal implants, both of which are adversely affected by the magnetic field.
 Computed tomography (CT), also known as CT scans, developed in the early 1970s. This imaging method X-rays the brain from many different angles, feeding the information into a computer that produces a series of cross-sectional images. CT is particularly useful for diagnosing blood clots and brain tumors. It is a much quicker process than magnetic resonance imaging and is therefore advantageous in certain situations - for example, with people who are extremely ill.
 This positron emission tomography (PET) scans of the brain shows the activity of brain cells in the resting state and during three types of auditory stimulation. PET uses radioactive substances introduced within the brain to measure such brain functions as cerebral metabolism, blood flow and volume, oxygen use, and the formation of neurotransmitters. This imaging method collects data from many different angles, feeding the information into a computer that produces a series of cross-sectional images.
 Changes in brain function due to brain disorders can be visualized in several ways. Magnetic resonance spectroscopy measures the concentration of specific chemical compounds in the brain that may change during specific behaviors. Functional magnetic resonance imaging (fMRI) maps changes in oxygen concentration that correspond to nerve cell activity.
 Positron emission tomography (PET), developed in the mid-1970s, uses computed tomography to visualize radioactive tracers, radioactive substances are introduced into the brain intravenously or by inhalation. PET can measure such brain functions as cerebral metabolism, blood flow and volume, oxygen use, and the formation of neurotransmitters. Single photon emission computed tomography (SPECT), developed in the 1950s and 1960s, used radioactive tracers to visualize the circulation and volume of blood in the brain.
 Brain-imaging studies have provided new insights into sensory, motor, language, and memory processes, as well as brain disorders such as epilepsy, cerebrovascular disease; Alzheimer's, Parkinson, and Huntington's diseases, and various mental disorders, such as schizophrenia.
 Although all vertebrate brains share the same basic three-part structure, the development of their constituent parts varies across the evolutionary scale. In fish, the cerebrum is dwarfed by the rest of the brain and serves mostly to process input from the senses. In reptiles and amphibians, the cerebrum is proportionally larger and begins to connect and form conclusions about this input. Birds have well-developed optic lobes, making the cerebrum even larger. Among mammals, the cerebrum dominates the brain. It is most developed among primates, in whom cognitive ability is the highest.
 In lower vertebrates, such as fish and reptiles, the brain is often tubular and bears a striking resemblance to the early embryonic stages of the brains of more highly evolved animals. In all vertebrates, the brain is divided into three regions: the forebrain (prosencephalon), the midbrain (mesencephalon), and the hindbrain (rhombencephalon). These three regions further sub-divide into different structures, systems, nuclei, and layers.
 The more highly evolved the animal, the more complex is the brain structure. Human beings have the most complex brains of all animals. Evolutionary forces have also resulted in a progressive increase in the size of the brain. In vertebrates lower than mammals, the brain is small. In meat-eating animals, particularly primates, the brain increases dramatically in size.
 The cerebrum and cerebellum of higher mammals are highly convoluted in order to fit the most gray matter surface within the confines of the cranium. Such highly convoluted brains are called gyrencephalic. Many lower mammals have a smooth, or lissencephalic (smooth head), cortical surfaces.
 There is also evidence of evolutionary adaption of the brain. For example, many birds depend on an advanced visual system to identify food at great distances while in flight. Consequently, their optic lobes and cerebellum are well developed, giving them keen sight and outstanding motor coordination in flight. Rodents, on the other hand, as nocturnal animals, do not have a well-developed visual system. Instead, they rely more heavily on other sensory systems, such as a highly-developed sense of smell and facial whiskers.
 Recent research in brain function suggests that there may be sexual differences in both brain anatomy and brain function. One study indicated that men and women may use their brains differently while thinking. Researchers used functional magnetic resonance imaging to observe which parts of the brain were activated as groups of men and women tried to determine whether sets of nonsense words rhymed. Men used only Broca's area in this task, whereas women used Broca's area plus an area on the right side of the brain.
 The Cell, in [biology] is the most basic unit of life. Cells are the smallest structures capable of basic life processes, such as taking in nutrients, expelling waste, and reproducing. All living things are composed of cells. Some microscopic organisms, such as bacteria and protozoa, are unicellular, meaning they consist of a single cell. Plants, animals, and fungi are multicellular; that is, they are composed of a great many cells working in concert. But whether it makes up an entire bacterium or is just one of the trillions in a human being, the cell is a marvel of design and efficiency. Cells carry out thousands of biochemical reactions each minute and reproduce new cells that perpetuate life.
 The word cell refers to several types of organisms. Cells such as paramecia, dinoflagellates, diatoms, and spirochetes are self-maintaining organisms; cells such as lymphocytes, erythrocytes, muscle cells, nerve cells, cardiac muscle, and chromoplasts are more specializing cells that are a part of higher multicellular organisms. Nonetheless, of its size or whether the cell is a complete organism or just part of an organism, all cells have certain structural components in common. All cells have some type of outer cell boundary that permits some materials to leave and enter the cell and a cell interior composed of a water-rich, fluid material called cytoplasm that contains hereditary material in the form of deoxyribonucleic acid (DNA).
 Cells vary considerably in size. The smallest cell, a type of bacterium known as a mycoplasma, measures 0.0001 mm. (0.000004 in.) in diameter; 10,000 mycoplasmas in a row are only as wide as the diameter of a human hair. Among the largest cells are the nerve cells that run down a giraffe’s neck; these cells can exceed 3 m. (9.7 ft.) in length. Human cells also display a variety of sizes, from small red blood cells that measure 0.00076 mm. (0.00003 in.) to liver cells that may be ten times larger. About 10,000 average-sized human cells can fit on the head of a pin.
 Along with their differences in size, cells present an array of shapes. Some, such as the bacterium Escherichia coli, resemble rods. The paramecium, a type of protozoan, is a slipper shaped.  The amoeba, another protozoan, has an irregular form that changes shape as it moves around. Plant cells typically resemble boxes or cubes. In humans, the outermost layers of skin cells are flat, while muscle cells are long and thin. Some nerve cells, with their elongated, tentacle-like extensions, suggest an octopus.
 In multicellular organisms, shape is typically tailored to the cell’s job. For example, flat skin cells pack tightly into a layer that protects the underlying tissues from invasions by bacteria. Long, thin muscle cells’ contract readily to move bones. The numerous extensions from a nerve cell enable it to connect to several other nerve cells in order to send and receive messages rapidly and efficiently.
 By itself, each cell is a model of independence and self-containment. Like some miniature, walled city in perpetual rush hour, the cell constantly bustles with traffic, shuttling essential molecules from place to place to carry out the business of living. Despite their individuality, however, cells also display a remarkable ability to join, communicate, and coordinate with other cells. The human body, for example, consists of an estimated 20 to 30 trillion cells. Dozens of different kinds of cells are organized into specialized groups called tissues. Tendons and bones, for example, are composed of connective tissue, whereas skin and mucous membranes are built from epithelial tissue. Different tissue types are assembled into organs, which are structures specialized to perform particular functions. Examples of organs include the heart, stomach, and brain. Organs, in turn, are organized into systems such as the circulatory, digestive, or nervous systems. All together, these assembled organ systems form the human body.
 The components of cells are molecules, nonliving structures formed by the union of atoms. Small molecules serve as building blocks for larger molecules. Proteins, nucleic acids, carbohydrates, and lipids, which include fats and oils, are the four major molecules that underlie cell structure and also participate in cell functions. For example, a tightly organized arrangement of lipids, proteins, and protein-sugar compounds forms the plasma membrane, or outer boundary, of certain cells. The organelles, membrane-bound compartments in cells, are built largely from proteins. Biochemical reactions in cells are guided by enzymes, specialized proteins that speed up chemical reactions. The nucleic acid deoxyribonucleic acid (DNA) contains the hereditary information for cells, and another nucleic acid, ribonucleic acid (RNA), works with DNA to build the thousands of proteins the cell needs.
 Cells fall into one of two categories: Prokaryotic or eukaryotic, in a prokaryotic cell, found only in bacteria and archaebacteria, all the components, including the DNA, mingle freely in the cell’s interior, a single compartment. Eukaryotic cells, which make up plants, animals, fungi, and all other life forms, contain numerous compartments, or organelles, within each cell. The DNA in eukaryotic cells is enclosed in a special organelle called the nucleus, which serves as the cell’s command center and information library. The term prokaryote comes from Greek words that mean ‘before the nucleus’ or ‘prenucleus,’ while eukaryote means ‘a true nucleus.’
 Bacteria’s cells typically are surrounded by a rigid, protective cell wall. The cell membrane, also called the plasma membrane, regulates passage of materials into and out of the cytoplasm, the semi-fluid that fill the cell. The DNA, located in the nucleoid region, contains the genetic information for the cell. Ribosomes carry out protein synthesis. Many bacteria contain some pilus (plural pili), a structure that extends out of the cell to transfer DNA to another bacterium. The flagellum, found in numerous species, is used for the locomotion. Some bacteria contain a plasmid, a small chromosomes with extra genes. Others have a capsule, a sticky substance external to the cell wall that protects bacteria from attack by white blood cells. Mesosomes were formerly thought to be structures with unknown functions, but now are known to be artifacts created when cells are prepared for viewing with electron microscopes.
 Prokaryotic cells are among the tiniest of all cells, ranging in size from 0.0001 to 0.003 mm. (0.000004 to 0.0001 in.) in diameter. About a hundred typical prokaryotic cells lined up in a row would match the thickness of a book page. These cells, which can be rod-like, spherical, or spiral in shape, are surrounded by a protective cell wall. Like most cells, prokaryotic cells live in a watery environment, whether it is soil moisture, a pond, or the fluid surrounding cells in the human body. Tiny pores in the cell wall enable water and the substances dissolved in it, such as oxygen, to flow into the cell; these pores also allow wastes to flow out.
 Pushed up against the inner surface of the prokaryotic cell wall is a thin membrane called the plasma membrane. The plasma membrane, composed of two layers of flexible lipid molecules and interspersed with durable proteins, is both supple and strong. Unlike the cell wall, whose open pores allow the unregulated traffic of materials in and out of the cell, the plasma membrane is selectively permeable, meaning it allows only certain substances to pass through. Thus, the plasma membrane actively separates the cell’s contents from its surrounding fluids.
 While small molecules such as water, oxygen, and carbon dioxide diffuse freely across the plasma membrane, the passage of many larger molecules, including amino acids (the building blocks’ of proteins) and sugars, is carefully regulated. Specialized transport proteins accomplish this task. The transport proteins span the plasma membrane, forming an intricate system of pumps and channels through which traffic is conducted. Some substances swirling in the fluid around the cell can enter it only if they bind to and are escorted in by specific transport proteins. In this way, the cell fine-tunes its internal environment.
 The plasma membrane encloses the cytoplasm, the semifluid that fill the cell. Composed of about 65 percent water, the cytoplasm is packed with up to a billion molecules per cell, a rich storehouse that includes enzymes and dissolved nutrients, such as sugars and amino acids. The water provides a favorable environment for the thousands of biochemical reactions that take place in the cell.
 Within the cytoplasm of all prokaryote is deoxyribonucleic acid (DNA), a complex molecule in the form of a double helix, a shape similar to a spiral staircase. The DNA is about 1,000 times the length of the cell, and to fit inside, it repeatedly twists and folds to form a compact structure called a chromosome. The chromosome in prokaryote is circular, and is located in a region of the cell called the nucleoid. Often, smaller chromosomes called plasmids are located in the cytoplasm. The DNA is divided into units called genes, just like a long train is divided into separate cars. Depending on the species, the DNA contains several hundred or even thousands of genes. Typically, one gene contains coded instructions for building all or part of a single protein. Enzymes, which are specialized proteins, determine virtually all the biochemical reactions that support and sustain the cell.
 Also, immersed in the cytoplasm are the only organelles in prokaryotic cells.  Tiny bead-like structures called ribosomes. These are the cell’s protein factories. Following the instructions encoded in the DNA, ribosomes churn out proteins by the hundreds every minute, providing needed enzymes, the replacements for worn-out transport proteins, or other proteins required by the cell.
 While relatively simple in construction, prokaryotic cells display extremely complex activity. They have a greater range of biochemical reactions than those found in their larger relatives, the eukaryotic cells. The extraordinary biochemical diversity of prokaryotic cells is manifested in the wide-ranging lifestyles of the archaebacteria and the bacteria, whose habitats include polar ice, deserts, and hydrothermal vents - deep regions of the ocean under great pressure where hot water geysers erupt from cracks in the ocean floor.
 An animal cell typically contains several types of membrane-bound organs, or organelles. The nucleus directs activities of the cell and carries genetic information from generation to generation. The mitochondria generates energy for the cell. Proteins are manufactured by ribosomes, which are bound to the rough endoplasmic reticulum or float free in the cytoplasm. The Golgi apparatus modifies, packages, and distributes proteins while lysosomes store enzymes for digesting food. The entire cell is wrapped in a lipid membrane that selectively permits materials to pass in and out of the cytoplasm.
  Eukaryotic cells are typically about ten times larger than prokaryotic cells. In animal cells, the plasma membrane, rather than a cell wall, forms the cell’s outer boundary. With a design similar to the plasma membrane of prokaryotic cells, it separates the cell from its surroundings and regulates the traffic across the membrane.
 The eukaryotic cell cytoplasm is similar to that of the prokaryote cell except for one major difference: Eukaryotic cells house a nucleus and numerous other membrane-enclosed organelles. Like separate rooms of a house, these organelles enable specialized functions to be carried out efficiently. The building of proteins and lipids, for example, takes place in separate organelles where specialized enzymes geared for each job are located.
 The plasma membrane that surrounds eukaryotic cells is a dynamic structure composed of two layers of phospholipid molecules interspersed with cholesterol and proteins. Phospholipids are composed of a hydrophilic, or water-loving, head and two tails, which are hydrophobic, or water-hating. The two phospholipid layers face each other in the membrane, with the heads directed outward and the tails pointing inward. The water-attracting heads anchor the membrane to the cytoplasm, the watery fluid inside the cell, and also to the water surrounding the cell. The water-hating tails block large water-soluble molecules from passing through the membrane while permitting fat-soluble molecules, including medications such as tranquilizers and sleeping pills, to freely cross the membrane. Proteins embedded in the plasma membrane carry out a variety of functions, including transport of large water soluble molecules such as sugars and certain amino acids. Glycoproteins, proteins bonded to carbohydrates, serve in part to identify the cell as belonging to a unique organism, enabling the immune system to detect foreign cells, such as invading bacteria, which carry different glycoproteins. Cholesterol molecules in the plasma membrane act as stabilizers that limit the movement of the two slippery phospholipids layer, which slide back and forth in the membrane. Tiny gaps in the membrane enable small molecules such as oxygen to diffuse readily into and out of the cell. Since cells constantly use up oxygen, decreasing its concentration within the cell, the higher concentration of oxygen outside the cell causes a net flow of oxygen into the cell. The steady stream of oxygen into the cell enables it to carry out aerobic respiration continually, a process that provides the cell with the energy needed to carry out its functions.
 The nucleus is the largest organelle in an animal cell. It contains numerous strands of DNA, the length of each strand being many times the diameter of the cell. Unlike the circular prokaryotic DNA, long sectors of eukaryotic DNA pack into the nucleus by wrapping around proteins. As a cell begins to divide, each DNA strand folds over onto itself several times, forming a rod-shaped chromosome.
 The nucleus is surrounded by a double-layered membrane that protects the DNA from potentially damaging chemical reactions that occur in the cytoplasm. Messages pass between the cytoplasm and the nucleus through nuclear pores, which are holes in the membrane of the nucleus. In each nuclear pore, molecular signals flash back and forth as often as ten times per second. For example, a signal to activate a specific gene comes into the nucleus and instructions for production of the necessary protein go out to the cytoplasm.
 The nucleus, present in eukaryotic cells, is a discrete structure containing chromosomes, which hold the genetic information for the cell. Separated from the cytoplasm of the cell by a double-layered membrane called the nuclear envelope, and the nucleus contains a cellular material called nucleoplasm. Nuclear pores, present around the circumference of the nuclear membrane, allow the exchange of cellular materials between the nucleoplasm and the cytoplasm.
 Attached to the nuclear membrane is an elongated membranous sac called the endoplasmic reticulum. This organelle tunnels through the cytoplasm, folding back and forth on itself to form a series of membranous stacks. Endoplasmic reticulums take two forms: Rough and smooth. A rough endoplasmic reticulum (RER) is so called because it appears bumpy under a microscope. The bumps are actually thousands of ribosomes attached to the membrane’s surface. The ribosomes in eukaryotic cells have the same function as those in prokaryotic cells - protein synthesis - but they differ slightly in structure. Eukaryote ribosomes bound to the endoplasmic reticulum help assemble proteins that typically are exported from the cell. The ribosomes work with other molecules to link amino acids to partially completed proteins. These incomplete proteins then travel to the inner chamber of the endoplasmic reticulum, where chemical modifications, such as the addition of a sugar, are carried out. Chemical modifications of lipids are also carried out in the endoplasmic reticulum.
 The endoplasmic reticulum and its bound ribosomes are particularly dense in cells that produce many proteins for export, such as the white blood cells of the immune system, which produce and secrete antibodies. Some ribosomes that manufacture proteins are not attached to the endoplasmic reticulum. These so-called free ribosomes are dispersed in the cytoplasm and typically make proteins - many of them enzymes - that remain in the cell.
 The second form of an endoplasmic reticulum, the smooth endoplasmic reticulum (SER), lacks ribosomes and has an even surface. Within the winding channels of the smooth endoplasmic reticulum are the enzymes needed for the construction of molecules such as carbohydrates and lipids. The smooth endoplasmic reticulum is prominent in liver cells, where it also serves to detoxify substances such as alcohol, drugs, and other poisons.
 Proteins are transported from free and bound ribosomes to the Golgi apparatus, an organelle that resembles a stack of deflated balloons. It is packed with enzymes that complete the processing of proteins. These enzymes add sulfur or phosphorus atoms to certain regions of the protein, for example, or chop off tiny pieces from the ends of the proteins. The completed protein then leaves the Golgi apparatus for its final destination inside or outside the cell. During its assembly on the ribosome, each protein has acquired a group of from 4 to 100 amino acids called a signal. The signal works as a molecular shipping label to direct the protein to its proper location.
 Lysosomes are small, often spherical organelles that function as the cell’s recycling center and garbage disposal. Powerful digestive enzymes concentrated in the lysosome break down worn-out organelles and ship their building blocks to the cytoplasm where they are used to construct new organelles. Lysosomes also dismantle and recycle proteins, lipids, and other molecules.
 The mitochondria is the powerhouse of the cell. Within these long, slender organelles, which can appear oval or bean shaped under the electron microscope, enzymes convert the sugar glucose and other nutrients into adenosine triphosphate (ATP). This molecule, in turn, serves as an energy battery for countless cellular processes, including the shuttling of substances across the plasma membrane, the building and transport of proteins and lipids, the recycling of molecules and organelles, and the dividing of cells. Muscle and liver cells are particularly active and require dozens and sometimes up to hundreds mitochondria per cell to meet their energy needs. Mitochondria is unusual in that they contain their own DNA in the form of a prokaryote-like circular chromosome; Have their own ribosomes, which resemble prokaryotic ribosomes, and divide independently of the cell.
 Unlike the tiny prokaryotic cell, the relatively large eukaryotic cell requires structural support. The cytoskeleton, a dynamic network of protein tubes, filaments, and fibers, crisscrosses the cytoplasm, anchoring the organelles in place and providing shape and structure to the cell. Many components of the cytoskeleton are assembled and disassembled by the cell as needed. During cell division, for example, a special structure called a spindle is built to move chromosomes around. After cell division, the spindle, no longer needed, is dismantled. Some components of the cytoskeleton serve as microscopic tracks along which proteins and other molecules travel like miniature trains. Recent research suggests that the cytoskeleton also may be a mechanical communication structure that converses with the nucleus to help organize events in the cell.
 Plant cells have all the components of animal cells and boast several added features, including chloroplasts, a central vacuole, and a cell wall. Chloroplasts convert light energy - typically from the Sun - into the sugar glucose, a form of chemical energy, in a process known as photosynthesis. Chloroplasts, like mitochondria, possess a circular chromosome and prokaryote-like ribosomes, which manufacture the proteins that the chloroplasts typically need.
 The central vacuole of a mature plant cell typically takes up most of the room in the cell. The vacuole, a membranous bag, crowds the cytoplasm and organelles to the edges of the cell. The central vacuole stores water, salts, sugars, proteins, and other nutrients. In addition, it stores the blue, red, and purple pigments that give certain flowers their colors. The central vacuole also contains plant wastes that taste bitter to certain insects, thus discouraging the insects from feasting on the plant.
 In plant cells, a sturdy cell wall surrounds and protects the plasma membrane. Its pores enable materials to pass freely into and out of the cell. The strength of the wall also enables a cell to absorb water into the central vacuole and swell without bursting. The resulting pressure in the cells provides plants with rigidity and support for stems, leaves, and flowers. Without sufficient water pressure, the cells collapse and the plant wilts.
 To stay alive, cells must be able to carry out a variety of functions. Some cells must be able to move, and most cells must be able to divide. All cells must maintain the right concentration of chemicals in their cytoplasm, ingest food and use it for energy, recycle molecules, expel wastes, and construct proteins. Cells must also be able to respond to changes in their environment.
 Although many forms of bacteria are not capable of independent movement, species such as the Salmonella bacterium pictured here can move by means of fine threadlike projections called flagella. The arrangement of flagella across the surface of the bacterium differs from species to species; they can be present at the ends of the bacterium or all across the body surface. Forward movement is accomplished either by a tumbling motion or in a forward manner without tumbling.
 Many unicellular organisms swim, glide, thrash, or crawl to search for food and escape enemies. Swimming organisms often move by means of a flagellum, a long tail-like structure made of protein. Many bacteria, for example, have one, two, or many flagella that rotate like propellers to drive the organism along. Some single-celled eukaryotic organisms, such as the euglena, also have a flagellum, but it is longer and thicker than the prokaryotic flagellum. The eukaryotic flagellums work by waving up and down like a whip. In higher animals, the sperm cell uses a flagellum to swim toward the female egg for fertilization.
 Movement in eukaryotes is also accomplished with cilia, short, hairlike proteins built by centrioles, which are barrel-shaped structures located in the cytoplasm that assemble and break down protein filaments. Typically, thousands of cilia extend through the plasma membrane and cover the surface of the cell, giving it a dense, hairy appearance. By beating its cilia as if they were oars, an organism such as the paramecium propels itself through its watery environment. In cells that do not move, cilia are used for other purposes. In the respiratory tract of humans, for example, millions of ciliated cells prevent inhaled dust, smog, and microorganisms from entering the lungs by sweeping them up on a current of mucus into the throat, where they are swallowed. Eukaryotic flagella and cilia are formed from basal bodies, small protein structures located just inside the plasma membrane. Basal bodies also help to anchor flagella and cilia.
 Still other eukaryotic cells, such as amoebas and white blood cells, move by amoeboid motion, or crawling. They extrude their cytoplasm to form temporary pseudopodia, or false feet, which actually are placed in front of the cell, rather like extended arms. They then drag the trailing end of their cytoplasm up to the pseudopodia. A cell using amoeboid motion would lose a race to a euglena or paramecium. But while it is slow, amoeboid motion is strong enough to move cells against a current, enabling water-dwelling organisms to pursue and devour prey, for example, or white blood cells roaming the blood stream to stalk and engulf a bacterium or virus.
 An amoeba, a single-celled organism lacking internal organs, is shown approaching a much smaller paramecium, which it begins to engulf with large outflowings of its cytoplasm, called pseudopodia. Once the paramecium is completely engulfed, a primitive digestive cavity, called a vacuole, forms around it. In the vacuole, acids break the paramecium down into chemicals that the amoeba can diffuse back into its cytoplasm for nourishment.
 All cells require nutrients for energy, and they display a variety of methods for ingesting them. Simple nutrients dissolved in pond water, for example, can be carried through the plasma membrane of pond-dwelling organisms via a series of molecular pumps. In humans, the cavity of the small intestine contains the nutrients from digested food, and cells that form the walls of the intestine use similar pumps to pull amino acids and other nutrients from the cavity into the bloodstream. Certain unicellular organisms, such as amoebas, are also capable of reaching out and grabbing food. They used a process known as endocytosis, in which the plasma membrane surrounds and engulfed the food particle, enclosing it in a sac, called a vesicle, that is within the amoeba’s interior.
 Cells require energy for a variety of functions, including moving, building up and breaking down molecules, and transporting substances across the plasma membrane. Nutrients contain energy, but cells must convert the energy locked in nutrients to another form - specifically, the ATP molecule, the cell’s energy battery - before it is useful. In single-celled eukaryotic organisms, such as the paramecium, and in multicellular eukaryotic organisms, such as plants, animals, and fungi, mitochondria is responsible for this task. The interior of each mitochondrion consists of an inner membrane that is folded into a mazelike arrangement of separate compartments called cristae. Within the cristae, enzymes form an assembly line where the energy in glucose and other energy-rich nutrients is harnessed to build ATP; thousands of ATP molecules are constructed each second in a typical cell. In most eukaryotic cells, this process requires oxygen and is known as aerobic respiration.
 Some prokaryotic organisms also carry out aerobic respiration. They lack mitochondria, however, and carry out aerobic respiration in the cytoplasm with the help of enzymes sequestered there. Many prokaryote species live in environments where there is little or no oxygen, environments such as mud, stagnant ponds, or within the intestines of animals. Some of these organisms produce ATP without oxygen in a process known as anaerobic respiration, where sulfur or other substances take the place of oxygen. Still other prokaryotes, and yeast, a single-celled eukaryote, build ATP without oxygen in a process known as fermentation.
 Almost all organisms rely on the sugar glucose to produce ATP. Glucose is made by the process of photosynthesis, in which light energy is transformed to the chemical energy of glucose. Animals and fungi cannot carry out photosynthesis and depend on plants and other photosynthetic organisms for this task. In plants, as we have seen, photosynthesis takes place in organelles called chloroplasts. Chloroplasts contain numerous internal compartments called thylakoids where enzymes aid in the energy conversion process. A single leaf cell contains 40 to 50 chloroplasts. With sufficient sunlight, one large tree is capable of producing upwards of two tons of sugar in a single day. Photosynthesis in prokaryotic organisms - typically aquatic bacteria - is carried out with enzymes clustered in plasma membrane folds called chromatophores. Aquatic bacteria produce the food consumed by tiny organisms living in ponds, rivers, lakes, and seas.
 A typical cell must have on hand, about.  30,000 proteins at any-one time. Many of these proteins are enzymes needed to construct the major molecules used by cells - carbohydrates, lipids, proteins, and nucleic acids - nor to aid in the breakdown of such molecules after they have worn out. Other proteins are part of the cell’s structure - the plasma membrane and ribosomes, for example. In animals, proteins also function as hormones and antibodies, and they function like delivery trucks to transport other molecules around the body. Hemoglobin, for example, is a protein that transports oxygen in red blood cells. The cell’s demand for proteins never ceases.
 Before a protein can be made, however, the molecular directions to build, it must be extracted from one or more genes. In humans, for example, one gene holds the information for the protein insulin, the hormone that cells need to import glucose from the bloodstream, while at least two genes hold the information for collagen, the protein that imparts strength to skin, tendons, and ligaments. The process of building proteins begins when enzymes, in response to a signal from the cell, bind to the gene that carries the code for the required protein, or part of the protein. The enzymes transfer the code to a new molecule called messenger RNA, which carries the code from the nucleus to the cytoplasm. This enables the original genetic code to remain safe in the nucleus, with messenger RNA delivering small bits and pieces of information from the DNA to the cytoplasm as needed. Depending on the cell type, hundreds or even thousands of molecules of messenger RNA are produced each minute.
 Once in the cytoplasm, the messenger RNA molecule links up with a ribosome. The ribosome moves along the messenger RNA like a monorail car along a track, stimulating another form of RNA - transfer RNA - to gather and link the necessary amino acids, pooled in the cytoplasm, to form the specific protein, or section of protein. The protein is modified as necessary by the endoplasmic reticulum and Golgi apparatus before embarking on its mission. Cells teem with activity as they forge the numerous, diverse proteins that are indispensable for life. For a more detailed discussion about protein synthesis, When there are a hundred or more cells, they formed a hollow ball of cells, called a blastula, surrounding a fluid-filled cavity. Later divisions produce three layers of cells - endoderm (inner), mesoderm (middle), and ectoderm (outer) - from which the principal features of the animal will differentiate.
 Most cells divide at some time during their life cycle, and some divide dozens of times before they die. Organisms rely on cell division for reproduction, growth, and repair and replacement of damaged or worn out cells. Three types of cell division occur: Binary fission, mitosis, and meiosis. Binary fission, the method used by prokaryotes, produces two identical cells from one cell. The more complex process of mitosis, which also produces two genetically identical cells from a single cell, is used by many unicellular eukaryotic organisms for reproduction. Multicellular organisms use mitosis for growth, cell repair, and cell replacement. In the human body, for example, an estimated 25 million mitotic cell divisions occur every second in order to replace cells that have completed their normal life cycles. Cells of the liver, intestine, and skin may be replaced every few days. Recent research indicates that even brain cell, once thought to be incapable of mitosis, undergo cell division in the part of the brain associated with memory.
 In a landmark intersection of science and fiction, cloning leapt from the world’s imagination to its front page in February 1997. It arrived in the innocent form of a sheep named Dolly: The first exact genetic duplicate of an adult mammal due to genetic engineering. Scottish scientists had created Dolly from deoxyribonucleic acid (DNA) - the basic unit of heredity - taken from a single adult sheep cell. The accomplishment threw open the door to profoundly ethical as well as scientific controversy over the potential uses and abuses of cloning. ‘However the debate is resolved,’ wrote Los Angeles Times science reporter Thomas H. Maugh II, ‘the genie is irretrievably out of the bottle.’
 The type of cell division required for sexual reproduction is meiosis. Sexually reproducing organisms include seaweeds, fungi, plants, and animals - including, of course, human beings. Meiosis differs from mitosis in that cell division begins with a cell that has a full complement of chromosomes and ends with gamete cells, such as sperm and eggs, that have only half the complement of chromosomes. When a sperm and egg unite during fertilization, the cell resulting from the union, called a zygote, contains the full number of chromosomes.
 The story of how cells evolved remains an open and actively investigated question in science. The combined expertise of physicists, geologists, chemists, and evolutionary biologists has been required to shed light on the evolution of cells from the nonliving matter of early Earth. The planet formed about 4.5 billion years ago, and for millions of years, violent volcanic eruptions blasted substances such as carbon dioxide, nitrogen, water, and other small molecules into the air. These small molecules, bombarded by ultraviolet radiation and lightning from intense storms, collided to form the stable chemical bonds of larger molecules, such as amino acids and nucleotides - the building blocks of proteins and nucleic acids. Experiments indicate that these larger molecules form spontaneously under laboratory conditions that simulate the probable early environment of Earth.
 Scientists speculate that rain may have carried these molecules into lakes to create a primordial soup - the breeding ground for the assembly of proteins, the nucleic acid RNA, and lipids. Some scientists postulate that these more complex molecules formed in hydrothermal vents rather than in lakes. Other scientists propose that these key substances may have reached Earth on meteorites from outer space. Regardless of the origin or environment, however, scientists do agree that proteins, nucleic acids, and lipids provided the raw materials for the first cells. In the laboratory, scientists have observed lipid molecules joining to form spheres that resemble a cell’s plasma membrane. As a result of these observations, scientists postulate that millions of years of molecular collisions resulted in lipid spheres enclosing RNA, the simplest molecule capable of self-replication. These primitive aggregations would have been the ancestors of the first prokaryotic cells.
 Fossil studies indicate that Cyanobacteria, bacteria capable of photosynthesis, were among the earliest bacteria to evolve, an estimated 3.4 billion to 3.5 billion years ago. In the environment of the early Earth, there were no oxygen, and cyanobacteria probably used fermentation to produce ATP. Over the eons, cyanobacteria performed photosynthesis, which produces oxygen as a byproduct; The result was the gradual accumulation of oxygen in the atmosphere. The presence of oxygen set the stage for the evolution of bacteria that used oxygen in aerobic respiration, a more efficient ATP-producing process than fermentation. Some molecular studies of the evolution of genes in archaebacteria suggest that these organisms may have evolved in the hot waters of hydrothermal vents or hot springs slightly earlier than cyanobacteria, around 3.5 billion years ago. Like cyanobacteria, archaebacteria probably relied on fermentation to synthesize ATP.
 Eukaryotic cells may have evolved from primitive prokaryotes about 2 billion years ago. One hypothesis suggests that some prokaryotic cells lost their cell walls, permitting the cell’s plasma membrane to expand and fold. These folds, ultimately, may have given rise to separate compartments within the cell - the forerunners of the nucleus and other organelles now found in eukaryotic cells. Another key hypothesis is known as endosymbiosis. Molecular studies of the bacteria-like DNA and ribosomes in mitochondria and chloroplasts indicate that mitochondrion and chloroplast ancestors were once free-living bacteria. Scientists propose that these free-living bacteria were engulfed and maintained by other prokaryotic cells for their ability to produce ATP efficiently and to provide a steady supply of glucose. Over generations, eukaryotic cells situated with mitochondria - the ancestors of animals - or with both mitochondria and chloroplasts - the ancestors of plants - evolved.
 The first observations of cells were made in 1665 by English scientist Robert Hooke, who used a crude microscope of his own invention to examine a variety of objects, including a thin piece of cork. Noting the rows of tiny boxes that made up the dead wood’s tissue, Hooke coined the term cell because the boxes reminded him of the small cells occupied by monks in a monastery. While Hooke was the first to observe and describe cells, he did not comprehend their significance. At about the same time, the Dutch maker of microscopes Antoni van Leeuwenhoek pioneered the invention of one of the best microscopes of the time. Using his invention, Leeuwenhoek was the first to observe, draw, and describe a variety of living organisms, including bacteria gliding in saliva, one-celled organisms cavorting in pond water, and sperm swimming in semen. Two centuries passed, however, before scientists grasped the true importance of cells.
 Many advances have been made in microscope technology. This article from the 1994 Collier’s Year Book begins with the microscope most young students are familiar with and tracks the breakthroughs in the development of new types of microscopes - including those that use ultrasonic imaging and those that ‘feel’ an object’s surface.
 Modern ideas about cells appeared in the 1800s, when improved light microscopes enabled scientists to observe more details of cells. Working together, German botanist Matthias Jakob Schleiden and German zoologist Theodor Schwann recognized the fundamental similarities between plant and animal cells. In 1839 they proposed the revolutionary idea that all living things are made up of cells. Their theory gave rise to modern biology: a whole new way of seeing and investigating the natural world.
 By the late 1800s, as light microscopes improved still further, scientists were able to observe chromosomes within the cell. Their research was aided by new techniques for staining parts of the cell, which made possible the first detailed observations of cell division, including observations of the differences between mitosis and meiosis in the 1880s. In the first few decades of the 20th century, many scientists focused on the behavior of chromosomes during cell division. At that time, it was generally held that mitochondria transmitted the hereditary information. By 1920, however, scientists determined that chromosomes carry genes and that genes transmit hereditary information from generation to generation.
 During this period, scientists began to understand some of the chemical processes in cells. In the 1920s, the ultracentrifuge was developed. The ultracentrifuge is an instrument that spins cells or other substances in test tubes at high speeds, which causes the heavier parts of the substance to fall to the bottom of the test tube. This instrument enabled scientists to separate the relatively abundant and heavy mitochondria from the rest of the cell and study their chemical reactions. By the late 1940s, scientists were able to explain the role of mitochondria in the cell. Using refined techniques with the ultracentrifuge, scientists subsequently isolated the smaller organelles and gained an understanding of their functions.
 The deoxyribonucleic acid (DNA) molecule is the genetic blueprint for each cell and ultimately the blueprint that determines every characteristic of a living organism. In 1953 American biochemist James Watson, left, and British biophysicist Francis Crick, right, described the structure of the DNA molecule as a double helix, somewhat like a spiral staircase with many individual steps. Their work was aided by X-ray diffraction pictures of the DNA molecule taken by British biophysicist Maurice Wilkins and British physical chemist Rosalind Franklin. In 1962 Crick, Watson, and Wilkins received the Nobel Prize for their pioneering work on the structure of the DNA molecule.
 While some scientists were studying the functions of cells, others were examining details of their structure. They were aided by a crucial technological development in the 1940s, the invention of the electron microscope, which uses high-energy electrons instead of light waves to view specimens. New generations of electron microscopes have provided resolution, or the differentiation of separate objects, thousands of times more powerful than that available in light microscopes. This powerful resolution revealed organelles such as the endoplasmic reticulum, lysosomes, the Golgi apparatus, and the cytoskeleton. The scientific fields of cell structure and function continue to complement each other as scientists explore the enormous complexity of cells.
 The discovery of the structure of DNA in 1953 by American biochemist James D. Watson and British biophysicist Francis Crick ushered in the era of molecular biology. Today, investigation inside the world of cells - of genes and proteins at the molecular level - constitutes one of the largest and fastest moving areas in all of science. One particularly active field in recent years has been the investigation of cell signaling, the process by which molecular messages find their way into the cell via a series of complex protein pathways in the cell.
 Another busy area in cell biology concerns programmed cell death, or apoptosis. Millions of times per second in the human body, cells commit suicide as an essential part of the normal cycle of cellular replacement. This also seems to be a check against disease: When mutations build up within a cell, the cell will usually self-destruct. If this fails to occur, the cell may divide and give rise to mutated daughter cells, which continue to divide and spread, gradually forming a growth called a tumor. This unregulated growth by rogue cells can be benign, or harmless, or cancerous, which may threaten healthy tissue. The study of apoptosis is one avenue that scientists explore in an effort to understand how cells become cancerous.
 Scientists are also discovering exciting aspects of the physical forces within cells. Cells employ a form of architecture called tensegrity, which enables them to withstand battering by a variety of mechanical stresses, such as the pressure of blood flowing around cells or the movement of organelles within the cell. Tensegrity stabilizes cells by evenly distributing mechanical stresses to the cytoskeleton and other cell components. Tensegrity also may explain how a change in the cytoskeleton, where certain enzymes are anchored, initiates biochemical reactions within the cell, and can even influence the action of genes. The mechanical rules of tensegrity may also account for the assembly of molecules into the first cells. Such new insights - made some 300 years after the tiny universe of cells was first glimpsed - show that cells continue to yield fascinating new worlds of discovery.
 The Nervous System signifies of those elements within the animal organism that are concerned with the reception of stimuli, the transmission of nerve impulses, or the activation of muscle mechanisms.
 The reception of stimuli is the function of special sensory cells. The conducting elements of the nervous system are cells called neurons; these may be capable of only slow and generalized activity, or they may be highly efficient and rapidly conducting units. The specific response of the neuron—the nerve impulse - and the capacities of the cell to be stimulated make this cell a receiving and transmitting unit capable of transferring information from one part of the body to another.
 Each nerve cell consists of a central portion containing the nucleus, known as the cell body, and one or more structures referred to as axons and dendrites. The dendrites are rather short extensions of the cell body and are involved in the reception of stimuli. The axon, by contrast, is usually a single elongated extension, it is especially important in the transmission of nerve impulses from the region of the cell body to other cells.
 Although all many-celled animals have some kind of nervous system, the complexity of its organization varies considerably among different animal types. In simple animals such as jellyfish, the nerve cells form a network capable of mediating only a relatively stereotyped response. In more complex animals, such as shellfish, insects, and spiders, the nervous system is more complicated. The cell bodies of neurons are organized in clusters called ganglia. These clusters are interconnected by the neuronal processes to form a ganglionated chain. Such chains are found in all vertebrates, in which they represent a special part of the nervous system, related especially to the regulation of the activities of the heart, the glands, and the involuntary Vertebrate animals have a bony spine and skull in which the central part of the nervous system is housed; The peripheral part extends throughout the remainder of the body. That part of the nervous system located in the skull is referred to as the brain that found in the spine is called the spinal cord. The brain and the spinal cord are continuous through an opening in the base of the skull; Both are also in contact with other parts of the body through the nerves. The distinction made between the central nervous system and the peripheral nervous system is based on the different locations of the two intimately related parts of a single system. Some of the processes of the cell bodies conduct sense impressions and others conduct muscle responses, called reflexes, such as those caused by pain.
 In the skin are cells of several types called receptors; each is especially sensitive to particular stimuli. Free nerve endings are sensitive to pain and are directly activated. The neurons so activated send impulses into the central nervous system and have junctions with other cells that have axons extending back into the periphery. Impulses are carried from processes of these cells to motor endings within the muscles. These neuromuscular endings excite the muscles, resulting in muscular contraction and appropriate movement. The pathway taken by the nerve impulse in mediating this simple response is in the form of a two-neuron arc that begins and ends in the periphery. Many of the actions of the nervous system can be explained on the basis of such reflex arcs, which are chains of interconnected nerve cells, stimulated at one end and capable of bringing about movement or glandular secretion at the other.
 The cranial nerves connect to the brain by passing through openings in the skull, or cranium. Nerves associated with the spinal cord pass through openings in the vertebral column and are called spinal nerves. Both cranial and spinal nerves consist of large numbers of processes that convey impulses to the central nervous system and also carry messages outward; the former processes are called afferent, and the latter are called efferent. Afferent impulses are referred to as sensory; efferent impulses are referred to as either somatic or visceral motor, according to what part of the body they reach. Most nerves are mixed nerves made up of both sensory and motor elements.
 The cranial and spinal nerves are paired; The number in humans are 12 and 31, respectively. Cranial nerves are distributed to the head and neck regions of the body, with one conspicuous exception: the tenth cranial nerve, called the vagus. In addition to supplying structures in the neck, the vagus is distributed to structures located in the chest and abdomen. Vision, auditory and vestibular sensation, and taste is mediated by the second, eighth, and seventh cranial nerves, respectively. Cranial nerves also mediate motor functions of the head, the eyes, the face, the tongue, and the larynx, as well as the muscles that function in chewing and swallowing. Spinal nerves, after they exit from the vertebrae, are distributed in a band-like fashion to regions of the trunk and to the limbs. They interconnect extensively, thereby forming the brachial plexus, which runs to the upper extremities, and the lumbar plexus, which passes to the lower limbs.
 Among the motor’s fibers may be found groups that carry impulses to viscera. These fibers are designated by the special name of autonomic nervous system. That system consists of two divisions, more or less antagonistic in function, that emerge from the central nervous system at different points of origin. One division, the sympathetic, arises from the middle portion of the spinal cord, joins the sympathetic ganglionated chain, courses through the spinal nerves, and is widely distributed throughout the body. The other division, the parasympathetic, arises both above and below the sympathetic, that is, from the brain and from the lower part of the spinal cord. These two divisions control the functions of the respiratory, circulatory, digestive, and urogenital systems.
 Consideration of disorders of the nervous system is the province of neurology; Psychiatry deals with behavioral disturbances of a functional nature. The division between these two medical specialties cannot be sharply defined, because neurological disorders often manifest both organic and mental symptoms.
 Diseases of the nervous system include genetic malformations, poisonings, metabolic defects, vascular disorders, inflammations, degeneration, and tumors, and they involve either nerve cells or their supporting elements. Vascular disorders, such as cerebral hemorrhage or other forms of a stroke, are among the most common causes of paralysis and other neurologic complications. Some diseases exhibit peculiar geographic and age distribution. In temperate zones, multiple sclerosis is a common degenerative disease of the nervous system, but it is rare in the Tropics.
 The nervous system is subject to infection by a great variety of bacteria, parasites, and viruses. For example, meningitis, or infection of the meninges investing the brain and spinal cord, can be caused by many different agents. On the other hand, one specific virus causes rabies. Some viruses causing neurological ills effect only certain parts of the nervous system. For example, the virus causing poliomyelitis commonly affects the spinal cord, as Viruses manufacturing encephalitis attack the brain.
 Inflammations of the nervous system are named according to the part affected. Myelitis is an inflammation of the spinal cord; Neuritis is an inflammation of a nerve. It may be caused not only by infection but also by poisoning, alcoholism, or injury. Tumors originating in the nervous system usually are composed of meningeal tissue or neuroglia (supporting tissue) cells, depending on the specific part of the nervous system affected, but other types of a tumors may metastasize to or invade the nervous system. In certain disorders of the nervous system, such as neuralgia, migraine, and epilepsy, no evidence may exist of organic damage. Another disorder, cerebral palsy, is associated with birth defects.
 Pain, an unpleasant sensory and emotional experience caused by real or potential injury or damage to the body or described in terms of such damage. Scientists believe that pain evolved in the animal kingdom as a valuable three-part warning system. First, it warns of injury. Second, pain protects against further injury by causing a reflexive withdrawal from the source of injury. Finally, pain leads to a period of reduced activity, enabling injuries to heal more efficiently.
 Pain is difficult to measure in humans because it has an emotional, or psychological component as well as a physical component. Some people express extreme discomfort from relatively small injuries, while others show little or no pain even after suffering severe injury. Sometimes pain is present even though no injury is apparent at all, or pain lingers long after an injury appears to have healed.
 The signals that warn the body of tissue damage are transmitted through the nervous system. In this system, the basic unit is the nerve cell or neuron. A nerve cell is composed of three parts: a central cell body, a single major branching fiber called an axon, and a series of smaller branching fibers known as dendrites. Each nerve cell meets other nerve cells at certain points on the axons and dendrites, forming a dense network of interconnected nerve fibers that transmit sensory information about touch, pressure, or warmth, as well as pain.
 Sensory information is transmitted from the different parts of the body to the brain via the spinal cord, which is a complex set of nerves that extend from the brain down along the back, protected by the bones of the spine. About as wide as a finger, the spinal cord is like a cable packed with many bundles of wires. The bundles are nerve pathways for transmitting information. But the spinal cord is more than just a message transmitter, it is also an extension of the brain. It contains neurons that process incoming sensory information, and generates messages to be sent back down to cells in other parts of the body.
 In the nervous system, a message-carrying impulse travels from one end of a nerve cell to the other by means of an electrical impulse. When it reaches the terminal end of a nerve cell, the impulse trigger’s tiny sacs called presynaptic vessicles to release their contents, chemical messengers called neurotransmitters. The neurotransmitters float across the synapse, or gap between adjacent nerve cells. When they reach the neighboring nerve cell, the neurotransmitters fit into specialized receptor sites much as a key fits into a lock, causing that nerve cell to ‘fire,’ or generate an electric message-carrying impulse. As the message continues through the nervous system, the presynaptic cell absorbs the excess neurotransmitters, and repackages them in presynaptic versicles in a process called neurotransmitter reuptake.
 Information being transmitted between and within the brain and spinal cord travels through the nervous system using both chemical and electrical mechanisms. A message-carrying impulse travels from one end of a nerve cell to another by means of an electric signal. When the electric signal reaches the terminal end of a nerve cell, a gap called a synapse prevents the electric signal from crossing to the next cell. The electric signal triggers the cell to release chemicals called neurotransmitters, which float across the synapse to the neighboring nerve cell. These neurotransmitters fit into specialized receptors found on the adjacent nerve cell, much as a key fits into a lock, generating an electric impulse in the neighboring cell. This new impulse travels to the end of the long cell, in turn triggering the release of neurotransmitters to carry the message across the next synapse. Not all neurotransmitters initiate a message in a neighboring nerve cell. Some specialize in preventing neighboring cells from generating an electrical signal, while others function as helpers, facilitating the message's journey to the brain.
 While most of the sensory nerves in the skin and other body tissues have special structures covering their nerve endings, those nerves that signal injury have free nerve endings. These simple nerve endings specialize in detecting noxious stimuli - a catchall term for injury-causing stimuli such as intense heat, extreme pressure, or sharp pricks or cuts. The nerve endings that detect pain are called nociceptors, and the process of transmitting pain signals when harmful stimulation occurs is called nociception. Several million nociceptors are interlaced through the tissues and organs of the body.
 When a person experiences an injury, such as a stubbed toe, specialized cells called nociceptors sense potential tissue damage (1) and send an electric signal, called an impulse, to the spinal cord via a sensory nerve (2). A specialized region of the spinal cord known as the dorsal horn (3) processes the pain signal, immediately sending another impulse back down the leg via a motor nerve (4). This causes the muscles in the leg to contract and pull the toe away from the source of injury (6). At the same time, the dorsal horn sends another impulse up the spinal cord to the brain. During this trip, the impulse travels between nerve cells. When the impulse reaches a nerve ending (7), the nerve released chemical messengers, called neurotransmitters, which carry the message to the adjacent nerve. When the impulse reaches the brain (8), it is analyzed and processed as an unpleasant physical and emotional sensation.
 An injury triggers pain signals in two types of nociceptors, one with large, insulated axons known as A-delta fibers and one with small, uninsulated axons known as C fibers. The large A-delta fibers conduct signals quickly, and the smaller C fibers transmit information slowly. The difference in the functions of these two fibers becomes obvious to a person who stubs a toe. At first the injured person is aware of a sharp, flashing pain at the point of injury. Generated by the A-delta fibers, this short-lived pain intrudes upon the thoughts and perceptions occurring in the brain. Just as this first pain subsides, a second pain begins that is vague, throbbing, and persistent. This sensation is derived from the C fibers.
 Pain information from the A-delta and C fibers travels through the spinal cord to the brain. When it receives the pain message, the spinal cord generates impulses that travel back down to muscles, which lead to a reflexive contraction that pulls the body away from the source of injury. Other reflexes may affect skin temperature, blood flow, sweating, and other changes.
 While this reflex action is underway, the pain message continues up the spinal cord to relay centers in the brain. The sensory information is routed to many other parts of the brain, including the cortex, where thinking processes occur
 The Adrenal Gland is the vital endocrine gland that secretes hormones into the bloodstream, situated, in humans, on top of the upper end of each kidney. The two parts of the gland - the inner portion, or medulla, and the outer portion, or the cortex - are like separate organs: They are composed of different types of tissue and perform different functions. The adrenal medulla, composed of chromaffin cells secretes the hormone epinephrine, also called adrenaline, in response to stimulation of the sympathetic nervous system at times of stress. The medulla also secretes the hormone norepinephrine, which plays a role in maintaining normal blood circulation. The hormones of the medulla are called catecholamines. Unlike the adrenal cortex, the medulla can be removed without endangering the life of an individual.
 The adrenal outer layer, or cortex, secretes about 30 steroid hormones, but only a few are secreted in significant amounts. Aldosterone, one of the most important hormones, regulates the balance of salt and water in the body. Cortisone and hydrocortisone are necessary to regulate fat, carbohydrate, and protein metabolism. Adrenal sex steroids have a minor influence on the reproductive system. Modified steroids, now produced synthetically, are superior to naturally secreted steroids for treatment of Addison's disease and other disorders.
 Adrenocorticotropic Hormone  is also known as corticotropin, hormones secreted by the anterior part of the pituitary gland. The specific function of ACTH is to stimulate the growth and secretions of the cortex (outer layers) of the adrenal gland. One of these secretions is cortisone, a hormone involved in carbohydrate and protein metabolisms. ACTH is used medically for its anti-inflammatory action to alleviate symptoms of allergies and arthritis. ACTH is a complex protein molecule containing 39 amino acids. Its molecular weight is approximately 5000. The biological activity of the ACTH of various animal species is similar to that of humans, but the sequence of amino acids has been found to vary somewhat among species. ACTH production is controlled in part by the hypothalamus and in part by the existing levels of adrenal gland hormones. ACTH levels increased in response to stress, disease, and decreased blood pressure.
 The Pituitary Gland is the master endocrine gland in vertebrate animals. The hormones secreted by the pituitary stimulate and control the functioning of almost all the other endocrine glands in the body. Pituitary hormones also promote growth and control the water balance of the body.
 The pituitary is a small bean-shaped, reddish-gray organ located in the saddle-shaped depression (sella turcica) in the floor of the skull (the sphenoid bone) and attached to the base of the brain by a stalk; it is located near the hypothalamus. The pituitary has two lobes - the anterior lobe, or adenohypophysis, and the posterior lobe, or neurohypophysis - which differ in structure and function. The anterior lobe is derived embryologically from the roof of the pharynx and is composed of groups of epithelial cells separated by blood channels; the posterior lobe is derived from the base of the brain and is composed of nervous connective tissue and nerve-like secreting cells. The area between the anterior and posterior lobes of the pituitary is called the intermediate lobe; it has the same embryological origin as the anterior lobe.
 Concentrated chemical substances, or hormones, which control 10 to 12 functions in the body, have been obtained as extracts from the anterior pituitary glands of cattle, sheep, and swine. Eight hormones have been isolated, purified, and identified; All of them are peptides, that is, they are composed of amino acids. A growth hormone (GH), or the somatotropic hormone (STH), is essential for normal skeletal growth and is neutralized during adolescence by the gonadal sex hormones. Thyroid-stimulating hormones (TSH) control the normal functioning of the thyroid gland, and the adrenocorticotropic hormone (ACTH) controls the activity of the cortex of the adrenal glands and takes part in the stress reaction. Prolactin, also called lactogenic, luteotropic, or mammotropic hormone, initiates milk secretion in the mammary gland after the mammary tissues have been prepared during pregnancy by the secretion of other pituitary and sex hormones. The two gonadotropic hormones are follicle-stimulating hormones (FSH) and a luteinizing hormone (LH). Follicle-stimulating hormones stimulates the formation of the Graafian follicle in the female ovary and the development of spermatozoa in the male. The luteinizing hormone stimulates the formation of ovarian hormones after ovulation and initiates lactation in the female, in the male, it stimulates the tissues of the testes to elaborate testosterone. In 1975 scientists identified the pituitary peptide endorphin, which acts in experimental animals as a natural pain reliever in times of stress. Endorphin and ACTH are made as parts of a single large protein, which subsequently splits. This may be the body's mechanism for coordinating the physiological activities of two stress-induced hormones. The same large prohormone that contains ACTH and endorphin also contains short peptides called melanocyte-stimulating hormones. These substances are analogous to the hormone that regulates pigmentation in fish and amphibians, but in humans they have no known function.
 Research has shown that the hormonal activity of the anterior lobe is controlled by chemical messengers sent from the hypothalamus through tiny blood vessels to the anterior lobe. In the 1950s, the British neurologist Geoffrey Harris discovered that cutting the blood supply from the hypothalamus to the pituitary impaired the function of the pituitary. In 1964, chemical agents called releasing factors were found in the hypothalamus; These substances, it was learned, affect the secretion of growth hormones, a thyroid-stimulating hormone called thyrotropin, and the gonadotropic hormones involving the testes and ovaries. In 1969 the American endocrinologist Roger Guillemin and colleagues isolated and characterized thyrotropin-releasing factors, which stimulates the secretion of thyroid-stimulating hormones from the pituitary. In the next few years his group and that of the American physiologist Andrew Victor Schally isolated the luteinizing hormone-releasing factor, which stimulates secretion of both LH and FSH, and somatostatin, which inhibits release of growth hormones. For this work, which proved that the brain and the endocrine system are linked, they shared the Nobel Prize in physiology or medicine in 1977. Human somatostatin was one of the first substances to be grown in bacteria by recombinant DNA.
 The presence of the releasing factors in the hypothalamus helped to explain the action of the female sex hormones, estrogen and progesterone, and their synthetic versions contained in oral contraceptives, or birth-control pills. During a woman's normal monthly cycle, several hormonal changes are needed for the ovary to produce an egg cell for possible fertilization. When the estrogen level in the body declines, the follicle-releasing factor (FRF) flows to the pituitary and stimulates the secretion of the follicle-stimulating hormone. Through a similar feedback principle, the declining level of progesterone causes a release of luteal-releasing factors (LRF), which stimulates secretion of the luteinizing hormone. The ripening follicle in the ovary then produces estrogen, and the high level of that hormone influences the hypothalamus to shut down temporarily the production of FSH. Increased progesterone feedback to the hypothalamus shuts down LH production by the pituitary. The daily doses of synthetic estrogen and progesterone in oral contraceptives, or injections of the actual hormones, inhibit the normal reproductive activity of the ovaries by mimicking the effect of these hormones on the hypothalamus.
 In lower vertebrates this part of the pituitary secretes melanocyte-stimulating hormones, which brings about skin-color changes. In humans, it is present only for a short time early in life and during pregnancy, and is not known to have any function.
 Two hormones are secreted by the posterior lobe. One of these is the antidiuretic hormone (ADH), vasopressin. Vasopressin stimulates the kidney tubules to absorb water from the filtered plasma that passes through the kidneys and thus controls the amount of urine secreted by the kidneys. The other posterior pituitary hormone is oxytocin, which causes the contraction of the smooth muscles in the uterus, intestines, and blood arterioles. Oxytocin stimulates the contractions of the uterine muscles during the final stage of pregnancy to stimulate the expulsion of the fetus, and it also stimulates the ejection, or let down, of milk from the mammary gland following pregnancy. Synthesized in 1953, oxytocin was the first pituitary hormone to be produced artificially. Vasopressin was synthesized in 1956.
 Pituitary functioning may be disturbed by such conditions as tumors, blood poisoning, blood clots, and certain infectious diseases. Conditions resulting from a decrease in anterior-lobe secretion include dwarfism, acromicria, Simmonds's disease, and Fröhlich's syndrome. The dwarfism occurs when anterior pituitary deficiencies occur during childhood; acromicria, in which the bones of the extremities are small and delicate, results when the deficiency occurs after puberty. Simmonds's disease, which is caused by extensive damage to the anterior pituitary, is characterized by premature aging, loss of hair and teeth, anemia, and emaciation; it can be fatal. Fröhlich's syndrome, also called adiposogenital dystrophy, is caused by both anterior pituitary deficiency and a lesion of the posterior lobe or hypothalamus. The result is obesity, dwarfism, and retarded sexual development. Glands under the influence of anterior pituitary hormones are also affected by anterior pituitary deficiency.
 Over secretion of one of the anterior pituitary hormones, somatotropin, results in a progressive chronic disease called acromegaly, which is characterized by enlargement of some parts of the body. Posterior-lobe deficiency results in diabetes insipidus.
 Tissue, - group of associated, similarly structured cells that perform specialized functions for the survival of the organism.  Animal tissues, to which this article is limited, take their first form when the blastula cells, arising from the fertilized ovum, differentiate into three germ layers: the ectoderm, mesoderm, and endoderm. Through further cell differentiation, or histogenesis, groups of cells grow into more specialized units to form organs made up, usually, of several tissues of similarly performing cells. Animal tissues are classified into four main groups.
 These tissues include the skin and the inner surfaces of the body, such as those of the lungs, stomach, intestines, and blood vessels. Because its primary function is to protect the body from injury and infection, epitheliums are made up of tightly packed cells with little intercellular substance between them.
 About 12 kinds of epithelial tissue occur. One kind is stratified squamous tissue found in the skin and the linings of the esophagus and vagina. It is made up of thin layers of flat, scalelike cells that form rapidly above the blood capillaries and is pushed toward the tissue surface, where they die and are shed. Another is a simple columnar epithelium, which lines the digestive system from the stomach to the anus; Simple columnar epithelium cells stand upright and not only control the absorption of nutrients but also secrete mucus through individual goblet cells. Glands are formed by the inward growth of epithelium-for examples, the sweat glands of the skin and the gastric glands of the stomach. Outward growth results in hair, nails, and other structures.
 These tissues, which support and hold parts of the body together, comprises the fibrous and elastic connective tissues, the adipose (fatty) tissues, and cartilage and bone. In contrast to an epithelium, the cells of these tissues are widely separated from one another, with a large amount of intercellular substance between them. The cells of fibrous tissue, found throughout the body, connect to one another by an irregular network of strands, forming a soft, cushiony layer that also supports blood vessels, nerves, and other organs. Adipose tissue has a similar function, except that its fibroblasts also contain store fat. Elastic tissue, found in ligaments, the trachea, and the arterial walls, stretches and contracts again with each pulse beat. In the human embryo, the fibroblast cells that originally secreted collagen for the formation of fibrous tissue later change to secrete a different form of protein called chondrion, for the formation of cartilage, some cartilage later becomes calcified by the action of osteoblast to form bones. Blood and lymph are also often considered connective tissues.
 Tissues, which contract and relax, comprise the striated, smooth, and cardiac muscles. Striated muscles, also called skeletal or voluntary muscles, include those that are activated by the somatic, or voluntary, nervous system. They are joined together without cell walls and have several nuclei. The smooth, or involuntary muscles, which are activated by the autonomic nervous system, are found in the internal organs and consist of simple sheets of cells. Cardiac muscles, which have characteristics of both striated and smooth muscles, are joined together in a vast network. These highly complex groups of cells, called ganglia, transfer information from one part of the body to another. Each neuron, or nerve cell, consists of a cell body with branching dendrites and one long fiber, or axons. The dendrites connect one neuron to another; The axon transmits impulses to an organ or collects impulses from a sensory organ.
 In the nervous system, a message-carrying impulse travels from one end of a nerve cell to the other by means of an electrical impulse. When it reaches the terminal end of a nerve cell, the impulse trigger’s tiny sacs called presynaptic vessicles to release their contents, chemical messengers called neurotransmitters. The neurotransmitters float across the synapse, or gap between adjacent nerve cells. When they reach the neighboring nerve cell, the neurotransmitters fit into specialized receptor sites much as a key fits into a lock, causing that nerve cell to fire or generate an electric message-carrying impulse. As the message continues through the nervous system, the presynaptic cell absorbs the excess neurotransmitters, and repackages them in presynaptic versicles in a process called neurotransmitter reuptake.
 Reflex, in physiology, is the involuntary response to a stimulus by the animal organism. In its simplest form, it consisted of the stimulation of an afferent nerve through a sense organ, or receptor, followed by transmission of the stimulus, usually through a nerve center, to an efferent motor nerve, resulting in action of a muscle or gland, called the effector. In most reflex action, however, the stimulus passes through one or more intermediate nerve cells, which modify and direct its action, sometimes to the extent of involving the muscular activity of the entire organism. For example, a painful stimulus applied to the hand causes a reflex withdrawal of the hand, which involves contraction of the flexor group of muscles and reflexation of the opposing extensor group; if the stimulus is strong, the coordinating nerve cells pass it to the arm muscles and also to the muscles of the trunk and legs, the result being a jump that removes not only the arm, but the entire person from the vicinity of the painful stimulus.
 The system of coordinating nerve cells is such that several different kinds of stimuli may produce the same result. For example, the stimulus produced by the sight of food and that caused by the smell of food travel different afferent pathways, but both have a common final path that stimulates the salivary glands to secretion. The final common path may also be activated through associated nerve tracts by a stimulus that ordinarily is not directly connected with the response. This type of reflex was named conditioned reflex by its discoverer, the Russian physiologist Ivan Pavlov, about 1904. Pavlov found that sounding a bell every time a dog was about to be given food eventually caused a reflex flow of saliva, which later persisted even when no food was produced. Elaborations of this habituative type of reflex are regarded by some physiologists and psychologists as an important basis for many behaviors, both voluntary and involuntary.
 The normal pathways of many reflexes are generally known, and the presence, absence, or exaggerations of the normal physical responses to certain stimuli are symptoms used by neurologists to determine the condition of the neural pathways involved. A familiar reflex commonly tested by physicians is the patellar reflex, in which an involuntary jerk of the knee is evoked by lightly striking the tendon of the patella, or kneecap, indicating the efficiency of certain nerve tracts in the spinal cord.
 Like all other cells, neurons contain charged ions: Potassium and sodium (positively charged) and chlorine (negatively charged). Neurons differ from other cells in that they are able to produce a nerve impulse. A neuron is polarized - that is, it has an overall negative charge inside the cell membrane because of the high concentration of chlorine ions and low concentration of potassium and sodium ions. The concentration of these same ions is exactly reversed outside the cell. This charge differential represents stored electrical energy, sometimes referred to as membrane potential or resting potential. The negative charge inside the cell is maintained by two features. The first is the selective permeability of the cell membrane, which is more permeable to potassium than sodium. The second feature is sodium pumps within the cell membrane that actively pump sodium out of the cell. When depolarization occurs, this charge differential across the membrane is reversed, and a nerve impulse is produced.
 Depolarization is a rapid change in the permeability of the cell membrane. When sensory input or any other kind of stimulating current is received by the neuron, the membrane permeability is changed, allowing a sudden influx of sodium ions into the cell. The high concentration of sodium, or action potential, changes the overall charges within the cell from negative to positive. The local changes in ion concentration triggers similar reactions along the membrane, propagating the nerve impulse. After a brief period called the refractory period, during which the ionic concentration returned to resting potential, the neuron can repeat this process.
 Nerve impulses travel at different speeds, depending on the cellular composition of a neuron. Where speed of impulse is important, as in the nervous system, axons are insulated with a membranous substance called myelin. The insulation provided by myelin maintains the ionic charge over long distances. Nerve impulses are propagated at specific points along the myelin sheath; These points are called the nodes of Ranvier. Examples of myelinated axons are those in sensory nerve fibers and nerves connected to skeletal muscles. In non-myelinated cells, the nerve impulse is propagated more diffusely.
 The nervous system has two divisions: The somatic, which allow voluntary control over skeletal muscle, and the autonomic, which is involuntary and controls cardiac and smooth muscle and glands. The autonomic nervous system has two divisions: The sympathetic and the parasympathetic. Many, but not all, of the muscles and glands that distribute nerve impulses to the larger interior organs possess a double nerve supply; in such cases the two divisions may exert opposing effects. Thus, the sympathetic system increases heartbeat, and the parasympathetic system decreases heartbeat. The two nervous systems are not always antagonistic, however. For example, both nerve supplies to the salivary glands excite the cells of secretion. Furthermore, a single division of the autonomic nervous system may both excite and inhibit a single effector, as in the sympathetic supply to the blood vessels of skeletal muscle. Finally, the sweat glands, the muscles that cause involuntary erection or bristling of the hair, the smooth muscle of the spleen, and the blood vessels of the skin and skeletal muscle are actuated only by the sympathetic division.
 Voluntary movement of head, limbs, and body is caused by nerve impulses arising in the motor area of the cortex of the brain and carried by cranial nerves or by nerves that emerge from the spinal cord to connect with skeletal muscles. The reaction involves both excitation of nerve cells stimulating the muscles involved and inhibition of the cells that stimulate opposing muscles. A nerve impulse is an electrical change within a nerve cell or fiber; Measured in millivolts, it lasts a few milliseconds and can be recorded by electrodes.
 The human brain has three major structural components: The large dome-shaped cerebrum, the smaller somewhat spherical cerebellum, and the brainstem. Prominent in the brainstem is the medulla oblongata (the egg-shaped enlargement at the center) and the thalamus (between the medulla and the cerebrum). The cerebrum is responsible for intelligence and reasoning. The cerebellum helps to maintain balance and posture. The medulla is involved in maintaining involuntary functions such as respiration, and the thalamus act as a relay center for electrical impulses traveling to and from the cerebral cortex. Lack of blood flow to any part of the brain results in a stroke, permanent damage that interferes with the functions of the affected part of the brain.
 Movement may occur also in direct response to an outside stimulus, thus, a tap on the knee causes a jerk, and a light shone into the eye makes the pupil contract. These involuntary responses are called reflexes. Various nerve terminals called receptors constantly send impulses into the central nervous system. These are of three classes: exteroceptors, which are sensitive to pain, temperature, touch, and pressure; interoceptors, which react to changes in the internal environment; and proprioceptors, which respond to variations in movement, position, and tension. These impulses terminate in special areas of the brain, as do of those special receptors concerned with sight, hearing, smell, and taste.
 Whereas most major nerves emerge from the spinal cord, the 12 pairs of cranial nerves project directly from the brain. All but 1 pair relay motor or sensory information (or both); the tenth, or vagus nerve, affects visceral functions such as heart rate, vasoconstriction, and contraction of the smooth muscle found in the walls of the trachea, stomach, and intestine.
 Muscular contractions do not always cause actual movement. A small fraction of the total number of fibers in most muscles is usually contracting. This serves to maintain the posture of a limb and enables the limb to resist passive elongation or stretch. This slight continuous contraction is called muscle tone.
 In 1946 Axelrod joined the laboratory of American pharmacologist Bernard Brodie at Goldwater Memorial Hospital in New York. The pair conducted research on pain-relieving drugs called analgesics. They identified a pain-relieving chemical known as acetaminophen. This drug was later developed and marketed by the drug company Johnson & Johnson under the brand-name Tylenol.
 In 1949 Axelrod took a position at the National Heart Institute, a branch of the National Institutes of Health (NIH). Their Axelrod studied how the body processes certain drugs that cause behavioral changes, including amphetamines, ephedrine, and mescaline. He identified a group of enzymes that help these drugs break down in the body. These enzymes, called cytochrome-P450 monoxygenases, have been studied extensively by other scientists, particularly in cancer research.
 Realizing that career advancement in the sciences requires a doctoral degree, in 1954 Axelrod took a leave of absence from his job at the National Heart Institute to attend The George Washington University. He earned his doctorate in pharmacology in 1955. That same year he was named chief of pharmacology at the National Institute of Mental Health (NIMH) another branch of NIH.
 At NIMH, Joseph Axelrod began research on neurotransmitters. A nerve cell releases a neurotransmitter to spur a neighboring cell into action. In the 1950s most scientists believed that a neurotransmitter became inactive once it stimulated a neighboring cell. But Axelrod’s research found that the neurotransmitter returns to the first nerve cell, in a process known as reuptake, where it is broken down by enzymes or repackaged for reuse. This research led to the creation of a number of drugs that prevent the reuptake process, enabling a neurotransmitter to remain active for a longer period of time.
 Axelrod’s research revolutionized the understanding of many mental-health disorders, including depression, anxiety, and schizophrenia. Prior to his research, psychiatry focused on the relationship of life experiences to mental health problems. But Axelrod's research proved that mental-health disorders were often the result of complicated brain chemistry. His research spurred the development of new drugs that advanced the treatment of mental-health conditions. Among these are selective serotonin reuptake inhibitors, including the antidepressants fluoxetine, sold under the brand name Prozac, sertraline(Zoloft) and paroxetine (Paxil).
 The study of the biochemistry of memory is another exciting scientific enterprise, but one that can only be touched upon here. Scientists estimate that an adult human brain contains about 100 billion neurons. Each of these is connected to hundreds or thousands of other neurons, forming trillions of neural connections. Neurons communicate by chemical messengers called neurotransmitters. An electrical signal travels along the neuron, triggering the release of neurotransmitters at the synapse, the small gap between neurons. The neurotransmitters travel across the synapse and act on the next neuron by binding with protein molecules called receptors. Most scientists believe that memories are somehow stored among the brain's trillions of synapses, rather than in the neurons themselves.
 Scientists who study the biochemistry of learning and memory often focus on the marine snail Aplysia because its simple nervous system allows them to study the effects of various stimuli on specific synapses. A change in the snail's behavior due to learning can be correlated with a change at the level of the synapse. One exciting scientific frontier is discovering the changes in neurotransmitters that occur at the level of the synapse.
 Other researchers have implicated glucose, a sugar and insulin(a hormone secreted by the pancreas) as important to learning and memory. Humans and other animals given these substances show an improved capacity to learn and remember. Typically, when animals or humans ingest glucose, the pancreas responds by increasing insulin production, so it is difficult to determine which substance contributes to improved performance. Some studies in humans that have systematically varied the amount of glucose and insulin in the blood have shown that insulin may be the more important of the two substances for learning.
 Scientists also have examined the influence of genes on learning and memory. In one study, scientists bred strains of mice with extra copies of a gene that helps build a protein called N-methyl-D-aspartate, or NMDA. This protein acts as a receptor for certain neurotransmitters. The genetically altered mice outperformed normal mice on a variety of tests of learning and memory. In addition, other studies have found that chemically blocking NMDA receptor impairs learning in laboratory rats. Future discoveries from genetic and biochemical studies may lead to treatments for memory deficits from Alzheimer's disease and other conditions that affect memory.
 Alzheimer's Disease, progressive brain disorders that causes a gradual and irreversible decline in memory, language skills, perception of time and space, and, eventually, the ability to care for oneself. First described by German psychiatrist Alois Alzheimer in 1906, Alzheimer's disease was initially thought to be a rare condition affecting only young people, and was referred to as prehensile dementia. Today late-onset Alzheimer's disease is recognized as the most common cause of the loss of mental function in those aged 65 and over. Alzheimer's in people in their 30s, 40s, and 50s, called early-onset Alzheimer's disease, occurs less frequently, accountings for less than 10 percent of the estimated 4 million Alzheimer's cases in the United States.
 Although Alzheimer's disease is not a normal part of the aging process, the risk of developing the disease increases as people grow older. About 10 percent of the United States population over the age of 65 is affected by Alzheimer's disease, and nearly 50 percent of those over age 85 may have the disease.
 Alzheimer's disease takes a devastating toll, not only on the patients, but also on those who love and care for them. Some patients experience immense fear and frustration as they struggle with once commonplace tasks and slowly lose their independence. Family, friends, and especially those who provide daily care suffer immeasurable pain and stress as they witness Alzheimer's disease slowly take their loved one from them.
 The onset of Alzheimer's disease is usually very gradual. In the early stages, Alzheimer's patients have relatively mild problems learning new information and remembering where they have left common objects, such as keys or a wallet. In time, they begin to have trouble recollecting recent events and finding the right words to express themselves. As the disease progresses, patients may have difficulty remembering what day or month it is, or finding their way around familiar surroundings. They may develop a tendency to wander off and then be unable to find their way back. Patients often become irritable or withdrawn as they struggle with fear and frustration when once commonplace tasks become unfamiliar and intimidating. Behavioral changes may become more pronounced as patients become paranoid or delusional and unable to engage in normal conversation.
 Eventually Alzheimer's patients become completely incapacitated and unable to take care of their most basic life functions, such as eating and using the bathroom. Alzheimer's patients may live many years with the disease, usually dying from other disorders that may develop, such as pneumonia. Typically the time from initial diagnosis until death is seven to ten years, but this is quite variable and can range from three to twenty years, depending on the age of the onset, other medical conditions present, and the care patients receive.
 The brains of patients with Alzheimer's have distinctive formations - abnormally shaped proteins called tangles and plaques - that are recognized as the hallmark of the disease. Not all brain regions show these characteristic formations. The areas most prominently affected are those related to memory.
 Tangles are long, slender tendrils found inside nerve cells, or neurons. Scientists have learned that when a protein-called tau becomes altered, it may cause the characteristic tangles in the brain of the Alzheimer’s patient. In healthy brains provides structural support for neurons, but in Alzheimer's patients this structural support collapses.
 Plaques, or clumps of fibers, form outside the neurons in the adjacent brain tissue. Scientists found that a type of protein, called amyloid precursor protein, forms toxic plaques when it is cut in two places. Researchers have isolated the enzyme beta-secretes, which is believed to make one of the cuts in the amyloid precursor protein. Researchers also identified another enzyme, called gamma secretes, that makes the second cut in the amyloid precursor protein. These two enzymes snip the amyloid precursor protein into fragments that then accumulate to form plaques that are toxic to neurons.
 Scientists have found that tangles and plaques cause neurons in the brains of Alzheimer's patients to shrink and eventually die, first in the memory and language centers and finally throughout the brain. This widespread neuron degeneration leaves gaps in the brain's messaging network that may interfere with communication between cells, causing some of the symptoms of Alzheimer’s disease.
 Alzheimer's patients have lower levels of neurotransmitters, chemicals that carry complex messages back and forth between the nerve cells. For instance, Alzheimer's disease seems to decrease the level of the neurotransmitter acetylcholine, which is known to influence memory. A deficiency in other neurotransmitters, including somatostatin and corticotropin-releasing factor, and, particularly in younger patients, serotonin and norepinephrine, also interferes with normal communication between brain cells.
 The causes of Alzheimer's disease remain a mystery, but researchers have found that particular groups of people have risk factors that make them more likely to develop the disease than the general population. For example, people with a family history of Alzheimer's are more likely to develop Alzheimer's disease.
 Some of the most promising Alzheimer's research is being conducted in the field of genetics to learn the role a family history of the disease has in its development. Scientists have learned that people who are carriers of a specific version of the apolipoprotein E gene (apoE genes), found on chromosome 19, are several times more likely to develop Alzheimer's than carriers of other versions of the apoE gene. The most common version of this gene in the general population is apoE3. Nearly half of all late-onset Alzheimer’s patients have the fewer in common apoE4 versions, however, and research has shown that this gene plays a role in Alzheimer's disease. Scientists have also found evidence that variations in one or more genes located on chromosomes 1, 10, and 14 may increase a person’s risk for Alzheimer's disease. Scientists have identified the gene variations on chromosomes 1 and 14 and learned that these genes produce mutations in proteins called presenilins. These mutated proteins apparently trigger the activity of the enzyme gamma secretase, which splices the amyloid precursor protein.
 Researchers have made similar strides in the investigation of early-onset Alzheimer's disease. A series of genetic mutations in patients with early-onset Alzheimer's has been linked to the production of amyloid precursor protein, the protein in plaques that may be implicated in the destruction of neurons. One mutation is particularly interesting to geneticists because it occurs on a gene involved in the genetic disorder Down syndrome. People with Down syndrome usually develop plaques and tangles in their brains as they get older, and researchers believe that learning more about the similarities between Down syndrome and Alzheimer's may further our understanding of the genetic elements of the disease.
 Some studies suggest that one or more factors other than heredity may determine whether people develop the disease. One study published in February 2001 compared residents of Ibadan, Nigeria, who eat a mostly low-fat vegetarian diet, with African Americans living in Indianapolis, Indiana, whose diet included a variety of high-fat foods. The Nigerians were less likely to develop Alzheimer’s disease compared to their U.S. counterparts. Some researchers suspect that health imposes on high blood pressure, atherosclerosis (arteries clogged by fatty deposits), high cholesterol levels, or other cardiovascular problems may play a role in the development of the disease.
 Other studies have suggested that environmental agents may be a possible cause of Alzheimer's disease; for example, one study suggested that high levels of aluminum in the brain may be a risk factor. Several scientists initiated research projects to further investigate this connection, but no conclusive evidence has been found linking aluminum with Alzheimer's disease. Similarly, investigations into other potential environmental causes, such as zinc exposure, viral agents, and food-borne poisons, while initially promising, have generally turned up inconclusive results.
 Some studies indicate that brain trauma can trigger a degenerative process that results in Alzheimer's disease. In one study, an analysis of the medical records scribed upon veterans of World War II (1939-1945) linked serious head injury in early adulthood with Alzheimer's disease in later life. The study also looked at other factors that could possibly influence the development of the disease among the veterans, such as the presence of the apoE gene, but no other factors were identified.
 Alzheimer’s disease is only positively diagnosed by examining brain tissue under a microscope to see the hallmark plaques and tangles, and this is only possible after a patient dies. As a result, physicians rely on a series of other techniques to diagnose probable Alzheimer's disease in living patients. Diagnosis begins by ruling out other problems that cause memory loss, such as stroke, depression, alcoholism, and the use of certain prescription drugs. The patient undergoes a thorough examination, including specialized brain scans, to eliminate other disorders. The patient may be given a detailed evaluation called a neuropsychological examination, which is designed to evaluate a patient’s ability to perform specific mental tasks. This helps the physician determine whether the patient is showing the characteristic symptoms of Alzheimer's disease - progressively worsening memory problems, language difficulties, and trouble with spatial direction and time. The physician also asks about the patient's family medical history to learn about any past serious illnesses, which may give a hint about the patient's current symptoms.
 Evidence shows that there is inflammation in the brains of Alzheimer's patients, which may be associated with the production of amyloid precursor protein. Studies are underway to find drugs that prevent this inflammation, to possibly slow or even halt the progress of the disease. Other promising approaches center on mechanisms that manipulate amyloid precursor protein production or accumulation. Drugs are in development that may block the activity of the enzymes that cut the amyloid precursor protein, halting amyloid production. Other studies in mice suggest those vaccinating animals with amyloid precursor protein can produce a reaction that clears amyloid precursor protein from the brain. Physicians have started vaccination studies in humans to determine if the same potentially beneficial effects can be obtained. There is still much to be learned, but as scientists better understand the genetic components of Alzheimer’s, the roles of the amyloid precursor protein and the tau protein in the disease, and the mechanisms of nerve cell degeneration, the possibility that a treatment will be developed is more likely.
 The responsibility for caring for Alzheimer's patients generally falls on their spouses and children. Care givers must constantly be on guard for the possibility of Alzheimer's patients wandering away or becoming agitated or confused in a manner that jeopardizes the patient or others. Coping with a loved one's decline and inability to recognize familiar face causes enormous pain.
 The increased burden faced by families is intense, and the life of the Alzheimer's care giver is often called a 36-hour day. Not surprisingly, care givers often develop health and psychological problems of their own as a result of this stress. The Alzheimer's Association, a national organization with local chapters throughout the United States, was formed in 1980 in large measure to provide support for Alzheimer's care givers. Today, national and local chapters are a valuable source for information, referral, and advice.
 Scottish physician William Cullen coined the term neurosis near the end of the 18th century to describe a variety of nervous behaviours with no apparent physical cause. The Austrian psychoanalyst Sigmund Freud and his followers popularized the word in the late 19th and early 20th centuries. Freud defined neurosis as one class of mental illnesses. In his view, people became neurotic when their conscious mind repressed inappropriate fantasies of the unconscious mind.
 The unconscious, in psychology, is given to the hypothetical region of the mind containing wishes, memories, fears, feelings, and ideas prevented from expression in conscious awareness. They manifest themselves, instead, by their influence on conscious processes and, most strikingly, by such anomalous phenomena as dreams and neurotic symptoms. Not all mental activity of which the subject is unaware belongs to the unconscious; for example, thoughts that may be made conscious by a new focussing of attention are termed foreconscious or preconscious.
 The concept of the unconscious was first developed in the period’s 1895 and 1900, when Sigmund Freud, theorized that it consists of a surviving feeling experienced during infantile life, including both instinctual drives or libido and their modifications by the development of the super-ego. According to the Swiss psychoanalyst Carl Jung, the unconscious also consists of a racial unconscious that contains certain inherited, universal, archaic fantasies belonging to what Jung termed the collective unconscious.
 Until 1980 neuroses appeared as a specific diagnostic category in the Diagnostic and Statistical Manual of Mental Disorders, a handbook for mental health professionals used in the US. Neurosis encompassed a variety of mental illnesses, including Dissociative disorders, anxiety disorders, and phobias.
 In the psychoanalytic model, neurosis differs from the psychosis, another general term used to describe mental illnesses. Individuals with neuroses can function at work and in social situations, whereas people with psychoses find it quite difficult to function adequately. People with neuroses do not grossly distort or misinterpret reality as those with psychoses do. In addition, neurotic individuals recognize that their mental functioning is disturbed while psychotic individuals usually do not. Most mental health professionals now use the term psychosis to call symptoms such hallucinations, delusions, and bizarre behaviour.
 Nevertheless, in 1886 Freud established a private practice in Vienna specializing in nervous disease. He met with violent opposition from the Viennese medical profession because of his strong support of Charcot’s unorthodox views on hysteria and Hypnotherapy. The resentment he incurred was to delay any acceptance of his subsequent findings on the origin of neurosis.
 Hypnotherapy, can be considered as an altered state of consciousness and heightened responsiveness to suggestion, it may be induced in normal persons by a variety of methods and has been used occasionally in medical and psychiatric treatment. Most frequently hypnosis is caused through the actions of an operator, the hypnotist, who engages the attention of a subject and assigns certain tasks to him or her while uttering monotonous, repetitive verbal commands; such tasks may include muscle relaxation, eye fixation, and arm levitation. Hypnosis also may be self-induced, by trained relaxation, concentration on one's own breathing, or by a variety of monotonous practices and rituals that are found in many mystical, philosophical, and religious systems.
 Hypnosis is ascendent from the results of the gradual inclining assumption by the attenuated subject in some standardization of consciousness. In which attention is withdrawn from the surrounding externalized world and is occasioned to a concentration of mental, sensory, and physiological experiences. When a hypnotist induces a trance, a close relationship or rapport develops between operator and subject. The responses of subjects in the trance state, and the phenomena or behaviour they manifest objectively, are the product of their motivational set; that is, behaviour reflects what is being sought from the experience.
 Most people can be easily hypnotized, but the depth of the trance varies widely. A profound trance is characterized by a forgetting of trance events and by an ability to respond automatically to posthypnotic suggestions that are not too anxiety-provoking. The depth of an achievable trance is made calculably fixed by  a determinant characteristic that, depends on the emotional condition of the succeeding subject and on the skill of the hypnotist. Only 20 percent of subjects could enter somnambulistic states through the usual methods of induction. Medically, this percentage is not significant, since therapeutic effects occur even in a light trance.
 Hypnosis can produce a deeper contact with one's emotional life, resulting in some lifting of repressions and exposure of buried fears and conflicts. This effect potentially lends itself to medical and educational use, but it also lends itself to misinterpretation. Thus, the revival through hypnosis of early, forgotten memories may be fused with fantasies. Research into hypnotically induced memories in recent years has in fact stressed their uncertain reliability. Therefore several state court systems in the US have placed increasing constraints on the use of evidence hypnotically obtained from witnesses, although most states still permit its legible presentation in court.
 Hypnosis has been used to treat a variety of physiological and behavioural problems. It can alleviate back pain and pain resulting from burns and cancer. It has been used by some obstetricians as the sole analgesia for normal childbirth. Hypnosis is sometimes also employed to treat physical problems with a possible psychological component, such as Raynaud's syndrome (a circulatory disease) and faecal incontinence in children. Researchers have demonstrated that the benefit of hypnosis is greater than the effect of a placebo and probably results from changing the focus of attention. Few physicians, however, include hypnosis as part of their practice.
 Some behavioural difficulties, such as cigarette smoking, overeating, and insomnia, are also amenable to resolution through hypnosis. Nonetheless, most psychiatrists think that fundamental psychiatric illness is better treated with the patient in a normal state of consciousness.
 The founder of phenomenology, German philosopher Edmund Husserl, introduced the term in his book Ideen zu einer reinen Phänomenolgie und phänomenologischen Philosophie (1913; Ideas: A General Introduction to Pure Phenomenology, 1931). Early followers of Husserl such as the German philosopher Max Scheler, influenced by his previous book, ‘Logische Untersuchungen’ (two volumes, 1900 and 1901, ‘Logical Investigations’, 1970), claimed that the task of phenomenology is to study essences, such as the essence of emotions. Although Husserl himself never gave up his early interest in essences, he later held that only the essences of certain special conscious structures are the proper objects of phenomenology. As formulated by Husserl after 1910, phenomenology is the study of the structures of consciousness that enable consciousness to refer to objects outside itself. This study requires reflection on the content of the mind to the exclusion of everything else. Husserl called this type of reflection the phenomenological reduction. On the acceptable consideration that can explain for the expounded account that the mind can be directed toward nonexistence, as well as real objects. In the things to oppose by arguing against the evidences as something took for granted and especially on trivial or inadequate grounds are actualized distinctions as having been known as having existence in space or time. Husserl noted that phenomenological reflection does not presuppose that anything that has recently come into existence, but amounts to a ‘bracketing of existence’ - that is, setting aside the question of the real existence of the contemplated object.
 Freud’s first published work, ‘On Aphasia,’ appeared in 1891, it was a study of the neurological disorder in which the ability to pronounce words or to name common objects is lost because of organic brain disease. His final work in neurology, was the article, ‘Infantile Cerebral Paralysis,’ was written in 1897 for an encyclopaedia only at the insistence from the editor. Since by this time Freud was occupied largely with psychological than physiological explanations for mental illnesses. His subsequent writings were devoted entirely to that field, which he had named psychoanalysis in 1896.
 Pierre Janet (1859-1947), the French psychologist, born and educated in Paris, he taught philosophy (1881-98) but was also interested in neurology and psychology, which he studied under Jean Martin Charcot. Janet did important pioneer work on the scientific treatment of neuroses and hysteria; his investigations of hypnosis as an aid to understanding the mind and the diagnosis of its disorders greatly influenced the early work of another pupil of Charcot, Sigmund Freud. Among Janet's works are ‘Neuroses’ (1898; trans. 1909), ‘Major Symptoms of Hysteria’ (1907; trans. 1920), and ‘Principles of Psychotherapy’ (1924).
 Freud’s new orientation was heralded by his collaborative work on hysteria with the Viennese physician Josef Breuer. The work was presented in 1893 in a preliminary paper and two years later in an expanded form under the title ‘Studies on Hysteria.’ In this work the symptoms of hysteria were ascribed to manifestations of undischarged emotional energy associated with forgotten psychic traumas. The therapeutic procedure involved the use of a hypnotic state in which the patient was led to recall and reenact the traumatic experience, thus discharging by catharsis the emotions causing the symptoms. The publication of this work marked the beginning of psychoanalytic theory formulated based on clinical observations.
 During the periods from 1895 to 1900 Freud developed many concepts that were later incorporated into psychoanalytic practice and doctrine. Soon after publishing the Studies on Hysteria, he abandoned the use of hypnosis as a cathartic procedure and substituted the investigations of the patient’s spontaneous flow of thoughts, called ‘free association’. In this was to reveal the unconscious mental processes at the root of the neurotic disturbance.
 In his clinical observations Freud found evidence for the mental mechanisms of repression and resistance. He described repression as a device operating unconsciously to make the memory of painful or threatening events inaccessible to the conscious mind. Resistance is the unconscious defence against awareness of repressed experiences to avoid the resulting anxiety. That to probe the unconscious mind, Freud developed the psychotherapy technique of free association. In free association, the patient reclines and talks about thoughts, wishes, memories, and whatever else comes to mind. The analyst tries to interpret these verbalizations to determine their psychological significance. In particular, Freud encouraged his couched patients to associate freely or talk unrestrictively about their dreams, which he believed were the ‘royal road to the unconscious’. According to Freud, dreams are disguised expressions of deep, hidden impulses. Thus, as patients recount the conscious manifest content of dreams, the psychoanalyst tries to unmask the underlying latent content, - what the dreams carries or attemptively communicates (as an idea) that something is held of a measurable understanding and to mean and give to expression of something potentially understood in the mind.
 He traced the operation of unconscious processes, using the free associations of the patient to guide him in the interpretation of dreams and slips of speech. Dream analysis led to his discoveries of infantile sexuality and of the so-called Oedipus complex, which constitutes the erotic attachment of the child for the parent of the opposite sex, with hostile feelings toward the other parent. In these years he also developed the ‘theory of transference’, the processes by which emotional attitudes, established originally toward parental figures in childhood, are transferred in later life to others. The end of this period was marked by the appearance of Freud’s most important work, ‘The Interpretation of Dreams’ (1899). Here Freud analyzed many of his own dreams recorded in the 3-year period of his self-analysis, begun in 1897. This work expounds all the fundamental concepts underlying psychoanalytic technique and doctrine.
 Freud introduced his new theory in The Interpretation of Dreams (1889), the first of 24 books he would write. The theory is summarized in Freud’s last book ‘An Outline of Psychoanalysis’ published in 1940, after his death. In contrast to Wundt and James, for whom psychology was the study of conscious experience, Freud believed that people are motivated largely by unconscious forces, including strong sexual and aggressive drives. He likened the human mind to an iceberg: The small tip that floats on the water is the conscious part, and the vast region beneath the surface comprises the unconscious. Freud believed that although unconscious motives can be temporarily suppressed, they must find a suitable outlet in order for a person to maintain a healthy personality.
 Recognition of these modes of operation in unconscious mental processes made possibly the understanding of such previously incomprehensible psychological phenomena as dreaming. Through analysis of unconscious processes, Freud saw dreams as serving to protect sleep against disturbing impulses arising from within and related to early life experiences. Thus, unacceptable impulses and thoughts, called the latent dream content, are transformed into a conscious, although no longer immediately comprehensible, experience called the manifest dream. Knowledge of these unconscious mechanisms permits the analyst to reverse the so-called dream work, that is, the process by which the latent dream is transformed into the manifest dream, and through dream interpretation, to recognize its underlying meaning.
 In 1902 Freud was appointed a full professor at Vienna University. This honour was granted not in recognition of his contributions but from the efforts of a highly influential patient. The medical world still regarded his work with hostility, and his next writings, ‘The Psychopathology of Everyday Life’ (1904) and ‘Three Contributions to the Sexual Theory’ (1905), only increased this antagonism. As a result Freud continued to work virtually alone in what he termed ‘splendid isolation’.
 By 1906, however, a few pupils and followers had gathered around Freud, including the Austrian psychiatrists William Stekel and Alfred Adler, the Austrian psychologist Otto Rank, the American psychiatrist Abraham Brill, and the Swiss psychiatrist’s Eugen Bleuler and Carl Jung. Other notable associates, joined the circle in 1908, as well, the Hungarian psychiatrist Sándor Ferenczi and the British psychiatrist Ernest Jones.
 Austrian doctor Sigmund Freud spent many hours refining his theories in this study within his home in Vienna, Austria. Freud pioneered the use of clinical observation to treat mental disease. The publication of The Interpretation of Dreams in 1899 detailed his technique of isolating the source of psychological problems by examining a patient’s spontaneous stream of thought.
 Increasing recognition of the psychoanalytic movement made possibly the formation in 1910 of a worldwide organization called the International Psychoanalytic Association. As the movement spread, gaining new adherents through Europe and the US, Freud was troubled by the dissension that arose among members of his original circle. Most disturbing was the defection from the group of Adler and Jung, each of whom developed a different theoretical basis for disagreement with Freud’s emphasis on the sexual origin of neurosis. Freud met these setbacks by developing further his basic concepts and by elaborating his own views in many publications and lectures.
 After the onset of World War I Freud devoted little time to clinical observation and concentrated on the application of his theories to the interpretation of religion, mythology, art, and literature. In 1923 he was stricken with pallative cancer of the jaw, which necessitated constant, painful treatment besides many surgical operations. Despite his physical suffering he continued his literary activity for the next 16 years, writing mostly on cultural and philosophical problems.
 When the Germans occupied Austria in 1938, Freud, a Jew, was persuaded by friends to escape with his family to England. He died in London on September 23, 1939.
 Freud created an entirely new approach to the understanding of human personality, by his demonstration of the existence and force of the unconscious in that he founded a new medical discipline and formulated basic therapeutic procedures that in modified form are applied widely in the present-day treatment of neuroses and psychoses. Although never accorded full recognition during his lifetime, Freud is generally acknowledged as one of the great creative minds of modern times.
 Among his other works are Totem and Taboo (1913), Ego and the Id (1923), New Introductory Lectures on Psychoanalysis (1933), and Moses and Monotheism (1939).
 The ego, the term occurring in psychoanalysis, that designates its term as denoting the central part of the personality structure that deals with reality and is influenced by social forces. According to the psychoanalytic theories developed by Sigmund Freud, the ego constitutes one of the three basic provinces of the mind, the other two, being the id and the superego. Formation of the ego begins at birth in the first encounters with the external world of people and things. The ego learns to modify behaviour by controlling those impulses that are socially unacceptable. Its role is that of a mediator between unconscious impulses and acquired social and personal standards.
 In philosophy, ego means the conscious self or ‘I.’ It was viewed by some philosophers, notably the 17th-century Frenchman René Descartes and the 18th-century German Johann Gottlieb Fichte, as the sole basis of reality; they saw the universe as existing only in the individual's knowledge and experience of it. Other philosophers, such as the 18th-century German Immanuel Kant, proposed two forms of the ego, one perceiving and the other thinking.
 As well, the term Id was oriented into psychoanalytic theory, one of the three basic elements of personality, the others being the ego and the super-ego. The id can be equated with the unconscious of common usage, which is the reservoir of the instinctual drives of the individual, including biological urges, wishes, and affective motives. The id is dominated by the pleasure principle, through which the individual is pressed for immediate gratification of his or her desires. In strict Freudian theory the energy behind the instinctual drives of the id is known as the libido, a generalized force, presented by its sexual nature, through which the sexual and psychosexual nature of the individual finds expression.
 Also, the Super-ego, in psychoanalytic theory is one of the three basic and most fundamental constituents of the mind, the others being the id and the ego. As postulated by Sigmund Freud, the term designates the element of the mind that, in normal personalities, automatically modifies and inhibits those instinctual impulses or drives of the id that directly addresses, by it’s very absence of an intervening agency, instrumentality or influence, where in having no direct knowledge of such unknowables. By linearity it is shown through the transparency of continuously and unbroken chain by passing into and through a decompressing static cause, is that, to only produce an antisocial actions and thoughts.
 According to psychoanalytic theory, the superego develops as the child gradually and unconsciously adopts the values and standards, first of his or her parents, and later of the social environment. According to modern Freudian psychoanalysts, the superego includes the positive ego, or conscious self-image, or ego ideal, that each individual develops.
 Psychoanalysis, is the name applied to a specific method of investigating unconscious mental processes and to a form of psychotherapy. The term refers, as well, to the systematic structure of psychoanalytic theory, which is based on the relation of conscious and unconscious psychological processes.
 The techniques of psychoanalysis and much of the psychoanalytic theory based on its application were developed by Sigmund Freud. His work concerning the structure and the functioning of the human mind had influential significance, both practically and scientifically, and it continues to influence contemporary thought.
 Of Freud’s three basic personality structures - id, ego, and super-ego - only the id is totally unconscious. The first of Freud's innovations was his recognition of unconscious psychiatric processes that follow laws different from those that govern conscious experience. Under the influence of the unconscious, thoughts and feelings that belong together may be shifted or displaced out of context; two disparate ideas or images may be condensed into one; thoughts may be dramatized in images rather than expressed as abstract concepts; and certain objects may be represented symbolically by images of other objects, although the resemblance between the symbol and the original object may be vague or farfetched. The laws of logic, indispensable for conscious thinking, do not apply to these unconscious mental productions.
 Recognition of these modes of operation in unconscious mental processes made possibly the understanding of such previously incomprehensible psychological phenomena as dreaming. Through analysis of unconscious processes, Freud saw dreams as serving to protect sleep against disturbing impulses arising from within and related to early life experiences. Thus, unacceptable impulses and thoughts, called the latent dream content, are transformed into a conscious, although no longer immediately comprehensible, experience called the manifest dream. Knowledge of these unconscious mechanisms permits the analyst to reverse the so-called dream work, that is, the process by which the latent dream is transformed into the manifest dream, and through dream interpretation, to recognize its underlying meaning.
 A basic assumption of Freudian theory is that the unconscious conflicts involve instinctual impulses, or drives, that originate in childhood. As these unconscious conflicts are recognized by the patient through analysis, his or her adult mind can find solutions that were unattainable to the immature mind of the child. This depiction of the role of instinctual drives in human life is a unique feature of Freudian theory.
 According to Freud's doctrine of infantile sexuality, adult sexuality is an end-set-product of a complex process of development, beginning in childhood, involving a variety of body functions or areas (oral, anal, and genital zones), and corresponding to various stages in the relation of the child to adults, especially to parents. This distinguishes the oedipus Complex, in psychoanalysis, a son’s largely unconscious sexual attraction toward his mother accompanied by jealousy toward his father. The terminological distinction of the oedipus complex, derived from the Greek legend of Oedipus, was first used in the late 1800's by Austrian psychiatrist Sigmund Freud, the founder of psychoanalysis. Freud thought that the Oedipus complex was the most important event of a boy’s childhood and affected his subsequent adult life. Freud claimed that in nearly all cases the boy represses the desire for his mother and the jealousy toward his father. Because of this unconscious experience, Freud believed, a boy with an Oedipus complex feels guilt and experiences strong emotional conflicts. Freud thought that young women went through a similar experience, in which they are attracted to their father and surmount the disconfirming antagonistic attitude toward their mother. He called this the Electra complex. According to Freud, if a woman remains under the influence of the Electra complex, she is likely to choose a husband with characteristics similar to those of her father.
 Of crucial importance is the so-called Oedipal period, occurring at about four to six years of age, because at this stage of development the child for the first time becomes capable of an emotional attachment to the parent of the opposite sex that is similar to the adult's relationship to a mate; the child simultaneously reacts as a rival to the parent of the same sex. Physical immaturity dooms the child's desires to frustration and his or her first step toward adulthood to failure. Intellectual immaturity further complicates the situation because it makes children afraid of their own fantasies. The extent to which the child overcomes these emotional upheavals and to which these attachments, fears, and fantasies continue to live on in the unconscious greatly influences later life, especially ‘loves’ relationships.
 The conflicts occurring in the earlier developmental stages are no less significant as a formative influence, because these problems represent the earliest prototypes of such basic human situations as dependency on others and relationship to authority. Also, basic in moulding the personality of the individual is the behaviour of the parents toward the child during these stages of development. The fact that the child reacts, not only to objective reality, but also to fantasy distortions of reality, however, greatly complicates even the best-intentioned educational efforts.
 The effort to clarify the bewildering number of interrelated observations uncovered by psychoanalytic exploration led to the development of a model of the structure of the psychic system. Three functional systems are distinguished that are conveniently designated as the id, ego, and super-ego.
 The first system refers to the sexual and aggressive tendencies that arise from the body, as distinguished from the mind. Freud called these tendencies Triebe, which literally means ‘drives,’ but which is often inaccurately translated as ‘instincts’ to indicate their innate character. These inherent drives claim immediate satisfaction, which is experienced as pleasurable; the id thus is dominated by the pleasure principle. In his later writings, Freud tended more toward psychological rather than biological conceptualization of the drives.
 How the conditions for satisfaction are to be brought about is the task of the second system, the ego, which is the domain of such functions as perception, thinking, and motor control that can accurately assess environmental conditions. In order to fulfill its function of adaptation, or reality testing, the ego must be capable of enforcing the postponement of satisfaction of the instinctual impulses originating in the id. To defend itself against unacceptable impulses, the ego develops specific psychic means, known as defence mechanisms. These include repression, the exclusion of impulses from conscious awareness; projection, the process of ascribing to others one's own unacknowledged desires; and reaction formation, the establishments of a pattern of behaviour directly opposed to a strong unconscious imperative necessarily in need for or required to employ of its relief. Such defence mechanisms are put into operation whenever anxiety signals a danger that the original unacceptable impulses may reemerge.
 The instructive voice regarding ‘neurophysiology’, is given to a commanding of issues, in that the study of how nerve cells, or neurons, receives and transmits information. Two types of phenomena are involved in processing nerve signals: Electrical and chemical. Electrical events propagate a signal within a neuron, and chemical processes transmit the signal from one neuron to another neuron or to a muscle cell.
 A neuron is a long cell that has a thick central area containing the nucleus, it also has one long process called an axon and one or more short, bushy processes called dendrites. Dendrites receive impulses from other neurons. (The exceptions are sensory neurons, such as those that transmit information about temperature or touch, in which the signal is generated by specialized receptors in the skin.) These impulses are propagated electrically along the cell membrane to the end of the axon. At the tip of the axon the signal is chemically transmitted to an adjacent neuron or muscle cell.
 Like all other cells, neurons contain charged ions: Potassium and sodium (positively charged) and chlorine (negatively charged). Neurons differ from other cells in that they can produce a nerve impulse. A neuron is polarized - that is, it has an overall negative charge inside the cell membrane because of the high concentration of chlorine ions and low concentration of potassium and sodium ions. The concentration of these same ions is exactly reversed outside the cell. This charge differential represents stored electrical energy, sometimes called membrane potential or resting potential. The negative charge inside the cell is maintained by two features. The first is the selective permeability of the cell membrane, which is more permeable to potassium than sodium. The second feature is sodium pumps within the cell membrane that actively pump sodium out of the cell. When depolarization occurs, this charge differential across the membrane is reversed, and a nerve impulse is produced.
 Depolarization is a rapid change in the permeability of the cell membrane. When sensory information or any other kind of stimulating current is received by the neuron, the membrane permeability is changed, allowing a sudden influx of sodium ions into the cell. The high concentration of sodium, or action potential, changes the overall charges within the cell from negative too positively. The local changes in ion concentration triggers similar reactions along the membrane, propagating the nerve impulse. After a brief period called the refractory period, during which the ionic concentration returned to resting potential, the neuron can repeat this process. Nerve impulses travel at different speeds, depending on the cellular composition of a neuron. Where speed of impulse is important, as in the nervous system, axons are insulated with a membranous substance called myelin. The insulation provided by myelin maintains the ionic charge over long distances. Nerve impulses are propagated at specific points along the myelin sheath; These points are called the nodes of Ranvier. Examples of myelinated axons are those in sensory nerve fibers and nerves connected to skeletal  muscles. In non-myelinated cells, the nerve impulse is propagated more diffusely.
 When the electrical signal reaches the tip of an axon, it stimulates small presynaptic vesicles in the cell. These vesicles contain chemicals called neurotransmitters, which are released into the microscopic space between neurons (the synaptic cleft). The neurotransmitter attaches on the surface of the adjacent neuron. This stimulus causes the adjacent cell to depolarize and propagate an action potential of its own. The duration of a stimulus from a neurotransmitter is limited by the breakdown of the chemicals in the synaptic cleft and the reuptake by the neuron that produced them. Formerly, each neuron was thought to make only one transmitter, but recent studies have shown that some cells make two or more.
 During the early 1900s, in examining the workings of the nervous system, physiologists were beginning to explore the idea that the transmission of nerve impulses takes place, in part, via chemical means. Loewi decided to explore this idea. During a stay in London in 1903, he met Sir Dale, who was also interested in the chemical transmission of nerve impulses. However, for Loewi, Dale, and all the other researchers pursuing a chemical transmitter of nerve impulses, years of effort produced no solid evidence. In 1921 Loewi suspended two frogs' hearts in solution, one with a major nerve removed. Removing fluid from the heart that still contained the nerve, and injecting the fluid into the nerveless heart, Loewi observed that the second heart behaved as if the missing nerve were present. The nerves, he concluded, do not act directly on the heart - it is the action of chemicals, freed by the stimulation of nerves, that causes increases in heart rate and other functional changes. In 1926 Loewi and his colleagues identified one of the chemicals in his experiment as acetylcholine. This was indisputably a neurotransmitter - a chemical that serves to transmit nerve impulses in the involuntary nervous system.
 We acknowledge the neurotransmitters are inherently made by chemically induced neurons, or nerve cells. Neurons send out neurotransmitters as chemical signals to activate or inhibit the function of neighboring cells.
 Within the central nervous system, which consists of the brain and the spinal cord, neurotransmitters pass from neuron to neuron. In the peripheral nervous system, which is made up of the nerves that run from the central nervous system to the rest of the body, the chemical signals pass between a neuron and an adjacent muscle or gland cells.
 Chemical compounds - belonging to three chemical families - are widely recognized as neurotransmitters. In addition, certain other body chemicals, including adenosine, histamine, enkephalins, endorphins, and epinephrine, have neurotransmitter-like properties. Experts believe that there are many more neurotransmitters yet undiscovered.
 The first of the three families is composed of amines, a group of compounds containing molecules of carbon, hydrogen, and nitrogen. Among the amines neurotransmitters are acetylcholine, norepinephrine, dopamine, and serotonin. Acetylcholine is the most widely used neurotransmitter in the body, and neurons that leave the central nervous system (for example, those running to skeletal muscle) use acetylcholine as their neurotransmitter; neurons that run to the heart, blood vessels, and other organs may use acetylcholine or norepinephrine. Dopamine is involved in the movement of muscles, and it controls the secretion of the pituitary hormone prolactin, which triggers milk production in nursing mothers.
 The second neurotransmitter family is composed of amino acids, organic compounds containing both an amino group (NH2) and a carboxylic acid group (COOH). Amino acids that serve as neurotransmitters include glycine, glutamic and aspartic acids, and gamma-amino butyric acid (GABA). Glutamic acid and GABA are the most abundant neurotransmitters within the central nervous system, and especially in the cerebral cortex, which is largely responsible for such higher brain functions as thought and interpreting sensations.
 The third neurotransmitter family is composed of peptides, which are compounds that contain at least two, and sometimes as many as 100 amino acids. Peptide neurotransmitters are poorly understood, but scientists know that the peptide neurotransmitter called substance P influences the sensation of pain.
 Overall, each neuron uses only a single compound as its neurotransmitter. However, some neurons outside the central nervous system can release both an amine and a peptide neurotransmitter.
 Neurotransmitters are manufactured from precursor compounds like amino acids, glucose, and the dietary amine-called choline. Neurons modify the structure of these precursor compounds in a series of reactions with enzymes. Neurotransmitters that comes from amino acids include serotonin, for which it is derived from tryptophan. Dopamine and norepinephrine, under which are derived from tyrosine, and glycine, which is derived from threonine. Among the neurotransmitters made from glucose are glutamate, aspartate, and GABA. The choline serves as the precursor for acetylcholine
 Neurotransmitters are released into a microscopic gap, called a synapse, that separates the transmitting neuron from the cell receiving the chemical signal. The cell that generates the signal is called the presynaptic cell, while the receiving cell is termed the postsynaptic cell.
 After their release into the synapse, neurotransmitters combine chemically with highly specific protein molecules, termed receptors, embedded in the surface membranes of the postsynaptic cell. When this combination occurs, the voltage, or electrical force, of the postsynaptic cell is either increased (excited) or decreased (inhibited).
 When a neuron is in its resting state, its voltage is about -70 millivolts. An excitatory neurotransmitter alters the membrane of the postsynaptic neuron, making it possible for ions (electrically charged molecules) to move back and forth across the neuron’s membranes. This flow of ions makes the neuron’s voltage rise toward zero. If enough excitatory receptors have been activated, the postsynaptic neuron responds by firing, generating a nerve impulse that causes its own neurotransmitter to be released into the next synapse. An inhibitory neurotransmitter causes different ions to pass back and forth across the postsynaptic neuron’s membrane, lowering the nerve cell’s voltage to -80 or -90 millivolts. The drop in voltage makes it less likely that the postsynaptic cell will fire.
 If the postsynaptic cell is a muscle cell rather than a neuron, an excitatory neurotransmitter will cause the muscle to contract. If the postsynaptic cell is a gland cell, an excitatory neurotransmitter will cause the cell to secrete its contents.
 While most neurotransmitters interact with their receptors to create new electrical nerve impulses that energize or inhibit the adjoining cell, some neurotransmitter interactions do not generate or suppress nerve impulses. Instead, they interact with a second type of receptor that changes the internal chemistry of the postsynaptic cell by either causing or blocking the formation of chemicals called second messenger molecules. These second messengers regulate the postsynaptic cell’s biochemical processes and enable it to conduct the maintenance necessary to continue synthesizing neurotransmitters and conducting nerve impulses. Examples of second messengers, which are formed and entirely contained within the postsynaptic cell, include cyclic adenosine monophosphate, diacylglycerol, and inositol phosphates.
 Once neurotransmitters have been secreted into synapses and have passed on their chemical signals, the presynaptic neuron clears the synapse of neurotransmitter molecules. For example, acetylcholine is broken down by the enzyme acetylcholinesterase into choline and acetate. Neurotransmitters like dopamine, serotonin, and GABA is removed by a physical process called reuptake. In reuptake, a protein in the presynaptic membrane acts as a sort of sponge, causing the neurotransmitters to reenter the presynaptic neuron, where they can be broken down by enzymes or repackaged for reuse.
 Neurotransmitters are known to be involved in many disorders, including Alzheimer’s disease. Victims of Alzheimer’s disease suffer from loss of intellectual capacity, disintegration of personality, mental confusion, hallucinations, and aggressive - even violent - behavior. These symptoms are the result of progressive degeneration in many types of neurons in the brain. Forgetfulness, one of the earliest symptoms of Alzheimer’s disease, is partly caused by the destruction of neurons that normally release the neurotransmitter acetylcholine. Medications that increase brain levels of acetylcholine have helped restore short-term memory and reduce mood swings in some Alzheimer’s patients.
 Neurotransmitters also play a role in Parkinson disease, which slowly attacks the nervous system, causing symptoms that worsen over time. Fatigue, mental confusion, a mask-like facial expression, stooping posture, shuffling gait, and problems with eating and speaking are among the difficulties suffered by Parkinson victims. These symptoms have been partly linked to the deterioration and eventual death of neurons that run from the base of the brain to the basal ganglia, a collection of nerve cells that manufacture the neurotransmitter dopamine. The reasons why such neurons die are yet to be understood, but the related symptoms can be alleviated. L-dopa, or levodopa, widely used to treat Parkinson disease, acts as a supplementary precursor for dopamine. It causes the surviving neurons in the basal ganglia to increase their production of dopamine, by that compensating to some extent for the disabled neurons.
 Many other effective drugs have been shown to act by influencing neurotransmitter behavior. Some drugs work by interfering with the interactions between neurotransmitters and intestinal receptors. For example, belladonna decreases intestinal cramps in such disorders as irritable bowel syndrome by blocking acetylcholine from combining with receptors. This process reduces nerve signals to the bowel wall, which prevents painful spasms.
 Other drugs block the reuptake process. One well-known example is the drug fluoxetine (Prozac), which blocks the reuptake of serotonin. Serotonin then remains in the synapse for a longer time, and its ability to act as a signal is prolonged, which contributes to the relief of depression and the control of obsessive-compulsive behaviors.
 Dopamine, chemical known as a neurotransmitter essential to the functioning of the central nervous system. During neurotransmission, dopamine is transferred from one nerve cell, or neuron, to another, playing a key role in brain function and human behavior.
 Dopamine forms from a precursor molecule called dopa, which is manufactured in the liver from the amino acid tyrosine. Dopa is then transported by the circulatory system to neurons in the brain, where the conversion to dopamine takes place.
 Dopamine is a versatile neurotransmitter. Among its many functions, it plays a major role in two activities of the central nervous system: one that helps control movement, and a second that are strongly associated with emotion-based behaviors.
 The pathway involved in movement control is called the nigrostriatal pathway. Dopamine is released by neurons that originate from an area of the brain called the substantia nigra and connect to the part of the brain known as the corpora striata, an area known to be important in controlling the musculoskeletal system.
 The second brain pathway in which dopamine plays a major role is called the mesocorticolimbic pathway. Neurons in an area of the brain called the ventral tegmentalarea transmits dopamine to other neurons connected to various parts of the limbic system, which is responsible for regulating emotion, motivation, behavior, the sense of smell, and variously autonomic, or involuntary, functions like heartbeat and breathing. A growing body of evidence suggests that dopamine be involved in several major brain disorders. Narcolepsy, a disorder characterized by brief, recurring episodes of sudden, deep sleep, is associated with abnormally high levels of both dopamine and a second neurotransmitter, acetylcholine. Huntington’s chorea, an inherited, fatal illness in which neurons in the base of the brain are progressively destroyed, is also linked to an excess of dopamine.
 Commonly known as shaking palsy, Parkinson disease is another brain disorder in which dopamine is involved. Besides tremors of the limbs, Parkinson patients suffer from muscular rigidity, which leads to difficulties in walking, writing, and speaking. This disorder results from the degeneration and death of neurons in the nigrostriatal pathway, resulting in low levels of dopamine. The symptoms of Parkinson disease can be reduced by treatment with a drug called levodopa, or L-dopa, which converts to dopamine in the brain.
 Schizophrenia is a psychiatric disorder characterized by loss of contact with reality and major changes in personality. Schizophrenics have normal levels of dopamine in the brain, but because they are highly sensitive to this neurotransmitter, these normal levels of dopamine triggers unusual behaviors. Drugs such as thorazine that blocks the action of dopamine have been found to decrease the symptoms of schizophrenia.
 Studies suggest that people who are addicted to alcohol and other drugs like, cocaine and nicotine have less dopamine in the mesocorticolimbic pathway. These drugs appear to increase dopamine levels, resulting in the pleasurable feelings associated with the drugs.
 Serotonin, neurotransmitter, or chemical that transmits messages across the synapses, or gaps, between adjacent cells. Among its many functions, serotonin is released from blood cells called platelets to activate blood vessel constriction and blood clotting. In the gastrointestinal tract, serotonin inhibits gastric acid production and stimulates muscle contraction in the intestinal wall. Its functions in the central nervous system and effects on human behavior - including mood, memory, and appetite control - have been the subject of a great deal of research. This intensive study of serotonin has revealed important knowledge about the serotonin-related cause and treatment of many illnesses.
 Serotonin is produced in the brain from the amino acid tryptophan, which is derived from foods high in protein, such as meat and dairy products. Tryptophan is transported to the brain, where it is broken down by enzymes to produce serotonin. During neurotransmission, serotonin is transferred from one nerve cell, or neuron, to another, triggering an electrical impulse that stimulates or inhibits cell activity as needed. Serotonin is then reabsorbed by the first neuron, in a process known as reuptake, where it is recycled and used again or converted into an inactive chemical form and excreted.
 While the complete picture of serotonin’s function in the body is still being investigated, many disorders are known to be associated with an imbalance of serotonin in the brain. Drugs that manipulate serotonin levels have been used to alleviate the symptoms of serotonin imbalances. Some of these drugs, known as selective serotonin reuptake inhibitors (SSRIs), block or inhibit the reuptake of serotonin into neurons, enabling serotonin to remain active in the synapses for a longer period. These medications are used to treat such psychiatric disorders as depression; Obsessive-compulsive disorder, in which repetitive and disturbing thoughts trigger bizarre, ritualistic behaviors, and impulsive aggressive behaviors. Fluoxetine (more commonly known by the brand name Prozac), is a widely prescribed SSRI used to treat depression, and more recently, obsessive-compulsive disorder.
 Drugs that affect serotonin levels may prove beneficial in the treatment of nonpsychiatric disorders as well, including diabetic neuropathy (degeneration of nerves outside the central nervous system in diabetics) and premenstrual syndrome. Recently the serotonin-releasing agent dexfenfluramine has been approved for patients who are 30 percent or more over their ideal body weight. By preventing serotonin reuptake, dexfenfluramine promotes satiety, or fullness, after eating less food.
 Other drugs serve as agonists that react with neurons to produce effects similar to those of serotonin. Serotonin agonists have been used to treat migraine headaches, in which low levels of serotonin cause arteries in the brain to swell, resulting in a headache. Sumatriptan is an agonist drug that mimics the effects of serotonin in the brain, constricting blood vessels and alleviating pain.
 Drugs known as antagonists bind with neurons to prevent serotonin neurotransmission. Some antagonists have been found effective in treating the nausea that typically accompanies radiation and chemotherapy in cancer treatment. Antagonists are also being tested to treat high blood pressure and other cardiovascular disorders by blocking serotonin’s ability to constrict blood vessels. Other antagonists may produce an effect on learning and memory in age-associated memory impairment.
 The Synapse is the signal conveying everything that human beings sense and think, and every motion they make, follows nerve pathways in the human body as waves of ions (atoms or groups of atoms that carries electric charges). Australian physiologist Sir John Eccles discovered many intricacies of this electrochemical signaling process, particularly the pivotal step in which a signal is conveyed from one nerve cell to another. He shared the 1963 Nobel Prize in physiology or medicine for this work, which he described in a 1965 Scientific American article.
 How does one nerve cell transmit the nerve impulse to another cell? Electron microscopy and other methods show that it does so by means of special extensions that deliver a squirt of transmitter substance
 The human brain is the most highly organized form of matter known, and in complexity the brains of the other higher animals are not greatly inferior. For certain purposes regarding the brain for being analogous to a machine is expedient. Even if it is so regarded, however, it is a machine of a totally different kind from those made by man. In trying to understand the workings of his own brain man meets his highest challenge. Nothing is given; There are no operating diagrams, no maker's instructions.
 The first step in trying to understand the brain is to examine its structure to discover the components from which it is built and how they are related to each another. After that one can attempt to understand the mode of operation of the simplest components. These two modes of investigation - the morphological and the physiological - have now become complementary. In studying the nervous system with today's sensitive electrical device, however, finding physiological events that cannot be correlated with any known anatomical structure is all too easy. Conversely, the electron microscope reveals many structural details whose physiological significance is obscure or unknown.
 At the close of the past century the Spanish anatomist Santiago Ramón Cajal showed how all parts of the nervous system are built up of individual nerve cells of many different shapes and sizes. Like other cells, each nerve cell has a nucleus and the surrounding cytoplasm. Its outer surface consists of many fine branches - the dendrites - that receive nerve impulses from other nerve cells, and one relatively long branch - the axon - that transmits nerve impulses. Near its end the axon divides into branches that end at the dendrites or bodies of other nerve cells. The axon can be as short as a fraction of a millimeter or if a meter, depending on its place and function. It has many properties of an electric cable and is uniquely specialized to conduct the brief electrical waves called nerve impulses. In very thin axons these impulses travel at less than one meter per second; In others, for example in the large axons of the nerve cells that activate muscles, they travel as fast as 100 meters per second.
 The electrical impulse that travels along the axon ceases abruptly when it comes to the point where the axon's terminal fibers contact another nerve cell. These junction points were given the name ‘synapses’ by Sir Charles Sherrington, who laid the foundations of what is sometimes called synaptology. If the nerve impulse is to continue beyond the synapse, it must be regenerated afresh on the other side. As recently as 15 years ago some physiologists held that transmission at the synapse was predominantly, if not exclusively, an electrical phenomenon. Now, however, there is abundant evidence that transmission is made by the release of specific chemical substances that trigger a regeneration of the impulse. In fact, the first strong evidence showing that some transmitter substance act across the synapse was provided more than 40 years ago by Sir Henry Dale and Otto Loewi.
 It has been estimated that the human central nervous system, which of course includes the spinal cord and the brain itself, consists of about 10 billion (1010) nerve cells. With rare exceptions each nerve cell receives information directly as impulses from many other nerve cells - often hundreds - and transmits information to a like number. Depending on its threshold of response, a given nerve cell may fire an impulse when stimulated by only a few incoming fibers or it may not fire until stimulated by many incoming fibers. It has long been known that this threshold can be raised or lowered by various factors. Moreover, it was supposed some 60 years ago that some incoming fibers must inhibit the firing of the receiving cell rather than excite it. The conjecture was subsequently confirmed, and the mechanism of the inhibitory effect has now been clarified. This mechanism and its equally fundamental counterpart - nerve-cell excitation - are of its topic.
 In the levels of anatomy there are some clues to show how the fine axon terminals impinging on a nerve cell can make the cell regenerate a nerve impulse of its own nerve cell and its dendrites are covered by fine branches of nerve fibers that end in knob-like structures. These structures are the synapses.
 The electron microscope has revealed structural details of synapses that fit in nicely with the view that a chemical transmitter is involved in nerve transmission. Enclosed in the synaptic knob are many vesicles, or tiny sacs, which appear to contain the transmitter substances that induce synaptic transmission. Between the synaptic knob and the synaptic membrane of the adjoining nerve cell is a remarkably uniform space of about 20 millimicrons that is termed the synaptic cleft. Many of the synaptic vesicles are concentrated adjacent to this cleft; It seems plausible that the transmitter substance is discharged from the nearest vesicles into the cleft, where it can act on the adjacent cell membrane. This hypothesis is supported by the discovery that the transmitter is released in packets of a few thousand molecules.
 The study of synaptic transmission was revolutionized in 1951 by the introduction of delicate techniques for recording electrically from the interior of single nerve cells. This is done by inserting into the nerve cell an extremely fine glass pipette with a diameter of .5 microns - about a fifty-thousandth of an inch. The pipette is filled with an electrically conducting salt solution such as concentrated potassium chloride. If the pipette is carefully inserted and held rigidly in place, the cell membrane appears to seal quickly around the glass, thus preventing the flow of a short-circuiting current through the puncture in the cell membrane. Impaled in this fashion, nerve cells can function normally for hours. Although there is no way of observing the cells during the insertion of the pipette, the insertion can be guided by using as clues the electric signals that the pipette picks up when close to active nerve cells.
 At the John Curtin School of Medical Research in Canberra first employed this technique, choosing to study the large nerve cells called motoneurons, which lie in the spinal cord whose function is to activate muscles. This was a fortunate choice: Intracellular investigations with motoneurons are easier and more rewarding than those with any other kind of mammalian nerve cell.
 Finding that when the nerve cell responds to the chemical synaptic transmitter, the response depends in part on characteristic features of ionic composition that are also concerned with the transmission of impulses in the cell and along its axon. When the nerve cell is at rest, its physiological makeup resembles that of most other cells in that the water solution inside the cell is quite different in composition from the solution in which the cell is bathed. The nerve cell can exploit this difference between external and internal composition and use it in quite different ways for generating an electrical impulse and for synaptic transmission.
 The composition of the external solution is well established because the solution is essentially the same as blood from which cells and proteins have been removed. The composition of the internal solution is known only approximately. Indirect evidence suggests that the concentrations of sodium and chloride ions outside the cell are respectively some 10 and 14 times higher than the concentrations inside the cell. In contrast, the concentration of potassium ions inside the cell is about 30 times higher than the concentration outside.
 How can one account for this remarkable state of affairs? Part of the explanation is that inside the cell is negatively charged with the respect of the cell about 70 millivolts. Since like charges repel each other, this internal negative charge tends to drive chloride ions (Cl-) outward through the cell membrane and, at the same time, to impede their inward movement. In fact, a potential difference of 70 millivolts is just sufficient to maintain the observed disparity in the concentration of chloride ions inside the cell and outside it; Chloride ions diffuse inward and outward at equal rates. A drop of 70 millivolts across the membrane therefore defines the ‘equilibrium potential’ for chloride ions.
 To obtain a concentration of potassium ions (K) that is 30 times higher inside the cell than outside would require that the interior of the cell membrane be about 90 millivolts negative with respect to the exterior. Since the actual interior is only 70 millivolts negative, it falls short of the equilibrium potential for potassium ions by 20 millivolts. Evidently the thirty-fold concentration can be achieved and maintained only if there is some auxiliary mechanism for ‘pumping’ potassium ions into the cell at a rate equal to their spontaneous net outward diffusion.
 The pumping mechanisms have fewer, but more difficult tasks of pumping sodium ions (Na) out of the cell against a potential gradient of 130 millivolts. This figure is obtained by adding the 70 millivolts of internal negative charge to the equilibrium potential for sodium ions, which is 60 millivolts of internal positive charge. If it were not for this postulated pump, the concentration of sodium ions inside and outside the cell would be almost the reverse of what is observed.
 In their classic studies of nerve-impulse transmission in the giant axon of the squid, A. L. Hodgkin, A. F. Huxley and Bernhard Katz of Britain proved that the propagation of the impulse coincides with abrupt changes in the permeability of the axon membrane. When a nerve impulse has been triggered in some way, what can be described as a gate opens and lets sodium ions pour into the axon during the advance of the impulse, making the interior of the axon locally positive. The process is self-reinforcing in that the flow of some sodium ions through the membrane opens the gate further and makes it easier for others to follow. The sharp reversal of the internal polarity of the membrane makes up the nerve impulse, which moves like a wave until it has traveled the length of the axon. In the wake of the impulse the sodium gate closes and a potassium gate opens, by that restoring the normal polarity of the membrane within a millisecond or less.
 With this understanding of the nerve impulse in hand, one is ready to follow the electrical events at the excitatory synapse. One might guess that if the nerve impulse results from an abrupt inflow of sodium ions and a rapid change in the electrical polarity of the axon's interior, something similar must happen at the body and dendrites of the nerve cell in order to generate the impulse in the first place. Indeed, the function of the excitatory synaptic terminals on the cell body and its dendrites is to depolarize the interior of the cell membrane essentially by permitting an inflow of sodium ions. When the depolarization reaches a threshold value, a nerve impulse is triggered.
 As a simple instance of this phenomenon we have recorded the depolarization that occurs in a single motoneuron activated directly by the large nerve fibers that enter the spinal cord from special stretch-receptors known as annulospiral endings. These receptors in turn are found in the same muscle that is activated by the motoneuron under study. Thus the whole system forms a typical reflex arc, such as the arc responsible for the patellar reflex, or ‘knee jerk.’
 To conduct the experiment we anesthetize an animal (most often a cat) and free by dissection a muscle nerves that contains these large nerve fibers. By applying a mild electric shock to the exposed nerve one can produce a single impulse in each of the fibers; Since the impulses travel to the spinal cord almost synchronously, they are referred to collectively as a volley. The number of impulses contained in the volley can be reduced by reducing the stimulation applied to the nerve. The volley strength is measured at a point just outside the spinal cord and is displayed on an oscilloscope. About half a millisecond after detection of a volley there is a wavelike change in the voltage inside the motoneuron that has received the volley. The change is detected by a microelectrode inserted in the motoneuron and is displayed on another oscilloscope.
 What we find is that the negative voltage inside the cell becomes progressively fewer negative as more of the fibers impinging on the cell are stimulated to fire. This observed depolarization is in fact a simple summation of the depolarization produced by each individual synapse. When the depolarization of the interior of the motoneuron reaches a critical point, a ‘spike’ suddenly appears on the second oscilloscope, showing that a nerve impulse has been generated. During the spike the voltage inside the cell changes from about 70 millivolts negative to as much as 30 millivolts positive. The spike regularly appears when the depolarization, or reduction of membrane potential, reaches a critical level, which is usually between 10 and 18 millivolts. The only effect of a further strengthening of the synaptic stimulus is to shorten the time needed for the motoneuron to reach the firing threshold. The depolarizing potentials produced in the cell membrane by excitatory synapses are called excitatory postsynaptic potentials, or EPSP's.
 Through one barrel of a double-barreled microelectrode one can apply a background current to change the resting potential of the interior of the cell membrane, either increasing it or decreasing it. When the potential is made more negative, the EPSP rises more steeply to an earlier peak. When the potential is made less negative, the EPSP rises more slowly to a lower peak. Finally, when the charge inside the cell is reversed so as to be positive with respect to the exterior, the excitatory synapses give rise to an EPSP that is actually the reverse of the normal one.
 These observations support the hypothesis that excitatory synapses produce what amounts virtually to a short circuit in the synaptic membrane potential. When this occurs, the membrane no longer acts as a barrier to the passage of ions but lets them flow through in response to the differing electric potential on the two sides of the membrane. In other words, the ions are momentarily allowed to travel freely down their electrochemical gradients, which means that the sodium ions flow into the cell and, to a lesser degree, potassium ions flow out. It is this net flow of positive ions that creates the excitatory postsynaptic potential. The flow of negative ions, such as the chloride ion, is apparently not involved. By artificially altering the potential inside the cell one can establish that there is no flow of ions, and therefore no EPSP, when the voltage drop across the membrane is zero.
 How is the synaptic membrane converted from a strong ionic barrier into an ion-permeable state? It is currently accepted that the agency of conversion is the chemical transmitter substance contained in the vesicles inside the synaptic knob. When a nerve impulse reaches the synaptic knob, some of the vesicles are caused to eject the transmitter substance into the synaptic cleft. The molecules of the substance would take only a few microseconds to diffuse across the cleft and become attached to specific receptor sites on the surface membrane of the adjacent nerve cell.
 Presumably the receptor sites are associated with fine channels in the membrane that are opened in some way by the attachment of the transmitter-substance molecules to the receptor sites. With the channels thus opened, sodium and potassium ions flow through the membrane thousands of times more readily than they normally do, by that producing the intense ionic flux that depolarizes the cell membrane and produces the EPSP. In many synapses the current flows strongly for only about a millisecond before the transmitter substance is eliminated from the synaptic cleft, either by diffusion into the surrounding regions or as a result of being destroyed by enzymes. The latter process is known to occur when the transmitter substance is acetylcholine, which is destroyed by the enzyme acetylcholinesterase.
 The substantiation of this general picture of synaptic transmission requires the solution of many fundamental problems. Since we do not know the specific transmitter substance for the vast majority of synapses in the nervous system, we do not know whether there are many different substances or only a few. The only one identified with reasonable certainty in the mammalian central nervous system is acetylcholine. We know practically nothing about the mechanism by which a presynaptic nerve impulse causes the transmitter substance to be injected into the synaptic cleft. Nor do we know how the synaptic vesicles not immediately next to the synaptic cleft follow to moved up to the firing line to replace the emptied vesicles. It is supposed that the vesicles contain the enzyme systems needed to recharge themselves. The entire process must be swift and efficient: The total amount of transmitter substance in synaptic terminals is enough for only a few minutes of synaptic activity at normal operating rates. There are also knotty problems to be solved on the other side of the synaptic cleft. What, for example, is the nature of the receptor sites? How are the ionic channels in the membrane opened?
 The second type of synapse that has been identified in the nervous system. These are the synapses that can inhibit the firing of a nerve cell even though it may be receiving a volley of excitatory impulses. When inhibitory synapses are examined in the electron microscope, they look very much like excitatory synapses. (There are probably some subtle differences, but they need not concern us here.) Microelectrode recordings of the activity of single motoneurons and other nerve cells have now shown that the inhibitory postsynaptic potential (IPSP) is virtually a mirror image of the EPSP. Moreover, individual inhibitory synapses, like excitatory synapses, have a cumulative effect. The chief difference is simply that the IPSP makes the cell's internal voltage more negative than it is normally, which is in a direction opposite to that needed for generating a spike discharge.
 By driving the internal voltage of a nerve cell in the negative direction inhibitory synapses oppose the action of excitatory synapses, which of course drive it in the positive direction. So if the potential inside a resting cell is 70 millivolts negative, a strong volley of inhibitory impulses can drive the potential to 75 or 80 millivolts depreciating count. One can easily see that if the potential is made more negative in this way the excitatory synapses find it more difficult to raise the internal voltage to the threshold point for the generation of a spike. Thus, the nerve cell responds to the algebraic sum of the internal voltage changes produced by excitatory and inhibitory synapses.
 If, as in the experiment described earlier, the internal membrane potential is altered by the flow of an electric current through one barrel of a double-barreled microelectrode, one can observe the effect of such changes on the inhibitory postsynaptic potential. When the internal potential is made less negative, the inhibitory postsynaptic potential is deepened. Conversely, when the potential is made more negative, the IPSP diminishes; it finally reverses when the internal potential is driven below minus 80 millivolts.
 One can therefore assume that inhibitory synapse’s share with excitatory synapses the ability to change the ionic permeability of the synaptic membrane. The difference is that inhibitory synapses enable ions to flow freely down an electrochemical gradient that has an equilibrium point at minus 80 millivolts rather than at zero, as is the case for excitatory synapses. This effect could be achieved by the outward flow of positively charged ions such as potassium or the inward flow of negatively charged ions such as chloride, or by a combination of negative and positive ionic flows such that the interior reaches equilibrium at minus 80 millivolts.
 If the concentration of chloride ions within the cell is increased as much as three times, the inhibitory postsynaptic potential reverses and acts as a depolarizing current; that is, it resembles an excitatory potential. On the other hand, if the cell is heavily injected with sulfate ions, which are also negatively charged, there is no such reversal. This simple test shows that under the influence of the inhibitory transmitter substance, which is still unidentified, the subsynaptic membrane becomes permeable momentarily to chloride ions but not to sulfate ions. During the generation of the IPSP the outflow of chloride ions is so rapid that it more than outweighs the flow of other ions that generate the normal inhibitory potential.
 The effect of injecting motoneurons with more than 30 kinds of negatively lunged ions. With one exception the hydrated ions (ions bound to water) to which the cell membrane is permeable under the influence of the inhibitory transmitter substance are smaller than the hydrated ions to which the membrane is impermeable. The exception is the formate ion (HCO2-), which may have an ellipsoidal shape and so be able to pass through membrane pores that block smaller spherical ions.
 Apart from the formate ion all the ions to which the membrane is permeable have a diameter not greater than 1.14 times the diameter of the potassium ion; That is, they are less than 2.9 angstrom units in diameter. Comparable investigations in other laboratories have found the same permeability effects, including the exceptional behavior of the formate ion, in fishes, toads and snails. It might be that the ionic mechanism responsible for synaptic inhibition is the same throughout the animal kingdom.
 The significance of these and other studies is that they strongly suggest that the inhibitory transmitter substance open the membrane to the flow of potassium ions but not to sodium ions. It is known that the sodium ion is somewhat larger than any of the negatively charged ions, including the formate ion, that are able to pass through the membrane during synaptic inhibition. Testing the effectiveness of potassium ions by injecting excess amounts into the cell is not possible, however, because the excess is immediately diluted by an osmotic flow of water into the cell.
 The concentration of potassium ions inside the nerve cell is about 30 times greater than the concentration outside, and to maintain this large difference in concentration without the help of some metabolic pumps inside of the membrane would have to be charged 90 millivolts negative with respect to the exterior. This implies that if the membrane were suddenly made porous to potassium ions, the resulting outflow of ions would make the inside potential of the membrane even more negative than it is in the resting state, and that is just what happens during synaptic inhibition. The membrane must not simultaneously become porous to sodium ions, because they exist in much higher concentration outside the cell than inside and their rapid inflow would more than compensate for the potassium outflow. In fact, the fundamental difference between synaptic excitation and synaptic inhibition is that the membrane freely passes sodium ions in response to the former and largely excludes the passage of sodium ions in response to the latter.
 This fine discrimination between ions that are not very different in size must be explained by any hypothesis of synaptic action. It is most unlikely that the channels through the membrane are created afresh and accurately maintained for a thousandth of a second every time a burst of transmitter substance is released into the synaptic cleft. It is more likely that channels of at least two different sizes are built directly into the membrane structure. In some way the excitatory transmitter substance would selectively unplug the larger channels and permit the free inflow of sodium ions. Potassium ions would simultaneously flow out and thus would tend to counteract the large potential change that would be produced by the massive sodium inflow. The inhibitory transmitter substance would selectively unplug the smaller channels that are large enough to pass potassium and chloride ions but not sodium ions.
 To explain certain types of inhibition other features must be added to this hypothesis of synaptic transmission. In the simple hypothesis chloride and potassium ions can flow freely through pores of all inhibitory synapses. It has been shown, however, that the inhibition of the contraction of heart muscle by the vagus nerve is due almost exclusively to potassium-ion flow. On the other hand, in the muscles of crustaceans and in nerve cells in the snail's brain synaptic inhibition is due largely to the flow of chloride ions. This selective permeability could be explained if there were fixed charges along the walls of the channels. If such charges were negative, they would repel negatively charged ions and prevent their passage; if they were positive, they would similarly prevent the passage of positively charged ions. One can now suggest that the channels opened by the excitatory transmitter are negatively charged and so do not permit the passage of the negatively charged chloride ion, even though it is small enough to move through the channel freely.
 One might wonder if a given nerve cell can have excitatory synaptic action at some of its axon terminals and inhibitory action at others. The answer is no. Two different kinds of nerve cells are needed, one for each type of transmission and synaptic transmitter substance. This can readily be shown by the effect of strychnine and tetanus toxins in the spinal cord; They specifically prevent inhibitory synaptic action and leave excitatory action unaltered. As a result the synaptic excitation of nerve cells is uncontrolled and convulsions result. The special types of cells responsible for inhibitory synaptic action are now being recognized in many parts of the central nervous system.
 This account of communication between nerve cells is necessarily oversimplified, yet it shows that some significant advances are being made at the level of individual components of the nervous system. By selecting the most favorable situations we have been able to throw light on some details of nerve-cell behavior. We can be encouraged by these limited successes. Nevertheless, the task of understanding in a comprehensive way how the human brain operates staggers its own imagination.
 Our brain begins with its portion of the central nervous system contained within the skull. The brain is the control center for movement, sleep, hunger, thirst, and virtually every other vital activity necessary to survival. All human emotions - including love, hate, fear, anger, elation, and sadness - are controlled by the brain. It also receives and interprets the countless signals that are sent to it from other parts of the body and from the external environment. The brain makes us conscious, emotional, and intelligent
 The human brain has three major structural components: the large dome-shaped cerebrum, the smaller somewhat spherical cerebellum, and the brainstem. Prominent in the brainstem are the medulla oblongata and the thalamus - between the medulla and the cerebrum. The cerebrum is responsible for intelligence and reasoning. The cerebellum helps to maintain balance and posture. The medulla is involved in maintaining involuntary functions such as respiration, and the thalamus act as a relay center for electrical impulses traveling to and from the cerebral cortex.
 The adult human brain is a 1.3-kg. (3-lb.) Mass of pinkish-gray jellylike tissue made up of approximately 100 billion nerve cells or neurons: The Neuroglia (supporting-tissue) cells, and vascular (blood-carrying) and other tissues.
 Between the brain and the cranium - the part of the skull that directly covers the brain - are three protective membranes, or meninges. The outermost membrane, the dura mater, is the toughest and thickest. Below the dura mater is a middle membrane, called the arachnoid layer. The innermost membrane, the pia mater, consists mainly of small blood vessels and follows the contours of the surface of the brain.
 A clear liquid, the cerebrospinal fluid, bathes the entire brain and fills a series of four cavities, called ventricles, near the center of the brain. The cerebrospinal fluid protects the internal portion of the brain from varying pressures and transports chemical substances within the nervous system.
 From the outside, the brain appears as three associatively distinct but connected parts, the cerebrum (the Latin word for brain) - two large, almost symmetrical hemispheres; the cerebellum ('little brain') - two smaller hemispheres located at the back of the cerebrum; and the brain stem - a central core that gradually becomes the spinal cord, exiting the skull through an opening at its base called the foramen magnum. Two other major parts of the brain, the thalamus and the hypothalamus, lie in the midline above the brain stem underneath the cerebellum.
 The brain and the spinal cord together make up the central nervous system, which communicates with the rest of the body through the peripheral nervous system. The peripheral nervous system consists of 12 pairs of cranial nerves extending from the cerebrum and brain stem; a system of other nerves branching throughout the body from the spinal cord, and the autonomic nervous system, which regulates vital functions is not very consciously of its own control, such as the activity of the heart muscle, smooth muscle (involuntary muscle found in the skin, blood vessels, and internal organs), and glands.
 Many motor and sensory functions have been ‘mapped’ to specific areas of the cerebral cortex, some of which are indicated here. In general, these areas exist in both hemispheres of the cerebrum, each serving the opposite side of the body. Fewer defined are the areas of association, located mainly in the frontal cortex, operatives in functions of thought and emotion and responsible for linking input from different senses. The areas of language are an exception: Both Wernicke’s area, concerned with the comprehension of spoken language, and Broca’s area, governing the production of speech, have been pinpointed on the cortex. 
 Most high-level brain functions take place in the cerebrum. Its two large hemispheres make up approximately 85 percent of the brain's weight. The exterior surface of the cerebrum, the cerebral cortex, is a convoluted, or folded, grayish layer of cell bodies known as the gray matter. The gray matter covers an underlying mass of fibers called the white matter. The convolutions are made up of ridge-like bulges, known as gyri, separated by small grooves called sulci and larger grooves called fissures. Approximately two-thirds of the cortical surface is hidden in the folds of the sulci. The extensive convolutions enable a very large surface area of brain cortices - roughly, 1.5 m2  (16 ft2) in an adult - to fit within the cranium. The pattern of these convolutions is similar, although not identical, in all humans.
 The two cerebral hemispheres are partially separated from each other by a deep fold known as the longitudinal fissure. Communication between the two hemispheres is through several concentrated bundles of axons, called commissures, the largest of which is the corpus callosum.
 Several major sulci divides the cortex into distinguishable regions. The central sulcus, or Rolandic fissure, runs from the middle of the top of each hemisphere downward, forwards, and toward another major sulcus, the lateral (side), or Sylvian, sulcus. These and other sulci and gyri divide the cerebrum into five lobes: The frontal, parietal, temporal, and occipital lobes and the insula.
 Although the cerebrum is symmetrical in structure, with two lobes emerging from the brain stem and matching motor and sensory areas in each, certain intellectual functions are restricted to one hemisphere. A person’s dominant hemisphere is usually occupied with language and logical operations, while the other hemisphere controls emotion and artistic and spatial skills. In nearly all right-handed and many left-handed people, the left hemisphere is dominant.
 The frontal lobe is the largest of the five and consists of all the cortices in front of the central sulcus. Broca's area, a part of the cortex related to speech, is located in the frontal lobe. The parietal lobe consists of the cortex behind the central sulcus to some sulcus near the back of the cerebrum known as the parieto-occipital sulcus. The parieto-occipital sulcus, in turn, forms the front border of the occipital lobe, which are the rearmost part of the cerebrum. The temporal lobe is to the side of and below the lateral sulcus. Wernicke's area, a part of the cortex related to the understanding of language, is located in the temporal lobe. The insula lies deep within the folds of the lateral sulcus.
 The cerebrum receives information from all the sense organs and sends motor commands (signals that results in activity in the muscles or glands) to other parts of the brain and the rest of the body. Motor commands are transmitted by the motor cortex, a strip of cerebral cortex extending from side to side across the top of the cerebrum just in front of the central sulcus. The sensory cortex, parallel strips of cerebral cortex just in back of the central sulcus, receives input from the sense organs.
 Many other areas of the cerebral cortex have also been mapped according to their specific functions, such as vision, hearing, speech, emotions, language, and other aspects of perceiving, thinking, and remembering. Cortical regions known as associative cortices are responsible for integrating multiple inputs, processing the information, and carrying out complex responses.
 The cerebellum coordinates body movements. Located at the lower back of the brain beneath the occipital lobes, the cerebellum is divided into two lateral (side-by-side) lobes connected by a finger-like bundle of white fibers called the vermis. The outer layer, or cortex, of the cerebellum consists of fine folds called folia. As in the cerebrum, the outer layer of cortical gray matter surrounds a deeper layer of white matter and nuclei (groups of nerve cells). Three fiber bundles called cerebellar peduncles connect the cerebellum to the three parts of the brain stem - the midbrain, the pons, and the medulla oblongata.
 The cerebellum coordinates voluntary movements by fine-tuning commands from the motor cortex in the cerebrum. The cerebellum also maintains posture and balance by controlling muscle tone and sensing the position of the limbs. All motor activity, from hitting a baseball to fingering a violin, depends on the cerebellum.
 The limbic system is a group of brain structures that play a role in emotion, memory, and motivation. For example, electrical stimulation of the amygdala in laboratory animals can provoke fear, anger, and aggression. The hypothalamus regulates hunger, thirst, sleep, body temperature, sexual drive, and other functions.
 The thalamus and the hypothalamus lie underneath the cerebrum and connect it to the brain stem. The thalamus consist of two rounded masses of gray tissue lying within the middle of the brain, between the two cerebral hemispheres. The thalamus are the main relay station for incoming sensory signals to the cerebral cortex and for outgoing motor signals from it. All sensory input to the brain, except that of the sense of smell, connects to individual nuclei of the thalamus.
 The hypothalamus lies beneath the thalamus on the midline at the base of the brain. It regulates or is involved directly in the control of many of the body's vital drives and activities, such as eating, drinking, temperature regulation, sleep, emotional behavior, and sexual activity. It also controls the function of internal body organs by means of the autonomic nervous system, interacts closely with the pituitary gland, and helps coordinate activities of the brain stem.
 The brain stem, shown here in colored cross section, is the lowest part of the brain. It serves as the path for messages traveling between the upper brain and spinal cord but is also the seat of basic and vital functions such as breathing, blood pressure, and heart rates, as well as reflexes like eye movement and vomiting. The brain stem has three main parts: the medulla, pons, and midbrain. A canal runs longitudinally through these structures carrying cerebrospinal fluid. Also distributed along its length is a network of cells, referred to as the reticular formation, that governs the state of alertness.
 The brain stem is revolutionarily the most primitive part of the brain and is responsible for sustaining the basic functions of life, such as breathing and blood pressure. It includes three main structures lying between and below the two cerebral hemispheres - the midbrain, pons, and medulla oblongata.
  The topmost structure of the brain stem is the midbrain. It contains major relay stations for neurons transmitting signals to the cerebral cortex, as well as many reflex centers - pathways carrying sensory (input) information and motor (output) command. Relays and reflex centers for visual and auditory (hearing) functions are located in the top portion of the midbrain. A pair of nuclei called the superior colliculus control reflex actions of the eye, such as blinking, opening and closing the pupil, and focusing the lens. A second pair of nuclei, called the inferior colliculus, controls auditory reflexes, such as adjusting the ear to the volume of sound. At the bottom of the midbrain are reflex and relay centers relating to pain, temperature, and touch, as well as several regions associated with the control of movement, such as the red nucleus and the substantia nigra.
 Continuous with and below the midbrain and directly in front of the cerebellum is a prominent bulge in the brain stem called the pons. The pons consists of large bundles of nerve fibers that connect the two halves of the cerebellum and also connect each side of the cerebellum with the opposite-side cerebral hemisphere. The pons serves mainly as a relay station linking the cerebral cortex and the medulla oblongata.
 The long, stalk-like lowermost portion of the brain stem is called the medulla oblongata. At the top, it is continuous with the pons and the midbrain; at the bottom, it makes a gradual transition into the spinal cord at the foramen magnum. Sensory and motor nerve fibers connecting the brain and the rest of the body cross over to the opposite side as they pass through the medulla. Thus, the left half of the brain communicates with the right half of the body, and the right half of the brain with the left half of the body.
 Running up the brain stem from the medulla oblongata through the pons and the midbrain is a netlike formation of nuclei known as the reticular formation. The reticular formation controls respiration, cardiovascular function, digestion, levels of alertness, and patterns of sleep. It also determines which parts of the constant flow of sensory information into the body are received by the cerebrum.
 There are two main types of brain cells, neurons and neuroglia. Neurons are responsible for the transmission and analysis of all electrochemical communication within the brain and other parts of the nervous system. Each neuron is composed of a cell body called a soma, and a major fiber called an axon, and a system of branches called dendrites. Axons, also called nerve fibers, convey electrical signals away from the soma and can be up to 1 m. (3.3 ft.) in length. Most axons are covered with a protective sheath of myelin, a substance made of fats and protein, which insulates the axon. Myelinated axons conduct neuronal signals faster than do unmyelinated axons. Dendrites convey electrical signals toward the soma, are shorter than axons, and are usually multiple and branching.
 Neuroglial cells are twice as numerous as neurons and account for half of the brain's weight. Neuroglia (from glia, Greek for 'glue') provides structural support to the neurons. Neuroglial cells also form myelin, guide developing neurons, take up chemicals involved in cell-to-cell communication, and contribute to the maintenance of the environment around neurons.
 Twelve pairs of cranial nerves arise symmetrically from the base of the brain and are numbered, from front to back, in the order in which they arise. They connect mainly with structures of the head and neck, such as the eyes, ears, nose, mouth, tongue, and throat. Some are motor nerves, controlling muscle movement; some are sensory nerves, conveying information from the sense organs; and others contain fibers for both sensory and motor impulses. The first and second pairs of cranial nerves - the olfactory (smell) nerves and the optic (vision) nerve - carry sensory information from the nose and eyes, respectively, to the undersurface of the cerebral hemispheres. The other ten pairs of cranial nerves originate in or end in the brain stem.
 The brain functions by complex neuronal, or nerve cell, circuits. Communication between neurons is both electrical and chemical and always travels from the dendrites of a neuron, through its soma, and out its axon to the dendrites of another neuron.
 Dendrites of one neuron receive signals from the axons of other neurons through chemicals known as neurotransmitters. The neurotransmitters set off electrical charges in the dendrites, which then carry the signals electrochemically to the soma. The soma integrates the information, which is then transmitted electrochemically down the axon to its tip.
 At the tip of the axon, small, bubble-like structures called vesicles’ release neurotransmitters that carries the signal across the synapse, or gap, between two neurons. There are many types of neurotransmitters, including norepinephrine, dopamine, and serotonin. Neurotransmitters can be excitatory (that is, they excite an electrochemical response in the dendrite receptors) or inhibitory (they block the response of the dendrite receptors).
 One neuron may communicate with thousands of other neurons, and many thousands of neurons are involved with even the simplest behavior. It is believed that these connections and their efficiency can be modified, or altered, by experience.
 Scientists have used two primary approaches to studying how the brain works. One approach is to study brain function after parts of the brain have been damaged. Functions that disappear or that is no longer normal after injury to specific regions of the brain can often be associated with the damaged areas. The second approach is to study the response of the brain to direct stimulation or to stimulation of various sense organs.
 Neurons are grouped by function into collections of cells called nuclei. These nuclei are connected to form sensory, motor, and other systems. Scientists can study the function of somatosensory (pain and touch), motor, olfactory, visual, auditory, language, and other systems by measuring the physiological (physical and chemical) change that occur in the brain when these senses are activated. For example, electroencephalography (EEG) measures the electrical activity of specific groups of neurons through electrodes attached to the surface of the skull. Electrodes incorporate directly into the brain can give readings of individual neurons. Changes in blood flow, glucose (sugar), or oxygen consumption in groups of active cells can also be mapped.
 Although the brain appears symmetrical, how it functions is not. Each hemisphere is specializing and dominates the other in certain functions. Research has shown that hemispheric dominance is related to whether a person is predominantly right-handed or left-handed. In most right-handed people, the left hemisphere processes arithmetic, language, and speech. The right hemisphere interprets music, complex imagery, and spatial relationships and recognizes and expresses emotion. In left-handed people, the pattern of brain organization is more variable.
 Hemispheric specialization has traditionally been studied in people who have sustained damage to the connections between the two hemispheres, as may occur with a stroke, an interruption of blood flow to an area of the brain that causes the death of nerve cells in that area. The division of functions between the two hemispheres has also been studied in people who have had to have the connection between the two hemispheres surgically cut in order to control severe epilepsy, a neurological disease characterized by convulsions and loss of consciousness.
 The visual system of humans is one of the most advanced sensory systems in the body. More information is conveyed visually than by any other means. In addition to the structures of the eye itself, several cortical regions - collectively called a primary visual and visual associative cortex - as well as the midbrain are involved in the visual system. Conscious processing of visual input occurs in the primary visual cortex, but reflexive - that is, immediate and unconscious - responses occur at the superior colliculus in the midbrain. Associative cortical regions - specialized regions that can associate, or integrate, multiple inputs - in the parietal and frontal lobes along with parts of the temporal lobe are also involved in the processing of visual information and the establishment of visual memories.
 Language involves specialized cortical regions in a complex interaction that allows the brain to comprehend and communicate abstract ideas. The motor cortex initiates impulses that travel through the brain stem to produce audible sounds. Neighboring regions of motor cortices, called the supplemental motor cortex, are involved in sequencing and coordinating sounds. Broca's area of the frontal lobe is responsible for the sequencing of language elements for output. The comprehension of language is dependent upon Wernicke's area of the temporal lobe. Other cortical circuits connect these areas.
 Memory is usually considered a diffusely stored associative process - that is, it puts together information from many different sources. Although research has failed to identify specific sites in the brain as locations of individual memories, certain brain areas are critical for memory to function. Immediate recall - the ability to repeat short series of words or numbers immediately after hearing them - is thought to be located in the auditory associative cortex. Short-term memory - the ability to retain a limited amount of information for up to an hour - is located in the deep temporal lobe. Long-term memory probably involves exchanges between the medial temporal lobe, various cortical regions, and the midbrain.
 The autonomic nervous system regulates the life support systems of the body reflexively - that is, without conscious direction. It automatically controls the muscles of the heart, digestive system, and lungs; Certain glands, and homeostasis - that is, the equilibrium of the internal environment of the body. The autonomic nervous system itself is controlled by nerve centers in the spinal cord and brain stem and is fine-tuned by regions higher in the brain, such as the midbrain and cortex. Reactions such as blushing indicate that cognitive, or thinking, centers of the brain are also involved in autonomic responses.
 The brain is guarded by several highly developed protective mechanisms. The bony cranium, the surrounding meninges, and the cerebrospinal fluid all contribute to the mechanical protection of the brain. In addition, a filtration system called the blood-brain barrier protects the brain from exposure to potentially harmful substances carried in the bloodstream.
 Brain disorders have a wide range of causes, including head injury, stroke, bacterial diseases, complex chemical imbalances, and changes associated with aging.
 Head injury can initiate a cascade of damaging events. After a blow to the head, a person may be stunned or may become unconscious for a moment. This injury, called - concussion, - usually leaves no permanent damage. If the blow is more severe and hemorrhage (excessive bleeding) and swelling occurs, however, severe headache, dizziness, paralysis, a convulsion, or temporary blindness may result, depending on the area of the brain affected. Damage to the cerebrum can also result in profound personality changes.
 Damage to Broca's area in the frontal lobe causes difficulty in speaking and writing, a problem known as Broca's aphasia. Injury to Wernicke's area in the left temporal lobe results in an inability to comprehend spoken language, called Wernicke's aphasia.
 An injury or disturbance to a part of the hypothalamus may cause a variety of different symptoms, such as loss of appetite with an extreme drop in body weight, increase in appetite leading to obesity; Extraordinary thirst with excessive urination (diabetes insipidus), failure in body-temperature control, resulting in either low temperature (hypothermia) or high temperature (fever), excessive emotionality, and uncontrolled anger or aggression. If the relationship between the hypothalamus and the pituitary gland is damaged, other vital bodily functions may be disturbed, such as sexual function, metabolism, and cardiovascular activity.
 Injury to the brain stem is even more serious because it houses the nerve centers that control breathing and heart action. Damage to the medulla oblongata usually results in immediate death.
 A stroke is damage to the brain due to an interruption in blood flow. The interruption may be caused by a blood clot, constriction of a blood vessel, or rupture of a vessel accompanied by bleeding. A pouch-like expansion of the wall of a blood vessel, called an aneurysm, may weaken and burst, for example, because of high blood pressure.
 Sufficient quantities of glucose and oxygen, transported through the bloodstream, are needed to keep nerve cells alive. When the blood supply to a small part of the brain is interrupted, the cells in that area die and the function of the area is lost. A massive stroke can cause a one-sided paralysis (hemiplegia) and sensory loss on the side of the body opposite the hemisphere damaged by the stroke.
 Some brain diseases, such as multiple sclerosis and Parkinson disease, are progressive, becoming worse over time. Multiple sclerosis damages the myelin sheath around axons in the brain and spinal cord. As a result, the affected axons cannot transmit nerve impulses properly. Parkinson disease destroys the cells of the substantia nigra in the midbrain, resulting in a deficiency in the neurotransmitter dopamine that affects motor functions.
 Cerebral palsy is a broad term for brain damage sustained close to birth that permanently affects motor function. The damage may take place either in the developing fetus, during birth, or just after birth and is the result of the faulty development or breaking down of motor pathways. Cerebral palsy is nonprogressive - that is, it does not worsen with time.
 A bacterial infection in the cerebrum or in the coverings of the brain, swelling of the brain, or an abnormal growth of healthy brain tissue can all cause an increase in intracranial pressure and result in serious damage to the brain.
 Scientists are finding that certain brain chemical imbalances are associated with mental disorders such as schizophrenia and depression. Such findings have changed scientific understanding of mental health and have resulted in new treatments that chemically correct these imbalances.
 During childhood development, the brain is particularly susceptible to damage because of the rapid growth and reorganization of nerve connections. Problems that originate in the immature brain can appear as epilepsy or other brain-function problems in adulthood.
 Several neurological problems are common in aging. Alzheimer's disease damages many areas of the brain, including the frontal, temporal, and parietal lobes. The brain tissue of people with Alzheimer's disease shows characteristic patterns of damaged neurons, known as plaques and tangles. Alzheimer's disease produces progressive dementia, characterized by symptoms such as failing attention and memory, loss of mathematical ability, irritability, and poor orientation in space and time.
 A magnetic resonance imaging (MRI) scan of the human brain reveals the contours of one of the brain’s hemispheres. The gyri, or ridges, appear in red, while the sulci, or valleys, are shown in blue. Each person has slightly different patterns of gyri and sulci, which reflect individual differences in brain development.
 Several commonly used diagnostic methods give images of the brain without invading the skull. Some portray anatomy - that is, the structure of the brain - whereas others measure brain function. Two or more methods may be used to complement each other, together providing a more complete picture than would be possible by one method alone.
 Magnetic resonance imaging (MRI), introduced in the early 1980s, beams high-frequency radio waves into the brain in a highly magnetized field that causes the protons that form the nuclei of hydrogen atoms in the brain to re-emit the radio waves. The re-emitted radio waves are analyzed by computer to create thin cross-sectional images of the brain. MRI provides the most detailed images of the brain and is safer than imaging methods that use X-rays. However, MRI is a lengthy process and also cannot be used with people who have pacemakers or metal implants, both of which are adversely affected by the magnetic field.
 Computed tomography (CT), also known as CT scans, developed in the early 1970s. This imaging method X-rays the brain from many different angles, feeding the information into a computer that produces a series of cross-sectional images. CT is particularly useful for diagnosing blood clots and brain tumors. It is a much quicker process than magnetic resonance imaging and is therefore advantageous in certain situations - for example, with people who are extremely ill.
 This positron emission tomography (PET) scans of the brain shows the activity of brain cells in the resting state and during three types of auditory stimulation. PET uses radioactive substances introduced within the brain to measure such brain functions as cerebral metabolism, blood flow and volume, oxygen use, and the formation of neurotransmitters. This imaging method collects data from many different angles, feeding the information into a computer that produces a series of cross-sectional images.
 Changes in brain function due to brain disorders can be visualized in several ways. Magnetic resonance spectroscopy measures the concentration of specific chemical compounds in the brain that may change during specific behaviors. Functional magnetic resonance imaging (fMRI) maps changes in oxygen concentration that correspond to nerve cell activity.
 Positron emission tomography (PET), developed in the mid-1970s, uses computed tomography to visualize radioactive tracers, radioactive substances are introduced into the brain intravenously or by inhalation. PET can measure such brain functions as cerebral metabolism, blood flow and volume, oxygen use, and the formation of neurotransmitters. Single photon emission computed tomography (SPECT), developed in the 1950s and 1960s, used radioactive tracers to visualize the circulation and volume of blood in the brain.
 Brain-imaging studies have provided new insights into sensory, motor, language, and memory processes, as well as brain disorders such as epilepsy, cerebrovascular disease; Alzheimer's, Parkinson, and Huntington's diseases, and various mental disorders, such as schizophrenia.
 Although all vertebrate brains share the same basic three-part structure, the development of their constituent parts varies across the evolutionary scale. In fish, the cerebrum is dwarfed by the rest of the brain and serves mostly to process input from the senses. In reptiles and amphibians, the cerebrum is proportionally larger and begins to connect and form conclusions about this input. Birds have well-developed optic lobes, making the cerebrum even larger. Among mammals, the cerebrum dominates the brain. It is most developed among primates, in whom cognitive ability is the highest.
 In lower vertebrates, such as fish and reptiles, the brain is often tubular and bears a striking resemblance to the early embryonic stages of the brains of more highly evolved animals. In all vertebrates, the brain is divided into three regions: the forebrain (prosencephalon), the midbrain (mesencephalon), and the hindbrain (rhombencephalon). These three regions further sub-divide into different structures, systems, nuclei, and layers.
 The more highly evolved the animal, the more complex is the brain structure. Human beings have the most complex brains of all animals. Evolutionary forces have also resulted in a progressive increase in the size of the brain. In vertebrates lower than mammals, the brain is small. In meat-eating animals, particularly primates, the brain increases dramatically in size.
 The cerebrum and cerebellum of higher mammals are highly convoluted in order to fit the most gray matter surface within the confines of the cranium. Such highly convoluted brains are called gyrencephalic. Many lower mammals have a smooth, or lissencephalic (smooth head), cortical surfaces.
 There is also evidence of evolutionary adaption of the brain. For example, many birds depend on an advanced visual system to identify food at great distances while in flight. Consequently, their optic lobes and cerebellum are well developed, giving them keen sight and outstanding motor coordination in flight. Rodents, on the other hand, as nocturnal animals, do not have a well-developed visual system. Instead, they rely more heavily on other sensory systems, such as a highly-developed sense of smell and facial whiskers.
 Recent research in brain function suggests that there may be sexual differences in both brain anatomy and brain function. One study indicated that men and women may use their brains differently while thinking. Researchers used functional magnetic resonance imaging to observe which parts of the brain were activated as groups of men and women tried to determine whether sets of nonsense words rhymed. Men used only Broca's area in this task, whereas women used Broca's area plus an area on the right side of the brain.
 The Cell, in [biology] is the most basic unit of life. Cells are the smallest structures capable of basic life processes, such as taking in nutrients, expelling waste, and reproducing. All living things are composed of cells. Some microscopic organisms, such as bacteria and protozoa, are unicellular, meaning they consist of a single cell. Plants, animals, and fungi are multicellular; that is, they are composed of a great many cells working in concert. But whether it makes up an entire bacterium or is just one of the trillions in a human being, the cell is a marvel of design and efficiency. Cells carry out thousands of biochemical reactions each minute and reproduce new cells that perpetuate life.
 The word cell refers to several types of organisms. Cells such as paramecia, dinoflagellates, diatoms, and spirochetes are self-maintaining organisms; cells such as lymphocytes, erythrocytes, muscle cells, nerve cells, cardiac muscle, and chromoplasts are more specializing cells that are a part of higher multicellular organisms. Nonetheless, of its size or whether the cell is a complete organism or just part of an organism, all cells have certain structural components in common. All cells have some type of outer cell boundary that permits some materials to leave and enter the cell and a cell interior composed of a water-rich, fluid material called cytoplasm that contains hereditary material in the form of deoxyribonucleic acid (DNA).
 Cells vary considerably in size. The smallest cell, a type of bacterium known as a mycoplasma, measures 0.0001 mm. (0.000004 in.) in diameter; 10,000 mycoplasmas in a row are only as wide as the diameter of a human hair. Among the largest cells are the nerve cells that run down a giraffe’s neck; these cells can exceed 3 m. (9.7 ft.) in length. Human cells also display a variety of sizes, from small red blood cells that measure 0.00076 mm. (0.00003 in.) to liver cells that may be ten times larger. About 10,000 average-sized human cells can fit on the head of a pin.
 Along with their differences in size, cells present an array of shapes. Some, such as the bacterium Escherichia coli, resemble rods. The paramecium, a type of protozoan, is a slipper shaped.  The amoeba, another protozoan, has an irregular form that changes shape as it moves around. Plant cells typically resemble boxes or cubes. In humans, the outermost layers of skin cells are flat, while muscle cells are long and thin. Some nerve cells, with their elongated, tentacle-like extensions, suggest an octopus.
 In multicellular organisms, shape is typically tailored to the cell’s job. For example, flat skin cells pack tightly into a layer that protects the underlying tissues from invasions by bacteria. Long, thin muscle cells’ contract readily to move bones. The numerous extensions from a nerve cell enable it to connect to several other nerve cells in order to send and receive messages rapidly and efficiently.
 By itself, each cell is a model of independence and self-containment. Like some miniature, walled city in perpetual rush hour, the cell constantly bustles with traffic, shuttling essential molecules from place to place to carry out the business of living. Despite their individuality, however, cells also display a remarkable ability to join, communicate, and coordinate with other cells. The human body, for example, consists of an estimated 20 to 30 trillion cells. Dozens of different kinds of cells are organized into specialized groups called tissues. Tendons and bones, for example, are composed of connective tissue, whereas skin and mucous membranes are built from epithelial tissue. Different tissue types are assembled into organs, which are structures specialized to perform particular functions. Examples of organs include the heart, stomach, and brain. Organs, in turn, are organized into systems such as the circulatory, digestive, or nervous systems. All together, these assembled organ systems form the human body.
 The components of cells are molecules, nonliving structures formed by the union of atoms. Small molecules serve as building blocks for larger molecules. Proteins, nucleic acids, carbohydrates, and lipids, which include fats and oils, are the four major molecules that underlie cell structure and also participate in cell functions. For example, a tightly organized arrangement of lipids, proteins, and protein-sugar compounds forms the plasma membrane, or outer boundary, of certain cells. The organelles, membrane-bound compartments in cells, are built largely from proteins. Biochemical reactions in cells are guided by enzymes, specialized proteins that speed up chemical reactions. The nucleic acid deoxyribonucleic acid (DNA) contains the hereditary information for cells, and another nucleic acid, ribonucleic acid (RNA), works with DNA to build the thousands of proteins the cell needs.
 Cells fall into one of two categories: Prokaryotic or eukaryotic, in a prokaryotic cell, found only in bacteria and archaebacteria, all the components, including the DNA, mingle freely in the cell’s interior, a single compartment. Eukaryotic cells, which make up plants, animals, fungi, and all other life forms, contain numerous compartments, or organelles, within each cell. The DNA in eukaryotic cells is enclosed in a special organelle called the nucleus, which serves as the cell’s command center and information library. The term prokaryote comes from Greek words that mean ‘before the nucleus’ or ‘prenucleus,’ while eukaryote means ‘a true nucleus.’
 Bacteria’s cells typically are surrounded by a rigid, protective cell wall. The cell membrane, also called the plasma membrane, regulates passage of materials into and out of the cytoplasm, the semi-fluid that fill the cell. The DNA, located in the nucleoid region, contains the genetic information for the cell. Ribosomes carry out protein synthesis. Many bacteria contain some pilus (plural pili), a structure that extends out of the cell to transfer DNA to another bacterium. The flagellum, found in numerous species, is used for the locomotion. Some bacteria contain a plasmid, a small chromosomes with extra genes. Others have a capsule, a sticky substance external to the cell wall that protects bacteria from attack by white blood cells. Mesosomes were formerly thought to be structures with unknown functions, but now are known to be artifacts created when cells are prepared for viewing with electron microscopes.
 Prokaryotic cells are among the tiniest of all cells, ranging in size from 0.0001 to 0.003 mm. (0.000004 to 0.0001 in.) in diameter. About a hundred typical prokaryotic cells lined up in a row would match the thickness of a book page. These cells, which can be rod-like, spherical, or spiral in shape, are surrounded by a protective cell wall. Like most cells, prokaryotic cells live in a watery environment, whether it is soil moisture, a pond, or the fluid surrounding cells in the human body. Tiny pores in the cell wall enable water and the substances dissolved in it, such as oxygen, to flow into the cell; these pores also allow wastes to flow out.
 Pushed up against the inner surface of the prokaryotic cell wall is a thin membrane called the plasma membrane. The plasma membrane, composed of two layers of flexible lipid molecules and interspersed with durable proteins, is both supple and strong. Unlike the cell wall, whose open pores allow the unregulated traffic of materials in and out of the cell, the plasma membrane is selectively permeable, meaning it allows only certain substances to pass through. Thus, the plasma membrane actively separates the cell’s contents from its surrounding fluids.
 While small molecules such as water, oxygen, and carbon dioxide diffuse freely across the plasma membrane, the passage of many larger molecules, including amino acids (the building blocks’ of proteins) and sugars, is carefully regulated. Specialized transport proteins accomplish this task. The transport proteins span the plasma membrane, forming an intricate system of pumps and channels through which traffic is conducted. Some substances swirling in the fluid around the cell can enter it only if they bind to and are escorted in by specific transport proteins. In this way, the cell fine-tunes its internal environment.
 The plasma membrane encloses the cytoplasm, the semifluid that fill the cell. Composed of about 65 percent water, the cytoplasm is packed with up to a billion molecules per cell, a rich storehouse that includes enzymes and dissolved nutrients, such as sugars and amino acids. The water provides a favorable environment for the thousands of biochemical reactions that take place in the cell.
 Within the cytoplasm of all prokaryote is deoxyribonucleic acid (DNA), a complex molecule in the form of a double helix, a shape similar to a spiral staircase. The DNA is about 1,000 times the length of the cell, and to fit inside, it repeatedly twists and folds to form a compact structure called a chromosome. The chromosome in prokaryote is circular, and is located in a region of the cell called the nucleoid. Often, smaller chromosomes called plasmids are located in the cytoplasm. The DNA is divided into units called genes, just like a long train is divided into separate cars. Depending on the species, the DNA contains several hundred or even thousands of genes. Typically, one gene contains coded instructions for building all or part of a single protein. Enzymes, which are specialized proteins, determine virtually all the biochemical reactions that support and sustain the cell.
 Also, immersed in the cytoplasm are the only organelles in prokaryotic cells.  Tiny bead-like structures called ribosomes. These are the cell’s protein factories. Following the instructions encoded in the DNA, ribosomes churn out proteins by the hundreds every minute, providing needed enzymes, the replacements for worn-out transport proteins, or other proteins required by the cell.
 While relatively simple in construction, prokaryotic cells display extremely complex activity. They have a greater range of biochemical reactions than those found in their larger relatives, the eukaryotic cells. The extraordinary biochemical diversity of prokaryotic cells is manifested in the wide-ranging lifestyles of the archaebacteria and the bacteria, whose habitats include polar ice, deserts, and hydrothermal vents - deep regions of the ocean under great pressure where hot water geysers erupt from cracks in the ocean floor.
 An animal cell typically contains several types of membrane-bound organs, or organelles. The nucleus directs activities of the cell and carries genetic information from generation to generation. The mitochondria generates energy for the cell. Proteins are manufactured by ribosomes, which are bound to the rough endoplasmic reticulum or float free in the cytoplasm. The Golgi apparatus modifies, packages, and distributes proteins while lysosomes store enzymes for digesting food. The entire cell is wrapped in a lipid membrane that selectively permits materials to pass in and out of the cytoplasm.
  Eukaryotic cells are typically about ten times larger than prokaryotic cells. In animal cells, the plasma membrane, rather than a cell wall, forms the cell’s outer boundary. With a design similar to the plasma membrane of prokaryotic cells, it separates the cell from its surroundings and regulates the traffic across the membrane.
 The eukaryotic cell cytoplasm is similar to that of the prokaryote cell except for one major difference: Eukaryotic cells house a nucleus and numerous other membrane-enclosed organelles. Like separate rooms of a house, these organelles enable specialized functions to be carried out efficiently. The building of proteins and lipids, for example, takes place in separate organelles where specialized enzymes geared for each job are located.
 The plasma membrane that surrounds eukaryotic cells is a dynamic structure composed of two layers of phospholipid molecules interspersed with cholesterol and proteins. Phospholipids are composed of a hydrophilic, or water-loving, head and two tails, which are hydrophobic, or water-hating. The two phospholipid layers face each other in the membrane, with the heads directed outward and the tails pointing inward. The water-attracting heads anchor the membrane to the cytoplasm, the watery fluid inside the cell, and also to the water surrounding the cell. The water-hating tails block large water-soluble molecules from passing through the membrane while permitting fat-soluble molecules, including medications such as tranquilizers and sleeping pills, to freely cross the membrane. Proteins embedded in the plasma membrane carry out a variety of functions, including transport of large water soluble molecules such as sugars and certain amino acids. Glycoproteins, proteins bonded to carbohydrates, serve in part to identify the cell as belonging to a unique organism, enabling the immune system to detect foreign cells, such as invading bacteria, which carry different glycoproteins. Cholesterol molecules in the plasma membrane act as stabilizers that limit the movement of the two slippery phospholipids layer, which slide back and forth in the membrane. Tiny gaps in the membrane enable small molecules such as oxygen to diffuse readily into and out of the cell. Since cells constantly use up oxygen, decreasing its concentration within the cell, the higher concentration of oxygen outside the cell causes a net flow of oxygen into the cell. The steady stream of oxygen into the cell enables it to carry out aerobic respiration continually, a process that provides the cell with the energy needed to carry out its functions.
 The nucleus is the largest organelle in an animal cell. It contains numerous strands of DNA, the length of each strand being many times the diameter of the cell. Unlike the circular prokaryotic DNA, long sectors of eukaryotic DNA pack into the nucleus by wrapping around proteins. As a cell begins to divide, each DNA strand folds over onto itself several times, forming a rod-shaped chromosome.
 The nucleus is surrounded by a double-layered membrane that protects the DNA from potentially damaging chemical reactions that occur in the cytoplasm. Messages pass between the cytoplasm and the nucleus through nuclear pores, which are holes in the membrane of the nucleus. In each nuclear pore, molecular signals flash back and forth as often as ten times per second. For example, a signal to activate a specific gene comes into the nucleus and instructions for production of the necessary protein go out to the cytoplasm.
 The nucleus, present in eukaryotic cells, is a discrete structure containing chromosomes, which hold the genetic information for the cell. Separated from the cytoplasm of the cell by a double-layered membrane called the nuclear envelope, and the nucleus contains a cellular material called nucleoplasm. Nuclear pores, present around the circumference of the nuclear membrane, allow the exchange of cellular materials between the nucleoplasm and the cytoplasm.
 Attached to the nuclear membrane is an elongated membranous sac called the endoplasmic reticulum. This organelle tunnels through the cytoplasm, folding back and forth on itself to form a series of membranous stacks. Endoplasmic reticulums take two forms: Rough and smooth. A rough endoplasmic reticulum (RER) is so called because it appears bumpy under a microscope. The bumps are actually thousands of ribosomes attached to the membrane’s surface. The ribosomes in eukaryotic cells have the same function as those in prokaryotic cells - protein synthesis - but they differ slightly in structure. Eukaryote ribosomes bound to the endoplasmic reticulum help assemble proteins that typically are exported from the cell. The ribosomes work with other molecules to link amino acids to partially completed proteins. These incomplete proteins then travel to the inner chamber of the endoplasmic reticulum, where chemical modifications, such as the addition of a sugar, are carried out. Chemical modifications of lipids are also carried out in the endoplasmic reticulum.
 The endoplasmic reticulum and its bound ribosomes are particularly dense in cells that produce many proteins for export, such as the white blood cells of the immune system, which produce and secrete antibodies. Some ribosomes that manufacture proteins are not attached to the endoplasmic reticulum. These so-called free ribosomes are dispersed in the cytoplasm and typically make proteins - many of them enzymes - that remain in the cell.
 The second form of an endoplasmic reticulum, the smooth endoplasmic reticulum (SER), lacks ribosomes and has an even surface. Within the winding channels of the smooth endoplasmic reticulum are the enzymes needed for the construction of molecules such as carbohydrates and lipids. The smooth endoplasmic reticulum is prominent in liver cells, where it also serves to detoxify substances such as alcohol, drugs, and other poisons.
 Proteins are transported from free and bound ribosomes to the Golgi apparatus, an organelle that resembles a stack of deflated balloons. It is packed with enzymes that complete the processing of proteins. These enzymes add sulfur or phosphorus atoms to certain regions of the protein, for example, or chop off tiny pieces from the ends of the proteins. The completed protein then leaves the Golgi apparatus for its final destination inside or outside the cell. During its assembly on the ribosome, each protein has acquired a group of from 4 to 100 amino acids called a signal. The signal works as a molecular shipping label to direct the protein to its proper location.
 Lysosomes are small, often spherical organelles that function as the cell’s recycling center and garbage disposal. Powerful digestive enzymes concentrated in the lysosome break down worn-out organelles and ship their building blocks to the cytoplasm where they are used to construct new organelles. Lysosomes also dismantle and recycle proteins, lipids, and other molecules.
 The mitochondria is the powerhouse of the cell. Within these long, slender organelles, which can appear oval or bean shaped under the electron microscope, enzymes convert the sugar glucose and other nutrients into adenosine triphosphate (ATP). This molecule, in turn, serves as an energy battery for countless cellular processes, including the shuttling of substances across the plasma membrane, the building and transport of proteins and lipids, the recycling of molecules and organelles, and the dividing of cells. Muscle and liver cells are particularly active and require dozens and sometimes up to hundreds mitochondria per cell to meet their energy needs. Mitochondria is unusual in that they contain their own DNA in the form of a prokaryote-like circular chromosome; Have their own ribosomes, which resemble prokaryotic ribosomes, and divide independently of the cell.
 Unlike the tiny prokaryotic cell, the relatively large eukaryotic cell requires structural support. The cytoskeleton, a dynamic network of protein tubes, filaments, and fibers, crisscrosses the cytoplasm, anchoring the organelles in place and providing shape and structure to the cell. Many components of the cytoskeleton are assembled and disassembled by the cell as needed. During cell division, for example, a special structure called a spindle is built to move chromosomes around. After cell division, the spindle, no longer needed, is dismantled. Some components of the cytoskeleton serve as microscopic tracks along which proteins and other molecules travel like miniature trains. Recent research suggests that the cytoskeleton also may be a mechanical communication structure that converses with the nucleus to help organize events in the cell.
 Plant cells have all the components of animal cells and boast several added features, including chloroplasts, a central vacuole, and a cell wall. Chloroplasts convert light energy - typically from the Sun - into the sugar glucose, a form of chemical energy, in a process known as photosynthesis. Chloroplasts, like mitochondria, possess a circular chromosome and prokaryote-like ribosomes, which manufacture the proteins that the chloroplasts typically need.
 The central vacuole of a mature plant cell typically takes up most of the room in the cell. The vacuole, a membranous bag, crowds the cytoplasm and organelles to the edges of the cell. The central vacuole stores water, salts, sugars, proteins, and other nutrients. In addition, it stores the blue, red, and purple pigments that give certain flowers their colors. The central vacuole also contains plant wastes that taste bitter to certain insects, thus discouraging the insects from feasting on the plant.
 In plant cells, a sturdy cell wall surrounds and protects the plasma membrane. Its pores enable materials to pass freely into and out of the cell. The strength of the wall also enables a cell to absorb water into the central vacuole and swell without bursting. The resulting pressure in the cells provides plants with rigidity and support for stems, leaves, and flowers. Without sufficient water pressure, the cells collapse and the plant wilts.
 To stay alive, cells must be able to carry out a variety of functions. Some cells must be able to move, and most cells must be able to divide. All cells must maintain the right concentration of chemicals in their cytoplasm, ingest food and use it for energy, recycle molecules, expel wastes, and construct proteins. Cells must also be able to respond to changes in their environment.
 Although many forms of bacteria are not capable of independent movement, species such as the Salmonella bacterium pictured here can move by means of fine threadlike projections called flagella. The arrangement of flagella across the surface of the bacterium differs from species to species; they can be present at the ends of the bacterium or all across the body surface. Forward movement is accomplished either by a tumbling motion or in a forward manner without tumbling.
 Many unicellular organisms swim, glide, thrash, or crawl to search for food and escape enemies. Swimming organisms often move by means of a flagellum, a long tail-like structure made of protein. Many bacteria, for example, have one, two, or many flagella that rotate like propellers to drive the organism along. Some single-celled eukaryotic organisms, such as the euglena, also have a flagellum, but it is longer and thicker than the prokaryotic flagellum. The eukaryotic flagellums work by waving up and down like a whip. In higher animals, the sperm cell uses a flagellum to swim toward the female egg for fertilization.
 Movement in eukaryotes is also accomplished with cilia, short, hairlike proteins built by centrioles, which are barrel-shaped structures located in the cytoplasm that assemble and break down protein filaments. Typically, thousands of cilia extend through the plasma membrane and cover the surface of the cell, giving it a dense, hairy appearance. By beating its cilia as if they were oars, an organism such as the paramecium propels itself through its watery environment. In cells that do not move, cilia are used for other purposes. In the respiratory tract of humans, for example, millions of ciliated cells prevent inhaled dust, smog, and microorganisms from entering the lungs by sweeping them up on a current of mucus into the throat, where they are swallowed. Eukaryotic flagella and cilia are formed from basal bodies, small protein structures located just inside the plasma membrane. Basal bodies also help to anchor flagella and cilia.
 Still other eukaryotic cells, such as amoebas and white blood cells, move by amoeboid motion, or crawling. They extrude their cytoplasm to form temporary pseudopodia, or false feet, which actually are placed in front of the cell, rather like extended arms. They then drag the trailing end of their cytoplasm up to the pseudopodia. A cell using amoeboid motion would lose a race to a euglena or paramecium. But while it is slow, amoeboid motion is strong enough to move cells against a current, enabling water-dwelling organisms to pursue and devour prey, for example, or white blood cells roaming the blood stream to stalk and engulf a bacterium or virus.
 An amoeba, a single-celled organism lacking internal organs, is shown approaching a much smaller paramecium, which it begins to engulf with large outflowings of its cytoplasm, called pseudopodia. Once the paramecium is completely engulfed, a primitive digestive cavity, called a vacuole, forms around it. In the vacuole, acids break the paramecium down into chemicals that the amoeba can diffuse back into its cytoplasm for nourishment.
 All cells require nutrients for energy, and they display a variety of methods for ingesting them. Simple nutrients dissolved in pond water, for example, can be carried through the plasma membrane of pond-dwelling organisms via a series of molecular pumps. In humans, the cavity of the small intestine contains the nutrients from digested food, and cells that form the walls of the intestine use similar pumps to pull amino acids and other nutrients from the cavity into the bloodstream. Certain unicellular organisms, such as amoebas, are also capable of reaching out and grabbing food. They used a process known as endocytosis, in which the plasma membrane surrounds and engulfed the food particle, enclosing it in a sac, called a vesicle, that is within the amoeba’s interior.
 Cells require energy for a variety of functions, including moving, building up and breaking down molecules, and transporting substances across the plasma membrane. Nutrients contain energy, but cells must convert the energy locked in nutrients to another form - specifically, the ATP molecule, the cell’s energy battery - before it is useful. In single-celled eukaryotic organisms, such as the paramecium, and in multicellular eukaryotic organisms, such as plants, animals, and fungi, mitochondria is responsible for this task. The interior of each mitochondrion consists of an inner membrane that is folded into a maze-like arrangement of separate compartments called cristae. Within the cristae, enzymes form an assembly line where the energy in glucose and other energy-rich nutrients is harnessed to build ATP; thousands of ATP molecules are constructed each second in a typical cell. In most eukaryotic cells, this process requires oxygen and is known as aerobic respiration.
 Some prokaryotic organisms also carry out aerobic respiration. They lack mitochondria, however, and carry out aerobic respiration in the cytoplasm with the help of enzymes sequestered there. Many prokaryote species live in environments where there is little or no oxygen, environments such as mud, stagnant ponds, or within the intestines of animals. Some of these organisms produce ATP without oxygen in a process known as anaerobic respiration, where sulfur or other substances take the place of oxygen. Still other prokaryotes, and yeast, a single-celled eukaryote, build ATP without oxygen in a process known as fermentation.
 Almost all organisms rely on the sugar glucose to produce ATP. Glucose is made by the process of photosynthesis, in which light energy is transformed to the chemical energy of glucose. Animals and fungi cannot carry out photosynthesis and depend on plants and other photosynthetic organisms for this task. In plants, as we have seen, photosynthesis takes place in organelles called chloroplasts. Chloroplasts contain numerous internal compartments called thylakoids where enzymes aid in the energy conversion process. A single leaf cell contains 40 to 50 chloroplasts. With sufficient sunlight, one large tree is capable of producing upwards of two tons of sugar in a single day. Photosynthesis in prokaryotic organisms - typically aquatic bacteria - is carried out with enzymes clustered in plasma membrane folds called chromatophores. Aquatic bacteria produce the food consumed by tiny organisms living in ponds, rivers, lakes, and seas.
 A typical cell must have on hand, about.  30,000 proteins at any-one time. Many of these proteins are enzymes needed to construct the major molecules used by cells - carbohydrates, lipids, proteins, and nucleic acids - nor to aid in the breakdown of such molecules after they have worn out. Other proteins are part of the cell’s structure - the plasma membrane and ribosomes, for example. In animals, proteins also function as hormones and antibodies, and they function like delivery trucks to transport other molecules around the body. Hemoglobin, for example, is a protein that transports oxygen in red blood cells. The cell’s demand for proteins never ceases.
 Before a protein can be made, however, the molecular directions to build, it must be extracted from one or more genes. In humans, for example, one gene holds the information for the protein insulin, the hormone that cells need to import glucose from the bloodstream, while at least two genes hold the information for collagen, the protein that imparts strength to skin, tendons, and ligaments. The process of building proteins begins when enzymes, in response to a signal from the cell, bind to the gene that carries the code for the required protein, or part of the protein. The enzymes transfer the code to a new molecule called messenger RNA, which carries the code from the nucleus to the cytoplasm. This enables the original genetic code to remain safe in the nucleus, with messenger RNA delivering small bits and pieces of information from the DNA to the cytoplasm as needed. Depending on the cell type, hundreds or even thousands of molecules of messenger RNA are produced each minute.
 Once in the cytoplasm, the messenger RNA molecule links up with a ribosome. The ribosome moves along the messenger RNA like a monorail car along a track, stimulating another form of RNA - transfer RNA - to gather and link the necessary amino acids, pooled in the cytoplasm, to form the specific protein, or section of protein. The protein is modified as necessary by the endoplasmic reticulum and Golgi apparatus before embarking on its mission. Cells teem with activity as they forge the numerous, diverse proteins that are indispensable for life. For a more detailed discussion about protein synthesis, When there are a hundred or more cells, they formed a hollow ball of cells, called a blastula, surrounding a fluid-filled cavity. Later divisions produce three layers of cells - endoderm (inner), mesoderm (middle), and ectoderm (outer) - from which the principal features of the animal will differentiate.
 Most cells divide at some time during their life cycle, and some divide dozens of times before they die. Organisms rely on cell division for reproduction, growth, and repair and replacement of damaged or worn out cells. Three types of cell division occur: Binary fission, mitosis, and meiosis. Binary fission, the method used by prokaryotes, produces two identical cells from one cell. The more complex process of mitosis, which also produces two genetically identical cells from a single cell, is used by many unicellular eukaryotic organisms for reproduction. Multicellular organisms use mitosis for growth, cell repair, and cell replacement. In the human body, for example, an estimated 25 million mitotic cell divisions occur every second in order to replace cells that have completed their normal life cycles. Cells of the liver, intestine, and skin may be replaced every few days. Recent research indicates that even brain cell, once thought to be incapable of mitosis, undergo cell division in the part of the brain associated with memory.
 In a landmark intersection of science and fiction, cloning leapt from the world’s imagination to its front page in February 1997. It arrived in the innocent form of a sheep named Dolly: The first exact genetic duplicate of an adult mammal due to genetic engineering. Scottish scientists had created Dolly from deoxyribonucleic acid (DNA) - the basic unit of heredity - taken from a single adult sheep cell. The accomplishment threw open the door too profoundly ethically as well as scientific controversy over the potential uses and abuses of cloning. ‘However the debate is resolved,’ wrote Los Angeles Times science reporter Thomas H. Maugh II, ‘the genie is irretrievably out of the bottle.’
 The type of cell division required for sexual reproduction is meiosis. Sexually reproducing organisms include seaweeds, fungi, plants, and animals - including, of course, human beings. Meiosis differs from mitosis in that cell division begins with a cell that has a full complement of chromosomes and ends with gamete cells, such as sperm and eggs, that have only half the complement of chromosomes. When a sperm and egg unite during fertilization, the cell resulting from the union, called a zygote, contains the full number of chromosomes.
 The story of how cells evolved remains an open and actively investigated question in science. The combined expertise of physicists, geologists, chemists, and evolutionary biologists has been required to shed light on the evolution of cells from the nonliving matter of early Earth. The planet formed about 4.5 billion years ago, and for millions of years, violent volcanic eruptions blasted substances such as carbon dioxide, nitrogen, water, and other small molecules into the air. These small molecules, bombarded by ultraviolet radiation and lightning from intense storms, collided to form the stable chemical bonds of larger molecules, such as amino acids and nucleotides - the building blocks of proteins and nucleic acids. Experiments indicate that these larger molecules form spontaneously under laboratory conditions that simulate the probable early environment of Earth.
 Scientists speculate that rain may have carried these molecules into lakes to create a primordial soup - the breeding ground for the assembly of proteins, the nucleic acid RNA, and lipids. Some scientists postulate that these more complex molecules formed in hydrothermal vents rather than in lakes. Other scientists propose that these key substances may have reached Earth on meteorites from outer space. Regardless of the origin or environment, however, scientists do agree that proteins, nucleic acids, and lipids provided the raw materials for the first cells. In the laboratory, scientists have observed lipid molecules joining to form spheres that resemble a cell’s plasma membrane. As a result of these observations, scientists postulate that millions of years of molecular collisions resulted in lipid spheres enclosing RNA, the simplest molecule capable of self-replication. These primitive aggregations would have been the ancestors of the first prokaryotic cells.
 Fossil studies indicate that Cyanobacteria, bacteria capable of photosynthesis, were among the earliest bacteria to evolve, an estimated 3.4 billion to 3.5 billion years ago. In the environment of the early Earth, there were no oxygen, and cyanobacteria probably used fermentation to produce ATP. Over the eons, cyanobacteria performed photosynthesis, which produces oxygen as a byproduct; The result was the gradual accumulation of oxygen in the atmosphere. The presence of oxygen set the stage for the evolution of bacteria that used oxygen in aerobic respiration, a more efficient ATP-producing process than fermentation. Some molecular studies of the evolution of genes in archaebacteria suggest that these organisms may have evolved in the hot waters of hydrothermal vents or hot springs slightly earlier than cyanobacteria, around 3.5 billion years ago. Like cyanobacteria, archaebacteria probably relied on fermentation to synthesize ATP.
 Eukaryotic cells may have evolved from primitive prokaryotes about 2 billion years ago. One hypothesis suggests that some prokaryotic cells lost their cell walls, permitting the cell’s plasma membrane to expand and fold. These folds, ultimately, may have given rise to separate compartments within the cell - the forerunners of the nucleus and other organelles now found in eukaryotic cells. Another key hypothesis is known as endosymbiosis. Molecular studies of the bacteria-like DNA and ribosomes in mitochondria and chloroplasts indicate that mitochondrion and chloroplast ancestors were once free-living bacteria. Scientists propose that these free-living bacteria were engulfed and maintained by other prokaryotic cells for their ability to produce ATP efficiently and to provide a steady supply of glucose. Over generations, eukaryotic cells situated with mitochondria - the ancestors of animals - or with both mitochondria and chloroplasts - the ancestors of plants - evolved.
 The first observations of cells were made in 1665 by English scientist Robert Hooke, who used a crude microscope of his own invention to examine a variety of objects, including a thin piece of cork. Noting the rows of tiny boxes that made up the dead wood’s tissue, Hooke coined the term cell because the boxes reminded him of the small cells occupied by monks in a monastery. While Hooke was the first to observe and describe cells, he did not comprehend their significance. At about the same time, the Dutch maker of microscopes Antoni van Leeuwenhoek pioneered the invention of one of the best microscopes of the time. Using his invention, Leeuwenhoek was the first to observe, draw, and describe a variety of living organisms, including bacteria gliding in saliva, one-celled organisms cavorting in pond water, and sperm swimming in semen. Two centuries passed, however, before scientists grasped the true importance of cells.
 Many advances have been made in microscope technology. This article from the 1994 Collier’s Year Book begins with the microscope most young students are familiar with and tracks the breakthroughs in the development of new types of microscopes - including those that use ultrasonic imaging and those that ‘feel’ an object’s surface.
 Modern ideas about cells appeared in the 1800s, when improved light microscopes enabled scientists to observe more details of cells. Working together, German botanist Matthias Jakob Schleiden and German zoologist Theodor Schwann recognized the fundamental similarities between plant and animal cells. In 1839 they proposed the revolutionary idea that all living things are made up of cells. Their theory gave rise to modern biology: a whole new way of seeing and investigating the natural world.
 By the late 1800s, as light microscopes improved still further, scientists were able to observe chromosomes within the cell. Their research was aided by new techniques for staining parts of the cell, which made possible the first detailed observations of cell division, including observations of the differences between mitosis and meiosis in the 1880s. In the first few decades of the 20th century, many scientists focused on the behavior of chromosomes during cell division. At that time, it was generally held that mitochondria transmitted the hereditary information. By 1920, however, scientists determined that chromosomes carry genes and that genes transmit hereditary information from generation to generation.
 During this period, scientists began to understand some of the chemical processes in cells. In the 1920s, the ultracentrifuge was developed. The ultracentrifuge is an instrument that spins cells or other substances in test tubes at high speeds, which causes the heavier parts of the substance to fall to the bottom of the test tube. This instrument enabled scientists to separate the relatively abundant and heavy mitochondria from the rest of the cell and study their chemical reactions. By the late 1940s, scientists were able to explain the role of mitochondria in the cell. Using refined techniques with the ultracentrifuge, scientists subsequently isolated the smaller organelles and gained an understanding of their functions.
 The deoxyribonucleic acid (DNA) molecule is the genetic blueprint for each cell and ultimately the blueprint that determines every characteristic of a living organism. In 1953 American biochemist James Watson, left, and British biophysicist Francis Crick, right, described the structure of the DNA molecule as a double helix, somewhat like a spiral staircase with many individual steps. Their work was aided by X-ray diffraction pictures of the DNA molecule taken by British biophysicist Maurice Wilkins and British physical chemist Rosalind Franklin. In 1962 Crick, Watson, and Wilkins received the Nobel Prize for their pioneering work on the structure of the DNA molecule.
 While some scientists were studying the functions of cells, others were examining details of their structure. They were aided by a crucial technological development in the 1940s, the invention of the electron microscope, which uses high-energy electrons instead of light waves to view specimens. New generations of electron microscopes have provided resolution, or the differentiation of separate objects, thousands of times more powerful than that available in light microscopes. This powerful resolution revealed organelles such as the endoplasmic reticulum, lysosomes, the Golgi apparatus, and the cytoskeleton. The scientific fields of cell structure and function continue to complement each other as scientists explore the enormous complexity of cells.
 The discovery of the structure of DNA in 1953 by American biochemist James D. Watson and British biophysicist Francis Crick ushered in the era of molecular biology. Today, investigation inside the world of cells - of genes and proteins at the molecular level - constitutes one of the largest and fastest moving areas in all of science. One particularly active field in recent years has been the investigation of cell signaling, the process by which molecular messages find their way into the cell via a series of complex protein pathways in the cell.
 Another busy area in cell biology concerns programmed cell death, or apoptosis. Millions of times per second in the human body, cells commit suicide as an essential part of the normal cycle of cellular replacement. This also seems to be a check against disease: When mutations build up within a cell, the cell will usually self-destruct. If this fails to occur, the cell may divide and give rise to mutated daughter cells, which continue to divide and spread, gradually forming a growth called a tumor. This unregulated growth by rogue cells can be benign, or harmless, or cancerous, which may threaten healthy tissue. The study of apoptosis is one avenue that scientists explore in an effort to understand how cells become cancerous.
 Scientists are also discovering exciting aspects of the physical forces within cells. Cells employ a form of architecture called tensegrity, which enables them to withstand battering by a variety of mechanical stresses, such as the pressure of blood flowing around cells or the movement of organelles within the cell. Tensegrity stabilizes cells by evenly distributing mechanical stresses to the cytoskeleton and other cell components. Tensegrity also may explain how a change in the cytoskeleton, where certain enzymes are anchored, initiates biochemical reactions within the cell, and can even influence the action of genes. The mechanical rules of tensegrity may also account for the assembly of molecules into the first cells. Such new insights - made some 300 years after the tiny universe of cells was first glimpsed - show that cells continue to yield fascinating new worlds of discovery.
 The Nervous System signifies of those elements within the animal organism that are concerned with the reception of stimuli, the transmission of nerve impulses, or the activation of muscle mechanisms.
 The reception of stimuli is the function of special sensory cells. The conducting elements of the nervous system are cells called neurons; these may be capable of only slow and generalized activity, or they may be highly efficient and rapidly conducting units. The specific response of the neuron—the nerve impulse - and the capacities of the cell to be stimulated make this cell a receiving and transmitting unit capable of transferring information from one part of the body to another.
 Each nerve cell consists of a central portion containing the nucleus, known as the cell body, and one or more structures referred to as axons and dendrites. The dendrites are rather short extensions of the cell body and are involved in the reception of stimuli. The axon, by contrast, is usually a single elongated extension, it is especially important in the transmission of nerve impulses from the region of the cell body to other cells.
 Although all many-celled animals have some kind of nervous system, the complexity of its organization varies considerably among different animal types. In simple animals such as jellyfish, the nerve cells form a network capable of mediating only a relatively stereotyped response. In more complex animals, such as shellfish, insects, and spiders, the nervous system is more complicated. The cell bodies of neurons are organized in clusters called ganglia. These clusters are interconnected by the neuronal processes to form a ganglionated chain. Such chains are found in all vertebrates, in which they represent a special part of the nervous system, related especially to the regulation of the activities of the heart, the glands, and the involuntary Vertebrate animals have a bony spine and skull in which the central part of the nervous system is housed; The peripheral part extends throughout the remainder of the body. That part of the nervous system located in the skull is referred to as the brain that found in the spine is called the spinal cord. The brain and the spinal cord are continuous through an opening in the base of the skull; Both are also in contact with other parts of the body through the nerves. The distinction made between the central nervous system and the peripheral nervous system is based on the different locations of the two intimately related parts of a single system. Some of the processes of the cell bodies conduct sense impressions and others conduct muscle responses, called reflexes, such as those caused by pain.
 In the skin are cells of several types called receptors; each is especially sensitive to particular stimuli. Free nerve endings are sensitive to pain and are directly activated. The neurons so activated send impulses into the central nervous system and have junctions with other cells that have axons extending back into the periphery. Impulses are carried from processes of these cells to motor endings within the muscles. These neuromuscular endings excite the muscles, resulting in muscular contraction and appropriate movement. The pathway taken by the nerve impulse in mediating this simple response is in the form of a two-neuron arc that begins and ends in the periphery. Many of the actions of the nervous system can be explained on the basis of such reflex arcs, which are chains of interconnected nerve cells, stimulated at one end and capable of bringing about movement or glandular secretion at the other.
 The cranial nerves connect to the brain by passing through openings in the skull, or cranium. Nerves associated with the spinal cord pass through openings in the vertebral column and are called spinal nerves. Both cranial and spinal nerves consist of large numbers of processes that convey impulses to the central nervous system and also carry messages outward; the former processes are called afferent, and the latter are called efferent. Afferent impulses are referred to as sensory; efferent impulses are referred to as either somatic or visceral motor, according to what part of the body they reach. Most nerves are mixed nerves made up of both sensory and motor elements.
 The cranial and spinal nerves are paired; The number in humans are 12 and 31, respectively. Cranial nerves are distributed to the head and neck regions of the body, with one conspicuous exception: the tenth cranial nerve, called the vagus. In addition to supplying structures in the neck, the vagus is distributed to structures located in the chest and abdomen. Vision, auditory and vestibular sensation, and taste is mediated by the second, eighth, and seventh cranial nerves, respectively. Cranial nerves also mediate motor functions of the head, the eyes, the face, the tongue, and the larynx, as well as the muscles that function in chewing and swallowing. Spinal nerves, after they exit from the vertebrae, are distributed in a band-like fashion to regions of the trunk and to the limbs. They interconnect extensively, thereby forming the brachial plexus, which runs to the upper extremities, and the lumbar plexus, which passes to the lower limbs.
 Among the motor’s fibers may be found groups that carry impulses to viscera. These fibers are designated by the special name of autonomic nervous system. That system consists of two divisions, more or less antagonistic in function, that emerge from the central nervous system at different points of origin. One division, the sympathetic, arises from the middle portion of the spinal cord, joins the sympathetic ganglionated chain, courses through the spinal nerves, and is widely distributed throughout the body. The other division, the parasympathetic, arises both above and below the sympathetic, that is, from the brain and from the lower part of the spinal cord. These two divisions control the functions of the respiratory, circulatory, digestive, and urogenital systems.
 Consideration of disorders of the nervous system is the province of neurology; Psychiatry deals with behavioral disturbances of a functional nature. The division between these two medical specialties cannot be sharply defined, because neurological disorders often manifest both organic and mental symptoms.
 Diseases of the nervous system include genetic malformations, poisonings, metabolic defects, vascular disorders, inflammations, degeneration, and tumors, and they involve either nerve cells or their supporting elements. Vascular disorders, such as cerebral hemorrhage or other forms of a stroke, are among the most common causes of paralysis and other neurologic complications. Some diseases exhibit peculiar geographic and age distribution. In temperate zones, multiple sclerosis is a common degenerative disease of the nervous system, but it is rare in the Tropics.
 The nervous system is subject to infection by a great variety of bacteria, parasites, and viruses. For example, meningitis, or infection of the meninges investing the brain and spinal cord, can be caused by many different agents. On the other hand, one specific virus causes rabies. Some viruses causing neurological ills affect only certain parts of the nervous system. For example, the virus causing poliomyelitis commonly affects the spinal cord, as Viruses manufacturing encephalitis attack the brain.
 Inflammations of the nervous system are named according to the part affected. Myelitis is an inflammation of the spinal cord; Neuritis is an inflammation of a nerve. It may be caused not only by infection but also by poisoning, alcoholism, or injury. Tumors originating in the nervous system usually are composed of meningeal tissue or neuroglia (supporting tissue) cells, depending on the specific part of the nervous system affected, but other types of a tumors may metastasize to or invade the nervous system. In certain disorders of the nervous system, such as neuralgia, migraine, and epilepsy, no evidence may exist of organic damage. Another disorder, cerebral palsy, is associated with birth defects.
 Pain, an unpleasant sensory and emotional experience caused by real or potential injury or damage to the body or described in terms of such damage. Scientists believe that pain evolved in the animal kingdom as a valuable three-part warning system. First, it warns of injury. Second, pain protects against further injury by causing a reflexive withdrawal from the source of injury. Finally, pain leads to a period of reduced activity, enabling injuries to heal more efficiently.
 Pain is difficult to measure in humans because it has an emotional, or psychological component as well as a physical component. Some people express extreme discomfort from relatively small injuries, while others show little or no pain even after suffering severe injury. Sometimes pain is present even though no injury is apparent at all, or pain lingers long after an injury appears to have healed.
 The signals that warn the body of tissue damage are transmitted through the nervous system. In this system, the basic unit is the nerve cell or neuron. A nerve cell is composed of three parts: a central cell body, a single major branching fiber called an axon, and a series of smaller branching fibers known as dendrites. Each nerve cell meets other nerve cells at certain points on the axons and dendrites, forming a dense network of interconnected nerve fibers that transmit sensory information about touch, pressure, or warmth, as well as pain.
 Sensory information is transmitted from the different parts of the body to the brain via the spinal cord, which is a complex set of nerves that extend from the brain down along the back, protected by the bones of the spine. About as wide as a finger, the spinal cord is like a cable packed with many bundles of wires. The bundles are nerve pathways for transmitting information. But the spinal cord is more than just a message transmitter, it is also an extension of the brain. It contains neurons that process incoming sensory information, and generates messages to be sent back down to cells in other parts of the body.
 In the nervous system, a message-carrying impulse travels from one end of a nerve cell to the other by means of an electrical impulse. When it reaches the terminal end of a nerve cell, the impulse trigger’s tiny sacs called presynaptic vessicles to release their contents, chemical messengers called neurotransmitters. The neurotransmitters float across the synapse, or gap between adjacent nerve cells. When they reach the neighboring nerve cell, the neurotransmitters fit into specialized receptor sites much as a key fits into a lock, causing that nerve cell to ‘fire,’ or generate an electric message-carrying impulse. As the message continues through the nervous system, the presynaptic cell absorbs the excess neurotransmitters, and repackages them in presynaptic versicles in a process called neurotransmitter reuptake.
 Information being transmitted between and within the brain and spinal cord travels through the nervous system using both chemical and electrical mechanisms. A message-carrying impulse travels from one end of a nerve cell to another by means of an electric signal. When the electric signal reaches the terminal end of a nerve cell, a gap called a synapse prevents the electric signal from crossing to the next cell. The electric signal triggers the cell to release chemicals called neurotransmitters, which float across the synapse to the neighboring nerve cell. These neurotransmitters fit into specialized receptors found on the adjacent nerve cell, much as a key fits into a lock, generating an electric impulse in the neighboring cell. This new impulse travels to the end of the long cell, in turn triggering the release of neurotransmitters to carry the message across the next synapse. Not all neurotransmitters initiate a message in a neighboring nerve cell. Some specialize in preventing neighboring cells from generating an electrical signal, while others function as helpers, facilitating the message's journey to the brain.
 While most of the sensory nerves in the skin and other body tissues have special structures covering their nerve endings, those nerves that signal injury have free nerve endings. These simple nerve endings specialize in detecting noxious stimuli - a catchall term for injury-causing stimuli such as intense heat, extreme pressure, or sharp pricks or cuts. The nerve endings that detect pain are called nociceptors, and the process of transmitting pain signals when harmful stimulation occurs is called nociception. Several million nociceptors are interlaced through the tissues and organs of the body.
 When a person experiences an injury, such as a stubbed toe, specialized cells called nociceptors sense potential tissue damage (1) and send an electric signal, called an impulse, to the spinal cord via a sensory nerve (2). A specialized region of the spinal cord known as the dorsal horn (3) processes the pain signal, immediately sending another impulse back down the leg via a motor nerve (4). This causes the muscles in the leg to contract and pull the toe away from the source of injury (6). At the same time, the dorsal horn sends another impulse up the spinal cord to the brain. During this trip, the impulse travels between nerve cells. When the impulse reaches a nerve ending (7), the nerve released chemical messengers, called neurotransmitters, which carry the message to the adjacent nerve. When the impulse reaches the brain (8), it is analyzed and processed as an unpleasant physical and emotional sensation.
 An injury triggers pain signals in two types of nociceptors, one with large, insulated axons known as A-delta fibers and one with small, uninsulated axons known as C fibers. The large A-delta fibers conduct signals quickly, and the smaller C fibers transmit information slowly. The difference in the functions of these two fibers becomes obvious to a person who stubs a toe. At first the injured person is aware of a sharp, flashing pain at the point of injury. Generated by the A-delta fibers, this short-lived pain intrudes upon the thoughts and perceptions occurring in the brain. Just as this first pain subsides, a second pain begins that is vague, throbbing, and persistent. This sensation is derived from the C fibers.
 Pain information from the A-delta and C fibers travels through the spinal cord to the brain. When it receives the pain message, the spinal cord generates impulses that travel back down to muscles, which lead to a reflexive contraction that pulls the body away from the source of injury. Other reflexes may affect skin temperature, blood flow, sweating, and other changes.
 While this reflex action is underway, the pain message continues up the spinal cord to relay centers in the brain. The sensory information is routed to many other parts of the brain, including the cortex, where thinking processes occur
 The Adrenal Gland is the vital endocrine gland that secretes hormones into the bloodstream, situated, in humans, on top of the upper end of each kidney. The two parts of the gland - the inner portion, or medulla, and the outer portion, or the cortex - are like separate organs: They are composed of different types of tissue and perform different functions. The adrenal medulla, composed of chromaffin cells secretes the hormone epinephrine, also called adrenaline, in response to stimulation of the sympathetic nervous system at times of stress. The medulla also secretes the hormone norepinephrine, which plays a role in maintaining normal blood circulation. The hormones of the medulla are called catecholamines. Unlike the adrenal cortex, the medulla can be removed without endangering the life of an individual.
 The adrenal outer layer, or cortex, secretes about 30 steroid hormones, but only a few are secreted in significant amounts. Aldosterone, one of the most important hormones, regulates the balance of salt and water in the body. Cortisone and hydrocortisone are necessary to regulate fat, carbohydrate, and protein metabolism. Adrenal sex steroids have a minor influence on the reproductive system. Modified steroids, now produced synthetically, are superior to naturally secreted steroids for treatment of Addison's disease and other disorders.
 Adrenocorticotropic Hormone  is also known as corticotropin, hormones secreted by the anterior part of the pituitary gland. The specific function of ACTH is to stimulate the growth and secretions of the cortex (outer layers) of the adrenal gland. One of these secretions is cortisone, a hormone involved in carbohydrate and protein metabolisms. ACTH is used medically for its anti-inflammatory action to alleviate symptoms of allergies and arthritis. ACTH is a complex protein molecule containing 39 amino acids. Its molecular weight is approximately 5000. The biological activity of the ACTH of various animal species is similar to that of humans, but the sequence of amino acids has been found to vary somewhat among species. ACTH production is controlled in part by the hypothalamus and in part by the existing levels of adrenal gland hormones. ACTH levels increased in response to stress, disease, and decreased blood pressure.
 The Pituitary Gland is the master endocrine gland in vertebrate animals. The hormones secreted by the pituitary stimulate and control the functioning of almost all the other endocrine glands in the body. Pituitary hormones also promote growth and control the water balance of the body.
 The pituitary is a small bean-shaped, reddish-gray organ located in the saddle-shaped depression (sella turcica) in the floor of the skull (the sphenoid bone) and attached to the base of the brain by a stalk; it is located near the hypothalamus. The pituitary has two lobes - the anterior lobe, or adenohypophysis, and the posterior lobe, or neurohypophysis - which differ in structure and function. The anterior lobe is derived embryologically from the roof of the pharynx and is composed of groups of epithelial cells separated by blood channels; the posterior lobe is derived from the base of the brain and is composed of nervous connective tissue and nerve-like secreting cells. The area between the anterior and posterior lobes of the pituitary is called the intermediate lobe; it has the same embryological origin as the anterior lobe.
 Concentrated chemical substances, or hormones, which control 10 to 12 functions in the body, have been obtained as extracts from the anterior pituitary glands of cattle, sheep, and swine. Eight hormones have been isolated, purified, and identified; All of them are peptides, that is, they are composed of amino acids. A growth hormone (GH), or the somatotropic hormone (STH), is essential for normal skeletal growth and is neutralized during adolescence by the gonadal sex hormones. Thyroid-stimulating hormones (TSH) control the normal functioning of the thyroid gland, and the adrenocorticotropic hormone (ACTH) controls the activity of the cortex of the adrenal glands and takes part in the stress reaction. Prolactin, also called lactogenic, luteotropic, or mammotropic hormone, initiates milk secretion in the mammary gland after the mammary tissues have been prepared during pregnancy by the secretion of other pituitary and sex hormones. The two gonadotropic hormones are follicle-stimulating hormones (FSH) and a luteinizing hormone (LH). Follicle-stimulating hormones stimulates the formation of the Graafian follicle in the female ovary and the development of spermatozoa in the male. The luteinizing hormone stimulates the formation of ovarian hormones after ovulation and initiates lactation in the female, in the male, it stimulates the tissues of the testes to elaborate testosterone. In 1975 scientists identified the pituitary peptide endorphin, which acts in experimental animals as a natural pain reliever in times of stress. Endorphin and ACTH are made as parts of a single large protein, which subsequently splits. This may be the body's mechanism for coordinating the physiological activities of two stress-induced hormones. The same large prohormone that contains ACTH and endorphin also contains short peptides called melanocyte-stimulating hormones. These substances are analogous to the hormone that regulates pigmentation in fish and amphibians, but in humans they have no known function.
 Research has shown that the hormonal activity of the anterior lobe is controlled by chemical messengers sent from the hypothalamus through tiny blood vessels to the anterior lobe. In the 1950s, the British neurologist Geoffrey Harris discovered that cutting the blood supply from the hypothalamus to the pituitary impaired the function of the pituitary. In 1964, chemical agents called releasing factors were found in the hypothalamus; These substances, it was learned, affect the secretion of growth hormones, a thyroid-stimulating hormone called thyrotropin, and the gonadotropic hormones involving the testes and ovaries. In 1969 the American endocrinologist Roger Guillemin and colleagues isolated and characterized thyrotropin-releasing factors, which stimulates the secretion of thyroid-stimulating hormones from the pituitary. In the next few years his group and that of the American physiologist Andrew Victor Schally isolated the luteinizing hormone-releasing factor, which stimulates secretion of both LH and FSH, and somatostatin, which inhibits release of growth hormones. For this work, which proved that the brain and the endocrine system are linked, they shared the Nobel Prize in physiology or medicine in 1977. Human somatostatin was one of the first substances to be grown in bacteria by recombinant DNA.
 The presence of the releasing factors in the hypothalamus helped to explain the action of the female sex hormones, estrogen and progesterone, and their synthetic versions contained in oral contraceptives, or birth-control pills. During a woman's normal monthly cycle, several hormonal changes are needed for the ovary to produce an egg cell for possible fertilization. When the estrogen level in the body declines, the follicle-releasing factor (FRF) flows to the pituitary and stimulates the secretion of the follicle-stimulating hormone. Through a similar feedback principle, the declining level of progesterone causes a release of luteal-releasing factors (LRF), which stimulates secretion of the luteinizing hormone. The ripening follicle in the ovary then produces estrogen, and the high level of that hormone influences the hypothalamus to shut down temporarily the production of FSH. Increased progesterone feedback to the hypothalamus shuts down LH production by the pituitary. The daily doses of synthetic estrogen and progesterone in oral contraceptives, or injections of the actual hormones, inhibit the normal reproductive activity of the ovaries by mimicking the effect of these hormones on the hypothalamus.
 In lower vertebrates this part of the pituitary secretes melanocyte-stimulating hormones, which brings about skin-color changes. In humans, it is present only for a short time early in life and during pregnancy, and is not known to have any function.
 Two hormones are secreted by the posterior lobe. One of these is the antidiuretic hormone (ADH), vasopressin. Vasopressin stimulates the kidney tubules to absorb water from the filtered plasma that passes through the kidneys and thus controls the amount of urine secreted by the kidneys. The other posterior pituitary hormone is oxytocin, which causes the contraction of the smooth muscles in the uterus, intestines, and blood arterioles. Oxytocin stimulates the contractions of the uterine muscles during the final stage of pregnancy to stimulate the expulsion of the fetus, and it also stimulates the ejection, or let down, of milk from the mammary gland following pregnancy. Synthesized in 1953, oxytocin was the first pituitary hormone to be produced artificially. Vasopressin was synthesized in 1956.
 Pituitary functioning may be disturbed by such conditions as tumors, blood poisoning, blood clots, and certain infectious diseases. Conditions resulting from a decrease in anterior-lobe secretion include dwarfism, acromicria, Simmonds's disease, and Fröhlich's syndrome. The dwarfism occurs when anterior pituitary deficiencies occur during childhood; acromicria, in which the bones of the extremities are small and delicate, results when the deficiency occurs after puberty. Simmonds's disease, which is caused by extensive damage to the anterior pituitary, is characterized by premature aging, loss of hair and teeth, anemia, and emaciation; it can be fatal. Fröhlich's syndrome, also called adiposogenital dystrophy, is caused by both anterior pituitary deficiency and a lesion of the posterior lobe or hypothalamus. The result is obesity, dwarfism, and retarded sexual development. Glands under the influence of anterior pituitary hormones are also affected by anterior pituitary deficiency.
 Over secretion of one of the anterior pituitary hormones, somatotropin, results in a progressive chronic disease called acromegaly, which is characterized by enlargement of some parts of the body. Posterior-lobe deficiency results in diabetes insipidus.
 Tissue, - group of associated, similarly structured cells that perform specialized functions for the survival of the organism.  Animal tissues, to which this article is limited, take their first form when the blastula cells, arising from the fertilized ovum, differentiate into three germ layers: the ectoderm, mesoderm, and endoderm. Through further cell differentiation, or histogenesis, groups of cells grow into more specialized units to form organs made up, usually, of several tissues of similarly performing cells. Animal tissues are classified into four main groups.
 These tissues include the skin and the inner surfaces of the body, such as those of the lungs, stomach, intestines, and blood vessels. Because its primary function is to protect the body from injury and infection, epitheliums are made up of tightly packed cells with little intercellular substance between them.
 About 12 kinds of epithelial tissue occur. One kind is stratified squamous tissue found in the skin and the linings of the esophagus and vagina. It is made up of thin layers of flat, scalelike cells that form rapidly above the blood capillaries and is pushed toward the tissue surface, where they die and are shed. Another is a simple columnar epithelium, which lines the digestive system from the stomach to the anus; Simple columnar epithelium cells stand upright and not only control the absorption of nutrients but also secrete mucus through individual goblet cells. Glands are formed by the inward growth of epithelium-for examples, the sweat glands of the skin and the gastric glands of the stomach. Outward growth results in hair, nails, and other structures.
 These tissues, which support and hold parts of the body together, comprises the fibrous and elastic connective tissues, the adipose (fatty) tissues, and cartilage and bone. In contrast to an epithelium, the cells of these tissues are widely separated from one another, with a large amount of intercellular substance between them. The cells of fibrous tissue, found throughout the body, connect to one another by an irregular network of strands, forming a soft, cushiony layer that also supports blood vessels, nerves, and other organs. Adipose tissue has a similar function, except that its fibroblasts also contain store fat. Elastic tissue, found in ligaments, the trachea, and the arterial walls, stretches and contracts again with each pulse beat. In the human embryo, the fibroblast cells that originally secreted collagen for the formation of fibrous tissue later change to secrete a different form of protein called chondrion, for the formation of cartilage, some cartilage later becomes calcified by the action of osteoblast to form bones. Blood and lymph are also often considered connective tissues.
 Tissues, which contract and relax, comprise the striated, smooth, and cardiac muscles. Striated muscles, also called skeletal or voluntary muscles, include those that are activated by the somatic, or voluntary, nervous system. They are joined together without cell walls and have several nuclei. The smooth, or involuntary muscles, which are activated by the autonomic nervous system, are found in the internal organs and consist of simple sheets of cells. Cardiac muscles, which have characteristics of both striated and smooth muscles, are joined together in a vast network. These highly complex groups of cells, called ganglia, transfer information from one part of the body to another. Each neuron, or nerve cell, consists of a cell body with branching dendrites and one long fiber, or axons. The dendrites connect one neuron to another; The axon transmits impulses to an organ or collects impulses from a sensory organ.
 In the nervous system, a message-carrying impulse travels from one end of a nerve cell to the other by means of an electrical impulse. When it reaches the terminal end of a nerve cell, the impulse trigger’s tiny sacs called presynaptic vessicles to release their contents, chemical messengers called neurotransmitters. The neurotransmitters float across the synapse, or gap between adjacent nerve cells. When they reach the neighboring nerve cell, the neurotransmitters fit into specialized receptor sites much as a key fits into a lock, causing that nerve cell to fire or generate an electric message-carrying impulse. As the message continues through the nervous system, the presynaptic cell absorbs the excess neurotransmitters, and repackages them in presynaptic versicles in a process called neurotransmitter reuptake.
 Reflex, in physiology, is the involuntary response to a stimulus by the animal organism. In its simplest form, it consisted of the stimulation of an afferent nerve through a sense organ, or receptor, followed by transmission of the stimulus, usually through a nerve center, to an efferent motor nerve, resulting in action of a muscle or gland, called the effector. In most reflex action, however, the stimulus passes through one or more intermediate nerve cells, which modify and direct its action, sometimes to the extent of involving the muscular activity of the entire organism. For example, a painful stimulus applied to the hand causes a reflex withdrawal of the hand, which involves contraction of the flexor group of muscles and reflexation of the opposing extensor group; if the stimulus is strong, the coordinating nerve cells pass it to the arm muscles and also to the muscles of the trunk and legs, the result being a jump that removes not only the arm, but the entire person from the vicinity of the painful stimulus.
 The system of coordinating nerve cells is such that several different kinds of stimuli may produce the same result. For example, the stimulus produced by the sight of food and that caused by the smell of food travel different afferent pathways, but both have a common final path that stimulates the salivary glands to secretion. The final common path may also be activated through associated nerve tracts by a stimulus that ordinarily is not directly connected with the response. This type of reflex was named conditioned reflex by its discoverer, the Russian physiologist Ivan Pavlov, about 1904. Pavlov found that sounding a bell every time a dog was about to be given food eventually caused a reflex flow of saliva, which later persisted even when no food was produced. Elaborations of this habituative type of reflex are regarded by some physiologists and psychologists as an important basis for many behaviors, both voluntary and involuntary.
 The normal pathways of many reflexes are generally known, and the presence, absence, or exaggerations of the normal physical responses to certain stimuli are symptoms used by neurologists to determine the condition of the neural pathways involved. A familiar reflex commonly tested by physicians is the patellar reflex, in which an involuntary jerk of the knee is evoked by lightly striking the tendon of the patella, or kneecap, indicating the efficiency of certain nerve tracts in the spinal cord.
 Like all other cells, neurons contain charged ions: Potassium and sodium (positively charged) and chlorine (negatively charged). Neurons differ from other cells in that they are able to produce a nerve impulse. A neuron is polarized - that is, it has an overall negative charge inside the cell membrane because of the high concentration of chlorine ions and low concentration of potassium and sodium ions. The concentration of these same ions is exactly reversed outside the cell. This charge differential represents stored electrical energy, sometimes referred to as membrane potential or resting potential. The negative charge inside the cell is maintained by two features. The first is the selective permeability of the cell membrane, which is more permeable to potassium than sodium. The second feature is sodium pumps within the cell membrane that actively pump sodium out of the cell. When depolarization occurs, this charge differential across the membrane is reversed, and a nerve impulse is produced.
 Depolarization is a rapid change in the permeability of the cell membrane. When sensory input or any other kind of stimulating current is received by the neuron, the membrane permeability is changed, allowing a sudden influx of sodium ions into the cell. The high concentration of sodium, or action potential, changes the overall charges within the cell from negative too positive. The local changes in ion concentration triggers similar reactions along the membrane, propagating the nerve impulse. After a brief period called the refractory period, during which the ionic concentration returned to resting potential, the neuron can repeat this process.
 Nerve impulses travel at different speeds, depending on the cellular composition of a neuron. Where speed of impulse is important, as in the nervous system, axons are insulated with a membranous substance called myelin. The insulation provided by myelin maintains the ionic charge over long distances. Nerve impulses are propagated at specific points along the myelin sheath; These points are called the nodes of Ranvier. Examples of myelinated axons are those in sensory nerve fibers and nerves connected to skeletal muscles. In non-myelinated cells, the nerve impulse is propagated more diffusely.
 The nervous system has two divisions: The somatic, which allow voluntary control over skeletal muscle, and the autonomic, which is involuntary and controls cardiac and smooth muscle and glands. The autonomic nervous system has two divisions: The sympathetic and the parasympathetic. Many, but not all, of the muscles and glands that distribute nerve impulses to the larger interior organs possess a double nerve supply; in such cases the two divisions may exert opposing effects. Thus, the sympathetic system increases heartbeat, and the parasympathetic system decreases heartbeat. The two nervous systems are not always antagonistic, however. For example, both nerve supplies to the salivary glands excite the cells of secretion. Furthermore, a single division of the autonomic nervous system may both excite and inhibit a single effector, as in the sympathetic supply to the blood vessels of skeletal muscle. Finally, the sweat glands, the muscles that cause involuntary erection or bristling of the hair, the smooth muscle of the spleen, and the blood vessels of the skin and skeletal muscle are actuated only by the sympathetic division.
 Voluntary movement of head, limbs, and body is caused by nerve impulses arising in the motor area of the cortex of the brain and carried by cranial nerves or by nerves that emerge from the spinal cord to connect with skeletal muscles. The reaction involves both excitation of nerve cells stimulating the muscles involved and inhibition of the cells that stimulate opposing muscles. A nerve impulse is an electrical change within a nerve cell or fiber; Measured in millivolts, it lasts a few milliseconds and can be recorded by electrodes.
 The human brain has three major structural components: The large dome-shaped cerebrum, the smaller somewhat spherical cerebellum, and the brainstem. Prominent in the brainstem is the medulla oblongata (the egg-shaped enlargement at the center) and the thalamus (between the medulla and the cerebrum). The cerebrum is responsible for intelligence and reasoning. The cerebellum helps to maintain balance and posture. The medulla is involved in maintaining involuntary functions such as respiration, and the thalamus act as a relay center for electrical impulses traveling to and from the cerebral cortex. Lack of blood flow to any part of the brain results in a stroke, permanent damage that interferes with the functions of the affected part of the brain.
 Movement may occur also in direct response to an outside stimulus, thus, a tap on the knee causes a jerk, and a light shone into the eye makes the pupil contract. These involuntary responses are called reflexes. Various nerve terminals called receptors constantly send impulses into the central nervous system. These are of three classes: exteroceptors, which are sensitive to pain, temperature, touch, and pressure; interoceptors, which react to changes in the internal environment; and proprioceptors, which respond to variations in movement, position, and tension. These impulses terminate in special areas of the brain, as do of those special receptors concerned with sight, hearing, smell, and taste.
 Whereas most major nerves emerge from the spinal cord, the 12 pairs of cranial nerves project directly from the brain. All but 1 pair relay motor or sensory information (or both); the tenth, or vagus nerve, affects visceral functions such as heart rate, vasoconstriction, and contraction of the smooth muscle found in the walls of the trachea, stomach, and intestine.
 Muscular contractions do not always cause actual movement. A small fraction of the total number of fibers in most muscles is usually contracting. This serves to maintain the posture of a limb and enables the limb to resist passive elongation or stretch. This slight continuous contraction is called muscle tone.
 In 1946 Axelrod joined the laboratory of American pharmacologist Bernard Brodie at Goldwater Memorial Hospital in New York. The pair conducted research on pain-relieving drugs called analgesics. They identified a pain-relieving chemical known as acetaminophen. This drug was later developed and marketed by the drug company Johnson & Johnson under the brand-name Tylenol.
 In 1949 Axelrod took a position at the National Heart Institute, a branch of the National Institutes of Health (NIH). Their Axelrod studied how the body processes certain drugs that cause behavioral changes, including amphetamines, ephedrine, and mescaline. He identified a group of enzymes that help these drugs break down in the body. These enzymes, called cytochrome-P450 monoxygenases, have been studied extensively by other scientists, particularly in cancer research.
 Realizing that career advancement in the sciences requires a doctoral degree, in 1954 Axelrod took a leave of absence from his job at the National Heart Institute to attend The George Washington University. He earned his doctorate in pharmacology in 1955. That same year he was named chief of pharmacology at the National Institute of Mental Health (NIMH) another branch of NIH.
 At NIMH, Joseph Axelrod began research on neurotransmitters. A nerve cell releases a neurotransmitter to spur a neighboring cell into action. In the 1950s most scientists believed that a neurotransmitter became inactive once it stimulated a neighboring cell. But Axelrod’s research found that the neurotransmitter returns to the first nerve cell, in a process known as reuptake, where it is broken down by enzymes or repackaged for reuse. This research led to the creation of a number of drugs that prevent the reuptake process, enabling a neurotransmitter to remain active for a longer period of time.
 Axelrod’s research revolutionized the understanding of many mental-health disorders, including depression, anxiety, and schizophrenia. Prior to his research, psychiatry focused on the relationship of life experiences to mental health problems. But Axelrod's research proved that mental-health disorders were often the result of complicated brain chemistry. His research spurred the development of new drugs that advanced the treatment of mental-health conditions. Among these are selective serotonin reuptake inhibitors, including the antidepressants fluoxetine, sold under the brand name Prozac, sertraline(Zoloft) and paroxetine (Paxil).
 The study of the biochemistry of memory is another exciting scientific enterprise, but one that can only be touched upon here. Scientists estimate that an adult human brain contains about 100 billion neurons. Each of these is connected to hundreds or thousands of other neurons, forming trillions of neural connections. Neurons communicate by chemical messengers called neurotransmitters. An electrical signal travels along the neuron, triggering the release of neurotransmitters at the synapse, the small gap between neurons. The neurotransmitters travel across the synapse and act on the next neuron by binding with protein molecules called receptors. Most scientists believe that memories are somehow stored among the brain's trillions of synapses, rather than in the neurons themselves.
 Scientists who study the biochemistry of learning and memory often focus on the marine snail Aplysia because its simple nervous system allows them to study the effects of various stimuli on specific synapses. A change in the snail's behavior due to learning can be correlated with a change at the level of the synapse. One exciting scientific frontier is discovering the changes in neurotransmitters that occur at the level of the synapse.
 Other researchers have implicated glucose, a sugar and insulin(a hormone secreted by the pancreas) as important to learning and memory. Humans and other animals given these substances show an improved capacity to learn and remember. Typically, when animals or humans ingest glucose, the pancreas responds by increasing insulin production, so it is difficult to determine which substance contributes to improved performance. Some studies in humans that have systematically varied the amount of glucose and insulin in the blood have shown that insulin may be the more important of the two substances for learning.
 Scientists also have examined the influence of genes on learning and memory. In one study, scientists bred strains of mice with extra copies of a gene that helps build a protein called N-methyl-D-aspartate, or NMDA. This protein acts as a receptor for certain neurotransmitters. The genetically altered mice outperformed normal mice on a variety of tests of learning and memory. In addition, other studies have found that chemically blocking NMDA receptor impairs learning in laboratory rats. Future discoveries from genetic and biochemical studies may lead to treatments for memory deficits from Alzheimer's disease and other conditions that affect memory.
 Alzheimer's Disease, progressive brain disorders that causes a gradual and irreversible decline in memory, language skills, perception of time and space, and, eventually, the ability to care for oneself. First described by German psychiatrist Alois Alzheimer in 1906, Alzheimer's disease was initially thought to be a rare condition affecting only young people, and was referred to as prehensile dementia. Today late-onset Alzheimer's disease is recognized as the most common cause of the loss of mental function in those aged 65 and over. Alzheimer's in people in their 30s, 40s, and 50s, called early-onset Alzheimer's disease, occurs less frequently, accountings for less than 10 percent of the estimated 4 million Alzheimer's cases in the United States.
 Although Alzheimer's disease is not a normal part of the aging process, the risk of developing the disease increases as people grow older. About 10 percent of the United States population over the age of 65 is affected by Alzheimer's disease, and nearly 50 percent of those over age 85 may have the disease.
 Alzheimer's disease takes a devastating toll, not only on the patients, but also on those who love and care for them. Some patients experience immense fear and frustration as they struggle with once commonplace tasks and slowly lose their independence. Family, friends, and especially those who provide daily care suffer immeasurable pain and stress as they witness Alzheimer's disease slowly take their loved one from them.
 The onset of Alzheimer's disease is usually very gradual. In the early stages, Alzheimer's patients have relatively mild problems learning new information and remembering where they have left common objects, such as keys or a wallet. In time, they begin to have trouble recollecting recent events and finding the right words to express themselves. As the disease progresses, patients may have difficulty remembering what day or month it is, or finding their way around familiar surroundings. They may develop a tendency to wander off and then be unable to find their way back. Patients often become irritable or withdrawn as they struggle with fear and frustration when once commonplace tasks become unfamiliar and intimidating. Behavioral changes may become more pronounced as patients become paranoid or delusional and unable to engage in normal conversation.
 Eventually Alzheimer's patients become completely incapacitated and unable to take care of their most basic life functions, such as eating and using the bathroom. Alzheimer's patients may live many years with the disease, usually dying from other disorders that may develop, such as pneumonia. Typically the time from initial diagnosis until death is seven to ten years, but this is quite variable and can range from three to twenty years, depending on the age of the onset, other medical conditions present, and the care patients receive.
 The brains of patients with Alzheimer's have distinctive formations - abnormally shaped proteins called tangles and plaques - that are recognized as the hallmark of the disease. Not all brain regions show these characteristic formations. The areas most prominently affected are those related to memory.
 Tangles are long, slender tendrils found inside nerve cells, or neurons. Scientists have learned that when a protein-called tau becomes altered, it may cause the characteristic tangles in the brain of the Alzheimer’s patient. In healthy brains provides structural support for neurons, but in Alzheimer's patients this structural support collapses.
 Plaques, or clumps of fibers, form outside the neurons in the adjacent brain tissue. Scientists found that a type of protein, called amyloid precursor protein, forms toxic plaques when it is cut in two places. Researchers have isolated the enzyme beta-secretes, which is believed to make one of the cuts in the amyloid precursor protein. Researchers also identified another enzyme, called gamma secretes, that makes the second cut in the amyloid precursor protein. These two enzymes snip the amyloid precursor protein into fragments that then accumulate to form plaques that are toxic to neurons.
 Scientists have found that tangles and plaques cause neurons in the brains of Alzheimer's patients to shrink and eventually die, first in the memory and language centers and finally throughout the brain. This widespread neuron degeneration leaves gaps in the brain's messaging network that may interfere with communication between cells, causing some of the symptoms of Alzheimer’s disease.
 Alzheimer's patients have lower levels of neurotransmitters, chemicals that carry complex messages back and forth between the nerve cells. For instance, Alzheimer's disease seems to decrease the level of the neurotransmitter acetylcholine, which is known to influence memory. A deficiency in other neurotransmitters, including somatostatin and corticotropin-releasing factor, and, particularly in younger patients, serotonin and norepinephrine, also interferes with normal communication between brain cells.
 The causes of Alzheimer's disease remain a mystery, but researchers have found that particular groups of people have risk factors that make them more likely to develop the disease than the general population. For example, people with a family history of Alzheimer's are more likely to develop Alzheimer's disease.
 Some of the most promising Alzheimer's research is being conducted in the field of genetics to learn the role a family history of the disease has in its development. Scientists have learned that people who are carriers of a specific version of the apolipoprotein E gene (apoE genes), found on chromosome 19, are several times more likely to develop Alzheimer's than carriers of other versions of the apoE gene. The most common version of this gene in the general population is apoE3. Nearly half of all late-onset Alzheimer’s patients have the fewer in common apoE4 versions, however, and research has shown that this gene plays a role in Alzheimer's disease. Scientists have also found evidence that variations in one or more genes located on chromosomes 1, 10, and 14 may increase a person’s risk for Alzheimer's disease. Scientists have identified the gene variations on chromosomes 1 and 14 and learned that these genes produce mutations in proteins called presenilins. These mutated proteins apparently trigger the activity of the enzyme gamma secretase, which splices the amyloid precursor protein.
 Researchers have made similar strides in the investigation of early-onset Alzheimer's disease. A series of genetic mutations in patients with early-onset Alzheimer's has been linked to the production of amyloid precursor protein, the protein in plaques that may be implicated in the destruction of neurons. One mutation is particularly interesting to geneticists because it occurs on a gene involved in the genetic disorder Down syndrome. People with Down syndrome usually develop plaques and tangles in their brains as they get older, and researchers believe that learning more about the similarities between Down syndrome and Alzheimer's may further our understanding of the genetic elements of the disease.
 Some studies suggest that one or more factors other than heredity may determine whether people develop the disease. One study published in February 2001 compared residents of Ibadan, Nigeria, who eat a mostly low-fat vegetarian diet, with African Americans living in Indianapolis, Indiana, whose diet included a variety of high-fat foods. The Nigerians were less likely to develop Alzheimer’s disease compared to their U.S. counterparts. Some researchers suspect that health imposes on high blood pressure, atherosclerosis (arteries clogged by fatty deposits), high cholesterol levels, or other cardiovascular problems may play a role in the development of the disease.
 Other studies have suggested that environmental agents may be a possible cause of Alzheimer's disease; for example, one study suggested that high levels of aluminum in the brain may be a risk factor. Several scientists initiated research projects to further investigate this connection, but no conclusive evidence has been found linking aluminum with Alzheimer's disease. Similarly, investigations into other potential environmental causes, such as zinc exposure, viral agents, and food-borne poisons, while initially promising, have generally turned up inconclusive results.
 Some studies indicate that brain trauma can trigger a degenerative process that results in Alzheimer's disease. In one study, an analysis of the medical records scribed upon veterans of World War II (1939-1945) linked serious head injury in early adulthood with Alzheimer's disease in later life. The study also looked at other factors that could possibly influence the development of the disease among the veterans, such as the presence of the apoE gene, but no other factors were identified.
 Alzheimer’s disease is only positively diagnosed by examining brain tissue under a microscope to see the hallmark plaques and tangles, and this is only possible after a patient dies. As a result, physicians rely on a series of other techniques to diagnose probable Alzheimer's disease in living patients. Diagnosis begins by ruling out other problems that cause memory loss, such as stroke, depression, alcoholism, and the use of certain prescription drugs. The patient undergoes a thorough examination, including specialized brain scans, to eliminate other disorders. The patient may be given a detailed evaluation called a neuropsychological examination, which is designed to evaluate a patient’s ability to perform specific mental tasks. This helps the physician determine whether the patient is showing the characteristic symptoms of Alzheimer's disease - progressively worsening memory problems, language difficulties, and trouble with spatial direction and time. The physician also asks about the patient's family medical history to learn about any past serious illnesses, which may give a hint about the patient's current symptoms.
 Evidence shows that there is inflammation in the brains of Alzheimer's patients, which may be associated with the production of amyloid precursor protein. Studies are underway to find drugs that prevent this inflammation, to possibly slow or even halt the progress of the disease. Other promising approaches center on mechanisms that manipulate amyloid precursor protein production or accumulation. Drugs are in development that may block the activity of the enzymes that cut the amyloid precursor protein, halting amyloid production. Other studies in mice suggest those vaccinating animals with amyloid precursor protein can produce a reaction that clears amyloid precursor protein from the brain. Physicians have started vaccination studies in humans to determine if the same potentially beneficial effects can be obtained. There is still much to be learned, but as scientists better understand the genetic components of Alzheimer’s, the roles of the amyloid precursor protein and the tau protein in the disease, and the mechanisms of nerve cell degeneration, the possibility that a treatment will be developed is more likely.
 The responsibility for caring for Alzheimer's patients generally falls on their spouses and children. Care givers must constantly be on guard for the possibility of Alzheimer's patients wandering away or becoming agitated or confused in a manner that jeopardizes the patient or others. Coping with a loved one's decline and inability to recognize familiar face causes enormous pain.
 The increased burden faced by families is intense, and the life of the Alzheimer's care giver is often called a 36-hour day. Not surprisingly, care givers often develop health and psychological problems of their own as a result of this stress. The Alzheimer's Association, a national organization with local chapters throughout the United States, was formed in 1980 in large measure to provide support for Alzheimer's care givers. Today, national and local chapters are a valuable source for information, referral, and advice.
 While most neurotransmitters interact with their receptors to create new electrical nerve impulses that energize or inhibit the adjoining cell, some neurotransmitter interactions do not generate or suppress nerve impulses. Instead, they interact with a second type of receptor that changes the internal chemistry of the postsynaptic cell by either causing or blocking the formation of chemicals called second messenger molecules. These second messengers regulate the postsynaptic cell’s biochemical processes and enable it to conduct the maintenance necessary to continue synthesizing neurotransmitters and conducting nerve impulses. Examples of second messengers, which are formed and entirely contained within the postsynaptic cell, include cyclic adenosine monophosphate, diacylglycerol, and inositol phosphates.
 Once neurotransmitters have been secreted into synapses and have passed on their chemical signals, the presynaptic neuron clears the synapse of neurotransmitter molecules. For example, acetylcholine is broken down by the enzyme acetylcholinesterase into choline and acetate. Neurotransmitters like dopamine, serotonin, and GABA is removed by a physical process called reuptake. In reuptake, a protein in the presynaptic membrane acts as a sort of sponge, causing the neurotransmitters to reenter the presynaptic neuron, where they can be broken down by enzymes or repackaged for reuse.
 Neurotransmitters are known to be involved in a number of disorders, including Alzheimer’s disease. Victims of Alzheimer’s disease suffer from loss of intellectual capacity, disintegration of personality, mental confusion, hallucinations, and aggressive - even violent - behaviour. These symptoms are the result of progressive degeneration in many types of neurons in the brain. Forgetfulness, one of the earliest symptoms of Alzheimer’s disease, is partly caused by the destruction of neurons that normally release the neurotransmitter acetylcholine. Medications that increase brain levels of acetylcholine have helped restore short-term memory and reduce mood swings in some Alzheimer’s patients.
 Neurotransmitters also play a role in Parkinson disease, which slowly attacks the nervous system, causing symptoms that worsen over time. Fatigue, mental confusion, a mask-like facial expression, stooping posture, shuffling gait, and problems with and speaking is among the difficulties suffered by Parkinson victims. These symptoms have been partly linked to the deterioration and eventual death of neurons that run from the base of the brain to the basal ganglia, a collection of nerve cells that manufacture the neurotransmitter dopamine. The reasons why such neurons die are yet to be understood, but the related symptoms can be alleviated. L-dopa, or levodopa, widely used to treat Parkinson disease, acts as a supplementary precursor for dopamine. It causes the surviving neurons in the basal ganglia to increase their production of dopamine, thereby compensating to some extent for the disabled neurons.
 Many other effective drugs have been shown to act by influencing neurotransmitter behaviour. Some drugs work by interfering with the interactions between neurotransmitters and intestinal receptors. For example, belladonna decreases intestinal cramps in such disorders as irritable bowel syndrome by blocking acetylcholine from combining with receptors. This process reduces nerve signals to the bowel wall, which prevents painful spasms.
 Other drugs block the reuptake process. One well-known example is the drug fluoxetine (Prozac), which blocks the reuptake of serotonin. Serotonin then remains in the synapse for a longer time, and its ability to act as a signal is prolonged, which contributes to the relief of depression and the control of obsessive-compulsive behaviours.
 Neurotransmitters are released into a microscopic gap, called a synapse, that separates the transmitting neuron from the cell receiving the chemical signal. The cell that generates the signal is called the presynaptic cell, while the receiving cell is termed the postsynaptic cell.
 After their release into the synapse, neurotransmitters combine chemically with highly specific protein molecules, termed receptors, that are embedded in the surface membranes of the postsynaptic cell. When this combination occurs, the voltage, or electrical force, of the postsynaptic cell is either increased (excited) or decreased (inhibited).
 When a neuron is in its resting state, its voltage is about -70 millivolts. An excitatory neurotransmitter alters the membrane of the postsynaptic neuron, making it possible for ions (electrically charged molecules) to move back and forth across the neuron’s membranes. This flow of ions makes the neuron’s voltage rise toward zero. If enough excitatory receptors have been activated, the postsynaptic neuron responds by firing, generating a nerve impulse that causes its own neurotransmitter to be released into the next synapse. An inhibitory neurotransmitter causes different ions to pass back and forth across the postsynaptic neuron’s membrane, lowering the nerve cell’s voltage to -80 or -90 millivolts. The drop in voltage makes it less likely that the postsynaptic cell will fire.
 If the postsynaptic cell is a muscle cell rather than a neuron, an excitatory neurotransmitter will cause the muscle to contract. If the postsynaptic cell is a gland cell, an excitatory neurotransmitter will cause the cell to secrete its contents.
 While most neurotransmitters interact with their receptors to create new electrical nerve impulses that energize or inhibit the adjoining cell, some neurotransmitter interactions do not generate or suppress nerve impulses. Instead, they interact with a second type of receptor that changes the internal chemistry of the postsynaptic cell by either causing or blocking the formation of chemicals called second messenger molecules. These second messengers regulate the postsynaptic cell’s biochemical processes and enable it to conduct the maintenance necessary to continue synthesizing neurotransmitters and conducting nerve impulses. Examples of second messengers, which are formed and entirely contained within the postsynaptic cell, include cyclic adenosine monophosphate, diacylglycerol, and inositol phosphates.
 Once neurotransmitters have been secreted into synapses and have passed on their chemical signals, the presynaptic neuron clears the synapse of neurotransmitter molecules. For example, acetylcholine is broken down by the enzyme acetylcholinesterase into choline and acetate. Neurotransmitters like dopamine, serotonin, and GABA is removed by a physical process called reuptake. In reuptake, a protein in the presynaptic membrane acts as a sort of sponge, causing the neurotransmitters to reenter the presynaptic neuron, where they can be broken down by enzymes or repackaged for reuse.
 Severe mental illness almost always alters a person’s life dramatically. People with severe mental illnesses experience disturbing symptoms that can make it difficult in holding down a job, or go to school, relate to others, or cope with ordinary life demands. Some individuals require hospitalization because they become unable to care for themselves or because they are at risk of committing suicide.
 The symptoms of mental illness can be very distressing. People who develop schizophrenia may hear voices inside their head that say nasty things about them or command them to act in strange or unpredictable ways. Or they may be paralyzed by paranoia - the deep conviction that everyone, including their closest family members, wants to injure or destroy them. People with major depression may feel that nothing brings pleasure and that life is so dreary and unhappy that it is better to be dead. People with panic disorder may experience heart palpitations, rapid breathing, and anxiety so extreme that they may not be able to leave home. People whom experience episodes of mania may engage in reckless sexual behaviour or may spend money indiscriminately, acts that later cause them to feel guilt, shame, and desperation.
 Other mental illnesses, while not always debilitating, create certain problems in living. People with personality disorders may experience loneliness and isolation because their personality style interferes with social relations. People with an eating disorder may become so preoccupied with their weight and appearance that they force themselves to vomit or refuse to eat. Individuals who develop post-traumatic stress disorder may become angry easily, experience disturbing memories, and have trouble concentrating.
 Experiences of mental illness often differ to be unlike or distinct in nature as it depends on one’s culture or social group, sometimes greatly so. For example, in most of the non-Western world, people with depression complain principally of physical ailments, such as lack of energy, poor sleep, loss of appetite, and various kinds of physical pain. And yet, even in North America these complaints are commonplace. But in the United States and other Western societies, depressed people and mental health professionals who treat them tend to emphasize psychological problems, such as feelings of sadness, worthlessness, and despair. The experience of schizophrenia also differs by culture. In India, one-third of the new cases of schizophrenia involve catatonia, a behavioural condition in which a person maintains a bizarre statue-like posture for hours or days. This condition is rare in Europe and North America.
 Schizophrenia, is a very severe mental illness characterized by a variety of symptoms, including loss of contact with reality, bizarre behaviour, disorganized thinking and speech, decreased emotional expressiveness, and social withdrawal. Usually only some of these symptoms occur in any one person. The term schizophrenia comes from Greek words meaning ‘split mind.’ However, contrary to common belief, schizophrenia does not refer to a person with a split personality or multiple personality. For a description of a mental illness in which a person has multiple personalities, to observers, schizophrenia may seem like madness or insanity, but persons with schizophrenia have disturbed, frightening thoughts and may have trouble telling the difference between real and unreal experiences.
 The intermittent period from 1895 to 1900 Freud developed many of the concepts that were later incorporated into psychoanalytic practice and doctrine. Soon after publishing the studies on hysteria he abandoned the use of hypnosis as a cathartic procedure and substituted the investigation of the patient’s spontaneous flow of thoughts, called free association, to reveal the unconscious mental processes at the root of the neurotic disturbance.
 In his clinical observations Freud found evidence for the mental mechanisms of repression and resistance. He described repression as a device operating unconsciously to make the memory of painful or threatening events inaccessible to the conscious mind. Resistance is defined as the unconscious defence against awareness of repressed experiences in order to avoid the resulting anxiety. He traced the operation of unconscious processes, using the free associations of the patient to guide him in the interpretation of dreams and slips of speech. Dream analysis led to his discoveries of infantile sexuality and of the so-called Oedipus complex, which constitutes the erotic attachment of the child for the parent of the opposite sex, together with hostile feelings toward the other parent. In these years he also developed the theory of transference, the processes by which emotional attitudes, established originally toward parental figures in childhood, are transferred in later life to others. The end of this period was marked by the appearance of Freud’s most important work, The Interpretation of Dreams (1899). Here Freud analyzed many of his own dreams recorded in the 3-year period of his self-analysis, begun in 1897. This work expounds all the fundamental concepts underlying psychoanalytic technique and doctrine.
 In 1902 Freud was appointed a full professor at Vienna University. This honour was granted not in recognition of his contributions but as a result of the efforts of a highly influential patient. The medical world still regarded his work with hostility, and his next writings, The Psychopathology of Everyday Life (1904) and Three Contributions to the Sexual Theory (1905), only increased this antagonism. As a result Freud continued to work virtually alone in what he termed ‘splendid isolation.’
 By 1906, however, a small number of pupils and followers had gathered around Freud, including the Austrian psychiatrists William Stekel and Alfred Adler, the Austrian psychologist Otto Rank, the American psychiatrist Abraham Brill, and the Swiss psychiatrist’s Eugen Bleuler and Carl Jung. Other notable associates, who joined the circle in 1908, were the Hungarian psychiatrist Sándor Ferenczi and the British psychiatrist Ernest Jones.
 Austrian doctor Sigmund Freud spent many hours refining his theories in this study of his home in Vienna, Austria. Freud pioneered the use of clinical observation to treat mental disease. The publication of The Interpretation of Dreams in 1899 detailed his technique of isolating the source of psychological problems by examining a patient’s spontaneous stream of thought.
 Increasing recognition of the psychoanalytic movement made possibly the formation in 1910 of a worldwide organization called the International Psychoanalytic Association. As the movement spread, gaining new adherents through Europe and the U.S., Freud was troubled by the dissension that arose among members of his original circle. Most disturbing was the defection from the group of Adler and Jung, each of whom developed a different theoretical basis for disagreement with Freud’s emphasis on the sexual origin of neurosis. Freud met these setbacks by developing further his basic concepts and by elaborating his own views in many publications and lectures.
 After the onset of World War I Freud devoted little time to clinical observation and concentrated on the application of his theories to the interpretation of religion, mythology, art, and literature. In 1923 he was stricken with cancer of the jaw, which necessitated constant, painful treatment in addition to many surgical operations. Despite his physical suffering he continued his literary activity for the next 16 years, writing mostly on cultural and philosophical problems.
 When the Germans occupied Austria in 1938, Freud, a Jew, was persuaded by friends to escape with his family to England. He died in London on September 23, 1939.
 Freud created an entirely new approach to the understanding of human personality by his demonstration of the existence and force of the unconscious. In addition, he founded a new medical discipline and formulated basic therapeutic procedures that in modified form are applied widely in the present-day treatment of neuroses and psychoses. Although never accorded full recognition during his lifetime, Freud is generally acknowledged as one of the great creative minds of modern times.
 Among his other works are Totem and Taboo (1913), Ego and the Id (1923), New Introductory Lectures on Psychoanalysis (1933), and Moses and Monotheism (1939).
 Psychoanalysis, its name is applied to a specific method of investigating unconscious mental processes and to a form of psychotherapy. The term refers, as well, to the systematic structure of psychoanalytic theory, which is based on the relation of conscious and unconscious psychological processes.
 In the late 19th century Viennese neurologist Sigmund Freud developed a theory of personality and a system of psychotherapy known as psychoanalysis. According to this theory, people are strongly influenced by unconscious forces, including innate sexual and aggressive drives. In this 1938 British Broadcasting Corporation interview, Freud recounts the early resistance to his ideas and later acceptance of his work. Freud’s speech is slurred because he was suffering from cancer of the jaw. He died the following year.
 The technique of psychoanalysis and much of the psychoanalytic theory based on its application were developed by Sigmund Freud. His work concerning the structure and the functioning of the human mind had far-reaching significance, both practically and scientifically, and it continues to influence contemporary thought.
 Sigmund Freud, the founder of psychoanalysis, compared the human mind to an iceberg. The tip above the water represents consciousness, and the vast region below the surface symbolizes the unconscious mind. Of Freud’s three basic personality structures—id, ego, and superego—only the id is totally unconscious.
 The first of Freud's innovations was his recognition of unconscious psychiatric processes that follow laws different from those that govern conscious experience. Under the influence of the unconscious, thoughts and feelings that belong together may be shifted or displaced out of context; two disparate ideas or images may be condensed into one; thoughts may be dramatized in the form of images rather than expressed as abstract concepts; and certain objects may be represented symbolically by images of other objects, although the resemblance between the symbol and the original object may be vague or farfetched. The laws of logic, indispensable for conscious thinking, do not apply to these unconscious mental productions.
 Recognition of these modes of operation in unconscious mental processes made possible the understanding of such previously incomprehensible psychological phenomena as dreaming. Through analysis of unconscious processes, Freud saw dreams as serving to protect sleep against disturbing impulses arising from within and related to early life experiences. Thus, unacceptable impulses and thoughts, called the latent dream content, are transformed into a conscious, although no longer immediately comprehensible, experience called the manifest dream. Knowledge of these unconscious mechanisms permits the analyst to reverse the so-called dream work, that is, the process by which the latent dream is transformed into the manifest dream, and through dream interpretation, to recognize its underlying meaning.
 A basic assumption of Freudian theory is that the unconscious conflicts involve instinctual impulses, or drives, that originate in childhood. As these unconscious conflicts are recognized by the patient through analysis, his or her adult mind can find solutions that were unattainable to the immature mind of the child. This depiction of the role of instinctual drives in human life is a unique feature of Freudian theory.
 According to Freud's doctrine of infantile sexuality, adult sexuality is an end product of a complex process of development, beginning in childhood, involving a variety of body functions or areas (oral, anal, and genital zones), and corresponding to various stages in the relation of the child to adults, especially to parents. Of crucial importance is the so-called Oedipal period, occurring at about four to six years of age, because at this stage of development the child for the first time becomes capable of an emotional attachment to the parent of the opposite sex that is similar to the adult's relationship to a mate; the child simultaneously reacts as a rival to the parent of the same sex. Physical immaturity dooms the child's desires to frustration and his or her first step toward adulthood to failure. Intellectual immaturity further complicates the situation because it makes children afraid of their own fantasies. The extent to which the child overcomes these emotional upheavals and to which these attachments, fears, and fantasies continue to live on in the unconscious greatly influences later life, especially love relationships.
 The conflicts occurring in the earlier developmental stages are no less significant as a formative influence, because these problems represent the earliest prototypes of such basic human situations as dependency on others and relationship to authority. Also basic in molding the personality of the individual is the behavior of the parents toward the child during these stages of development. The fact that the child reacts, not only to objective reality, but also to fantasy distortions of reality, however, greatly complicates even the best-intentioned educational efforts.
 The effort to clarify the bewildering number of interrelated observations uncovered by psychoanalytic exploration led to the development of a model of the structure of the psychic system. Three functional systems are distinguished that are conveniently designated as the id, ego, and superego.
 The first system refers to the sexual and aggressive tendencies that arise from the body, as distinguished from the mind. Freud called these tendencies Triebe, which literally means 'drives,' but which is often inaccurately translated as 'instincts' to indicate their innate character. These inherent drives claim immediate satisfaction, which is experienced as pleasurable; the id thus is dominated by the pleasure principle. In his later writings, Freud tended more toward psychological rather than biological conceptualization of the drives.
 How the conditions for satisfaction are to be brought about is the task of the second system, the ego, which is the domain of such functions as perception, thinking, and motor control that can accurately assess environmental conditions. In order to fulfill its function of adaptation, or reality testing, the ego must be capable of enforcing the postponement of satisfaction of the instinctual impulses originating in the id. To defend itself against unacceptable impulses, the ego develops specific psychic means, known as defense mechanisms. These include repression, the exclusion of impulses from conscious awareness; projection, the process of ascribing to others one's own unacknowledged desires; and reaction formation, the establishment of a pattern of behavior directly opposed to a strong unconscious need. Such defense mechanisms are put into operation whenever anxiety signals a danger that the original unacceptable impulses may reemerge.
 An id impulse becomes unacceptable, not only as a result of a temporary need for postponing its satisfaction until suitable reality conditions can be found, but more often because of a prohibition imposed on the individual by others, originally the parents. The totality of these demands and prohibitions constitutes the major content of the third system, the superego, the function of which is to control the ego in accordance with the internalized standards of parental figures. If the demands of the superego are not fulfilled, the person may feel shame or guilt. Because the superego, in Freudian theory, originates in the struggle to overcome the Oedipal conflict, it has a power akin to an instinctual drive, is in part unconscious, and can give rise to feelings of guilt not justified by any conscious transgression. The ego, having to mediate among the demands of the id, the superego, and the outside world, may not be strong enough to reconcile these conflicting forces. The more the ego is impeded in its development because of being enmeshed in its earlier conflicts, called fixations or complexes, or the more it reverts to earlier satisfactions and archaic modes of functioning, known as regression, the greater is the likelihood of succumbing to these pressures. Unable to function normally, it can maintain its limited control and integrity only at the price of symptom formation, in which the tensions are expressed in neurotic symptoms.
 A cornerstone of modern psychoanalytic theory and practice is the concept of anxiety, which institutes appropriate mechanisms of defense against certain danger situations. These danger situations, as described by Freud, are the fear of abandonment by or the loss of the loved one (the object), the risk of losing the object's love, the danger of retaliation and punishment, and, finally, the hazard of reproach by the superego. Thus, symptom formation, character and impulse disorders, and perversions, as well as sublimations, represent compromise formations—different forms of an adaptive integration that the ego tries to achieve through more or less successfully reconciling the different conflicting forces in the mind.
 Ego, found its use in psychoanalysis, the term denoting the central part of the personality structure that deals with reality and is influenced by social forces. According to the psychoanalytic theories developed by Sigmund Freud, the ego constitutes one of the three basic provinces of the mind, the other two being the id and the superego. Formation of the ego begins at birth in the first encounters with the external world of people and things. The ego learns to modify behavior by controlling those impulses that are socially unacceptable. Its role is that of mediator between unconscious impulses and acquired social and personal standards.
 In philosophy, ego means the conscious self or 'I.' It was viewed by some philosophers, notably the 17th-century Frenchman René Descartes and the 18th-century German Johann Gottlieb Fichte, as the sole basis of reality; they saw the universe as existing only in the individual's knowledge and experience of it. Other philosophers, such as the 18th-century German Immanuel Kant, proposed two forms of ego, one perceiving and the other thinking.
 An Id impulse, in psychoanalytic theory, is one of the three basic elements of personality, the others being the ego and the superego. The id can be equated with the unconscious of common usage, which is the reservoir of the instinctual drives of the individual, including biological urges, wishes, and affective motives. The id is dominated by the pleasure principle, through which the individual is pressed for immediate gratification of his or her desires. In strict Freudian theory the energy behind the instinctual drives of the id is known as the libido, a generalized force, basically sexual in nature, through which the sexual and psychosexual nature of the individual finds expression.
 Superego, in psychoanalytic theory, one of the three basic constituents of the mind, the others being the id and the ego. As postulated by Sigmund Freud, the term designates the element of the mind that, in normal personalities, automatically modifies and inhibits those instinctual impulses or drives of the id that tend to produce antisocial actions and thoughts.
 According to psychoanalytic theory, the superego develops as the child gradually and unconsciously adopts the values and standards, first of his or her parents, and later of the social environment. According to modern Freudian psychoanalysts, the superego includes the positive ego, or conscious self-image, or ego ideal, that each individual develops.
 People have tried to understand the causes of mental illness for thousands of years. The modern era of psychiatry, which began in the late 19th and early 20th centuries, has witnessed a sharp debate between biological and psychological perspectives of mental illness. The biological perspective views mental illness in terms of bodily processes, whereas psychological perspectives emphasize the roles of a person’s upbringing and environment.
 These two perspectives are exemplified in the work of German psychiatrist Emil Kraepelin and Austrian psychoanalyst Sigmund Freud. Kraepelin, influenced by the work in the mid-1800s of German psychiatrist Wilhelm Griesinger, believed that psychiatric disorders were disease entities that could be classified like physical illnesses. That is, Kraepelin believed that the fundamental causes of mental illness lay in the physiology and biochemistry of the human brain. His classification system of mental disorders, first published in 1883, formed the basis for later diagnostic systems. Freud, on the other hand, argued that the source of mental illness lay in unconscious conflicts originating in early childhood experiences. Freud found evidence for this idea through the analysis of dreams, free association, and slips of speech.
 This debate has continued into the late 20th century. Beginning in the 1960s, the biological perspective became dominant, supported by numerous breakthroughs in psychopharmacology, genetics, neurophysiology, and brain research. For example, scientists discovered many medications that helped to relieve symptoms of certain mental illnesses and demonstrated that people can inherit a vulnerability to some mental illnesses. Psychological perspectives also remain influential, including the psychodynamic perspective, the humanistic and existential perspectives, the behavioral perspective, the cognitive perspective, and the sociocultural perspective.
 Many mental health professionals today favor a combination of perspectives, acknowledging that both biology and a person’s environment play important roles in mental illness. This approach recognizes that people are not only products of the genes inherited from their parents, but products of the families and social worlds into which they are born. In this view, environments shape how biological factors will be manifested. For example, an infant may inherit genes that could enable her to become a tall adult, but if she is malnourished as a child, she will never achieve that potential. Likewise, an individual who does not possess a biological vulnerability for depression may nevertheless become severely depressed following the death of a loved one or after experiencing an act of torture.
 Psychiatry has increasingly emphasized a biological basis for the causes of mental illness. Studies suggest a genetic influence in some mental illnesses, such as schizophrenia and bipolar disorder, although the evidence is not conclusive.
 Clinical depression is one of the most common forms of mental illness. Although depression can be treated with psychotherapy, many scientists believe there are biological causes for the disease. In this June 1998 Scientific American article, neurobiologist Charles B. Nemeroff discusses the connection between biochemical changes in the brain and depression.
 Scientists have identified a number of neurotransmitters, or chemical substances that enable brain cells to communicate with each other, that appear important in regulating a person’s emotions and behavior. These include dopamine, serotonin, norepinephrine (see epinephrine), gamma-amino butyric acid (GABA), and acetylcholine. Excesses and deficiencies in levels of these neurotransmitters have been associated with depression, anxiety, and schizophrenia, but scientists have yet to determine the exact mechanisms involved.
 Research shows that the more genetically related a person is to someone with schizophrenia, the greater the risk that person has of developing the illness. For example, children of one parent with schizophrenia have a 13 percent chance of developing the illness, whereas children of two parents with schizophrenia have a 46 percent chance of developing the disorder.
 Advances in brain imaging techniques, such as magnetic resonance imaging (MRI) and positron emission tomography (PET), have enabled scientists to study the role of brain structure in mental illness. Some studies have revealed structural brain abnormalities in certain mental illnesses. For example, some people with schizophrenia have enlarged brain ventricles (cavities in the brain that contain cerebrospinal fluid). However, this may be a result of schizophrenia rather than a cause, and not all people with schizophrenia show this abnormality.
 A variety of medical conditions can cause mental illness. Brain damage and strokes can cause loss of memory, impaired concentration and speech, and unusual changes in behavior. In addition, brain tumors, if left to grow, can cause psychosis and personality changes. Other possible biological factors in mental illness include an imbalance of hormones, deficiencies in diet, and infections from viruses.
 The psychodynamic perspective views mental illness as caused by unconscious and unresolved conflicts in the mind. As stated by Freud, these conflicts arise in early childhood and may cause mental illness by impeding the balanced development of the three systems that constitute the human psyche: the id, which comprises innate sexual and aggressive drives; the ego, the conscious portion of the mind that mediates between the unconscious and reality; and the superego, which controls the primitive impulses of the id and represents moral ideals. In this view, generalized anxiety disorder stems from a signal of unconscious danger whose source can only be identified through a thorough analysis of the person’s personality and life experiences. Modern psychodynamic theorists tend to emphasize sexuality less than Freud did and focus more on problems in the individual’s relationships with others.
 Both the humanistic and existential perspectives view abnormal behavior as resulting from a person’s failure to find meaning in life and fulfill his or her potential. The humanistic school of psychology, as represented in the work of American psychologist Carl Rogers, views mental health and personal growth as the natural conditions of human life. In Rogers’s view, every person possesses a drive toward self-actualization, the fulfillment of one’s greatest potential. Mental illness develops when circumstances in a person’s environment block this drive. The existential perspective sees emotional disturbances as the result of a person’s failure to act authentically—that is, to behave in accordance with one’s own goals and values, rather than the goals and values of others.
 The pioneers of behaviorism, American psychologists John B. Watson and B. F. Skinner, maintained that psychology should confine itself to the study of observable behavior, rather than explore a person’s unconscious feelings. The behavioral perspective explains mental illness, as well as all of human behavior, as a learned response to stimuli. In this view, rewards and punishments in a person’s environment shape that person’s behavior. For example, a person involved in a serious car accident may develop a phobia of cars or generalize the fear to all forms of transportation.
 The cognitive perspective holds that mental illness results from problems in cognition— - that is, problems in how a person reasons, perceives events, and solves problems. American psychiatrist Aaron Beck proposed that some mental illnesses—such as depression, anxiety disorders, and personality disorders—result from a way of thinking learned in childhood that is not consistent with reality. For example, people with depression tend to see themselves in a negative light, exaggerate the importance of minor flaws or failures, and misinterpret the behavior of others in negative ways. It remains unclear, however, whether these kinds of cognitive problems actually cause mental illness or merely represent symptoms of the illnesses themselves.
 the sociocultural perspective regards mental illness as the result of social, economic, and cultural factors. Evidence for this view comes from research that has demonstrated an increased risk of mental illness among people living in poverty. In addition, the incidence of mental illness rises in times of high unemployment. The shift in the world population from rural areas to cities—with their crowding, noise, pollution, decay, and social isolation—has also been implicated in causing relatively high rates of mental illness. Furthermore, rapid social change, which has particularly affected indigenous peoples throughout the world, brings about high rates of suicide and alcoholism. Refugees and victims of social disasters—warfare, displacement, genocide, violence—have a higher risk of mental illness, especially depression, anxiety, and post-traumatic stress disorder.
 Social scientists emphasize that the link between social ills and mental illness is correlational rather than causal. For example, although societies undergoing rapid social change often have high rates of suicide the specific causes have not been identified. Social and cultural factors may create relative risks for a population or class of people, but it is unclear how such factors raise the risk of mental illness for an individual.
 psychiatrist Nancy C. Andreasen, chair of psychiatry at the University of Iowa College of Medicine in Iowa City and the author of The Broken Brain: The Biological Revolution in Psychiatry (1984), holds a National Medal of Science for her work on mental disorders. In this question-and-answer format, Andreasen touches on a variety of issues involving mental disorders. Is schizophrenia hereditary? How can you distinguish between a child with attention-deficit hyperactivity disorder (ADHD) and a child who is simply more active than other children? Is mental decline inevitable with aging? Is medication available to treat obsessive-compulsive disorders? Andreasen discusses these and many other questions.
 There are no blood tests, imaging techniques, or other laboratory procedures that can reliably diagnose a mental illness. Thus, the diagnosis of mental illness is always a judgment or an interpretation by an observer based on the speech, ideas, behaviors, and experiences of the patient.
 For the most part, mental health professionals determine the presence of mental illness in an individual by conducting an interview intended to reveal symptoms of abnormal behavior. That is, the professional asks the patient questions about his or her mental state: 'Do you hear voices of people who are not with you?' 'Have you felt depressed or lost interest in most activities?' 'Have you experienced a marked increase or decrease in your appetite?' 'Have you been sleeping less than normal?' 'Are you easily distracted?' The answers to these questions will suggest other questions. Eventually, the clinician will feel that he or she has enough information to determine whether the patient is suffering from a mental illness and, if so, to make a diagnosis.
 The process of diagnosis is not as simple as it might seem. Patients often have difficulty remembering symptoms or feel reluctant to talk about their fantasies, sex life, or use of drugs and alcohol. Many patients suffer from more than one disorder at a time—for example, depression and anxiety, or schizophrenia and depression—and determining which symptoms constitute the primary problem is complex. In addition, symptoms may not be specific to mental illnesses. For example, brain tumors, malaria, and infections of the central nervous system can produce symptoms that mimic those of psychotic disorders.
 Another problem in diagnosis is that mental health professionals may interpret symptoms differently based on their personal or cultural biases. One study examined this effect by showing 300 American and British psychiatrists videotaped interviews of eight patients with mental illnesses. Although the psychiatrists’ diagnoses substantially agreed for patients with 'textbook' cases of schizophrenia, their diagnoses varied widely for patients who had symptoms of both schizophrenia and other disorders, depending on whether the psychiatrist was American or British. The risk of misdiagnosis is even greater when the mental health professional and the patient come from different cultural groups.
 Mental health professionals use a number of methods to treat people with mental illnesses. The two most common treatments by far are drug therapy and psychotherapy. In drug therapy, a person takes regular doses of a prescription medication intended to reduce symptoms of mental illness. Psychotherapy is the treatment of mental illness through verbal and nonverbal communication between the patient and a trained professional. A person can receive psychotherapy individually or in a group setting.
 The type of treatment administered depends on the type and severity of the disorder. For example, doctors usually treat schizophrenia primarily with drugs, but specialized forms of psychotherapy may more effectively relieve phobias. For some mental illnesses, such as depression, the most effective treatment seems to be a combination of drug therapy and psychotherapy. Although some people with severe mental illnesses may never fully recover, most people with mental illnesses improve with treatment and can resume normal lives. Despite the availability of effective treatments, only about 40 percent of people with mental illnesses ever seek professional help.
 A variety of mental health professionals offer treatment for mental illness. These include psychiatrists, psychologists, psychotherapists, psychiatric social workers, and psychiatric nurses.
 Drugs introduced in the mid-1950's enabled many people who otherwise would have spent years in mental institutions to return to the community and live productive lives. Since then, advances in psychopharmacology have led to the development of drugs of even greater effectiveness. These drugs often relieve symptoms of schizophrenia, depression, anxiety, and other disorders. However, they may produce undesirable and sometimes serious side effects. In addition, relapse may occur when they are discontinued, so long-term use may be required. Drugs that control symptoms of mental illness are called psychotherapeutic drugs. The major categories of psychotherapeutic drugs include antipsychotic drugs, antianxiety drugs, antidepressant drugs, and antimanic drugs.
 Antipsychotic drugs, also called neuroleptics and major tranquilizers, control symptoms of psychosis, such as hallucinations and delusions, which characterize schizophrenia and related disorders. They can also prevent such symptoms from returning. Antipsychotic drugs may produce side effects ranging from dry mouth and blurred vision to tardive dyskinesia, a permanent condition that produces involuntary movements of the lips, mouth, and tongue.
 Antianxiety drugs, also called minor tranquilizers, reduce high levels of anxiety. They may help people with generalized anxiety disorder, panic disorder, and other anxiety disorders. Benzodiazepines, a class of drugs that includes diazepam (Valium), are the most widely prescribed antianxiety drugs. Benzodiazepines can be addictive and may cause drowsiness and impaired coordination during the day.
 Antidepressant drugs help relieve symptoms of depression. Some antidepressant drugs can relieve symptoms of other disorders as well, such as panic disorder and obsessive-compulsive disorder. Antidepressant drugs comprise three major classes: tricyclics, monoamine oxidase inhibitors (MAO inhibitors), and selective serotonin reuptake inhibitors (SSRIs). Side effects of tricyclics may include dizziness upon standing, blurred vision, dry mouth, difficulty urinating, constipation, and drowsiness. People who take MAO inhibitors may experience some of the same side effects, and must follow a special diet that excludes certain foods. SSRIs generally produce fewer side effects, although these may include anxiety, drowsiness, and sexual dysfunction. One type of SSRI, fluoxetine (Prozac), is the most widely prescribed antidepressant drug.
 Antimanic drugs help control the mania that occurs as part of bipolar disorder. One of the most effective antimanic drugs is lithium carbonate, a natural mineral salt (see Lithium). Common side effects include nausea, stomach upset, vertigo, and increased thirst and urination. In addition, long-term use of lithium can damage the kidneys.
 Psychotherapy can be an effective treatment for many mental illnesses. Unlike drug therapy, psychotherapy produces no physical side effects, although it can cause psychological damage when improperly administered. On the other hand, psychotherapy may take longer than drugs to produce benefits. In addition, sessions may be expensive and time-consuming. In response to this complaint and demands from insurance companies to reduce the costs of mental health treatment, many therapists have started providing therapy of shorter duration.
 Psychotherapy encompasses a wide range of techniques and practices. Some forms of psychotherapy, such as psychodynamic therapy and humanistic therapy, focus on helping people understand the internal motivations for their problematic behavior. Other forms of therapy, such as behavioral therapy and cognitive therapy, focus on the behavior itself and teach people skills to correct it. The majority of therapists today incorporate treatment techniques from a number of theoretical perspectives. For example, cognitive-behavioral therapy combines aspects of cognitive therapy and behavioral therapy.
 Psychodynamic therapy is one of the most common forms of psychotherapy. The therapist focuses on a person’s past experiences as a source of internal, unconscious conflicts and tries to help the person resolve those conflicts. Some therapists may use hypnosis to uncover repressed memories. Psychoanalysis, a technique developed by Freud, is one kind of psychodynamic therapy. In psychoanalysis, the person lies on a couch and says whatever comes to mind, a process called free association. The therapist interprets these thoughts along with the person’s dreams and memories. Classical psychoanalysis, which requires years of intensive treatment, is not as widely practiced today as in previous years.
 Psychotherapists who practice behavioral therapy do not focus on a person’s past experiences or inner life. Instead, they help the person to change patterns of abnormal behavior by applying established principles of conditioning and learning. Behavioral therapy has proven effective in the treatment of phobias, obsessive-compulsive disorder, and other disorders. See Behavior Modification.
 The goal of cognitive therapy is to identify patterns of irrational thinking that cause a person to behave abnormally. The therapist teaches skills that enable the person to recognize the irrationality of the thoughts. The person eventually learns to perceive people, situations, and himself or herself in a more realistic way and develops improved problem-solving and coping skills. Psychotherapists use cognitive therapy to treat depression, panic disorder, and some personality disorders.
 Rehabilitation programs assist people with severe mental illnesses in learning independent living skills and in obtaining community services. Counselors may teach them personal hygiene skills, home cleaning and maintenance, meal preparation, social skills, and employment skills. In addition, case managers or social workers may help people with mental illnesses obtain employment, medical care, housing, education, and social services. Some intensive rehabilitation programs strive to provide active follow-up and social support to prevent hospitalization.
 Therapists often use play therapy to treat young children with depression, anxiety disorders, and problems stemming from child abuse and neglect. The therapist spends time with the child in a playroom filled with dolls, puppets, and drawing materials, which the child may use to act out personal and family conflicts. The therapist helps the child recognize and confront his or her feelings.
 In group therapy, a number of people gather together to discuss problems under the guidance of a therapist. By sharing their feelings and experiences with others, group members learn their problems are not unique, receive emotional support, and learn ways to cope with their problems. Psychodrama is a type of group therapy in which participants act out emotional conflicts, often on a stage, with the goals of increasing their understanding of their behaviors and resolving conflicts. Group therapy generally costs less per person than individual psychotherapy.
 Family intervention programs help families learn to cope with and manage a family member’s chronic mental illness, such as schizophrenia. Family members learn to monitor the illness, help with daily life problems, ensure adherence to medication, and cope with stigma.
 Electroconvulsive therapy (ECT) is a treatment for severe depression in which an electrical current is passed through the patient’s brain for one or two seconds to induce a controlled seizure. The treatments are repeated over a period of several weeks. For unknown reasons, ECT often relieves severe depression even when drug therapy and psychotherapy have failed. The treatment has created controversy because its side effects may include confusion and memory loss. Both of these effects, however, are usually temporary.
 Seeking a treatment for extreme cases of mental illness, Portuguese neurologist António Egas Moniz invented the lobotomy, a surgical technique that destroys tissue in the frontal lobe of the brain. The procedure, widely performed in the 1940's and 1950's, often left people in a vegetative state or caused drastic changes in personality and behavior.
 Even more controversial than ECT is psychosurgery, the surgical removal or destruction of sections of the brain in order to reduce severe and chronic psychiatric symptoms. The best known example of psychosurgery is the lobotomy, a procedure developed by Portuguese neurologist António Egas Moniz that was widely performed in the 1940s and early 1950s. Psychosurgery is now rarely performed because no research has proven it effective and because it can produce drastic changes in personality and behavior.
 A significant portion of the homeless population in the United States suffers from a chronic mental illness, such as schizophrenia. The shortage of mental health treatment centers in many cities may partly account for the large number of mentally ill people who are homeless or in jail.
 Treatment for mental illness takes places in a number of settings. Mental hospitals or psychiatric wards in general hospitals are used to treat patients in acute phases of their illnesses and when the severity of their symptoms requires constant supervision. Most individuals who suffer from severe mental illness, however, do not require such close attention, and they can usually receive treatment in community settings.
 Often, patients who have just completed a period of hospitalization go to group homes or halfway houses before returning to independent living. These facilities offer patients the opportunity to take part in group activities and to receive training in social and job skills. In supportive housing, mentally ill individuals can live independently in an environment that offers an array of mental health and social services. Some people with chronic and severe mental illnesses require care in long-term facilities, such as nursing homes, where they can receive close supervision.
 Unfortunately, many areas have a shortage of treatment centers, especially community mental health centers and supportive housing environments. This shortage may partly account for the large number of mentally ill people who are homeless or in jail.
 Most non-Western countries still lack adequate treatment facilities and services for the mentally ill. In China, with its 1.2 billion people, there are 4.5 million patients with schizophrenia, but only about 100,000 beds for the mentally ill and fewer than 10,000 psychiatrists. On the other hand, there are hundreds of thousands of traditional healers, many of whom treat mentally ill patients. Other people with mental illnesses receive treatment from general physicians. In most countries of sub-Saharan Africa, psychiatric services are so limited that most people with mental illnesses receive little if any professional care. Some developing countries, however, have begun substantial reform and expansion of mental health services.
 Evidence for trepanning, the surgical procedure of cutting a hole in the skull, dates back 4,000 to 5,000 years. Some anthropologists speculate that Stone Age societies performed trepanning on people with mental illnesses to release evil spirits or demons from their heads. In the absence of written records, however, it is impossible to know why the operation was performed.
 The Greek physician Hippocrates was one of the first scholars to challenge the notion that disease was punishment sent from the gods. He believed that all illnesses, including mental illnesses, had natural origins.
 The literature of ancient Greece and Rome contains evidence of the belief that spirits or demons cause mental illness. In the 5th century bc the Greek historian Herodotus wrote an account of a king who was driven mad by evil spirits. The legend of Hercules describes how, driven insane by a curse, he killed his own children. The Roman poets Virgil and Ovid repeated these themes in their works. The early Babylonian, Chinese, and Egyptian civilizations also viewed mental illness as possession, and used exorcism—which sometimes involved beatings, restraint, and starvation—to drive the evil spirits from their victim.
 Not all ancient scholars agreed with this theory of mental illness. The Greek physician Hippocrates believed that all illnesses, including mental illnesses, had natural origins. For example, he rejected the prevailing notion that epilepsy had its origins in the divine or sacred, viewing it as a disease of the brain. Hippocrates classified mental illnesses into categories that included mania, melancholia (depression), and phrenitis (brain fever), and he advocated humane treatment that included rest, bathing, exercise, and dieting. The Greek philosopher Plato, although adhering to a somewhat supernatural view of mental illness, believed that childhood experiences shaped adult behaviors, anticipating modern psychodynamic theories by more than 2000 years.
 The Middle Ages in Europe, from the fall of the Roman empire in the 5th century ad to about the 15th century, was a period in which religious beliefs, specifically Christianity, dominated concepts of mental illness. Much of society believed that mentally ill people were possessed by the devil or demons, or accused them of being witches and infecting others with madness (see Witchcraft). Thus, instead of receiving care from physicians, the mentally ill became objects of religious inquisition and barbaric treatment. On the other hand, some historians of medicine cite evidence that even in the Middle Ages, many people believed mental illness to have its basis in physical and psychological disturbances, such as imbalances in the four bodily humors (blood, black bile, yellow bile, and phlegm), poor diet, and grief.
 The Islamic world of North Africa, Spain, and the Middle East generally held far more humane attitudes toward people with mental illnesses. Following the belief that God loved insane people, communities began establishing asylums beginning in the 8th century ad, first in Baghdād and later in Cairo, Damascus, and Fez. The asylums offered patients special diets, baths, drugs, music, and pleasant surroundings.
 The Renaissance, which began in Italy in the 14th century and spread throughout Europe in the 16th and 17th centuries, brought both deterioration and progress in perceptions of mental illness. On the one hand, witch-hunts and executions escalated throughout Europe, and the mentally ill were among those persecuted. The infamous Malleus Maleficarum,which served as a handbook for inquisitors, claimed that witches could be identified by delusions, hallucinations, or other peculiar behavior. To make matters worse, many of the most eminent physicians of the time fervently advocated these beliefs.
 On the other hand, some scholars vigorously protested these supernatural views and called renewed attention to more rational explanations of behavior. In the early 16th century, for example, the Swiss physician Paracelsus returned to the views of Hippocrates, asserting that mental illnesses were due to natural causes. Later in the century, German physician Johann Weyer argued that witches were actually mentally disturbed people in need of humane medical treatment.
 French physician Philippe Pinel supervises the unchaining of mentally ill patients in 1794 at La Salpêtrière, a large hospital in Paris. Pinel believed in treating mentally ill people with compassion and patience, rather than with cruelty and violence. This painting, Pinel Frees the Insane from Their Chains, was completed by French artist Tony Robert-Fleury in 1876.
 During the Age of Enlightenment, in the 18th and early 19th centuries, people with mental illnesses continued to suffer from poor treatment. For the most part, they were left to wander the countryside or committed to institutions. In either case, conditions were generally wretched. One mental hospital, the Hospital of Saint Mary of Bethlehem in London, England, became notorious for its noisy, chaotic conditions and cruel treatment of patients.\
 The Hospital of Saint Mary of Bethlehem, a London mental hospital commonly known as Bedlam, sold admission tickets to the public in the 18th century, becoming a popular tourist attraction. In this engraving by English artist William Hogarth, part of his series A Rake’s Progress (1735), two women (seen in the background) tour the hospital, watching the mentally ill patients for their amusement. The hospital became notorious for its miserable conditions and cruel treatment of patients.
 Yet as the public’s awareness of such conditions grew, improvements in care and treatment began to appear. In 1789 Vincenzo Chiarugi, superintendent of a mental hospital in Florence, Italy, introduced hospital regulations that provided patients with high standards of hygiene, recreation and work opportunities, and minimal restraint. At nearly the same time, Jean-Baptiste Pussin, superintendent of a ward for 'incurable' mental patients at La Bicêtre hospital in Paris, France, forbade staff to beat patients and released patients from shackles. Philippe Pinel continued these reforms upon becoming chief physician of La Bicêtre’s ward for the mentally ill in 1793. Pinel began to keep case histories of patients and developed the concept of 'moral treatment,' which involved treating patients with kindness and sensitivity, and without cruelty or violence. In 1796 a Quaker named William Tuke established the York Retreat in rural England, which became a model of compassionate care. The retreat enabled people with mental illnesses to rest peacefully, talk about their problems, and work. Eventually these humane techniques became widespread in Europe.
 In 1908, after his release from a mental asylum, Clifford Whittingham Beers wrote A Mind That Found Itself, which exposed the poor conditions he had suffered while confined. He went on to establish several organizations dedicated to the promotion of mental health reforms in the United States.
 People living in the colonies of North America in the 17th and 18th centuries generally explained bizarre or deviant behavior as God’s will or the work of the devil. Some people with mental illnesses received care from their families, but most were jailed or confined in almshouses with the poor and infirm. By the mid-18th century, however, American physicians came to view mental illnesses as diseases of the brain, and advocated specialized facilities to treat the mentally ill. The Pennsylvania Hospital in Philadelphia, which opened in 1752, became the first hospital in the American colonies to admit people with mental illnesses, housing them in a separate ward. However, in the hospital’s early years, mentally ill patients were chained to the walls of dark, cold cells.
 After suffering a mental breakdown in 1900, Clifford Beers, an aspiring American businessman, spent the next three years in treatment at various mental hospitals. Upon his recovery, Beers wrote A Mind That Found Itself (1908), which chronicled the hardships he endured and revealed the callousness of many hospital attendants to the suffering of patients. The book aroused public concern about the care of people with mental illnesses and launched a worldwide movement for mental health. In the following excerpt, Beers describes his experiences in the violent ward of a state hospital. The passage also reveals the delusions brought about by his state of 'elation,' or mania.
 In the 1780's American physician Benjamin Rush instituted changes at the Pennsylvania Hospital that greatly improved conditions for mentally ill patients. Although he endorsed the continued use of restraints, punishment, and bleeding, he also arranged for heat and better ventilation in the wards, separation of violent patients from other patients, and programs that offered work, exercise, and recreation to patients. Between 1817 and 1828, following the examples of Tuke and Pinel, a number of institutions opened that devoted themselves exclusively to the care of mentally ill people. The first private mental hospital in the United States was the Asylum for the Relief of Persons Deprived of the Use of Their Reason (now Friends Hospital), opened by Quakers in 1817 in what is now Philadelphia. Other privately established institutions soon followed, and state-sponsored hospitals—in Kentucky, New York, Virginia, and South Carolina - opened beginning in 1824.
 American reformer Dorothea Dix championed the causes of prison inmates, the mentally ill, and the destitute. Horrified by the conditions provided for the mentally ill in Massachusetts, Dix successfully petitioned the state government for improvements in 1843. She was directly responsible for building or enlarging 32 mental hospitals in North America, Europe, and Japan.
 Nevertheless, circumstances for most mentally ill people in the United States, especially those who were poor, remained dreadful. In 1841 Dorothea Dix, a Boston schoolteacher, began a campaign to make the public aware of the plight of mentally ill people. By 1880, as a direct result of her efforts, 32 psychiatric hospitals for the poor had opened. Increasingly, society viewed psychiatric institutions as the most appropriate form of care for people with mental illnesses. However, by the late 19th century, conditions in these institutions had deteriorated. Overcrowded and understaffed, psychiatric hospitals had shifted their treatment approach from moral therapy to warehousing and punishment. In 1908 Clifford Whittingham Beers aroused new concern for mentally ill individuals with the publication of A Mind That Found Itself, an account of his experiences as a mental patient. In 1909 Beers founded the National Committee for Mental Hygiene, which worked to prevent mental illness and ensure humane treatment of the mentally ill.
 Following World War II (1939-1945), a movement emerged in the United States to reform the system of psychiatric hospitals, in which hundreds of thousands of mentally ill persons lived in isolation for years or decades. Many mental health professionals—seeing that large state institutions caused as much, if not more, harm to patients than mental illnesses themselves - came to believe that only patients with severe symptoms should be hospitalized. In addition, the development in the 1950's of antipsychotic drugs, which helped to control bizarre and violent behavior, allowed more patients to be treated in the community. In combination, these factors led to the deinstitutionalization movement: the release, over the next four decades, of hundreds of thousands of patients from state mental hospitals. In 1950, 513,000 patients resided in these institutions. By 1965 there were 475,000, and by 1990 state mental hospitals housed only 92,000 patients on any given night. Many patients who were released returned to their families, although many were transferred to questionable conditions in nursing homes or board-and-care homes. Many patients had no place to go and began to live on the streets.
 The National Mental Health Act of 1946 created the National Institute of Mental Health as a center for research and funding of research on mental illness. In 1955 Congress created a commission to investigate the state of mental health care, treatment, and prevention. In 1963, as a result of the commission’s findings, Congress passed the Community Mental Health Centers Act, which authorized the construction of community mental health centers throughout the country. Implementation of these centers was not as extensive as originally planned, and many people with severe mental illnesses failed to receive care of any kind.
 One of the most important developments in the field of mental health in the United States has been the establishment of advocacy and support groups. The National Alliance for the Mentally Ill (NAMI), one of the most influential of these groups, was founded in 1972. NAMI’s goal is to improve the lives of people with severe mental illnesses and their families by eliminating discrimination in housing and employment and by improving access to essential treatments and programs.
 During the 1980s, all levels of government in the United States cut back on funding for social services. For example, the Social Security Administration discontinued benefits for approximately 300,000 people between 1981 and 1983. Of these, an estimated 100,000 were people with mental illnesses. Although the government eventually restored Social Security benefits to many of these people, the interruption of services caused widespread hardship.
 The emergence of managed care in the 1990s as a way to contain health care costs had a tremendous impact on mental health care in the United States. Health insurance companies and health maintenance organizations increasingly scrutinized the effectiveness of various psychotherapies and drug treatments and put stricter limits on mental health care. In response to these restrictions, Congress passed the Mental Health Parity Act of 1996. This law required private medical plans that offer mental health coverage to set equal yearly and lifetime payment limits for coverage of both mental and physical illnesses.
 In 1997 the US. Equal Employment Opportunity Commission issued new guidelines intended to prevent discrimination against people with mental illnesses in the workplace. The rules, based on the Americans with Disabilities Act of 1990, prohibit employers from asking job applicants if they have a history of mental illness and require employers to provide reasonable accommodations to workers with mental illnesses.
 In recent years international agencies, led by the World Health Organization (WHO) of the United Nations (UN) have developed mental health policies that seek to reduce the huge burden of mental illness worldwide. These agencies are working to improve the quality of mental health services in Africa, Asia, Latin America, the Middle East, and elsewhere by educating governments on prevention and treatment of mental illness and on the rights of the mentally ill.
 Psychiatry is a branch of medicine specializing in mental illnesses. Psychiatrists not only diagnose and treat these disorders but also conduct research directed at understanding and preventing them.
 Pychiatrist is a doctor of medicine who has had four years of postgraduate training in psychiatry. Many psychiatrists take further training in psychoanalysis, child psychiatry, or other subspecialties. Psychiatrists treat patients in private practice, in general hospitals, or in specialized facilities for the mentally ill (psychiatric hospitals, outpatient clinics, or community mental health centers). Some spend part or all of their time doing research or administering mental health programs. By contrast, psychologists, who often work closely with psychiatrists and treat many of the same kinds of patients, are not trained in medicine; consequently, they neither diagnose physical illness nor administer drugs.
 The province of psychiatry is unusually broad for a medical specialty. Mental disorders may affect most aspects of a patient's life, including physical functioning, behavior, emotions, thought, perception, interpersonal relationships, sexuality, work, and play. These disorders are caused by a poorly understood combination of biological, psychological, and social determinants. Psychiatry's task is to account for the diverse sources and manifestations of mental illness.
 Physicians in the Western world began specializing in the treatment of the mentally ill in the 19th century. Known as alienists, psychiatrists of that era worked in large asylums, practicing what was then called moral treatment, a humane approach aimed at quieting mental turmoil and restoring reason. During the second half of the century, psychiatrists abandoned this mode of treatment and, with it, the tacit recognition that mental illness is caused by both psychological and social influences. For a while, their attention focused almost exclusively on biological factors. Drugs and other forms of somatic (physical) treatment were common. The German psychiatrist Emil Kraepelin identified and classified mental disorders into a system that is the foundation for modern diagnostic practices. Another important figure was the Swiss psychiatrist Eugen Bleuler, who coined the word schizophrenia and described its characteristics.
 The discovery of unconscious sources of behavior—an insight dominated by the psychoanalytic writings of Sigmund Freud in the early 20th century—enriched psychiatric thought and changed the direction of its practice (see Psychoanalysis). Attention shifted to processes within the individual psyche, and psychoanalysis came to be regarded as the preferred mode of treatment for most mental disorders. In the 1940s and 1950s emphasis shifted again: this time to the social and physical environment. Many psychiatrists had all but ignored biological influences, but others were studying those involved in mental illness and were using somatic forms of treatment such as electroconvulsive therapy (electric shock) and psychosurgery.
 Dramatic changes in the treatment of the mentally ill in the United States began in the mid-1950s with the introduction of the first effective drugs for treating psychotic symptoms. Along with drug treatment, new, more liberal and humane policies and treatment strategies were introduced into mental hospitals. More and more patients were treated in community settings in the 1960s and 1970s. Support for mental health research led to significant new discoveries, especially in the understanding of genetic and biochemical determinants in mental illness and the functioning of the brain. Thus, by the 1980s, psychiatry had once again shifted in emphasis to the biological, to the relative neglect of psychosocial influences in mental health and illness. See Psychotherapy.
 Psychiatrists use a variety of methods to detect specific disorders in their patients. The most fundamental is the psychiatric interview, during which the patient's psychiatric history is taken and mental status is evaluated. The psychiatric history is a picture of the patient's personality characteristics, relationships with others, and past and present experience with psychiatric problems - all told in the patient's words (sometimes supplemented by comments from other family members). Psychiatrists use mental-status examinations much as internists use physical examinations. They elicit and classify aspects of the patient's mental functioning.
 Some diagnostic methods rely on testing by other specialists. Psychologists administer intelligence and personality tests, as well as tests designed to detect damage to the brain or other parts of the central nervous system. Neurologists also test psychiatric patients for evidence of impairment of the nervous system. Other physicians sometimes examine patients who complain of physical symptoms. Psychiatric social workers explore family and community problems. The psychiatrist integrates all this information in making a diagnosis according to criteria established by the psychiatric profession.
 Psychiatric treatments fall into two classes: organic and nonorganic forms. Organic treatments, such as drugs, are those that affect the body directly. Nonorganic types of treatment improve the patient's functioning by psychological means, such as psychotherapy, or by altering the social environment.
 Psychotropic drugs (see Psychoactive Drugs) are by far the most commonly used organic treatment. The first to be discovered were the antipsychotics, used primarily to treat schizophrenia. The phenothiazines are the most frequently prescribed class of antipsychotic drugs. Others are the thioxanthenes, butyrophenones, and indoles. All antipsychotic drugs diminish such symptoms as delusions, hallucinations, and thought disorder. Because they can reduce agitation, they are sometimes used to control manic excitement in manic-depressive patients and to calm geriatric patients. Some childhood behavior disorders respond to these drugs.
 Despite their value, the antipsychotic drugs have drawbacks. The most serious is the neurological condition tardive dyskinesia, which occurs in patients who have taken the drugs over extended periods. The condition is characterized by abnormal movements of the tongue, mouth, and body. It is especially serious because its symptoms do not always disappear when the drug is stopped, and no known treatment for it has been developed.
 Most psychotropic drugs are chemically synthesized. Lithium carbonate, however, is a naturally occurring element used to prevent, or at least reduce, the severity of shifts of mood in manic-depression (see Depression). It is especially effective in controlling mania. Psychiatrists must monitor lithium dosages carefully, because only a small margin exists between an effective dose and a toxic one.
 Three major classes of antidepressant drugs are used. The tricyclic and tetracyclic antidepressants, the most frequently prescribed, are used for the most common form of serious depression. Monoamine oxidase (MAO) inhibitors are used for so-called atypical depressions. Serotonin-selective reuptake inhibitors (SSRIs) are effective against both typical and atypical depressions. Although all three classes are quite effective in relieving depression in correctly matched patients, they also have disadvantages. The tricyclics and tetracyclics can take two to five weeks to become effective and can cause such side effects as oversedation and cardiac problems. MAO inhibitors can cause severe hypertension in patients who ingest certain types of food (such as cheese, beer, and wine) or drugs (such as cold medicines). SSRI drugs, such as fluoxetine (Prozac), take 2 to 12 weeks to become effective and can cause headaches, nausea, insomnia, and nervousness.
 Anxiety, tension (see Stress-Related Disorders), and insomnia are often treated with drugs that are commonly called minor tranquilizers. Barbiturates have been used for the longest time, but they produce more severe side effects and are more often abused than the newer classes of antianxiety drugs. Of the new drugs, the benzodiazepines are the most frequently prescribed, very often in nonpsychiatric settings.
 The stimulant drugs, such as amphetamine—a drug that is often abused—have legitimate uses in psychiatry. They help to control overactivity and lack of concentration in hyperactive children and to stimulate the victims of narcolepsy, a disorder characterized by sudden, uncontrollable episodes of sleep.
 Another organic treatment is electroconvulsive therapy, or ECT, in which seizures similar to those of epilepsy are produced by a current of electricity passed through the forehead. ECT is most commonly used to treat severe depressions that have not responded to drug treatment. It is also sometimes used to treat schizophrenia. Other forms of organic treatment are much less frequently used than drugs and ECT. They include the controversial technique psychosurgery, in which fibers in the brain are severed; this technique is now used very rarely.
 The most common nonorganic treatment is psychotherapy. Most psychotherapies conducted by psychiatrists are psychodynamic in orientation—that is, they focus on internal psychic conflict and its resolution as a means of restoring mental health. The prototypical psychodynamic therapy is psychoanalysis, which is aimed at untangling the sources of unconscious conflict in the past and restructuring the patient's personality. Psychoanalysis is the treatment in which the patient lies on a couch, with the psychoanalyst out of sight, and says whatever comes to mind. The patient relates dreams, fantasies, and memories, along with thoughts and feelings associated with them. The analyst helps the patient interpret these associations and the meaning of the patient's relationship to the analyst. Because it is lengthy and expensive, often several years in duration, classical psychoanalysis is now infrequently used.
 More common are shorter forms of psychotherapy that supplement psychoanalytic principles with other theoretical ideas and scientifically derived information. In these types of therapy, psychiatrists are more likely to give the patient advice and try to influence behavior. Some use techniques derived from behavior therapy, which is based on learning theory (although these methods are more commonly used by psychologists).
 Besides psychotherapy, the other major form of nonorganic treatment used in psychiatry is milieu therapy. Usually carried out in psychiatric wards, milieu therapy directs social relations among patients and staff toward therapeutic ends. Ward activities, too, are planned to serve specific therapeutic goals.
 In general, psychotherapy is relied on more heavily for the treatment of neuroses and other nonpsychotic conditions than it is for psychoses. In psychotic patients, who usually receive psychoactive drugs, psychotherapy is used to improve social and vocational functioning. Milieu therapy is limited to hospitalized patients. Increasingly, psychiatrists use a combination of organic and nonorganic techniques for all patients, depending on their diagnosis and response to treatment.
 Despite radical implications for theory of psychoanalytic techniques and others in a dialectical way, is often without awareness. Where these psychoanalysts disagree in their conceptual frame, create the recognition that analyst and patient cannot simply avoid having an impact on each other. Even so, we cannot be to remove obstructions from whether we have related this to our deliberate technical interventions or intentional aspects drawn upon the conceptual interactions. As for reasons that are useful and necessary to distinguish between theory of techniques, which the interconnectivity established through the conjunctive relationships have in relation of what seemed allowable for us to expand our knowledge of the complex and subtle factors that account for therapeutic action. This, however, can ultimately become the most effective basis for refining and developing our understanding of how best to serve of ourselves to advance the analytic situation and too aculeate more profound and very acute satisfactory depictions in the psychoanalytic engagements, no matter whatever our accountable resultants may be of our theoretical orientation.
 An appreciation of the power of interactive forces in the analytic field not only challenges many traditionally held beliefs about the nature of therapeutic action. However, these take upon the requirement for us to recognize the untenability of the traditional view that analysts can be an objective source in the work. They have better to understand it, for example, where patients and analysts may express as a quantity that which the analyst is of a position to be an objective interpreter of the patient's experiential processes. That in this may reflect a form of collusive enactment and a convergence of the needs of both to see the analyst as an authority, and if the patient and analysts' both submit to needs to believe that the analyst is the omniscient other or the benevolent authority to which one can entrust ones' own. As the functional structure of the relationship might serve to obscure recognition of the fact that it is inclined to encourage the belief that, as once put, that wherever a coordinative system is complicating and hardens of its complexities, as recognized of the mind or brain, immediately 'indeterminacy' so then arises, not necessarily because of some preconditional unobtainability but holds accountably to subjective matters' from which grow stronger in obtaining the right prediction, least of mention, that so many things are yet to be known, in that the stray consequences of studying them will disturb the status quo, and of not-knowing to what influential persuasions do really occur between the protective cranial wall of vertebral anatomy. It is therefore that our manifesting awarenesses cannot accord with the inclining inclinations beheld to what is meant in how. History is not and cannot be determinate. Thus, the supposed causes may only produce the consequences we expect, this has rarely been more true than of those whose thoughts and interaction in psychoanalytic interrelatedness are in a way that no dramatist would ever dare to conceive.
 In Winnicott (1969) has noted that there are times when 'analysers' can serve as holding operations and become interminable without any real growth occurring.
 An interactive perspective also helps to clarify why in some instances the analysers 'abstinence' carriers as much risk of negative iatrogenic consequences as does active intervention. Although silence at time obviously can be respectful and facilitating, at other times it can be cruel and sadistic, or it can be based on fear of engagement, among a host of possible other meanings and equally attributive to the distributional dynamical functions.
 An appreciation of interactive factors also allows us to consider that, to whatever degree the patient's perceptions of the analyst are plausible and even valid (Ferenczi 1933, Little 1951, Levenson 1973, Searles 1975, Gill 1982, Hoffman 1983), this may be due to the patient's expertise of stimulating precisely this kind of responsiveness in the analyst. The reverse is true as well thus, though patient and analyst each will have unique vulnerabilities, sensitivities, strengths, and needs, we must consider why such peculiarities have excited the particular qualities or sensibilities of either patient or analyst at a give moment and not at others. At any moment patient or analyst might be involved in some kind of collusive enactment (Racker 1957, 1959, Grotstein 1981, and McDougall 1979), they have held that their considerations explain of reasons  that posit of themselves of why clinicians often seem to practice in ways that contradict their own shared beliefs and theoretical positions, least of mention, principles by way of enacting to some unfiltered dialectical discourse.
 Yet, these differences, which occur within and between the diverse analytic traditions, in that an interactive view of the analytic field has some theoretical and technical implications that bridge all psychoanalytically perceptively which each among us cannot ignore. Its premise lies in the fact that we recognize that the analyst and patient cannot simply avoid having an impact on each other, even if both are totally silent, require us to realize that even if a treatment is productive or successful, we cannot be clear whether they have related this to our deliberate technical interventions or to aspects of the interaction that have eluded our awareness.
 We have premised its owing intentionality that the recognition that analyst and patient cannot simply avoid having an impact on each other, even if both are totally silent, requires us to realize that even if some treatment is productive or successful, we cannot be clear whether we have related this to our deliberate technical interventions or to aspects of the interaction that have eluded austereness.
 Psychoanalysts of diverse orientations increasingly have come to recognize that patient and analysts are continually influencing and being influenced by each other in a dialectical way, often without awareness. This has radical implications for abstractive views drawn upon psychoanalytic technique. Where these psychoanalysts disagree is in their conceptions of what the specific implications of an interactive view of the analytic field might be.
 It is therefore that distinguishing between theory of technique is useful and necessary, which relates to what we do with awareness and intention, and theory of therapeutic action, which deals with what is healing in the psychoanalytic interaction whether or not it evolves from our ‘technique’: That recognizing this can allow us to expand our knowledge of the complex and subtler factors that account for therapeutic action. This can ultimately become the most effective basis for refining and developing our understanding of how best to use ourselves to advance the analytic work and to simplify more profound and incisive kinds of psychoanalytic engagement, no matter what our theoretical orientation.
 An appreciation of the power of interactive forces in the analytic subject field not only challenges many traditionally held beliefs about the nature of therapeutic action, but also requires us to recognize the untenability of the traditional view that the analyst can be an objective participant in the work? It also helps us to grasp the extent to which presumably therapeutic interpretations, for example, can be ways of harassing, demeaning, patronizing, impinging on, penetrating, or violating the patient, or particular ways of gratifying, supporting, complying, among several of other possibilities. Where patient and analysts assume that the analyst can be an objective interpreter of the patient’s experience, this may factually reflect a form of collusive enactment and a convergence of the needs of both to see the analyst as an authority. If patient and analyst both have needs to believe that the analyst is the omniscient other or the benevolent authority to which one can entrust ones' own, the structure of the relationship might serve to obscure recognition of the fact that they are enacting such a drama. In this regard, Winnicott (1969) has noted that on that point are times when ‘analyses’ can serve as holding operations and become interminable, without any real growth occurring.
 An interactive perspective also helps to clarify why sometimes the analyst’s ‘abstinence’ carries as much risk of negative iatrogenic consequences as does actively intervention. Although silence at times obviously can be respectful and facilitating, at other times it can be cruel and sadistic, or it can be based on fear of engagement, among a host of possible other meanings and contributing functions.
 The contextual meaning of the patient’s free association also has to be reconsidered from such a perspective. Usually viewed as the medium of analytic work, free association may at times be a profound frame of resistance, and to avoid rather than engage in an analytic process. Alternatively it can reflect a form of compliance or collusion, conscious or unconscious, with the analyst’s needs, fears, resistances.
 Amid the welter of competing or complementary theories that have characterized psychoanalyses over the century of its existence, the ideas of transference and the convictions very important in the therapeutic process are an unfiling theme. None of Freud's epochal discoveries - the power to the dynamic unconscious, the meaningfulness of the dream, the uniformity of intrapsychgic conflict - having been more heuristically productive or more clinically valuable than his demonstration that human regularly and inevitably repeat with the analyst and with other important figures in their current live patterned of relationship, of fantasy, and of conflict with the crucial figures in their childhood - primarily their parents?
 Even for Freud, however, the awareness of this phenomenon and the understanding of its specific significance in the analytic situation itself came gradually. In his clinical observations Freud found evidence for the mental mechanisms of repression and resistance. He described repression as a device operating unconsciously to make the memory of painful or threatening events inaccessible to the conscious mind. Resistance is defined as the unconscious defense against awareness of repressed experiences in order to avoid the resulting anxiety. He traced the operation of unconscious processes, using the free associations of the patient to guide him in the interpretation of dreams and slips of speech. Dream analysis led to his discoveries of infantile sexuality and of the so-called Oedipus complex, which constitutes the erotic attachment of the child for the parent of the opposite sex, together with hostile feelings toward the other parent. In these years he also developed the theory of transference, the process by which emotional attitudes, established originally toward parental figures in childhood, are transferred in later life to others. The end of this period was marked by the appearance of Freud’s most important work, The Interpretation of Dreams (1899). Here Freud analyzed many of his own dreams recorded in the 3-year period of his self-analysis, begun in 1897. This work expounds all the fundamental concepts underlying psychoanalytic technique and doctrine. The flamboyant transference events in Breuer's patient Anna O and the unfortunate outcome in the patient of Dora served to consolidate in Freud's mind a view of transference as a resistance phenomenon, as an obstacle to the recollection of traumatic events that, in his view at the time, formed the true essence of the psychoanalytic process. Emphasis in this early period, thus, was on the 'management' of the transference, on finding ways to prevent its interference with the proper business of the analysis - recognizing, always, the inevitability of its occurrence. Freud was most concerned about the interferences generate by the 'negative' (i.e., hostile) and the erotised transference, the 'positive' transference he considered 'unobjectable,' the vehicle of success in the psychoanalysis.
 Freud was also concerned to distinguish the analytic transference from the effects of suggestion in the hypnotic treatment he had learned in France, where he interdependently studying from Professor Charcot at the Salpêtrière hospital, and had been the forerunner of his own psychoanalysis technique. He, and his early followers and students, were at great pains to define the transference as a spontaneous product of the analytic situation, emerging from the patient rather than imposed by the analyst. Ultimately, Freud came to view as essentially for analytic cures the development of a new mental structure, the 'transference neurosis' - re-creation of the original neurosis in the analytic situation itself, with the patient experiencing the analyst as the object of his or her infantile wishes and the focus of his or her pathogenic conflicts. The crucial importance of the transference neurosis - it's very reality as a clinical phenomenon - has been and continues to be a matter of debate among psychoanalysts to this day.
 Over the resulting decades several themes appear and reappear. One to which Freud alluded is that of the uniqueness versus the ubiquity of transference, is it a special creation of the analytic situation or is it an inevitable and universal aspect of all human relation? More central and perhaps more heated in the continuing debate, as the primary of transference interpretation in which Strahey called the 'mutative' effects of analysis - for example, whether such interpretations are simply more convincing than others or are the only kinds that are truly an effective therapy constitutionally begotten. Echoes of this debate have resounded through the years and to be perspectively descendable in most recent literary works. Finally, are all of the patient's reactions to the analyst in the analytic situations to be of counter-transference or do some partake of the 'real' 'non-neurotic' relationship or of the 'working alliance'?
 It is only to mention, at the outset that resistance is, in certain fundamental references, an operational equivalent of defence, its scope is really far larger and more complicated. The thoughts of its nature and motivations on resistances to the psychoanalytic process use an array of mechanisms that sometimes defy classification in the way that fundamental genetically determined defences, derived from importantly and common developmental trends, can be classified. From falling asleep too brilliant argument, there is a limitless and mobile of devices with which the patient may protect the current integrations of his personality, including his system of permanent defences. In fact, Resistances of a surface, conscious type, related to individual character and to educational and cultural background, often present themselves are the patient’s first confrontations with a unique and often puzzling treatment method. While some of these phenomena are continuous with deeper resistances, a closer, and perhaps balancing equilibrium held in bondage to the mutuality within the continuity that we must meet others at their own level. All the same, it now leaves to a greater extent, the much-neglected faculty of informed and reflective common sense, and moves onto the less readily accessible and explicable dynamism, which inevitably supervene in analytic work, even if these initial surface Resistances have been largely or wholly mastered. Its submissive providences lay order to perfect connectivity, premising with which is the specific influence of the immediate cultural climate, stressed of the general attitude of many young people (Anna Freud 1968) toward the psychoanalytic process and its goals.
 When Freud gave up the use of hypnosis for several reasons, beginning with the personal difficulty in inducing the hypnotic state and culminating in his ultimate and adequate reason - that it bypassed the essential lever of lasting therapeutic change, the confrontation with the repressing forces themselves - he turned to the method of waking discourse with the patient, in which insistence, with a sense of infallibility, accompanied by head pressure and release, were the essential tools for the overcoming of resistance (Breuer and Freud 1893-1895). Although the affording the unformidable combinations that are awaiting the presence to the future attributions in which the valuing qualities that allow us the privilege to have observed various forms of resistance ( in a general sense) before, as for example, inability to be hypnotized, as far as possible in totality and a willful rejection of hypnosis, selective refusal to discuss certain topics under hypnosis, adverse reactions to testing for stances, it was the effectiveness of insistence in inducing the patient to fill memory gaps or to accept the physician’s constructions that reapproached of extending its lead, in that Freud was to a first and enduring formulation: Since effort
- psychic work - by the physician was required, a physical; evidently force, a resistance opposed to the pathogenic ideas, becomingly conscious (or being remembered), had to be overcome. They thought this to be the same psychic force that had initiated the symptom formation by preventing the original pathogenic ideas from achieving adequate affective discharge and establishing adequate associations - in short, from remaining or becomingly conscious. The motive for invoking such a force would be the abolition (or avoidance) of some form of physical distress or pain, such as shame, self-reproach, fear of harm, or equivalent cause for rejecting or wishing to forget the experience. Such are the appreciative attributions, in that the distributive contributional dynamic functions bestow the factoring understructure of the constellation of ideas, have already comforted us, yet, the later is clearly the ego and especially the character of it. It was thought important to show the patient that his resistance was the same as the original ‘repulsion’ which had initiated pathogenesis. The step later was short to the essential equivalent and permanent concept of defence at first repression. That is, though Freud gave tremendous sight to the effectiveness of the hand pressure manoeuver, he saw it essentially for distancing the patient’s will and conscious attention and thus simplifying the emergence of latent ideas (or images). From a present-day point of view, one cannot but think of the powerful transference excited by an infallible parental figure in a procedure only one step removed from the relative abdication of will. Consciousnessly involved in hypnosis, and that this quasi-archaic qualitative pattern of relationship was more important to effectiveness or failure than was the exchange of a psychic energy postulate by Freud. In this sense, the ‘laying on of hands’ granted its effect on attention, was probably even more significant in inducing transference regression than in the role that the great discoverer assigned to it.
 What is important, in whatever way, is the establishment of a viable scientific and working idea of resistance to the therapeutic process as a manifestation of a reactivated intrapsychic conflict in a new interpersonal context. This in its essentials persists to this day in psychoanalytic work, in the concept of ego resistances.
 At the same proven capability, as measuring with this development, less explicitly formulated but often described or inferred, was the marginal total rejecting or hostile or unruly attitude of the patient, sometimes evoking spontaneous antagonistic reactions in the physician. In occasional direct references in the early work and in the choice of figurative phraseology for years after that, Freud recognizes this ‘balky child’ type of struggle against the doctor’s efforts. One needs only recall Elizabeth von R., who would tell Freud that she was not better, 'with a sly look of satisfaction' at his discomfiture (Breuer and Freud 1893-1895). When deep hypnosis failed with her, Freud 'was glad enough that once, she refrained from triumphantly protesting ‘I am not asleep, you know, and cannot be hypnotized'; in this context that show with which this categorical type of resistance phenomenon that it represents the evolutionary whisper, though Freud and many others found it to come within the evolving gait of steps in a whisper, after-all, the advance of applied science was bringing to light curious new phenomena that, however hard men might try, would not be fitted into the existing order of things. All this is to encourage along the side of the paradigms of science to agree of it achievable obtainability through with of those has witnessed the impregnable future, least mentions, far and above is the first essentially forced finality to agree that fighting a great adventure in thought at lengths to come safely to shore is necessary, in this glare, the human figure has had to apply formally to be enlarged so that the brave stands which make for civic and academic freedom. It also taken to applicate the form to encourage the belief that, as nicely put, 'all men dance to the tune of an invisible piper. Because, we did not attest the big bang, but call its evolution of a particular type of ego-syntonic struggle with the physician that remains potentially important during any analysis by what the negative transference, whatever its particular nuances of motivation. This is, of course, a manifestly different phenomenon from the earnest effortful struggles of the cooperative patient whose associations fail to attend to him, or who forgets his dream, or who comes at the wrong hour, to his extreme humiliation. Still, in that respect is an important dynamic relationship between the two sets of phenomena.
 Nonetheless, Freud made the analysis of resistance the central obligation of analytic work and proceeded from primitive beginnings, with rapidly increasing sophistication, both technical and psychopathologic, ideas that remain valid to this day; that conscious knowledge transmitted to the patient may have no, or an adverse, effect in the mobilization of what is similar or identical in the unconscious; that the repressing forces, the resistances, are more like infiltrates than discrete foreign-body capsules in their relation to preconscious associative systems; that the physician must begin with the surface and continue centripetally; that hysterical symptoms are more often serial and multiple than mononuclear, and the resistances participate in all productions and must be dealt with at every step of analytic work, and other matters of equal significance (Breuer and Freud 1893-1895).
 Freud always maintained the central concept of resistance, and bequeathed it (reinforced later by the structural theory) to the generations of analysts who have followed him. Still, as the years went on, he elaborated the general scope of resistance far beyond the basic concept of intrapsychic defence, anticathexis that a great variety and range of mechanisms could impede the psychoanalysis as a recognizable process or, beyond this, making it ineffective or reverse expected therapeutic responses, or extend indefinitely the patient’s dependence on the analyst. When extended its direct equation with the anticathexis of defences, the variety of sources - not to speak of manifestations - of resistance multiplied rapidly. To remark upon the merely secondary realizations of illnesses (Freud 1905), under which the ‘external’ resistances are, for example, the hostility of the unmurmuring family line of treatment (Freud 1917), evenhandedly as the  persistence of illness, with its detachment, superciliousness, and mechanical compliance as some weapons system for frustrating the analyst, as with the utterly troubled young girl (Freud 1920). The relevant sense of securing the symptomatic primary modes of perturbation conflict solution, and most crucially, the analysable obtainability of such subtly evolving concept of ‘transference-resistance,’ in its oscillating pluralistic sense, for example, (Breuer and Freud 1893-1895: Freud 1912, 1917). In his last writings, conspicuously in Analysis Terminable and Interminable (1937), in considering several possible factors in human personality that obstruct or render ineffectually the successful end of the analytic procedure, Freud offered a variety of psychodynamic considerations that could be fundamental in the extended or broadened concept of resistance: The question of the constitutional strength of instincts and their relation to ego strength; the problem of the accessibility of latent conflicts when undisturbed by the patient’s life situation (briefly but pointedly) the impingement of the analyst’s personality on the analytic situation and process; the existence of certain qualities of the libidinal cathexes - especially undue adhesiveness or excessive mobility; rigid character structure; the existence of certain sex-linked ‘bedrock’ conflicts that Freud regarded as biologically determined (insoluble penis envy in the female, and the male’s persisting conflict with his passivity). Finally and most formidable, there was the cluster of dynamism and phenomena that Freud, beginning in, Beyond the Pleasure Principle (1920) and The Ego and the Id (1923), attributed consistently and with deepening conviction to the operation of a death instinct. That is to say, to the ‘unconscious sense of guilt’ and demands the need for punishment, the repetition compulsion, the negative therapeutic reaction, and the more general operations of the need to suffer or to die or to seek outer or inner worldly concern. Yet, it remains an inexorable truth that the resistances underlying and hidden of representationally inherent cases or certain limitations implicit like psychoanalytic work, are moderately invincibly formidable, and cannot be disestablished by theoretical position any more than they can be thus created.
 The varied clinical manifestations of resistance are dealt with extensively throughout Freud’s own writings, in many individual papers of other analysts, and in comprehensive works on analytic technique, for example, those of Fenichel (1941), Glover (1955), and more recently Greenson (1967) of which only makes a selective and occasional reference to their kaleidoscopic variety.
 When free association and interpretation displaced hypnosis and derivative primitive techniques, the psychoanalysis as we now construe it came into being. To the extent that free association was the patient’s active participation, it was in this sphere that his ‘resistance’ to the new technique was most clearly recognized as such, cessation, slowing, circumlocution and a lack of informative or relevant content, emotional detachment, and obsessional doubt or circumstantiality became established as obvious impediments to the early (no longer exclusive but still radically important) topographic goals: To convert unconscious ideas largely via the interpretation of preconscious derivatives into conscious ideas. Only with time and increasing sophistication did fluency, even vividness of associative content, tendentious ‘relevancy’ itself evidently can, like over-compliant acceptance of interpretation, conceal and carrying out resistances that were the more formidable because expressed in such ‘good behaviour’.
 One may define resistance (and in so doing include a liberal and augmenting paraphrase of Freud’s own most pithy definition [The Interpretation of Dreams 1900]) as anything of essentially intrapsychic significance in the patient that impedes or interrupts the progress of psychoanalytic work or interferes with its basic purposes and goals. In specifying ‘in the patient’ one is to imply as not underestimate the possibly decisive importance of the analyst’s resistances, to separate the ‘counterresistance’ as a different matter, in a practical sense, requiring separate study. One may concur, that as a generalized infraction forwarded of a direction with Glover’s statement (1955) that 'however we may approach the mental apparatus there is no part of its function that cannot serve the purposes of mental defence and therefore give apparency during the analysis to the phenomena of resistances.' One may also concur with his formulation that the most successful resistances (in contrast with those employing manifest expressions) are silent, but disagree with the paradoxical sequel '. . . they might say that the sign of their existence is our unawareness of them.' For the absence of important material is a given sign, and becoming aware of such an absence is necessary, if possible.
 Freud, in his technical papers and in many other writings, despite his reluctance in this direction did lay down the general and essential technical principles and precepts for analytic practice. We must note, however, that the clear and useful technical precepts are largely in that may be regarded as the ‘tactical sphere’, i.e., they deal with the manifest process phenomena of ego resistances. Other resistances, those largely contained in the ‘silent’ group, for example, detainment or unsuccessful symptomatic alteration, omission of decisive conflict material form free association or [more often] from the transference neurosis, inability to accept cancellation of the analysis, and allied matters. In that saying, the ‘strategic sphere’, relating to the depths of the patient’s psychopathology and personality structure and to his total reactions to the psychoanalytic situation, process, and the person of the analyst. Its use of the tern ‘strategic’ and ‘tactical’ differ from their user by others, for example, Kaiser (1934). While it is not to presume to offer simple precepts for the ready liquidation of the massive silent resistances, heedfully to contribute of something, however slight. To understanding them better and thus, potentially, to their better management but some of these considerations, for example, iatrogenic regression, as to context (1961, 1966). In the ‘strategic’ arena of resistance, so often manifested by total or relative ‘absence’, it is the informed surmise regarding the existence of the silent territory, by way of ongoing reconstructive activity, which is the first and essential ‘activity’ of the analyst. Beyond this mindfulness and subtle potentialities of the shaping and selection of interpretative direction and emphasis and the tactful indication of tendentious distortion or absence.
 Because of a possible variety of factors, beginning with the estranging dissimulations that magnetism that the verbal statement of unconscious content puts into action of the analysts and patients alike (of itself is a frequent resistance or counterresistance) the priority of the analysis of resistance over the analysis of content, as discretely separate, did not readily come to its carry out quality. This might have been owing to the difficulties of dealing with more complicated resistances or developing an adequate methodology in this arena, or even the fact that an extensive interval over its timed and tactful reference to content (or its overall nature) sometimes seems the only way of mobilizing (reflexively) and thus exposing the corresponding resistance for interpretation and ‘working through’, an echo of Freud’s early, never fully relinquished diphasic process (1940).
 Since this is not a technical paper, the admissive structural functionality, over which an extended discussion of the evolution of views on methods of resistance analysis, although substantiated functions has inevitably related such views to our immediate subject matter. Its mindful approaches that range from the strict systematic analysis of character resistances of Wilhelm Reich (1933) or the absolute exclusion of content interpretation of Kaiser (1934), to the special efforts toward dramatization of the transference of Ferenczi and Rank (1925) or Ferenczi’s own experiments with active techniques of deprivation and (on the other hand) the gratification of regressed transference wishes in adults (for example, 1919, 1920, 1930, 1931, 1932). Developments in ego psychology (for example, Anna Freud’s classical contribution on the mechanisms of defence [1936] brought the variety and importance of defence mechanisms securely into the foreground of analytic work, and the subsequential extent of which is widely accepted priority of defence analysis has rectified a great deal of the original [and not entirely inexplicable] ‘cultural cover with lagging’ in this describing importance, that if not exclusive, spheres of resistance analysis. Concomitant with a more widespread functional acceptance of the essentiality and priority (in principle) of resistance analysis over content interpretation, there is usually a more flexible view of the technical application of the essential precepts, permitting interpretive mobility, according to intuitive certainty or judgement between the psychic structures, according to Anna Freud (1936) principle of ‘equidistance’. Discrete specification may sometimes deal resistance with other than those apart from the intrinsic conceptual difficultly in the latter intellectual process, i.e., the specifying of a resistance without suggesting that against which it is directed (Waelder 1960). There is also a general broadening of the scope of interpretive method. Witness, for example, Loewenstein’s ‘reconstruction upward’ (1951) and Stone, having his own differently derived but often an allied conception, the ‘integrative interpretation’ (1951), both of which recognize that resistance may be directed ‘upward’ or against the integration of experience, than against the affirmative extent and exclusively infantile or against the past. Similar considerations are also reflected in Hartmann’s ‘principle of multiple appeal’ (1951).
 It may, nonetheless be of note that while the emphasis on resistance in Freud’s early clinical presentations is overall proportionate to his theoretical statements, his methods of dealing with the concealed and more formidable resistances are not clear, except in certain active interventions, such as the magical intestinal prognosis in the 'Wolf Man' (1918), or the ‘time limit’ in the same case, or the principle that at a certain point patients should confront phobic symptoms directly (1910), or the suggestion to transfer to a woman analyst, with the homosexual woman (1920). In these manoeuvres and attitudes it is recognized that (1) interpretation, the prime working instrument of analysis, may often reach an impasse in relation to powerful ‘strategic’ resistances, and (2) an implicit recognition that elements in the personal relationship of the analytic situation, specifically the transference, may subvert the most skilful analytic work by producing massive although ‘silent’ resistances to ultimate goals, and that sometimes where energetic elements are formidable, they may have to be dealt with directly and holistically, in the patient’s living and actual situation.
 Freud’s own interest in active techniques stimulated Ferenczi to extreme developments in this sphere (1912, 1920), later combined with his oppositely oriented methods of indulgence (1930). As time presses on, noninterpretative methods, particularly those involving gratifications of transference wishes, whether libidinal or masochistic, were set aside with increasing severity, in recognition of their contravention of the indispensability of the undistorted transference and the unique importance of transference analysis in analytic work. The same has been largely true of tendentious, selective instinctual frustrations (Ferenczi 1919, 1020). However, there is no doubt that the use of interpretive alternatives (sometimes suggests for the deliberate control of obstinate resistance phenomena in this spheric arena) has been sharpened by - partially coloured by - the earlier experiments in prohibition, whose transference implications were fully apparent at the time of their introduction. The type of active intervention introduced by Freud (the time limit, the confrontation of symptoms), confined in actuality to the sphere of the demonstrable clinical relationship, has retained a certain optional place in our work, although the potential transference meaning and impact of such interventions, with corresponding variations or limitations of effectiveness, are increasingly understood and considered. The broad general principle of abstinence in the psychoanalytic situation, stated by Freud in its sharpest epitome in 1919, remains a basic and indispensable context of psychoanalytic technique. The nuances of application remain open to, in fact to require, continuing study (Stone 1961, 1966).
 In assent to important developments in ego psychology and characterology (for conspicuous examples, Anna Freud 1936, Kris 1956, Hartmann 1951, Loewenstein 1851, Waelder 1930, the principle factor in deepening, broadening, and complicating the conceptual problem of resistance, and thus modifying the strict latter-like sequential approach (Reich 1933) to the analysis of resistance ad content respectively, even in principle, has been the progressive emergence of transference analysis as the central and decisive task of analytic work. For, to state it over succinctly, and thus to risk some inaccuracy, the transference is far more than the most difficult tool of resistances and (simultaneously) an indispensable element in the therapeutic effort. Given the mature capacity for working alliance, it is the central dynamism of the patient’s participation in the analytic process and, while the proximal or remote source of all significant resistances, but those manifest phenomena originating in the conscious personal or cultural attitudes and experiences of the adult patient or those deriving from the inevitable cohesive-conservative forces in the patient’s personality, for which we must still summon briefly the Goethe-Freud ‘witch’, metapsychology (Freud 1937).
 In relation to the ‘tactical’, i.e., process, resistances, an overall view of what is immediate and confronting for example, the threatening emergence of ego-dystonic sexual or aggressive material, may be adequate. All the same, to any casual access to what may be called the ‘strategic’ sphere of resistance. One must have a tentative working formulation of the total psychic situation in mind, including an informed surmise regarding large and essential unconscious trends. Such suggested procedure is, accessibly open to discussion on more than one scope, and it does involve one immediately in some basic epistemological problems of psychoanalysis. Unfortunately, we cannot become involved in this fascinating sphere of dialectic in this brief essay on a large subject nevertheless, in his early work Freud relied enthusiastically on his own capacity to fill primary gaps in the patient’s memory through informed inherences from the available data, and then, with an aura of infallibility, actively persuaded the patient to accept these constructions. However, with the further elaboration of psychoanalysis as process, in the sense of the increasing importance of free association, of the analyst’s relative passivity, and other characteristics of the process as we now know it, there have inevitably been some important modifications of the attitudes reelected in such procedures. While, as far as it had never been revised or revoked, Freud’s view that the resistances are operatives in every step of the analytic work, and knowing that there exists in many minds paradoxical mystiques to the effect that the patient’s free associations as such, unimpeded (and uninterpreted), could ultimately provide the whole and meaningful story of his neurosis, in the sense of direct information. This is, of course, manifestly at variances with Freud’s basic assumptions about the role of resistance, and the germane roles of defence and conflict in the origin of illness.
 Nonetheless, in Freud’s, Recommendations (1912) is his advice against attempting to reconstruct the essentials of a case while the case is in progress. Such a reconstruction, here assumes, would be undertaken for scientific reasons. The caution, nevertheless, rests on both scientific and therapeutic grounds, on the assumption that the analyst’s receptiveness to new data and his capacity for evenly suspended attention would be impaired by such an effort. It is true, of course, that rigid preoccupation with an intellectual formulation can impair the capacities. Even so, it is also true that the ‘formulation’ or structuring of a case can and largely does go on preconsciously, in some references even unconsciously, and usually quite spontaneously. One must assume at the very least, that some such process reaches the analyst’s first perception of a ‘resistance’. Some have thought that Freud would have disagreed with using such a process. Still, its use, whatever the form, is a necessity, and, at times, it requires and should have the hypercathexis of conscious and concentrated reflection? One may, of course, assign the more purposive intellectual processes to periods outside hours, and thus better preserve the other equally important responses to the dual intellectual demand of psychoanalytic technique. The ‘voice of the intellect’, all the same, should not be deprived of this essential place in analytic work. It is well known that it must never be allowed to foreclose mobile intuitive perceptiveness or openness to unexpected data. Nor must ongoing formulations in the mind of the analyst be allowed to cram the spontaneity of the patient’s association. They should remain ‘in the analyst’s head’. To epitomize the technical situation: Strategic considerations require varying degrees of reflective thought, possibly outside hours. Except the perspectives and critiques they silently lend to understanding, they should not influence the natural and spontaneous, often intuitive, responses of the disciplined analyst to the never-ending variable nuances of his patient’s ‘tactics’. In relation to any category of clinical psychoanalytic problem. It is the structure of the transference neurosis and its unfolding, with the adumbrative material in characterology, symptom formation, personal and clinical history and the clues from specific data of the psychoanalytic process, taken as an ensemble, which provide the most reliable basis for general tentative reconstruction and thus for the understanding of resistances. While we must marshal our entire body of data, theory, and technology to see the transference neurosis as an epitome of the patient’s emotional life, our comprehension of it is nonetheless based essentially on something that is right before us. Again, the total ensemble is essential, and the objectively observable phenomena of the transference neurosis are of crucial and central valences.
 In the background data, the large outlines of life history are uniquely important because they do represent, or at least strikingly suggest, the patient’s gross strategies of survival and growth, of avoidance and affirmation. One may infer that they will be invoked again in the conformation with the analyst, in his pluralistic significance. Some oversimplified and fragmentary illustrations are chosen in the occupational commitments with children and the mood in which they are carried out, with the general character of manifest sexual adaptation, can contribute to rational surmise about whether neurotic childlessness is based predominantly on disturbances of the Oedipus complex, on an original inability to achieve an adequate psychic separation from parent representations, or on the vicissitudes of extreme sibling rivalry. It must surely crystallize illnesses and analytic process if one knows that some patient lives, by choice, the breadth of an ocean removed from parents and siblings with whom there has been no evident quarrel, when this is not a crucial matter of occupational opportunity or equivalently important reality. Necessarily a male patient’s gross psychosexual biography helps us to understand which ‘side’ of the incestuous transference is more likely to be surfacing in his first paroxysm of heterosexual ‘acting out’. While it is true that dreams, parapraxes, and other traditionally dependable psychoanalytic material may dramatically reveal the ego-dystonic directions of impulse and fantasy life, and the specific nature of opposing forces, it is, only, the composite situation that historical and current picture that reveals the prevailing or alternative defences, the large-scale economic patterns, and the preferred or stable, i.e., most strongly over determined, trends of conflict solution.
 Tactical problems of resistance were earliest observed largely in disturbances of free association, which, in frequent tacit assumptions, would, or in principle could, lead without assistance to the ultimate genetic truth. This truth was construed to be the awareness of previously repressed memory (or the acceptance of convincing and germane constructions). As time went on, in Freud’s own writing, terms of conative import appeared - such as ‘tendency’ or, more of vividly, ‘impulsiveness’. However, the critical etiological and (reciprocally) therapeutic importance of memory has, of course, never really lost its importance. For, while the recovery of traumatic memories, with an abreaction, is still dramatic in its therapeutic effect, for example, in war neuroses or equivalently civilian experiences and occasionally in isolated sexual experiences of childhood or adolescence, neuroses of isolated traumatic origin are rare in current psychoanalytic experience. Traumata is usually multiple, repetitive, often serving to crystallize, dramatize and fix (something even ‘covers’) more chronic disturbances, such as distortions or pathological pressures in the instinct life, against the background of larger problems of basic object relationships. Freud was already becoming aware of the complex structure of neuroses when he wrote his general discussion for the Studies on Hysteria (Breuer and Freud 1893-1895). Thus, to put it all too briefly, when structurized impulses or general reaction tendencies can truly be accepted for memory, i.e., as matters of the past, other than in a tentative explanatory sense, much of the analytic work with the dynamics of the transference neurosis has necessarily been accomplished. One does not readily give up a love or hatred, personal or national, only because one learns that it is based on a crushing defeat of the remote past.
 The manifest communicative phenomena of resistance remain very important, just as the common cold remains important in clinical medicine. Morally justified in those of whom walk continuously among the corpsed of times generations, their circulatory momentum around the cross and forever finding its same death but it's comforting solice and refuge, from which, they dwell of the unknown infinity. It will never cease to be important to tell a patient that he is avoiding the emergence of sexual fantasies, that his blank silence covers latent thoughts about the analyst, or (in a measure more sophisticated) that apparent and enthusiastic erotic fantasies about the analyst conceal and include a wish to humiliate or degrade him. However, we can be better prepared, even for these problems, because of ongoing holistic reconstruction. Surely we are better prepared for the formidable resistances of patients who apparently do ‘tell all’ or even ‘feel all’, in a most convincing way and in all sincerity, yet may finish apparently thorough analysis without having touched certain nuclear conflicts of their lives and characters or, (more often) having failed to meet the  transference neurosis, with a sense of affective reality. These instances, for instance refers to the instances described by Freud (1937) in which such conflicts remain dormant because current life does not impinge on them, but to those in which the ‘acting out’, in life or the solution in severe symptoms is desperately elected by the personality in apparently paradoxical preferences to the subjective vicissitudes of the transference neurosis (Stone 1966).
 In brief, is a tentative formulation of the respective natures of the two peculiar and yet particular groups of resistance phenomena, ultimately and vestigially related and exists in varying degree in all analyses. It is, however, one or the other is usually important and is, in practical and prognostic sense, quite differently as: (1) Those progress to evidently large discernible impediments of the psychoanalytic process in its immediate operational sense. These are usual in the neuroses, in persons who have achieved satisfactory separation of the 'self' from the primary y object. Nevertheless, whose lives are disturbed by the residues of instinctual and other intrapsychic conflicts in relation to the unconscious representations of early objects and thus to transference objects. (2) Those that may be similarly manifested at times but maybe or even exaggeratedly free of them. Where the essential avoidance is of the genuine and effective e diphasic involvement in the transference neurosis, with regard too fundamental and critical conflicted, and thus of the potential relinquishment of symptomatic solutions and the ultimate satisfactory separation from the analyst. In this context, among other phenomena, there may be large-scale hiatuses in analytic material in the usual experiential sense, or there may be a striking absence of available and appropriate cues of connection with the transference, or failure, this complex of phenomena may repeat an original disturbance in ‘separation and individuation’ (Mahler 1965). Alternatively of other severe disturbances in early object relationships or related pregenital (particular oral) conflicts can have produced tenacious narcissistic avoidance of transference involvement, to facade involvement, or to the alternative of inveterate regressed and ambivalent dependency. Dependable and largely affirmative secondary identifications have usually not been achieved originally, and this phenomenon, related to basic disturbances of separation, contributes importantly to the variously manifested fears of the transference.
 Intuitively, the phenomena of the two groups may overlap. There may be deceptively benign ‘aponeuroses’ in the more severe group. In the troublesome phenomenon of ‘acting out’, for example, one may deal with a transitory resistance to an emergent transference fragment, in some instances due to a delay of effective interpretation, or one may be confronted by a deep-seated, variably structuralized, and sometimes even ego-syntonic ‘refusal’ to accept the verbal mode of communication with an unresponsive transference parent in dealing with insistent disturbing and gross affects implored by impulsive unintelligibility.
 Freud (1925), pointed out that everything said in the analytic situation must have some coefficient of reflection to the situation in which it is said. This is, of course, consistent not only with reflective common sense but also with the theory of transference and the current view of the central position of the transference neurosis in analytic work. Furthermore, despite his earliest view of the ‘false connection’ as pure resistance (Breuer and Freud 1893-1895) and the continuing high opinion of this aspect of transference, Freud early established the (non-conflictual) positive transference as the analyst’s chief ally against resistances. So, he never stretched out in his appreciation of the primitive driving power of the transference and its indispensable function of conferring a vivid and living sense of reality on the analytic process (Freud 1912). However, in past commination, the transfer is the central dynamism of the entire psychoanalytic situation, and the transference neurosis provides the one framework which give essential and accessible form to the potentially panpsychic scope of free association (Stone 1961, 1966). In this frame of reference the irredentist drive to reunion with the primal mother, as opposed to the benign processes of maturation and separation, underlies neurotic conflict in its broadest sense and is the basis of what is called the ‘primordial transference’, whose striving renewed physical approximation or merger. Speech, which is the veritable stuff of psychoanalysis, serves as the chief ‘bridge’ of mastery for the progressive somatic separations of earliest childhood. The ‘mature transference’, in continuum, alternative and contrast, is that series and complex of attitudes contingent on maturation and benign predisposing elements of early object relationships (conspicuously, the wish to be understood, to learn, and to be taught) that enables increasing somatic separation in a continuing affirmative context of object relationship, as later reelected in the psychoanalytic situation. In this interplay, speech - our essential working tool - plays as these oscillating, curiously intermediates roles, ranging from the threat of regression in the direction of its primitive oral substrate to it is ultimately purely communicative-referential function linked with insight (Stone 1961, 1966).
 Nonetheless, the origin of the ‘transference’ as we usually perceive it clinically, and as the term is traditionally employed, is in the primordial transference. Be it essentially the classical triadic incestuous complex or an oral drive toward incorporation or toward permanent nursing dependency or a sadomasochistic and shriving toward a parent, it will be re-experience in the analytic situation, in good part in regressive response to its derivations (Macalpine 1950), and produce the central, and ultimately the most formidable, manifest resistance, the transference-resistance.
 The ‘transference-resistance’, while sometimes used in varying references, meant originally the resistance to effective insight into the genetic origins and prototypes of the transference, expressed in the very fact of its emergence (originally, the ‘false connection’ described by Freud [Breuer and Freud, 1893-1895]). Afterwards, as the transference became established in its own autochthonous validity, the same resistance could be viewed as an obstruction to genetic understanding of the transference, and thus putatively to its dissolution. Alternatively, such dissolutions (using this word in a relative and  pragmatic sense) are contingent on much germane analytic work, on analysis of the dynamics of the attitude as represented in the transference neurosis, on working through, and on complicated and gradual responsive emotional processes in the patient (Stone 1966). Nevertheless, this genuine genetic insight is indispensable for the demarcation of the transference from the real relationship and for the intellectual incentive toward its dissolution within the framework of the therapeutic alliance.
 While to the ‘resistance to the awareness of transference’ the confrontations of patients are characterized by the immediate emergence of intense (even stormy) transference reactions, most patients experience these emergent altitudes as essentially ego dystopia, except in the sense of the attenuate derivatives that enter (or vitiate) the therapeutic alliance or in the sense of chronic characterological reactions that would appear in other parallel situations, however superficial and approximate the parallel might be.
 The clinical actuality of emergent transference requires analysis in its usual technical sense, including the prior analysis of defence. Transference may appear in dreams long before it is emotionally manifest; in parapraxes, in symptomatic reactions, in acting out within the analytic situation, or - most formidable - in acting out in the patient’s essential life situation. Except in cases of dangerous acting out, or very intense anxiety or equivalent symptoms, which can form emergencies, the technical approach involves the same patient centripetal address to the surface prescribed for analysis and its comprising it. However, as for this, it would suggest a modification of the classical precept that one does not interpret the transference until it becomes a manifest resistance. At this point, the interpretation is obligatory. The resistance to awareness should be interpreted, and its content brought to awareness, when the analyst believes that the libidinal or aggressive investment of the analyst’s person is economically a sufficient reality to influence the dynamics of the analytic situation and the patient’s everyday life situation.
 Stripping the matter of nuances is useful, reservations, and exceptions, for clarity in an essential direction. The avoidance of awareness of transference derives from all of the hazards that accompany consciousness: Accessibility of the voluntary nervous system, therefore heightened ‘temptation’ to action; heightened conflict in relation to the sanctions and satisfactions of impulse materialization; the multiple subjective dangers of communication of 'I-you' impulses and wishes or germane fears to an object invested with parental authority; heightened sense of responsibility (in that way, guilt) connected with the same complex, and, very far from least, the fear of direct humiliating disappointment - the narcissistic would have rejection or, perhaps worse of all, no affective response, the avoidance of this helplessness of impact, plays and important part. There is also the exceedingly important fact that the transference conflicts remaining outside awareness retain their unique access to autoplastic symptomatic expression, in compact and narcissistically omnipotent, if painful, solution, without the direct challenge and confrontation with alternative (and essentially ‘hopeless’) solutions.
 Why, then, if such fears weigh heavily against the analytic effort and the ultimate therapeutic advantage of awareness, does the patient cling tenaciously to his views of the analyst and the system of wishes connected with this view, once it has become established in his consciousness? In the earliest view, where the cognitive elements in analysis were heavily preponderant, not only in technique but also in the understanding of process, such clinging to transference attitudes was thought to be, since the essence of subjective matters' amounted of what was significantly the essential goal of the analytic effort and was thought to be, itself, the essential therapeutic mechanism. Still, why is the patient not willing, like the historian Leaky’s dinner partner, to ‘let bygones be bygones’? Unless one accepts this aversion to recall or reconstruction, a preference for ‘present pain’, as a primary built-in aversion, in its self of an unexplained fact of ‘human nature’, one must look further. Yet, on the person of the patient might informally reject these elements of ‘insight’ because they vitiate or diminish both the affective and cognitive significance of this central object relationship, which is a current materialization of crucial unconscious wish and fantasy, originally warded off. If it is to be given up, why was it pried out of its secure nest in the unconscious? Such resolution is always felt, at least incidentally, as an attack on the patient’s narcissism and on his secure sense of self, secondarily reestablished. Moreover, to the extent that there is a genuine translation of the subjectively experienced somatic drive elements into verbal and ideational terms related to past objects, there is an inevitable step toward separation from the current object that parallels the original and corresponding development movement.
 An essential dynamic difference from the past lies in the different somatic and psychological context in which the renewed struggle is fought. Old desires, old hatreds, old irredentist urges toward mastery, have been reawakened in a mature and resourceful adult, in certain spheres still helpless subjectively but no longer literally and objectively, a fact of which he is also aware. It was pointed out by Freud (1910) that this great quantitative discrepancy between infant conflict and adult resources make possibly and eases therapeutic change, through insight. In many important respects, this remains true. However, the remorseless dialectic of psychoanalysis again asserts itself. Truly effective insight requires validating emotional experience, which is only rarely achieved through recollections alone. The affective realities of the transference neurosis are necessary (now and again, inevitable), and with this experience comes the renewal of the ancient struggle, in which, with varying degrees of depth, the maturity and resources of the analysand often play a role at valiance with his capacity fort understanding. This is true not only of the subjective quality and experience of his striding but of the resources which support his resistances, in either phase of the transference involvement. Whether the wish is to seduce, to cling, to defeat and humiliate, to spite, or to win love, mature resources of mind - sometimes of body - may be involved to start this purpose, including what may occasionally be an uncanny intuitiveness regarding the analyst’s personal traits, especially his vulnerabilities?
 The persistence of old desires for gratification and the urge to consummate them, or the given urges to restore and maintain an original relationship with an omnipotent (and omniscient) parent, are intelligible to everyday modes of thought. That the transference, like the neurosis itself, may also entail guilt, anxiety, flustration, disappointment and narcissistic hurt are another matter. If it gives so much trouble, why does it reappear? Freud’s latter-day explanation involved the complex general theory of primary masochism and the repetition compulsion. One cannot, in a brief discussion, reach a disputation that has already occasioned voluminous writing. In ultimate condensation, the operational view to which are the elements to be understood, as perhaps, of (1) accompanying the renewed unregenerate drive for gratification of previously warded off wishes, whether libidinal or aggressive, based on the presentation of an actual object who bears significant functional ‘resemblances’ to the indispensable parent of early childhood, in a climate and structure of instinctual abstinence, and
(2) based on the latent alternative urge to understand, assimilate, perhaps alters parental response, or otherwise master poignantly a painful situation as they were  experienced in state of relative helplessness in the past. Both may be viewed as independent of adult motivations, although the power of the first may at times importantly subserve such motivations, and the second may often be phenomenologically congruent with them. Implicit in both, in contrast with the experienced plasticities and varieties of mature ego development, is the persistent and a continuous theme of adhesion to the psychic representation of the decisive original parent figure or a perceptually variant substitute. Still, it is profoundly important against original separation from the primal mother, with its potential phase specifications, as opposed to the powerful urges toward independence development, providing the underlying basis for developmental and later, neurotic conflict, that these conflicting tendencies, in the sense of the profundity that of them provide a certain parallel to the Thanatos-Eros struggle that assumed a decisive role in Freud’s final contributions. In a recent study of aggression (Stone 1971), examined Freud’s views on this subject. Although - in a paradox - by which the existence of a profound ‘alternative’ impulse to die at least conceptually tenable and susceptible to clinical inferential support, it is the conviction of those, that from both observation and inference, that aggression as this is an essential instrumental phenomenon (or can serve self-preservation and sexual impulses alike, and that it is thus, in its original forms, pitted against a postulated latent impulse to die, as it is against external threats to life. These urges and instrumentalities find primal organismic expression and experience in the phenomenon of birth and the immediate neonatal period, the biological prototype of all subsequent specifications, elaborations, and transmutations of the experience of separation. At the very outset the ‘conflict’ may find expression in the delay of breathing or, shortly after that, in the disinclination of suck. There is thus an intertwining of the two conceptions of basic conflict. It may characterize that 'time' will validate Freud’s latter-day views of the fundament of human conflict. For the time being, however, it has to the presents that are an empirically more accessible and a heuristically more useful view of the ultimate human intrapsychic struggle. Thus the originally unmastered or regressively reactivated struggle around separation, revived by developmental conflict, would in this schema represent the ‘bedrock’ of ultimate resistances, although never - at least in theory - utterly and finally insusceptible to influence. If we assume that the vicissitudes of object relationships, initiated by the special relationship of the human infant of his family, are fundamental in the accessible process of personality (thus, structural) development and thus of neuroses, and that, in ‘mirror images’. The transference and thus the transference-resistance has a comparable strategic position in the psychoanalytic process, can we extend these assumptions inti the detailed technical phenomenology of process resistance in its endless variety of expression? Yet it remains that this extension is altogether valid.
 What is more, is whether or not one thinks of it as ‘motivation’ in its usual sense, one can without extravagance postulate and even more intense cohesiveness at the first signal of that stimulus that contributed to the establishment of the organization and its basic strategies in the first place, i.e., the analyst as transference object. In the subjective good sense, the regressive trend of the transference, by the total structure of the psychoanalytic situation (i.e., the basic rule of free association and the systematic deprivations of the personal relationship) confronts the patient with one who has perceived ultimately as his first and an all-important object, the prototypical source of all gratification, all deprivation, all rejection, all punishment - the object involved in the primordial serial experience of separation (Stone 1961). This may seem an exaggeratedly magniloquent way to view a practitioner who puts himself in a seating position, usually in an armchair, listens, tries to understand, and then interprets, when he can, toward a therapeutic end. To a large portion of the adult's patient’s personality, the ‘observing’ portions of his ego, the portion that enters the therapeutic alliance, that is just what he is and that of what he should remain. To another portion, largely unchanged from its past, sequestered in the unconscious but influential although in derivative and indirect ways, he is a formidable object. It is in this field of force that, along with the drive toward better solutions, the range of clinical transferences as we know they are awakened. As, the entire efforts to translate the patient’s view of drives for reunion and contact, whether libidinal or aggressive, into genuine language, insights and voluntary control (or appropriate conative accomplishment elsewhere) is ‘resisted’. As it was originally, as an expression (or at least precursors) of separation, thus repeating aspects of the original developmental conflict. It is, however, it also true that the later and clinically more accessible vicissitudes of childhood create more accessible resistances within the postulated Metapsychological context created by the infant-mother relationship. Such changes as those patients in whom the phenomena of general the unity or approximations have been largely renounced, not only as a physical fait's accompli in perceptual and linguistic fact but also with deployment of the cathexis among other essential intrapsychic representations. These changes remain subject to regression or to the primary investment of certain phase strivings, conspicuously the Oedipus complex, in an excessive libidinal or aggressive cathexis. Such strivings, paradigmatically the incest complex, are in themselves the narrowed, potentially adaptive, maturational expressions of the basic conflict arouse by separation. If the analyst, to this infantile portion of the patient’s personality, an indispensable parent because cognition is, in this reference, subordinate to drive, it follows that the analyst becomes the central object in the complicated infant system of desires, needs, and fears that have previously been incorporated in symptoms and character distortion. The patient must, furthermore, tell these ‘secrets’ to the very object of a complex of disturbing impulses. This is a new vicissitude, not usually encountered in childhood and guarded forthwith. Even within the patient’s own personality, by the very existence of the unconscious. Ordinarily, he does not even have to ‘tell himself’ about them, in the sense that he is to a considerable degree identified with his parents, originally in his ego, then, in a punitive or disciplinary sense, in his superego? To be sure, the adult ‘observing’ portion of his personality, except where matters of adult guilt, embarrassments, or shame interfere, usually cooperates with the analyst. It can at least try to maintain the flow of derivative associations, which give the analyst material for informed inferences. The tolerant and accepting attitudes of the analyst tested by patients' rational and intuitive capacities, evened more decisively his interpretative activity, which suggestively an unredeemed child in the patent that he, ‘knows’ (or at least surmises) already, ‘gradually overcome the patient’s far of his own warded-off material and finally the fear of is frank expression'.
 There are, then, three broad aspects of the relationship between resistance and transference. Assuming technical adequacy, the proportional importance of each, one will vary with the individual patient, especially with the depth of psychopathology. First, the resistance awareness of the transference and its subjective elaboration in the transference neurosis; second, the resistance to the dynamic and genetic reductions of the transference neurosis and ultimately the transference attachment itself, once established in awareness; third, the transference presentation of the analyst to the ‘experiencing’ portion of the patient’s ego, as id object and as externalized super-ego simultaneously in juxtaposition to the therapeutic alliance between the analyst in his real function and the rational ‘observing’ portion of the patient’s ego. These phenomena give intelligible dynamic meaning to resistances ordinarily observed in the cognitive-communicative aspects of the analytic process. These are the process or ‘tactical’ resistances, largely deriving from the ego under the pressure or threat of the superego.
 As for this, the word ‘working through’ was sometimes, as Freud made mention (1914), that the structure yields only when a peak manifestation of resistance has apparently been achieved. The patient appears to require time, repetition, and a sort of increasing familiarity with the forces involved for real change to occur. In addition, Freud originally thought of the energy transactions as having some relation to the phenomenon of an abreaction in the earlier methods. One is impressed with the insistent recurrence of transference effects, conspicuously irrational anger in essentially rational patients, as though the structuralized tendency from which they derive can be directorially based on repetitive re-enactment and gradual reduction of effect. Since circumscribed symptom formations equivalent forms of neurotic suffering (and gratification) play an ongoing and inevitable economic role in the psychoanalytic situation and process, apart from having usually been the basis for its initiation, one might assume that they bear an important relationship to working through. Even when extinguished short of fear or long since under the influence of the transferee, their continued latent existence (or potentialities) is opposed to the vicissitudes of the current transference neurosis or it through which gradual relinquishment via working. This is true whether one thinks of the symptom in the quasi-neurophysiological sense of Breuer’s early formation of pathways of ‘lowered resistance’ (Breuer and Freud 1893-1895) or in a more empirical sense as a perennially seductive regressive condensation of impulse, gratification, and punishment, a useful and well-grounded concept, allied with the struggle against separation, is the relationship of working through to the process of mourning (Freud 1917).
 While from the adult point of view the gratifications may be small and the crucial change for the worse, the symptom is nevertheless autoplastic, narcissistic in an isolated sense, already structuralized, and subject too no outside interference (except by the analysis), an expression of localized infantile omnipotent fantasy, however large or small this fantasy kingdom may be. Similarly, considering unconscious processes administering both the challenges and sanctions of the world of reality, and from the temporary disruptive intrusions of new elements into the narcissistically invested conscious personality organization. In working through, there is the diphasic and arduous problem of restoring original or potential object cathexes' in the transference neurosis, reducing their pathological intensities or distortions, and the deploying them in relation to the outer world. One may thus think of ‘working through’ as opposed to the renewal, symptom formation and as repeating some postulated vicissitude of one of the earliest conceptions of ‘transference’, the infantile transition from autoerotism to an object of love (Ferenczi 190-9). In this sense, the clinging to the incestuous object, represented in the clinical transference, would represent an intermediate process.
 There is thus a tenacious reluctance of the ‘observing’ ego, might seduce the involved portion from its inveterate clinging to the actual transference object or to its autoplastically equivalent symptomatic representation. The postulated two portions of the ego (Freud 1940, Sterba 1934 in different references) are, after all, ‘of the same blood’ to put it mildly, and the urge to reunion in integrated function, the libidinal (synthetic) bonds, is quite strong. This affinity between ego divisions may, of course, take an opposite and adverse turn, a triumph of the ‘resistance’. As to instances of chronic severe transference regression, where the adult segment of the ego is ‘pulled down’ with the other and remains recalcitrant to interpretative e effort (Freud 1940). While this is, often contingent on the depth of manifest or latent illness, it may be simplified by iatrogenic factors, such as excessive and superfluous derivation in inappropriate and essentially irrelevant spheres. With these considerations, of whose importance is increasingly convincing with the passage of time.
 Mentioning it is important, even if briefly, that certain special factors, sometimes extrinsic to analysis as such, may indefinitely prolong apparent satisfactory analyses. Real guilt, for example, may not be faced. Emotional distress based on real-life problems may not be confronted and accepted as such. A person of the type described by Freud (1916) as an ‘exception’, who feels of himself as having been abused by the fortune of fate, even if in other respects not more ill than others, may consciously or unconsciously reject the psychoanalytic discipline or the instinctual renunciation derived from its insights. Fixed and unpromising life situations or organic incapacities may permit so little current or anticipated gratification that the attractiveness of the regressive, aim-inhibited analytic relationship is strongly in comparison with the barrenness of the extraanalytic situation. The last general consideration is, of course, always an essential (if silent) constituent of the psychoanalytic field of force, especially in relation to the dissolution of the transference-resistance (Stone 1966). Or alternatively more accessibly, the ‘rules of procedures’ of analysis itself may be consciously or unconsciously exploited by the patient. He may, in ‘obedience’ to a traditional rule, delay certain decisions to the point of absurdity, invoking the analytic work in support of his neurosis and sometimes in contempt of important obligations in real life. Financial support t of the analysis by someone other than the analysand can provide a basis for chronic, concealed ’acting out’. Usually, the analysis itself can, on occasion, become a lever for subtle erasion of obligations, vicissitudes, and contingent gratifications of everyday life, and thus, paradoxically, become a resistance to its on essential goals and purposes. It may become too much like the dream, to which it bears certain dynamic resemblances (Lewin 1954, 1955). The analyst’s perceptive and tactfully illuminating obligation is no less important in these spheres than in other sectors of his commitment.
 It is sometimes thought that by the ‘mature transference’ is meant, inflects the ‘therapeutic alliance’ or a group of mature ego functions that enter such an alliance. Now, there is sone blurring and overlapping the conceptual edges in both instances, but the concept as this is largely distinct from either one, as it is from the primitive transference. Either the concept is thought by others to comprehend a demonstrated actuality is a further question, that this question, is, of course, only to follow on conceptual clarity. In other words, the purposeful nonrational urge is not dependent on the perception of immediate clinical purposes, a true ‘transference; in the sense that it is displaced (in current relearnt form) from the parent of early childhood to the analyst. Its content is nontransitional but largely nonsenual (sometimes transitional, as in the child’s pleasure in so-called dirty words) (Ferenczi 1911) and encompasses a special and does not misuse spheric object relationship? : The wish to understand, and to be understood, the wish to be given understanding, i.e., teaching, specifically by the parent (or later surrogate), the wish to be taught ‘controls’ in a nonpunitive way, corresponding to the growing perception of hazard and conflict, and very likely to an implicit wish to provide with and taught channels of substitutive drive discharge. With this, there might be a wish, corresponding as the element in Loewald’s ascription (1960) by therapeutic process, to be seen as for one’s developmental potentialities by the analyst. However, the list could be extended into many subtleties, details, and variations. However, one should not omit to specify that, in its developments, it would include the wish for increasing accurate interpretation and the wish to ease such interpretations by providing sad adequate material: Ultimately, of course, by identification, to participate for being of its interpreter. The childhood system of wishes that underlie the transference is a correlate of biological maturation, and the latent (i.e., teachable) autonomous ego functions appearing with it (Hartmann 1939). However, there is a drive like quality in the particular phenomena that disqualifies any conception of the urge as identical with the functions, no one who has at any time watched a child importunes engendering questions, or experiment with new words, or solicit her interest in a new game, or demand storytelling or reading, can doubt this. That this finds powerful support and integration in the ego identification with a loved parent is undoubtedly true, just like the identification with an analyst toward whom a positive relationship has been established. That functional pleasure’ particates, certain ego energies perhaps, very likely the ego’s urge to extend its hegemony in the personality (Waelder 1936), however, the drive element, even the special phase patterns and colourations, and with it the importance of object relations, libidinal and aggressive, for a special reason. For just as the primordial transference seeks to into separation, in a sense to prevent object relationships as we know then ‘mature transference’ tends toward separation and individuation (Mahler 1965) and increasing contact with the environment, optimally with a large affirmative (increasing neutralized) relationship toward the original object, toward whom (or her surrogates) a different system of demands is now increasingly discrete. The further consideration that has to emphasize the drive like elements in these attitudes as integrated phenomena, as example of ‘multiple function’ than as the discrete exercise of function or functions, is the conviction that there is continuing dynamic relation of relative interchangeability between the two series, at least based on the responses to gratification, a significant zone of complicated energid overlap, possibly including the phenomenon of neutralization. That the empirical ‘interchangeability’ is limited, but this in no way diminishes its decisive importance. In the psychoanalytic situation, both the gratifications offered by the analyst and the freedom of expression by the patient are much more severely limited and concentrated practically entirely (in as much as the day is demonstrable sense) in the sphere of speech, on the analyst’s side, further, in the transmission of understanding.
 Whereas the primordial transference exploits the primitive aspects of speech, the mature transference urges seek the heightened mastery of the outer and inner environment, a mastery to which the mature elements in speech contribute importantly. Likewise, the most clear-cut genetic prototype for the free association-interpretation dialogue is in the original learning and teaching of speech, the dialogue between child and mother. It is interesting that just as the profundities of understanding between people often include - ‘in the service of the ego’ - transitory interjections and identification, the very word ‘communication’ represents the central ego function of speech, is intimately related etymologically, even in certain actual usages, to the word chosen for that major religious sacrament that is the physical ingestion of the body and blood of the Deity. Perhaps, this is just another suggestion that the oldest of individual problems does, after all, continues to seek its solution in its own terms, if only in a minimal sense and in channels so remote as to be unrecognisable.
 The mature transference is a dynamic and integral part of the ‘therapeutic alliance’, along with the tender aspects of the erotic transference, evens more attenuated (and more dependable) ‘friendly feeling’ of adult type, and the ego identification with the analyst. Indispensable, of course, are the genuine adult need for help, the crystallizing rational and intuitive appraisals of the analyst, the adult sense of confidence in him, and innumerable other nuances of adult thought and feeling. With these giving a driving momentum and power to the analytic process - always by it’s very nature in a potential course of resistance - and always requiring analysis, is the primordial transference and its various appearances in the specific therapeutic transference. That is, if well managed, not only a reelection of the repetition compulsion in its baleful sense, but a living presentation from the id, seeking new solutions, ‘trying again’, so to speak, to find a place in the patient’s conscious and effective life, has important affirmative potentialities. This has been specifically emphasized by Nunberg (1951), Lagache (1953, 1954), and Loewald (1960), among others. Loewald (1960) has recently elaborated very effectively the idea of ‘ghosts’ seeking to become ‘ancestors’, based on an earlier figure of speech of Freud (1900). The mature transference, in its own infantile right, provides some unique quality of propulsive force, which comes from the world of feeling, than the world of thought. If one views it in a purely figurative sense, that fraction of the mature transference that derives from ‘conversion’ is like the propulsive fraction of the wind in a boat navigating through close-haulage away from the wind: The strong headwind, the ultimate source of both resistance and propulsion, is the primordial transference. This view, however, should not displace the original and independent, if cognate, origin of the mature transference. To cohere to the figure of speech a favourable tide or current would also be required. It is not that the mature transference is itself entirely exempt from analytic clarification and interpretation. For one thing, like other childhood spheres of experience, there may have been traumas in this sphere, punishments, serious defects or lack or parental communication, listening, attention, or interest. Overall, this is probably far more important than has previously appeared in our prevalent paradigmatic approach to adult analysis, even taking into account the considerable changes die to the growing interest in ego psychology. ‘Learning’ in the analysis can, of course, be a troublesome intellectualizing resistance. Furthermore, both the patient’s communications and his reception and use of interpretations may exhibit only too clearly, as sometimes with other ego mechanisms, their origin in and tenacious relation to instinctual or analytic dynamism, greediness for the analyst to talk (rarely the opposite), uncritical acceptance (or rejections) of interpretations, parroting without actual assimilation, fluent, ‘rich’, endlessly detailed associations without spontaneous reflection or integration, direct demands for solution of moral and practical problems entirely within the patient’s own intellectual scope, and a variety of others. Discriminating it between the use of speech by an essentially instinctual demand and an intellectual may not always be easy or linguistic trait, or habit, determined by specific factors in their own developmental sphere. However, the underlying essentially genuine dynamism remains largely of a character favourable to the purposes and processes of analysis, as it was the original process of maturational development, communication, and benign separation. Lagache (1953, 1954) comments that on the desirability of separating the current unqualified usage. ‘Positive’ and ‘Negative’ transference, as based on the patient’s immediate state of feeling, from a classification based on the essential affect on analytic process. In the latter sense, the mature transference is usually, a ‘positive transference’.
 A few remarks about clinical considerations in the transference neurosis and the problem of transference interpretation, may be offered at this given directions held within time. The whole structural situation of analysis (in contrast with other personal relationships), its dialogue of frees association and interpretation, and its deprivation as to most ordinary cognitive and emotional interpersonal dispensing tends toward the separation of discrete transference from one another with defences, in character or symptoms, and with deepening regression, toward the re-enactment of the essentials of the infantile neurosis in the transference neurosis. In additional relationships, the ‘cooperative’ outlook - gratifying, aggressive, punitive, or in other ways abounding with responsibly, and the open mobility of search for alternative or greater satisfaction - put activities of profound dynamic and economic influence so that the only extraordinary situation or transference of pathologically comparable both, occasion comparable repression.
 It is a curious fact that whereas the dynamic meaning and importance of the transference neurosis have been well established since Freud gave this phenomenon a central position in his clinical thinking, the clinical reference, when the term is used, remains variable and ambiguous. For example, Greenson, in his paper of 1965, speaks of it as appearing 'when the analyst and the analysis become the central concern in the patient’s life.' Yet, to specify certain aspects of Greenson’s definition, for the term ‘central’ is justifiable, in that the term would apply to the analyst’s symbolic position in relation to the patient’s experiencing ego (Sterba 1934) and the symbolically decisive position that he correspondingly assumes in relation to the other important figures in the patient’s current life. Although the analysis is in any case, and for many reasons, exceedingly important to the seriously involved patient, there is a free-observing portion of his ego, as involved, but not in the same sense as that involved in the transference regression and revived infantile conflicts. There is, of course, always the integrated adult personality, however diluted it may seem at times, to whom the analysis is one of many important realistic life activities. Rarely, although it unavoidably does occur, that the analysis factually thrives of importance to other major concerns, attachments, and responsibilities of the patient’s life, and, perhaps, it is not as desirable that this should occur. On the other hand, if construed with proper attention to the economic considerations, the idea is important both theoretically and clinically. In the theoretical direction, we are to assume that there is a continuing system of object relationships and conflict situations, most important in unconscious representations but participating often in all others, deriving in a successive series of transferences from the experiences of separation from the original object, the mother. In this sense, the analyst is substantially, the uniquely important portion of the patient’s personality, the portion that ‘never grew up’, a central figure. In the clinical sense, its importance is felt of the transference neurosis as outlining for us the essential and central analytic tasks, provided by the informatics adjacencies of currents of relative fugaciousness and demonstrability, a secure cognitive base for analytic work. By its inclusion of the patient’s essential psychopathological processes and tendencies in their original functional connections, it offers in its resolution or marked reduction, the most formidable lever for an analytic cure. The transference neurosis must be seen in its interweaving with the patient’s extra-analytic system of personal contacts. The relationship to the analyst may influence the course of relationships to others, in the same sense that the clinical neurosis did, except that the former is alloplastic, proportionally exposed, and subject to constant interpretations. It is also an important fact that, except in those rare instances where the original dyadic relationship appears to return, the analyst, even in strictly transference spheres, cannot be assigned all the transference roles simultaneously. Other actors are required. He may at times oscillate with confusing rapidity between the status of mother and father, but he usually predominantly in one of these roles for long periods, someone else representing the other. Moreover, apart from ‘acting out’, complicate and mutually inconsistent attitudes, anterior to awareness and verbalization, may require the seeking of other transference objects: Husband or wife, friend, another analyst, and so forth. Children, even the patient’s own children, may be invested with early strivings of the patient, displaced from the analysis, to permit the emergence or maintenance of another system of strivings. Physicians, of course, may encouragingly be more aware of in their patients and their own strivings, mobilized by the analysis, even experience the impulses that they would wish to call forth in the analyst. Transference interpretation therefore often had inescapably had some sorted paradoxical inclusiveness, which is an important reality of technique. There is another aspect, and that is the dynamic and economic impact of the intimate and actualized dramatis personae of the transference neurosis on the progress of the analysis as such and on the patient’s motivations, and his real-life avenues for recovery. For the person in his milieu may fulfill their ‘positive’ or ‘negative’ roles in transference only too well, in the sense that an analyst motivated by a ‘blind’ countertransference may do the same. Apart from their roles in the transference drama, which may ease or impede interpretative effectiveness, they can provide the substantial and dependable real-life gratifications that ultimately ease the analysis of the residual analytic transferences, or their capacities or attitudes may occasion an over-load of the anaclitic and instinctual needs in the transference, rendering the same process far more difficult. In the most unhappy instances, there can be a serious undercutting of the motivations for basic change.
 There is also the fundamental question of the role of the transference interpretation, is but nonetheless, the variances reserved as to details and emphasis on the other important aspects of the therapeutic process, in that, there are still many to whom, if not in doubt regardless the quality value of transference interpretation, are inclined doubts their uniqueness and to stress the importance of economic considerations in determining the choice about whether transference or extratransference (In a sense, the necessarily ‘distributed’ character of a variable fraction of transference interpretation), there is the fact that the extra analytic life of the patient often provides indispensable data for the understanding of detailed complexities of his psychic functioning, because of the sheer variety of its references, some of which cannot be reproduced in the relationship to the psychoanalyst. For example, there is not repartee (in the ordinary sense) in the analysis. This way the patient handles the dialogue with an angry employer may be importantly revealing. The same may be true of the quality of his reaction to a real danger of dismissal. There are not only the realities’ not also the ‘formal’ aspects of his responses. These expressions of his personality remain important, though his ‘acting out’ of the transference (assuming this was the case) may have been even more revealing and, of course, requiring transference interpretation. Furthermore, these expressions remain useful, if discriminating and conservatively treated, even if they are inevitable always subject to that epistemological reservation, which haunts so much of the data as placed in the analytic situation. Of course, the ‘positive’ transference simplifies intensified interpretations, but it is what might render their enabling capabilities that the abling of the patient’s acceptably to listen into them and directly take them seriously.
 In an operational sense, it seems that extratransference interpretations cannot be set aside or underestimated. However, the unique effectiveness of transference interpretations is not by that disestablished. No other interpretation is free, without reason. Of considering unlikely introduced apart from not substantially knowing the ‘other person’s’ involvement in a feel deep affection for, quarrelling, criticism, or whatever is being hoped-for. No other situation provides for the patient’s combinational sense of cognitive acquisition, with the experience of complete personal tolerance and acceptance, that is implicit in. an interpretation made by an individual who is an object of the emotions, drives or even defences, which are active at the time. There is no doubt that such interpretations must not only (in common with all others) include personal tactfulness but also must be offered with special care as to their intellectual reasonableness, in relation to the immediate context, lest they defeat their essential purpose. It is not too often likely that a patient who had just been jilted in a long-standing love affair and id suffering exceedingly will find useful an immediate interpretation that his suffering is because the analyst does not reciprocate his love, although a dynamism in this general sphere may be ultimate shown, and acceptable to the patient. On the other hand, once the transference neurosis is established, with accompanying subtle (sometimes gross) colourations of the patient’s story, transference interpretations are indicative, for, if all of the patient’s libido and aggressions are not, in fact, invested in the analyst, he has at least an unconscious role in all important emotional transactions, and if the assumption is correct, that the regressive drive, mobilized by the analytic situation, acceding the directorial restoration of a single all-encompassing relationship, specified pragmatically in the individual case by the actual attained level of development, then there is a dynamic factor at work, importantly meriting interpretation as such, to the extent that available material supports it. This would be the immediate clinical application of the material regarding a ‘cognitive lag’.
 Freud’s first formal reference to transference (Breuer and Freud 1893-1895) set the tone for all that followed. In discussion resistance and obstacles too effective cathartic (analytic) work, he offers as one possibility that ‘the patient is frightened at finding that she is transferring into the figure of the physician the distressing ideas that arise from the content of the analysis . . . Transference onto the physician takes place through a ‘false connection’. Freud then offers an example of a woman who developed a hysterical symptom based on her wish many years earlier (and now relegated to the unconscious) that the man she was talking to at the time might slowly take the initiative and gives her a kiss. He then described how, toward the end of one session, a similar wish came up within the patient toward himself - Freud. The patient was horrified and unable to work in the next hour, and obstacle to the therapeutic work that was removed once Freud had discovered its basis and pointed it out to the patient. In her response, the patient could recall the pathogenic recollections that accounted for her reactions to Freud the unconscious wish, according to Freud, had become conscious but was linked to the person based on a false connection by the transference,
 Importantly, the present of issues is the finding that Freud’s monumental discovery of transference was founded upon his realization that his patient’s conscious fantasy about him was based on an earlier experience with another man. This displacement from an earlier figure (in later writings this person would often be linked to the patient’s father or other childhood figure) was seen as having no foundation in the analyst’s behaviours and as based entirely on the patient’s inner wish. Freud repeatedly characterized such responses as the real for the patient though unfounded in the actualities of the analytic relationships.
 Once, again, in his well-known postscript to the case of Dora, Freud (1905) showed an appreciation of the unconscious basis for transference, though he maintained as his clinical reference point some type of conscious allusion to a reaction toward the analyst. Freud defined transference as a special class of mental structures that for the most parts are unconscious. Descriptively, he identified them as; untried additions or facsimiles of the impulses and phantasies that are suspensefully made conscious during the progression of the analysis. . . . They replace some earlier person by the person of the physician. Freud stared that some transferences differ from their earlier models in no way except the substitution of the physician for the earlier figure. He abstractively supposed of these to be new impressions or reprint, but stated that other transferences are more ingeniously constructed and have been subjected to a modifying influence he termed sublimation, the implication was that these transferences took advantage of some real peculiarity in the physician’s person or circumstance and attached themselves to that factor. These transferences he considered revised editions. Through transference, the past of the patient is revived as belonging to the present. Even with the patient Dora, the main transference was seen as a replacement for her father with Freud, and much of this found expression through conscious comparisons such as her question about whether Freud was keeping secrets from her as had her father. Other manifest concerns that Dora expressed in her relationship with Freud were traced to the relationship with Herr K.
 Throughout his discussion, Freud maintained the clinical view of transference as involving some direct reference to himself as the analyst. While he clearly stated that transference structures are largely unconscious, his evidently stressed on the role of unrecognized displacement s and an unawareness with the patient of intrapsychic and genetic sources of her direct responses to the analyst. It is this peculiarity of the conceptualization of transference - a recognition of its unconscious basis, which is seldom specified in any detail, and a simultaneous maintenance of the ides that it is expressed through direct references to the analyst - that has contributed too much uncertainty in this area.
 Freud and others have treated manifest and conscious fantasies about the analyst as if they represented either the direct awareness of a fantasy influencing the patient’s psychopathology or the breakthrough of as previous unconscious fantasy or memory, originally attached to an earlier figure. This has caused considerable confusion; for all practical purposes, conscious fantasies about the analyst and defences against them have been taken as the substance of the patient’s transference neurosis, while the role of the unconscious fantasies has been neglected.
 While Freud and other analysts have at times stressed the critical role of unconscious fantasy constellations in the development of neurosis, in their actual clinical work conscious fantasies are often taken at face value and held responsibly for the patient’s illness. Some of this contradiction has been rationalized away with the idea that these conscious fantasies represent direct breakthroughs of previously unconscious fantasies, a position adopted despite the acknowledgment in other contexts (Arlow 1969, Brenner 1976) that defences and resistances are always at work and that pure breakthroughs are extremely either rare or nonexistent (the conscious product is always a compromise and always contains some degree of disguise).
 While this view pats-lip service to the idea of nondistorted reactions by the patient, there has been virtually no consideration of his continuous, essentially sound functioning, or of his conscious and unconscious interventions. This is in keeping with the overriding stress on pathological unconscious fantasies in the etiology of neuroses and in transference, to the neglect of unconscious perceptions and introjects, a factor neglected to this day.
 Most of what Freud had to say about unconscious fantasies and derivatives appeared in papers unrelated to technique and transference. In an important contribution in 1908, Hysterical Phantasies and Their Relation to Bisexuality, he specifically identified the role of unconscious fantasies in symptom formation, borrowing heavily from his insights into dreams. Freud had discovered that hysterical symptoms are based on fantasies that represent the satisfactions of wishes. He noted, however, that these fantasies can be conscious or unconscious initially, but that the critical factor in neurosogenesis is the presence of an unconscious fantasy expressing itself through hysterical symptoms and attacks. Freud felt that at times these unconscious fantasies can quickly be made conscious and that both the conscious and the unconscious fantasy may be some derivative of a formally conscious fantasy, suggesting by that the disguise involves the unconscious rather than the conscious fantasy. In this early use of the concept of derivatives, then, it was no the conscious fantasy that was the derivative of the underlying fantasy, but the reverse.
 But, nonetheless, his paper on the dynamics of transference, Freud (1912) described transferences as based on a stereotyped plate that is constantly repeated
- repeated afresh - during a person’s life. The underlying fantasias were seen as partly accessible to consciousness, and as partly unconscious. Transference, then, is the introduction of one of these stereotypical plates into the patient’s relationship with the analyst.
 It was also that Freud stated that when associations fail or become blocked. They have become connected with the analyst. Freud stressed the role of unconscious complexes in psychopathology and suggested that they are represented consciously and that their roots in the unconscious have to be traced out. The key to analysis is the distortion of pathogenic material expressed through the patient’s transference.
 In Remembering, Repeating, and Working Through, Freud (1914) saw transference as involving repetitions of the past in the actual relationship with the analyst. In stressing, once, again, the extent to which the patient experiences these transferences as real and contemporize, Freud again used the term transference to refer to direct reactions to the analyst. In his paper on transference love (1915) Freud is clearly alluding to conscious erotic wishes and fantasies about the analyst. He stated that he was discussing situations in which women patients declare their love for a male analyst and make direct demands for the return of his love, using such demands as resistances. Similar thinking is revealed in An Outline of Psycho-Analysis, (1940), in which Freud discusses how the patient sees the analyst as a reincarnation of figures from his childhood, and transfers feelings and reactions based on this prototype. Freud was to  escape an understanding by which, once, again attributive to positive and negative attitudes toward the analyst, and the plastic clarity with which patients experience such transferences.
 The clearest evidence for Freud’s clinical definition of transference appears in his presentation of the opening phase of the analysis of the Rat Man (1909). The note’s of Freud decanting of this example, to reveal that with one exception, each time Freud used the term transference he was calling a conscious knowing fantasied illusion about himself or his family unit of measure. Persistently, Freud would attempt to identify the genetic basis for these transferences, largely, the main unconscious aspect was the mechanisms of displacement. It followed, then, that resistance, and in particular transference resistance, became defined as efforts by the patient to avoid the expression or realization of conscious fantasies about the analyst, and that the term could be extended to include unconscious avoidance as well. This is a reminder that the definition of resistance depends largely on the definition of transference - that is to say, that Freud took allusions toward an outside person as displacements from himself, and from ‘the transference’. In this context, it is well to recall that Freud’s original definition o acting out (Freud 1905) alluded to behaviours, directed toward the analyst, such as Dora’s flight from analysis, and to a lesser extent as to natural actions involved with other persons.
 Freud’s narrow view of transference concerning direct references to the analyst is also reflected in one of his rare comments on the nature of material from patients’ (Freud 1937). In discussing the kinds of material that patient’s put at the disposal of analysts for recovering lost pathogenic memories. Freud refers to dreams, free association, the repetition of effects, actions performed by the patient both inside and outside the analytic situation, and the relation of transference that becomes established toward the analyst. In addition, his archaeological model of repressed unconscious memories can be seen to imply the discovery of previously repressed fantasies integrated as though it were also to leave room for fragmented representations. Finally, we may note a comparable comment by Freud in the Outliner (1940): 'We gather the material for our work from a variety of sources - from what communication has been made a reduction by giving us by the patient and by his free associations, from what her shows us in his transference, from what we reason out by interpreting his dreams and from what he betrays by his slips or parapraxes.'
 Moreover, Freud leaned toward the divorce of his discussion of the transference neurosis and transferences from his consideration of the nature of psychopathology. In keeping with this trend, his discussion of the nature of unconscious fantasies and processes, and of derivative communication, appeared primarily in two metaphysical papers - Repression (Freud 1915) and The Unconscious (Freud 1915). In both papers he was concerned with communication between the unconscious mind and the preconscious or conscious mind? He noted that this takes place by means of derivatives that express and represent unconscious instinctual impulses. He also pointed out that unconscious fantasies can be highly organized and logical even thought outside the awareness of the patient, suggesting again the possibility of the direct breakthrough of such fantasy material. In these writings, it is the unconscious fantasy that expresses itself consciously through derivatives as substitute formations such as symptoms or preconscious thought formations. What has been repressed, Freud noted? Can become conscious only if it is sufficiently disguised? On this basis, unconscious fantasies can be appeared in a patient’s free association (the reference to free association rather than to transference), through remote and distorted derivative expressions. These are substitute formations that include the return of the repressed, the repressed instinctual impulses modified by defensive operations such as displacement.
 Let it be said, that Freud left considerable room for uncertainty regarding his conceptualization of transference. Theoretically, he implied that transferences are based on unconscious fantasias and memories derived from experiences and brought into play in the relationship with the analyst. He himself never applied his insights into the nature of derivative comminations to the subject of transference. As a result, his clinical referent for transference remained throughout his writings that of a direct reference to the analyst. While he acknowledged the important role of unconscious processes and contented the analyst at face value and to understand them as direct representations displaced from the past. A major contradiction by that unfolded. In that Freud correctly understood neuroses to be based on unconscious fantasy constellations, including unconscious transference fantasies, and yet he worked analytically with the patient’s conscious fantasies toward himself as analyst. Freud’s contention that sometimes unconscious fantasies break through unmodified into conscious awareness is clearly insufficient justification for this approach. There is abundant clinical evidence that unconscious fantasy constellations are always expressed through derivative formations, and that even when elements of the underlying unconscious fantasy break through in unmodified form - or are recovered through interpretation - there always remains an additional cloak-and-dagger element. Further, at the point of realization of an undisguised unconscious fantasy, it seems likely that its own expression would be itself function as a disguised and defensive derivative of a different and still repressed unconscious fantasy (Gill 1963).
 The failure by analysts to maintain the essential definition of transference - as based on an unconscious fantasy constellation expressed, almost without acceptation, through derivatives - has led to many mistaken formulations regarding the nature of psychopathology, the analytic process itself, and the techniques of the psychoanalyst and psychotherapist. In their discussion of neuroses, analysts have consistently maintained and documented the thesis that psychopathological syndrome is based on unconscious processes and contents - fantasy constellations. It seems evident, that analytic work with manifest fantasies per se cannot provide access to, or interpretations of, these unconscious constellations.
 The need to clarify the contextual significance of ‘transference’ and what it serves to achieve, or prevent, or avoid, and becomes apparent. For example, relating to the analyst based on some preconceived fantasy, rather than as the person he or she is, can function to prevent the possibility of engaging meaningfully and experiencing the anxiety a more mutual and intimate engagement might arouse.
 An appreciation of interactive factors also allows us to consider that, to whatever degree the patient’s perceptions of the analyst are plausible and eve valid (Ferenczi, 1933; Little, 1951; Levenson, 1972; Searles, 1975; Gill, 1982; Hoffman, 1983), this may be due to the patient’s expertise at stimulating precisely this kind of responsiveness in the analyst. The reverse is true as well. Thus, though patient and analyst each will have unique vulnerabilities, sensitivities, strengths, and needs, we must consider why particular qualities or sensitivities of either patient or analyst are begun at a given moment and not at others. At any moment patient or analyst might be involved in some find of collusive enactment (Racker, 1957, 1968; Levenson, 1972, 1983; Sandler, 1976, Bion, 1967, 1983; Ogden, 1979; Grotstein, 1981; McDougall, 1979). These considerations to illuminate why clinicians often seem to practice in ways that contradict their own stated beliefs and theoretical positions.
 The powerful impact of unwitting communication between patient and analyst is, of course, one reason the analyst’s countertransference experience can be a source of vital data about the patient and may become the ‘key’ to understanding aspects of the interactions that might otherwise remain impenetrable (Heimann, 1950).
 An appreciation of interactive factors also requires us to reconsider what makes up analytic ‘mistake’. In this regard Winnicott (1956, 1963) has expressed the views that there are times when our patients need us to fail. In the end the patient uses the analyst’s failure, often quite: Small ones, perhaps manoeuverer by the patient: The operative factors are that the patient now hates the analyst for the failure that originally came as an environmental factor, outside the infant’s area of omnipotent control, that is now staged in the transference. So in the end we succeed by failing the patient’s way. This is a long distance from the simple theory of cures by corrective experience (Winnicott, 1963)
 From-Reichmann (1939, 1950, 1952), has emphasized that at times the analyst’s mistakes may become the basis for a ‘golden (analytic) opportunity’. From this vantage point we might consider that how an analyst deals in the accompaniment with wished, in that he or she has in possession of some inevitable fallibility that maybe on of the defining aspects of his or her techniques.
 An appreciation of interactive considerations thus requires us to rethink important issues of technique and the question of how we define ‘analysis’. It also requires us to consider that the pattern’s so-called ‘analyzability’ may depend on the nature of the analyst’s participation than has previously been recognized. The dilemma is how to move into a new mode of thinking about clinical technique that is not beset by the inherent limitations of traditional thinking or by those of more radical new perspectives.
 The unformidable combinations of others before have thought that the psychoanalytic situation and process as such have a general unconscious meaning, which reproduces certain fundamental aspects of early developments. For example, in Greenacre and in 1956 Spitz offered ideas of the psychoanalytic situation and of the origins of transference, based largely on the mother-child relationship of the first months of life. Greenacre used the term ‘primary transference’ (with two alternatives). As far as the ideas of Greenacre and Spitz emphasize the prototypic position of the first months of life, as reproduced in the current situation, there are subtle but important differences from the view presents. Nacht and Viderman in 1960 extended related ideas to their conceptual extreme, requiring metaphysical terminology. One can readily understand the regressive transference drive set up by the situation as having such general direction, i.e., toward primitive quasi union, a reservation that Spitz accepted and specified, in response to Anna Freud. It is te activation of this drive and its opposing cognate that underlies the construction of the psychoanalytic situation, which is seen primarily as a state of separation, of ‘deprivation-in-intimacy’.
 With the prolonged and strictly abstinent contact of the classical analytic situation, there is inevitably for the patient, some growing and paradoxical experience of cognitive and emotional deprivation in the personal sphere, the cognitive and emotional modalities in certain respects overlapping or interchangeable, in the same sense that the giving of interpretations may satisfy to varying degree either cognitive or emotional requirements. The patient, also renounces the important expression of a locomotion. If developed beyond a certain conventional communicative degree, even gesture or other bodily expressions tend, by interpretive pressure, to be translated into the mainstream of oral-vocal-auditory language. The suppression of hand activity, considering both its phylogenetic and ontogenetic relation to the mouth (Hoffer 1949), exquisitely epitomizes the general burdening of the function of speech, regarding its latent instinctual components, especially the oral aggressions.
 From the objective features of this real and purposive adult relationship, one may derive the inference that 'its representational advance presents of unintentional consciousness, one of disguising itself in its primary and most extensive impact, the superimposed series of basic separation experiences in the child’s relation to his mother.' In that, the analyst would represent the mother-of-separation, as differentiated from the traditional physician who, by contrast, represent the mother associated with intimate bodily care. This latent unconscious continuum-polarity eases the oscillation from ‘psychosomatic’ reactions and proximal archaic impulses and fantasies, up to the integration of impulse and fantasy life within the scope of the ego’s control and activities (Stone 1961).
 Within this structure, the critical function of speech is seen in a similar perspective, as a continuous telescopic phenomenon ranging from its primitive meanings as physiological contact, resolution of excess or residual primitive oral drive tensions, through the conveyance of expressive or demanding or other primitive communications, on up to its role as a securely established autonomous ego function, genuinely communicative in a referential-symbolic sense. To the extent that an important fraction of human impulse life is directed against separation from birth onward, the role of speech, which develops rapidly as the modalities of actual bodily intimacy are disappearing or becoming stringently attenuated (Sharpe 1940), has a unique importance as a bridge for the state of bodily separation. In the instinctual contribution to speech, considering it as a phenomenon of organic or maturational ‘multiple function’ (Waelder 1936), the cannibalistic urges loom large; they, and more manifestly, their civilized cognates (partially, derivative?), Introjection tracings and their preserving capabilities for re-emergence as such, always. In such view, the most primitive and summary form of mastery of separation, fantasized oral incorporation, is in a continuous line of development with the highest form of objective dialogue between adults. The demonstrable level of response of the given patient, in this general unconscious setting, will be determined (in ideal principle) by his effectively attained level of psychosexual development and ego functioning in its broadest sense and by his potentiality for regression.
 Advances in our understanding of the therapeutic action of the psychoanalysis should be based on deeper insight into the psychoanalytic process. By ‘psychoanalytic process’ is to mean the significant interactions between patient which ultimately leads to structural changes in the patient’s personality. Today, after more than fifty years of psychoanalytic investigation and practice, we can appreciate, if not to understand better, the role which interaction with environment plays within the core organizational formation, development, and continued integrity of the psychic apparatus. Psychoanalysis ego-psychology, based on a variety of investigations concerned with
Ego-development, has given us some tools to deal with the central problem of the relationship between the development of psychic and interaction with other psychic structure, and of the connexion between ego-formation and other object-relations.
 If ‘structural changes in the patient’s personality’ mean anything, it must mean that we assume that ego-development is resumed in the therapeutic process in the psychoanalysis. This resumption of ego-development is contingent on the relationship with a new object, the analyst. The nature and the effects of this new relationship are under what should be the fruitful attempt to correlate our understanding of the significance of object-relations for the formation and development of the psychic apparatus with the dynamics of the therapeutic process.
 Problems, however, of essentially established psychoanalysis theory and tradition concerning object-relations the phenomenon of transference, the relations between instinctual drives and ego, and concerning the function of the analyst in the analytic situation, have to be dealt with, least of mention, it is unavoidable, for clarification to those who think of a divergent repetition from the cental theme to deal with such problems. Thus and so, the existent discussion is anything but a systematic presentation of the subject-matter. Therefore, in continuing further details of attempting to suggest modifications or variations in techniques, but the psychoanalytic changes for the better understanding of therapeutic action of the psychoanalysis in that it may lead to changes in technique, as anything of such clarification may entail as a technique is concerned should be worked out carefully and is not the topic but its psychometric test?
 While the fact of an object-relationship between patient and analyst is taken for granted, classical formulations concerning therapeutic action and concerning the role of the analysts in the analytic relationship do not reflect our present understanding of the dynamic organization of the psychic apparatus, and not merely of ego. In that, the modern psychoanalytic ego-psychology that expressed directly or indirectly, as far more than an additional psychoanalytic theory of instinctual drives. It is however the elaboration of a more comprehensive theory of the dynamic organization of the psychic apparatus, and the psychoanalysis are in the process of integrating our knowledge of instinctual drives, gained during earlier stages of its history, into such a psychological theory. The impact of psychoanalytic ego-psychology has on the development of the psychoanalysis, in that is to suggest that ego-psychology be not concerned with just another part of the psychic apparatus, given but a new continuum to the conception of the psychic apparatus as an undivided whole.
 In an analysis, one is to think that we have opportunities to observe and investigate primitively and more advanced interaction-processes, that is, interactions between patient and analyst that leads to or from steps in ego-integration and disintegration. Such interactions, or integrative (and disintegrative) experiences, occur often but do not often as such become the focus of attention and observation, and go unnoticed. Apart from the difficulty for the analyst of self-observation while in interaction with his patient, there is a specific reason, stemming from theoretical bias, why such interactions not only go unnoticed but are frequently denied. The theoretical bias is the view of the psychic apparatus as a closed system. Thus the analyst is seen, not as a co-actor on the analytic stage, on which the childhood development, culminating in the infantile neurosis, is restaged and reactivated in the development, crystallization and resolution of the transference neurosis, but as a reflecting mirror, even if of the unconscious, and characterized by scrupulous neutrality.
 This neutrality of the analyst is required (1) in the interest of scientific objectivity, to keep the field of observation from being contaminated by the analyst’s own emotional intrusions, and (2) to guarantee an unformed mind for the patient’s transferences. While the latter reason is closely related to the general demand for scientific objectivity and avoidance of the interference of the personal equation, it has its specific relevance for the analytic procedure as such in as far as the analyst is supposed to function not only as an observer of certain precess, but as a mirror that actively reflects back to the patient the latter’s conscious and particularly his unconscious processes through communications. A specific aspect of this neutrality is that the analyst must avoid falling into the role of the environmental figure (or of his opposite) the relationship to whom the patient is transferring to the analyst. Instead of falling into the assigned role, he must be objective and neutral enough to reflect back to the patient what role the latter has assigned to the analyst and to himself in the transference situation. Nevertheless, such objectivity and neutrality now need to be understood more clearly as to their meaning in a therapeutic setting.
 It is all the same that ego development is a process of increasingly higher integration and differentiation of the psychic apparatus and does not stop at any given point except in neurosis and psychosis: although it is true that there is normally a marked consolidation of ego-organization around the period of the Oedipus complex. Another consolidation normally takes place toward the end of adolescence, and further, often less marked and less visible, consolidation occurs at various other life-stages. These later consolidations - and this is important - follow periods of relative ego-disorganization and reorganization, characterized by ego-regression. Erickson has described certain types of such periods of ego-regression with subsequent new consolidations as identity crises. An analysis can be characterized, from this standpoint, as a period or periods of induced ego-disorganization and reorganization. The promotion of the transference neurosis is the induction of such ego-disorganization and reorganization. Analysis is thus understood as an intervention designed to set ego-development in motion, be it from a point of relative arrest, or to promote what we conceive of as a healthier direction or comprehensiveness of such development. This is achieved by the promotion and use of (controlled) regression. This regression is one important aspect under which the transference neurosis can be understood. The transference neurosis, in the sense of reactivation of the childhood neurosis, is set in motion not simply by the technical skill of the analyst, but by the fact that the analyst makes himself available for the development of a new ‘object-relationship’ between the patient and the analyst. The patient having a tendency to make this potentially new object-relationship into an old, on the other hand, its total extent from which the patient develops ‘positive transference’ (not in the sense of transference as resistance, but in the sense in which ‘transference’ carries the whole process of an analysis). He keeps this potentiality of a new object-relationship alive through all the various stages of resistance. The patient can dare to take the plunge into the regressive crisis of the transference e neurosis that brings him face to face again with his childhood anxieties and conflicts, if he can hold to the potentiality of a new object-relationship, represented by the analyst.
 We know from analytic s well as from life experience that new spurts of self-development may be intimately connected with such ‘regressive’ rediscoveries of oneself as may occur through the establishment of new object-relationships, and this means: New discovery of ‘objects’. Seemingly enough, new discovery of objects, and not discovery of new objects, because the essence of such new object-relationships is the opportunity they offer for rediscovery of the early paths of the development of object-relations, leading to a new way of relating to objects and of being and relating to ones' own. This new discovery of oneself and of objects, this reorganization of ego and objects, is made possible by the encounter with a ‘new object’ which has to possess certain qualification to promote the process. Such a new object-relationship for which the analyst holds himself available to the patient and to which the patient has to hold on throughout the analysis is one meaning of the term ‘positive transference’.
 What is the neutrality of the analyst? Its significance branches the intangible quantification upon stemming from the encounter with a potentially new object, the analyst, which new object has to possess certain qualifications to be able to promote the process of ego-reorganization implicit in the transference neurosis. One of these qualifications is objectivity. This objectivity cannot mean the avoidance of being available to the patient as an object. The objectivity of the analyst has reference to the patient’s transference distortions. Increasingly, through the objective analysis of them, the analyst overcomes not only a potentiality but the subjective expanding activities available are of a new object, by eliminating in stages impediments, represented by these transferences, to a new object-relationship. There is a tendency to consider the analyst’s availability as an object merely as a device on his part to attract transference onto himself. His availability is seen as to his being a screen or mirror onto which the patient projects his transference, which reflects them back to him as interpretations. In this view, at the ideal endpoint of the analysis no further transference occurs, no projections are thrown on the mirror, the mirror having nothing now to reflect, can be discarded.
 This is only a half-truth. The analyst in actuality does not reflect the transference distortions. In his interpretations he implies aspects of undistorted reality that the patient begins to grasp the successive sequence as the transferences are interpreted. This undistorted reality is mediated to the patient by the analyst, mostly by the process of chiselling away the transference distortions, or, as Freud has beautifully put it, using an expression of Leonardo da Vinci, ‘per via di levare’ as, insomuch as of sculpturing, not ‘per via di porre’ as, in producing a painting. In sculpturing, the figure to be created comes into being by taking away from the material: In painting, by adding something to the canvas. In analysis, we bring out the true form by taking away the neurotic distortions. However, as in sculpture, we must have, if only in rudiments, an image of that which needs to be brought into its own. The patient, in such a way he contributes of himself to the analyst, and provides rudiment infractions of such a continuous image of fragmented fluctuations imbedded by distortion - an image that the analyst has to focus in his mind, thus holding it in safe keeping for the patient to whom it is mainly lost. It is this tenuous reciprocal tie that represents the germ of a new object-relationship.
 The objectivity of the analyst regarding the patient’s transference distortions, his neutrality in this sense, should not be confused with the ‘neutral’ attitude of the pure scientist toward his subject of study. Nonetheless, the relationship between a scientific observer and his subject of study has been taken as the model for the analytic relationship, with the following deviation: The subject, under the specific conditions of the analytic experiment, directs his activities toward the observer, and the observer expresses his findings directly to the subject with the goal of modifying the findings. These deviations from the model, however, change the whole structure of the relationship to the extent that the model is not representative and useful but, in earnest, very much misleading. As the subject directs his activities toward the analyst, the latter are not integrated by the subject as an observer: As the observer expresses his findings to the patient, the latter are no longer integrated by the ‘observer’ as a subject of study.
 While the relationship between analyst and patient does not possess the structure, scientist-scientific subject, and is not characterized by neutrality in that sense by the analyst, the analyst may become a scientific observer to the extent to which he can observe objectively the patient and himself in interaction. The interaction itself, however, cannot be adequately represented by the model of scientific neutrality. Using this model is unscientific, based on faulty observation? The confusion about the issue of countertransference relates to this. It hardly needs to be pointed out that such a view in no way denies or reduces the role scientific knowledge, understanding, and methodology play in the analytic process, nor does it have anything to do with advocating an emotionally-charged attitude toward the patient or ‘role-taking’. In that a showing attempt to disentangle the justified and requirement of objectivity and neutrality from a model of neutrality that has its origin in propositions that may be untenable.
 One of these is that therapeutic analysis is an objective scientific research method, of a special nature to be sure, but falling within the general category of science as an objective, detached study of natural phenomena, their genesis and interrelations. The ideal image of the analyst is that of a detached scientist. The research method and the investigative procedure in themselves, carried out by unspecified scientists, are said to be therapeutic. It is not self-explanatory why a research project should have a therapeutic effort on the subject of study. The therapeutic effect appears to have something to do with the requirement, in analysis, that the subject, the patient himself, gradually becomes an associate, as it was, in the research work, that he himself becomes increasingly engaged in the ‘scientific project’ which is, of course, directed art himself. We speak of the patient’s observing ego on which we need to be able to rely to a certain extent, which we attempt to strengthen and with which we collaborate among ourselves. We encounter and make to some functional applicability of what is known under the general title, ‘identification’. The patient and the analyst acknowledge the fact for being equally increasing to the evolving principles that govern the political nature as deployed to the accessorial evolution for a better and mutually actualized understanding, if the analysis proceeds, in their ego-activity of scientifically guided self-scrutiny.