Psychochemistry: Personality by Prescription

As anyone can plainly see, this is one of mankind's strangest eras. On the one hand, all is pessimism: The world is plagued by violence, starvation, overpopulation and alienation. Yet never have so many well-informed men been so rosily optimistic: There is a strong school of thought holding that all our problems are basically chemical and will soon yield to solution as readily as the question of what happens when two atoms of hydrogen join with an atom of oxygen. (In case you have forgotten, H2+O=H2O; namely, water. As simple as all that.)

It is typical of our era that Dr. Glenn Seaborg, chairman of the Atomic Energy Commission, should have taken time out from worrying about the atom to tell an audience of women, not entirely in jest, that they will soon have a marvelous "antigrouch pill" to sweeten the dispositions of their menfolk. (Presumably, it could be slipped into the unsuspecting male's morning coffee, like a lump of sugar, to turn him from terrible tiger to purring kitten.)

It is also typical that two other respected thinkers, one a scientist and one an author, should have placed the rather humorous-sounding antigrouch pill on a serious global basis. The scientist, Dr. Heinz Lehmann of Canada's McGill University, has predicted an "antiaggression drug" that will overcome what seem up to now to be the natural human tendencies to pick quarrels and to make war. The author, Arthur Koestler, claims in his The Ghost in the Machine that most of man's troubles are caused by a conflict between his "old brain," which controls his emotions, and his "new brain," which determines his thoughts; this gap will eventually be bridged by a drug that will give us all a "coordinated, harmonious state of mind," making us far too contented to fret or to fight.

There are also respected researchers on record as believing that man will soon have drugs that will cure his major mental disturbances, eliminate his fears and anxieties, keep him fat or lean at will, let him decide for himself how long, if at all, he cares to sleep, make him much smarter than ever before and even permit him to live longer. You name it and there is somebody—not a wild-eyed visionary but a sane and skeptical scientist—who believes it is just around the corner.

Are we really on the verge of a chemical breakthrough in the control of human personality?

If you were a psychiatrist at a mental hospital, you would have to think so. You might be inclined to say, indeed, that the breakthrough has already been made. What has happened in the mental hospitals has taken place so rapidly and spectacularly that the events have outsped communications; they constitute one of the great untold and unappreciated stories of our time. Few people know about it except the veteran staff members who worked in the hospitals in the old days—meaning before about 1955—and who work there yet.

In the mid-Fifties, there were 560,000 patients in mental hospitals and the figure was rising by 12,000 a year. For all practical purposes, the hospitals might have borne the same legend that Dante said was inscribed on the gates of hell, "All hope abandon, ye who enter here." Some of the patients were in strait jackets, lest they kill one another or the guards. Some of them were in wet packs—wrapped in wet sheets in a bathtub—in an attempt to cool them down. The wards were full of men and women tearing out their hair, cursing, using the floors for toilets. Even the calmest of the patients were terrified of the future. The staffs were overworked and frustrated; there was time only to guard the overcrowded buildings and prevent trouble, no time at all to practice the intensive psychotherapy that was then considered the only possible glimmer of chance for improvement. Everybody knew that the very atmosphere of a mental hospital was enough to drive a normal man crazy, that almost nobody could be expected to recover there; yet for the hopelessly disturbed patients of the day, there was no alternative.

Into this dismal picture, one day, there suddenly dropped the first of the chemical weapons against mental disease—two tranquilizers discovered at almost the same instant, chlorpromazine and reserpine. Physicians gave one or the other to their most difficult patients and sat back in utter disbelief. Dr. Nathan S. Kline, the veteran research director of New York's Rockland State Hospital, still displays the excitement of the successful explorer when he recalls what happened: "We knew the minute we tried the drugs that this was it. We knew it not after the first one hundred patients, not after the first fifty, but after the first six."

Today, of course, there are many tranquilizers, all of which have a remarkably benign effect on the schizophrenic patients who have the world's most crippling psychosis. There are also drugs to combat the symptoms of depression, another common psychosis, as well as the symptoms of the manic state that often alternates with depression. The atmosphere in the mental hospitals has totally changed. They are less crowded now—425,000 patients instead of 560,000. The patients are far less destructive, far less terrified, far more "normal" in their behavior. The staffs have more time to treat the patients, with individual or group psychotherapy as well as medicine. And patients do recover; more than twice as many as before go back to rejoin their families and to work at jobs, like anybody else. In human terms, the improvement is nothing short of magnificent. Even in cold financial terms, the drugs to control mental disturbances have been of astounding value. Dr. Kline estimates that they have saved the U.S. some 20 billion dollars in the cost of new buildings and beds and continuing care that would otherwise have had to be provided for the mentally disturbed.

All this, in the almost unanimous opinion of the researchers, is only the beginning. It is a cliché in psychiatric circles to say that the present mind drugs do not cure mental disturbance but only relieve the symptoms, thus enabling the patient to live a more normal life and sometimes making him amenable to the talking-out benefits of intensive psychotherapy that may get at the roots of his conflicts. That is to say, most psychiatrists and psychologists and almost all psychoanalysts continue to believe that mental disturbances are usually functional—caused by some kind of disturbance in personality dynamics—rather than due to physical causes. Yet even the functional theorists tend to believe that better drugs are on the way. Dr. Sherwyn Woods, director of graduate education in psychiatry at the University of Southern California, is, for example, one of those who believe that the basic cause of schizophrenia lies in functional problems in thinking and human relations. Yet Dr. Woods also believes that the functional problems lead to or are associated with biochemical disturbances that determine the symptoms of schizophrenia, and he believes that even the most stubborn symptoms will mostly prove treatable with new drugs. "Within twenty years," he says, "we should have chemicals that are effective in controlling hallucinations and delusions and making patients far more comfortable than they are even today."

Even more optimistic are those psychiatrists who, impressed by the success of the tranquilizers and antidepressants, are beginning to think that all serious mental disturbance is basically biochemical in nature, some kind of abnormal bodily chemistry that poisons the brain and makes it act in strange and unfortunate ways. Dr. Kline, for example, says flatly, "I think schizopherenia is probably an organic disorder, and I'm almost sure that 80 percent of depressions are organic." In his private practice, Dr. Kline relies strictly on medications and no longer practices any psychotherapy at all. ("Some of my patients," he concedes, "seem to be disappointed that I don't ask them about their sex lives and masturbation and sibling rivalry and all that; I guess I lose some of them that way.") And Dr. Kline is one of those who forecast that new medicines will prevent even that currently hopeless form of psychosis caused by damage to the brain due to senility. ("The trouble with the human brain," he says, "is that it's grown too big for the human skull; it doesn't get enough blood supply, especially as we get older. But someday we'll find a new way of nourishing it and keeping its cells from dying off.")

If all psychoses are organic, then all of them theoretically can be cured—or at least controlled, completely and permanently, like disbetes—with the right kind of medicine. Indeed, a situation might arise similar to one of the present ironies in physical medicine. Nowadays, it is almost better to have pneumonia, which can easily be cured with antibiotics, than a common cold, for which no cure exists. Someday it may be better to have a mahor psychosis, curable with some specific drug of the future, than to have one of the minor psychoneurotic disorders, such as an anxiety state or a sexual obsession, which even Dr. Kline and his fellow theorists consider to be functional in origin and treatable only with psychotherapy.

What is the layman to think about the argument of functional versus organic? Until recently, the functional viewpoint had all the better of it; all attempts to find a physical basis ended in either failure or controversy. Now, however, the scales may be tipping; there is strong new evidence that any one of several physical abnormalities may be associated with schizophrenia. One of them concerns a part of the blood plasma known as alpha-2-globulin. This substance is present in everybody's blood stream; but in the blood of schizophrenics, it has been found in amounts far above normal. The finding is particularly impressive because it was made independently by three research laboratories, two in the United States and one in the Soviet Union. One of the researchers, Dr. Jacques Gottlieb of the Lafayette Clinic in Detroit, theorizes that an excess amount of alpha-2-globulin may bore its way into brain cells and cause them to function something like a short-circuited switchboard.

Another possibility also has been discovered by several researchers, among them, C. A. Clark of the University of Liverpool; they have found that the urine of schizophrenics, but not the urine of normal people, often contains a complicated chemical called DMPE. This chemical has a structure that is similar both to adrenaline, which is secreted in large amounts by the human adrenal gland in states of stress and emotion, and to mescaline, a chemical found in a Southwestern cactus plant that was chewed by primitive American Indians to produce a binge that looks for all the world like some forms of schizophrenia. The Clarke findings would seem to indicate that schizophrenics, owing to some hereditary defect in burning off their adrenaline, might be continuously intoxicated by a mescaline-like chemical produced by their own bodies.

Without much fanfare, this sort of possibility has now been carried a step further. Dr. Mark D. Altschule, a Harvard scientist, and his colleague Dr. Zoltan L. Hegedus have announced the discovery, made in a test tube, that human blood contains enzymes that can convert adrenaline into several chemicals called "brain poisoning indoles," presumably capable of causing all kinds of mental aberrations. Moreover, reported Drs. Altschule and Hegedus, the tendency to produce large quantities of these indoles seems to be greater in schizophrenics than in normal people and also to be hereditary; it appears to be higher among the relatives of schizophrenics than among other people. Score another point for the theory that the body and brain of the schizophrenic might be a sort of hereditary chemical factory for converting adrenaline into its own intoxicants.

A great many scientists are now working on biochemical research into mental disturbances, following these leads and seeking new ones. Even Dr. Linus Pauling, the Nobel Prize winner, came out this year with a new organic theory of mental disturbance. Dr. Pauling has decided that normal mental functioning depends on the presence of many kinds of molecules, including those of many of the B vitamins, vitamin C, uric acid and other substances normally present in the brain. The average person, Dr. Pauling contends, gets enough of these substances from his daily diet or produces them in sufficient quantity through his own bodily chemistry. The mentally ill person, however, owing to some kind of hereditary difference, needs more of them, because he burns them off faster or cannot produce them as efficiently. His bodily chemistry, especially the chemistry of his brain, is off in such a way as to make him suffer, in effect, from a deficiency disease, like rickets or scurvy. The way to treat him, say Dr. Pauling, is to pinpoint the deficiency and correct it—a new kind of treatment that he calls orthomolecular psychiatry (meaning to provide the right amount of the right molecules at the right time and place). Dr. Pauling's theory has been challenged by some psychiatrists— but his record shows that it is hardly safe to dismiss his ideas.

There is one form of brain abnormality, it should be added, that has been treated successfully with a specific drug for many years. This is epilepsy, not a psychosis but a strange disorder in which parts of the brain seem to become overexcitable, leading from time to time to what might be called electrical explosions, accompanied by seizures ranging from mild blackouts to intense convulsions. Julius Caesar suffered from epileptic "fits," and so would more than 1,000,000 people today, were it not for a drug called Dilan-tin. Taken daily, Dilantin restores the brain's nerve cells to normal excitability and prevents them from firing too quickly or too often; its use permits most epilepsy patients to lead perfectly normal lives, free from fear of a seizure. Recently, there has been speculation that Dilantin may also relieve some kinds of depression, control irrational anger and break the obsessive, "round-and-round" thinking patterns that seem to plague many people. (The noted financier Jack Dreyfus. Jr., who reports that his own mood and thinking abilities have been greatly improved by Dilantin, has set up a foundation to explore these possibilities.)

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Besides relieving the symptoms of mental disease—or possibly even curing it—what else can the chemical breaking through do? One thing it has already done is revolutionize human sexual behavior; for the first time in man's history, it has separated the sex act from the act of procreation. To most Americans today, the word "pill" means one thing first and foremost—the birth-control Pill, 99.7 percent effective in preventing pregnancy. The pill is by far the most efficient method of birth control ever invented; indeed, it is the only sure method, short of sterilization. It works by delicately tinkering with the female hormone cycle and thus preventing the monthly release of a ripe egg. No egg, no pregnancy—regardless of when sexual intercourse takes place.

As good as the pill is, it has some disadvantages. Some women object to the fact that it must be taken every day for 20 days and then stopped for eight days; they have trouble remembering. Never mind. Soon a woman will be able to go to her physician and get a single shot that will do the job for three months, and no remembering necessary. Or if she finds it more convenient, she will switch to the new "minipill," already tested and found effective. This one will be taken every day of the year, and no need to consult the calendar. The same hormones used in the minipill could even be implanted under the skin, in a slightly (continued on Page 134)Psychochemistry(continued from page 112) porous capsule that would permit the proper dose to leak into the blood stream each day. Without causing any undue problems, the capsule might be large enough to last for 20 years, thus constituting a sort of "20-year pill." (If the woman decided at any time during this period to have a baby, she would simply take another kind of chemical to cancel out the effects of her 20-year pill.) Or, if the right technique can be perfected, it is entirely possible that the woman of the future can have herself vaccinated against pregnancy; this would be done with a serum producing antibodies in her blood stream that would make her immune to the effect of sperm, just as present vaccinations make her immune to smallpox germs. The woman who has sexual intercourse only rarely, and does not want to bother with any of the other techniques, may be able to indulge without fear of pregnancy because of the availability of the "morning-after pill," already tested but not yet perfected; the morning-after pill will prevent the fertilized egg, if there should be one, from becoming implanted in the wall of the womb. Even pills for men, safely making them temporarily sterile by preventing the development of living sperm, are theoretically possible. In fact, one such pill has already been found effective; it has never been marketed, because the user suffers a violent reaction if he takes as much as a single alcoholic drink.

The pill already controls pregnancy, and more convenient versions of it are just around the corner. What about that other fear of so many women (and of men as well)—the problem called obesity? Here one gets into difficult psychological ground. Many psychiatrists think that people get fat strictly as a form of self-protection: the overweight man is shielding himself (or, more often, the overweight woman is shielding herself) from life's obligations to be socially attractive and adept and to lead a normally active sex life. Making a fat person skinny, according to this school of thought, will only add to his (more often, her) anxieties. Yet it is well known that bodily weight depends upon how much food is eaten, and the amount of food that is eaten seems to depend upon two small areas in the brain. When one of these areas is removed from the brain of a rat, the animal loses almost all interest in food; it has no appetite at all to speak of. When the other area is removed, the animal seems to be constantly hungry and soon becomes grossly fat. Taken together, the two areas serve as a sort of "appestat" that says when to eat and when to stop. Why not assume that the fat person's appestat is simply off kilter—in a way that could be corrected by some specific drug? (There already are drugs that can reduce appetite after a fashion, but all of them are also stimulants and therefore not specific.)

What about drugs to make people happy—not just to get them out of depressions or to tranquilize them but to make them actively and buoyantly happy? We already have drugs that put people in a happy mood; the most accepted one is alcohol, and among the legally forbidden ones is marijuana. But alcohol and marijuana are what one researcher calls "sloppy drugs," even though alcohol is such an integral part of social ritual that it will probably always remain on the human scene. There undoubtedly are better drugs, just waiting to be discovered, that would make a person wake up smiling and sing through his day, without ever affecting his mental judgment or getting him in trouble with the law. There probably also are drugs yet to be found that will enhance a person's ability to perceive the beauty in his world—to recapture the delight of the child who thinks of a shiny penny as not only a piece of money but an object of art. And if human perception can be enhanced, why not human intelligence?

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Intelligence is a strange thing; the unhappy fact is that no one even has an acceptable theory as to why one person should be smarter than another. Certainly, intelligence (or lack of it) depends in some way on the brain, whose trillions of possible nerve circuits act as a feedback system that absorbs information from the eyes and ears, processes it, stores it and at the appropriate time sends it back to the vocal cords, to be uttered as words of wisdom, or to the finger tips, to become the written evidence of learning. But why one brain should be better at this job than another is a mystery. Mere size does not tell the story; most human brains run about three pounds and deviations from this weight are not necessarily related to intelligence; there doubtless have been Eskimo fishermen with bigger brains than Einstein's. Mere numbers are not the answer; while the genius has upward of ten billion nerve cells in his brain, so in many cases does the low-grade moron. (Indeed, a young low-grade moron may have more brain cells than an older genius, for these cells die off at the rate of 100,000 a day after a person reaches 35.) The efficiency of the nerve cells and their fibers as conductors of the nervous impulse does not seem to be crucial; the long fibers that stretch from our spinal cords and enable us to wiggle our toes, and that presumably have scant effect on how' smart we are at atomic physics, are better and faster conductors than the fibers inside the brain.

There has been much speculation that learning depends upon a permanent alteration of a living chemical called RNA inside the nerve cell; this theory stems from the work of a Swedish scientist named Holger Hydén, who trained rats to balance on a wire, then analyzed individual nerve cells and found changes in the molecular structure of their RNA. This chemical is closely related to DNA, which carries the code of human heredity (see Second Genesis, Playboy, June 1968); and, like DNA, it is so complicated in structure as to be capable of taking trillions of possible forms, each a little unlike any other. If the molecules for DNA can contain the entire code that directs the development of some cells into the human bone structure and others into the human heart, and can make some people tall and brown-eyed and others short and blue-eyed, then it seems reasonable to suppose that the RNA molecules inside the nerve cells might possibly carry the code for all the most complicated details of human learning.

More recently, Dr. Hydén has reported a further complication involving the 100 billion so-called glial cells that support and help nourish the nerve cells of the brain. In a new experiment, he trained right-handed rats to use their left paws to pull food from a tube, and left-handed rats to use their right paws. When he analyzed their brains, he found not only altered RNA molecules but also new forms of protein. It is his theory that the RNA instructed the glial cells to manufacture these new proteins, which then became part or all of the memory trace. Another investigator working along similar lines with pigeons, Boston's Dr. Samuel Bogoch, has also reported finding new brain proteins—plus, just to add another complication, new chemicals that are a combination of protein and sugar.

If learning depends on chemical changes of the RNA inside nerve cells, or on the manufacture of new chemicals as directed by RNA, then some exciting possibilities open up. Researchers have been quick to explore them, and the result has been a series of the most fascinating—and controversial—experiments in all scientific history. The first occurred at the University of Michigan, where a psychologist named James V. McConnell taught some primitive little animals called flatworms to escape a shock signaled by a flashing light, then chopped them up and fed them to some other flatworms. The "cannibals," he found, were unusually quick to solve the problem of escaping the shock—for all the world as if they had absorbed knowledge along with their food.

As if this were not enough of a scientific sensation, psychologist Allan Jacobson of UCLA soon came up with a topper. Using rats and hamsters, he taught half (continued on page 182)Psychochemistry (continued from page 134) of his animals that they could get a food pellet by pressing a bar whenever a light flashed; the other half, whenever a click sounded. When they had thoroughly learned their lessons, he killed them, extracted RNA from their brains and injected the RNA into a new group of rats and hamsters. Lo and behold, he found that the new animals injected with RNA from those trained to respond to a light flash showed a significant tendency to do the same thing. Those who received RNA from the click group showed a strong tendency to respond to the click. This time, it appeared that learning had been transferred with a hypodermic needle.

The implications of these experiments are fantastic. They would seem to forecast a day when the laborious process of education could be short-cut; college students would learn about atomic physics not by hitting their books but by receiving injections of surplus RNA from the brains of their instructors. The immense learning of a man such as Einstein could be preserved by feeding slices of his brain to a selected group of young scholars. But, alas, this whole area of transfer of learning is currently surrounded by doubt. Shortly after Dr. Jacobson reported his findings, other scientists tried to duplicate his results; 18 such experiments were set up and all 18 failed. The question now is whether he did something wrong or the other experimenters did, and an attempt to find the answer is being made in many laboratories across the nation. Some of the early results look promising for transfer of training, and one scientist who took part in the 18 experiments that appeared to prove Dr. Jacobson wrong has now changed his mind. But other results have thus far been inconclusive or flatly negative. At the moment, it appears to be the majority opinion among scientists that transfer of learning is impossible and the RNA theory of memory, dubious.

If not the RNA inside the nerve cell, then what about the myriad switching points inside the brain? As everyone who has taken a freshman psychology course knows, each nerve fiber ends in branches that form connections called synapses with other nerve fibers. The nervous impulse, though it is a tiny electrical charge, cannot leap like a spark of electricity across a synapse. Instead, it can only trigger the release of a chemical that may or may not stimulate the next nerve to fire. Could it be that efficiency at getting a message through the synapses is the reason one person is brighter than another?

Under the electromicroscope, it would not seem so, for all synapses look remarkably similar. There seems to be no reason to think that the synapses are any closer or tighter in the genius than in the dullard or, for that matter, than in the monkey. On the other hand, it is known that learning can cause a nerve cell to grow, like a tree proliferating its roots and branches, and form additional synapses with other nerve cells from which it had previously been isolated (just as the tree taps new sources of food and light). At the same time, other changes take place that may act as a sort of soldering of connections at the synapses.

Some quite remarkable results have been reported by Dr. David Krech, a psychologist at the University of California at Berkeley, who had the ingenuity to undertake what he has called a Head Start program for young rats. He placed the rats together in a special cage, where they could react not only to one another but also to all kinds of "creative playthings," such as ladders to climb and wheels to turn; at the same time, they could watch all the sights and hear all the sounds of a bustling human laboratory. Simultaneously, he raised their twins in solitary confinement, in quiet and dimly lit cages, where they got no intellectual stimulation at all. The Head Start rats proved much smarter at solving rat-type problems than did their twins, and post-mortem examination of their brains showed some striking differences. The cortex—the highest or "thinking" part of the brain—was much better developed. The nerve cells were bigger; there were more glial cells and larger blood vessels. Moreover, the cortex contained more of the enzyme (called acetylcholineesterase) that acts to transfer the nerve impulse across the synapse.

In thinking of a "smart pill" that would improve human intelligence, perhaps it does not matter whether the feedback circuit depends on RNA, the synapses or something as yet unimagined. One scientist who has speculated on this point is Dr. John Eric Holmes, a physiology professor at the University of Southern California Medical School, whose learning experiments have even included an unsuccessful attempt to teach the mimosa to fold its leaves in response to light and darkness as well as to touch. Says Dr. Holmes, "Whether RNA is the key or a blind alley, it still should be possible to increase an individual's learning ability." Indeed, the world already possesses a smart pill that has worked, for reasons unknown, on mice. As Dr. James L. McGaugh has found at the University of California at Riverside, injections of such powerful central-nervous-system stimulants as strychnine or Metrazol can greatly improve the ability of a mouse to learn a maze. The effect seems to be more pronounced for dull mice than for smart mice, possibly indicating that the ideal smart pill, when it is discovered, will do more for the mentally retarded than for those who are already near the biological limit of human performance. At least two drug companies are known to have been testing such a pill for human beings, composed of chemicals much less lethal than strychnine but nonetheless promising.

Just as it has been found possible to stimulate learning in lower animals, so has it been found possible to stop learning. Dr. Murray Jarvik, at the Albert Einstein Medical School in New York City, has experimented with rats placed on a small platform above the floor of a cage. The rat's natural tendency is to very quickly step down from the platform. If it gets a painful electrical shock from the floor, however, it learns right then and there to stay on the platform; the next time, it will remain there without budging for as long as the experimenter cares to wait. What Dr. Jarvik has done is to teach a rat to expect the shock, then quickly disrupt its brain chemistry by using a sort of electroshock treatment. The next time the rat is placed on the platform, instead of remembering its lesson, it steps right down, as if it had never learned to expect a shock. (Human beings who undergo electroshock treatment also lose their memory for recent events.)

At the University of Michigan, Dr. Bernard W. Agranoff has blotted out the memories of goldfish by injecting them with puromycin, an antibiotic drug that interferes with the ability of RNA to perform its normal function of synthesizing new protein materials inside the cell. He teaches the goldfish to avoid an electric shock by swimming across a barrier to the unlighted end of its tank; if he then immediately injects puromycin into the fish's skull, all memory of the training vanishes. Oddly enough, even a "stupid pill," such as puromycin seems to be, might have value to human beings. As Dr. Krech has pointed out, a drug of this type might boost the learning ability of a person who remembers so many details as to get hopelessly bogged down at the task of sorting out what is essential.

In functional terms, human intelligence or learning ability seems to depend on three quite different skills. First, one must be able to pay attention, to concentrate, to get the message or, in the words of Dr. Sidney Cohen of the UCLA Medical School, to "comb down on the problem." Next, one's brain must lay down some sort of lasting memory trace, perhaps in the form of changed RNA molecules, perhaps in the form of proteins manufactured under the direction of RNA, perhaps in chemical changes at the synapses, perhaps in some other way. Lastly, one must have a retrieval system, a method of scanning the memory traces and focusing on the right one. "All three processes," says Dr. Cohen, "could possibly be improved chemically; so I see no reason chemicals couldn't be contrived that would improve our thinking abilities." The smart pill may be not just one pill but several, to influence the various processes involved in learning. The drugs may work best, as Dr. Krech's studies would indicate and as Dr. Cohen also believes, in conjunction with improved psychological methods of training and disciplining that wonderful and as-yet-unrealized instrument called the human mind. But they seem to be merely waiting for a discoverer.

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Like intelligence, sleep is another of nature's great mysteries. We need sleep; many of us need eight hours'; we must spend a full third of our lives in this state of unconsciousness. But why? At one time it was thought that the waste products of normal activity accumulated in the blood stream and eventually drugged the brain; while the body was at rest during sleep, these waste products were then eliminated. But studies of Siamese twins, who share a common blood stream, have disproved this theory; scientists have observed one Siamese baby sound asleep while the other remained wide awake. Now, sleep has been traced to two centers in the brain. If one of these centers is removed from an animal, it will sleep constantly. If the other is removed, it will not sleep at all—but eventually, proving that sleep is a biological necessity, it will go into a coma and die, as if from utter exhaustion.

Brain waves change during sleep; indeed, electroencephalograph studies of human beings have shown four recognizable patterns of waves that seem to indicate four stages of sleep, ranging from light to very deep. Obviously, something goes on during sleep, certainly in the brain and possibly elsewhere; this something is essential to good health and even to staying alive. But why this should be is unknown. Dr. Nathan Kline, one of the researchers who have been fascinated by the problem, speculates that at the beginning of mankind's history, perhaps not all men needed to sleep. But man's nighttime vision is poor; a man who wandered around through the darkness would have been subject to accident and fair game for beasts of prey. Thus, evolution favored those men who, for some reason, were forced by the requirements of their own brains and bodies to spend the hours of darkness in a state of suspended animation and in a protected spot. If Dr. Kline's thoughts are correct, we sleep today, though there is no longer any evolutionary need for it, because only those of our ancestors who required sleep managed to survive and pass along their trait. Dr. Kline has also pointed out that the old Mogul emperors, in contrast to most more-or-less-modern human beings, are said to have got along just fine on no more than three-and-a-half hours' sleep a night. Was this also an inherited trait, passed along by some strange evolutionary accident? Or did the Mogul emperors have a drug?

Some drugs have already been found to reduce the need for sleep; patients who go on the antidepressants often find themselves, like the Mogul emperors, getting along on three to four hours' for as long as they take the medicine. (These medicines are usually prescribed for only brief periods; what would happen to the patients if they continued to sleep so little is not known.) At any rate, there seems scant doubt that the mystery will eventually be solved. Says Dr. L. R. Hines, director of biological research for the Hoffmann-La Roche drug company, "There's unquestionably a biochemical explanation for sleep and someday somebody will find it." Will this mean that we will then simply swallow a pill when tired, instead of going to bed? Conceivably, it will mean exactly that.

If science can promise us a pill that will end the need for sleep, then why not something that is really far out? Why should science not bring true the ancient dream of a Fountain of Youth and give us some magic elixir that will keep us young and active to an age denied to previous generations? Why not, indeed? One scientist who believes the dream may be within grasp is Dr. Denham Harman of the University of Nebraska Medical School, who has already had considerable success in lengthening the life expectancy of his laboratory mice. Dr. Harman's secret is hardly a secret at all; it is nothing more than a well-known chemical called BHT, commonly used to prevent spoilage of the fats and oils in potato chips and bottled salad dressings. When Dr. Harman fed his mice a special diet including BHT, they lived 50 percent longer on the average than other mice of the same breed—presumably because the BHT slowed down some of the chemical reactions inside the body that cause aging and eventually death. He has not yet had much luck at increasing the maximum age to which the hardiest of his mice live; in human terms, he has helped more of his mice live to 80, rather than pushed the maximum age to 120. Moreover, a good deal of additional testing must be done before anyone would recommend for the human race a daily dose of BHT or something similar. But Dr. Harman is convinced that an increase in the human life span, through diet and the addition of chemicals, is almost sure to come.

Dr. Harman's predictions, of course, raise an interesting philosophical problem. It has long been accepted that the benefits of science and medicine should belong to everyone. But suppose the day actually arrives when science has a pill that will lengthen the human life span. Should everyone have it—the moron as well as the genius, the criminal as well as the philanthropist? Would a Republican Government try to limit it to Republicans and a Democratic Government to Democrats? At this time, when overpopulation threatens man's future, should anybody at all be entitled to the pill?

The antisleep pill would also introduce some tricky new problems into human affairs. Social scientists are already worried about the new age of leisure that is being spawned by automation; they wonder how man will ever manage to fill his time. How would he occupy himself if he suddenly found his waking hours, thanks to an antisleep pill, increased by one half? As for the smart pill and the stupid pill, if these are perfected, who will decide who gets which? If the smart pill creates a world in which everyone is equally bright, will man be happier, or will his affairs grind to a halt?

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Even today's drugs have already created problems—for example, the tranquilizers. When a tranquilizing drug is given to a mental-hospital patient who would otherwise murder the attendants or beat his own head bloody against a wall, there seems to be no moral issue involved. But what if the same tranquilizer, or one of its cousins, is taken in large doses by an ordinary, everyday, more-or-less-normal person who is not about to do himself or others any harm, is getting along all right at his job, has no burning personal conflicts and merely likes the relaxed and easygoing feeling that the medicine produces, just as he might like to take a cocktail or two before dinner?

In this early stage of the pharmacological revolution, there already are millions of people in the U.S. who are on some kind of behavior-controlling drug. Physicians write more prescriptions for various kinds of tranquilizers, antidepressants, sleeping pills and pep pills than for medicines to combat pain or heart disease; about a third of all new prescriptions written this week by doctors across the nation will be of this type. (So great is the demand that the doctor has to write the prescription, whether he believes the patient needs the drug or not, else he loses the patient to another doctor.) In some circles, especially among businessmen and middle- and upper-class housewives, pills to calm jittery nerves or to help get the day's work done are a chief topic of social conversation. At parties, people exchange pills like recipes or golfing tips: "Here, try one of mine." "This pill has made a new man of me; take one and see." "My pills don't seem to be working anymore; let me have one of yours."

The thought of all this is already working as a sort of antisleep pill for researchers in the drug field; worrying about it causes them many a restless night. In the first place, all known drugs have side effects; even the common aspirin tablet possesses its dangers, and the behavior-controlling drugs are far more potent than aspirin. Some of them cause temporary sexual impotence; some of them create muscular pain or spasms so severe that a doctor who did not know the cause might well be inclined to perform surgery. Some drugs are dangerous when taken along with alcohol or sleeping pills; some will shoot blood pressure to alarming heights when taken along with even such a common food as cheese. Some are addicting and some, if improperly used, can actually kill the patient. Thus, the indiscriminate passing around of pills is the most risky kind of self-medication. "The potential hazards," says Dr. Sherwyn Woods, "are really horrendous."

Besides the physical dangers, there are also moral dangers; this is especially apparent today in the case of the tranquilizers. "Who's to say," asks Dr. Woods, "what the appropriate level of tranquillity is? Certainly, we know that too much of it interferes with motivation and creativity. In fact, the kind of problem solving in general that has got man where he is today has been stimulated mostly by a lack of tranquillity." Dr. Cohen says, "I'm not in favor of reducing anxiety except when it gets to be disintegrating to the patient; I can't think of any kind of anxiety-free, conflict-free, challenge-free society that would be a worthy society. Muscles atrophy when they have nothing to work against, and so does the mind." And one drug-company executive adds, "The last thing on earth I'd want to see, in a world still as imperfect as ours, is everyone walking around so completely tranquil as to be oblivious to all the defects."

To most of the experts, the thought of an antiaggression drug, as suggested by Dr. Lehmann, or of the "harmony drug" suggested by Arthur Koestler, is one of the great hopes of the pharmacological age. "It would be wonderful," says Dr. Cohen, "if we could control criminality, violence and cruelty. And it certainly seems possible that we can find a calming agent, rather than a tranquilizer, that will reduce man's hostilities without taking the edge off his awareness and enjoyment of life." Yet even here there are conceivable dangers. If everyone in the U.S. were taking a calming pill and harboring not a single harsh thought toward anyone, our nation might be at the mercy of another aggression-bound nation that chose to ban the pill. Like the Industrial Revolution and the discovery of atomic energy, the pharmacological revolution has its hazards. We will have to learn to live with them, for the effects of the revolution are here to stay.