Exploring the Frontiers of the Mind

The most mysterious, least-known area of man's universe does not lie in the farthest reaches of outer space. Nor is it found in the most remote Amazonian jungle or in the inky blackness of the Mariana Trench. It is located instead in side the human skull, and consists of some 3 1/2 pounds of pinkish-gray mate rial with the consistency of oat meal. It is, of course, the human brain.

The brain is the most important of the body's organs. The heart, after all, is merely a pump; the lungs are an oxygenation system. But the brain is the master control, the guiding force behind all of man's actions. It is the seat of all human thought and consciousness, the source of the in genuity that made it possible for man's ancestors to survive and eventually to dominate their physically more powerful adversaries and evolve into the planet's highest form of life. Everything that man has ever been, everything he will be, is the product of his brain. It is the brain that enabled the first humanoid to use tools and that gives his genetic successors the ability to build spacecraft, explore the universe and analyze their discoveries. It is the brain that makes man man.

But it took man centuries to comprehend that there was a miraculous mechanism in side his head and begin to in vestigate its workings. Aristotle taught his pupils that the brain was merely a radiator or cooling system for the blood; he identified the heart as the organ of thought. Pliny the Elder was one of the first to identify the brain as "the citadel of sense perception." But nei ther he nor generations of scientists who followed him had the knowledge or techniques to explore it. Investigation was also stymied by philosophical obstacles. The brain was considered the seat of the soul; its nature and its workings were considered not only unfathomable but sacrosanct.

Now man has embarked on a great voyage of discovery. In dozens of lab oratories in cities round the world, psychologists, biologists, physicists and chemists, recognizing that what goes on inside the brain cannot be divorced from what goes on outside, in increasing numbers are poking, prodding and analyzing the organ in an attempt to unlock its secrets. Man has split the atom, cracked the genetic code and, in a Promethean step unimaginable less than a quarter-century ago, leaped from his own terrestrial home to the moon. But he has yet to solve the mysteries of memory, learning and consciousness or managed to understand himself.

The brain is the newest and perhaps last frontier in man's exploration of himself. Crossing that frontier could have the same impact on humanity as the discovery that the earth was round. "We are like the Europeans of the 15th century," rhapsodizes one brain researcher. "We're standing on the shores of Spain or Portugal, looking out over the Atlantic. We know that there is something on the other side and that our discovery of exactly what this is will mean that things in our world will never be the same again."

The rapidly growing interest and activity in brain research parallels an energetic, worldwide investigation of genetics that preceded James Watson and Francis Crick's 1953 discovery of the structure of the DNA molecule. Indeed, many outstanding biochemists and microbiologists who helped lay the groundwork for that monumental breakthrough have recognized that the brain now represents science's greatest challenge. Some have announced their conversion to neuroscience, the discipline that deals with the brain and nervous system. The work of the neuroscientists has already produced an exponential increase in man's understanding of the brain--and a good bit of immediately applicable knowledge as well. It has led to a host of new medical and surgical treatments for such disorders as schizophrenia, depression, Parkinson's disease and epilepsy. It has also resulted in improved and promising new techniques for relieving pain and controlling some forms of violence.

Even these accomplishments could seem insignificant once the modern Magellans attain their goal of understanding the brain's functions in thought, memory and in consciousness--the sense of identity that distinguishes man from all other known forms of life. Finding the key to these mysteries of the brain, a discovery that would suddenly explain these functions, could lead to better ways of treating the psychoses and neuroses that plague millions. It could result in identification and correction of the causes of many neurological disorders and, by revealing how the brain works, revolutionize thought, education and communication. It might even help man turn away from what some see as a headlong pursuit of self-destruction. "If man could discover why he is unique, he might not destroy himself," says M.I.T. Professor Francis Schmitt, one of the leading brain researchers (see box page 58). "He might respect himself more than he now does."

None of those engaged in neuroscientific research underestimate the difficulty of reaching that understanding, for the brain is an organ of enormous complexity. While a sophisticated electronic computer can store and recall some 100 billion "bits" of information, for example, the capacity of the brain seems infinite. The computer can make out a payroll, compute the trajectory of a spacecraft or figure the odds against drawing a straight flush far faster than any human. But the computer is, after all, a machine, capable of doing only what its human builders tell it to do.

The brain, on the other hand, performs a bewildering variety of far more subtle functions. It regulates man's heart and respiratory rates, controls his body temperature and tells him when to take his hands off hot stoves--all without his really being aware of that control. The brain keeps man in touch with the world around him by constantly sorting out the auditory, visual, olfactory, gustatory and tactile information his senses receive, processing it and enabling him to act upon it. It switches emotions on and off and regulates sexual drives.

Furthermore, the brain, unlike the computer, can repair itself: one area can learn to perform the functions of another in some cases of brain damage. And, unlike the computer, which can be turned off at the flip of a switch, the brain remains continuously active, whether waking or sleeping. It can, like an infinitely repeated image in a hall of mirrors, think about itself as it thinks about itself thinking about itself.

The scientific effort to fathom the miracle of the brain is proceeding on many fronts, often apparently unrelated. Some of the most fascinating yet arcane work in the neurosciences is being done by zoologists like Theodore Bullock, 58, of the Scripps Institution of Oceanography in La Jolla, Calif. He is studying electric fish in order to identify interior pathways of brain communication. That knowledge could lead to an understanding of how a brain communicates within itself. Other apparently tangential but vitally important research is being undertaken by Nobel-Prizewinning Immunologist Gerald Edelman, 44, of New York's Rockefeller University. Edelman notes that the immune system (TIME, March 19), which enables the body to defend itself against disease, is capable of memory. He has suggested that mechanisms similar to those that enable immunologically active cells to recognize

bes and other foreign material may also play a role in the brain's own memory system. The mechanisms could also conceivably tell cells where they fit into the "wiring diagram" of the brain while the organ is developing.

Most neuroscientists are conducting their research on cellular and subcellular levels, figuring that only by understanding how individual neurons work can they understand how the brain it self functions. "Studying the brain is like looking at a building called a bank and trying to figure out what it's for," says Dr. David Bodian, professor and director of the department of anatomy at Johns Hopkins University School of Medicine in Baltimore. "You can get some idea of its function by watching people go in and out. You can get an even better idea if you go inside and ob serve more closely."

The most advanced and exciting brain research now being conducted is directed toward discovering how the brain perceives, processes and stores in formation. Some scientists confine their work to only one area at a time; the brain is too complex and knowledge still too limited to do otherwise. Others, like Professor Hans-Lukas Teuber, 57, who heads M.I.T.'s department of psychology, insist on studying the three aspects together. "The way we perceive pat terns, whether through sight, touch or other senses," he says, "is intimately linked to the way we pattern our skilled movements, and both perception and movement inevitably involve problems of memory."

Teuber believes that such knowledge is essential for an understanding of high er brain functions, which intrigue him far more than investigations into so-called psychic phenomena. "The mys tery lies where we least expect it: in sen sory rather than extrasensory perception," he says. "What fascinates me is the way that you and I are able to sit opposite each other and make sounds that we receive, decode, process and then use as a basis for making more sounds. Now that is a real mystery."

Others, too, are interested in solving that mystery. Robert Galambos, 59, a professor of neurosciences at the University of California at San Diego, is at tempting to track auditory impulses from the ear, through the brain stem and into the cortex. He is studying several brain-wave patterns, including what is called the "Aha wave," which the brain generates when it finds what it is looking for.

Hugh Christopher Longuet-Higgins of the University of Edinburgh is trying to make computer models of the way people produce sentences and understand language. Floyd Bloom, 37, chief of the laboratory of neuropharmacology at the National Institute of Mental Health in Bethesda, Md., and Walle Nauta, 57, of M.I.T., are using special staining techniques to trace the brain's neuronal pathways. "We have a long way to go," says Bloom, "but every little piece of information we gather leads us toward a better understanding of the way that the brain reacts to the outside world."

Twin Mysteries. In their work, all of these researchers are striving toward two major goals: explaining learning and memory. Anatomically, there is no specific learning center in the brain, and there is no explanation for learning. "There is no known basis for learning; it cannot take place," says Teuber. "In fact," he adds jokingly, "as a teacher, I sometimes wonder if it does."

But learning does occur, and most researchers believe that a crucial factor in the process is protein synthesis--the creation of complex molecules. Steven Rose, 35, a professor at Britain's Open University, has found that as chicks were trained to master certain simple skills, certain brain proteins increased.

Sweden's Holger Hyden, 56, director of the Institute of Neurobiology at the University of Goteborg, has found even more convincing evidence that proteins play a role in learning. Hyden (pronounced he-dayn) trained rats and then killed them so that their brains could be studied. He found that certain nervous-system proteins were produced in greater amounts during the first part of learning, when the animals were striving to cope with a new problem; overtraining the animals produced no higher levels of the substances. Hyden then injected animals with antibodies against the protein, which is called S-100. The injection, which blocked the protein's activity, also caused the animals' learning rate to lessen markedly. Other findings tend to reinforce this conclusion. Protein-deficient rats learn much more slowly than well-fed animals. Also, protein-deficient children from poor families habitually trail better-fed, middle-class children in intellectual development, even when the children receive the same education.

Of equal fascination to researchers is the persistence of memory, the ability not only to store but also to recall information and experiences. In Proust's Remembrance of Things Past, Marcel released a flood of memories by tasting a tea-soaked petite Madeleine. Others have found that a memory-jogging whiff of perfume, a word, a few notes of music can conjure up similar--and often realistic--recollections of events they experienced many years earlier. A landmark discovery was made by the great Canadian neurosurgeon, Wilder Penfield, when he found that he could stimulate memories electrically. Probing a patient's brain with an electrode in order to locate the source of her epileptic seizures, Penfield was amazed when the young woman recalled an incident from her childhood in vivid detail. Penfield continued his studies and found that touching various parts of his patients' cerebral cortices with an electrode could enable them to remember songs long forgotten and experiences they thought were lost forever.

Subsequent experiments have proved that though the cortex is involved with memory, it does not act like a computer's memory bank, in which each bit of information is stored in a single electronic "cell." Memory, it has been found, is "delocalized" or spread throughout the cortex, and perhaps throughout the higher brain. Removing half the cortex may cause a proportional loss of capacity to remember, but it does not destroy specific memories.

Experiments and observations now support a three-level theory of memory. The lowest level is short-term memory, lasting no more than a few seconds; every moment of life, hundreds of sensory impressions flow into the human brain and are promptly forgotten. On the next level is medium-term memory, which lasts from a few minutes to a few hours, and enables man to remember something like a telephone number just long enough to dial it or to cram for an examination. At the highest level is long-term memory, which is sifted out of all the impressions and information entering the brain and preserved because of its importance, usefulness or vividness.

Long-term memory takes time to register permanently on the brain. If rats are given an electric shock immediately after learning a new skill, memory of the skill is lost. If the shock is delayed for half an hour, the memory is impaired. But if 24 hours elapse between learning and shock, most of the memory remains. Human beings react in the same way.

Most researchers agree that the limbic, or feeling brain plays a key role in long-term memory. The limbic system is concerned with affects--strong emotional experiences, for example--which people obviously remember. One part of the limbic system, the hippocampus, is indisputably vital to memory. Patients whose hippocampi have been destroyed or partially removed cannot recall new information. Dr. Robert Livingston of the University of California at San Diego postulates that the structure plays the same role in memory as the "now store" button does on a computer, determining whether a particular bit of information is to be stored or discarded.

Theoretical Leap. Many researchers feel that memories are stored and recalled by a combination of macromolecules or large molecules that probably differ considerably from one individual to another. Thus they reject the notion of some science-fiction writers that memory molecules--and thereby memories--may one day be transferred from one brain to another. "The immune response is a learned reaction," says Rockefeller University's Edelman, again citing the parallel between memory and immunology. "There is no Marcel Proust for immunology. I doubt that there's one for the neurosciences."

While focusing down on individual cells in the course of their investigations into the grand scheme of the brain, neuroscientists--like the Persian fairy tale's three princes of Serendip--have been making fortuitous discoveries that have already resulted in improved clinical treatment of several serious illnesses.

Among them:

SCHIZOPHRENIA. Doctors know that two groups of drugs, which include chlorpromazine and haloperidol, are remarkably effective in relieving the thought disorders, hallucinations and extreme withdrawal of schizophrenia, a chronic psychosis that affects one person out of every 100. Both drugs, if administered in excess, can produce symptoms similar to those of Parkinson's disease, a neurological disorder characterized by uncontrollable tremors and lack of coordination. Parkinson's disease is caused by a lack of dopamine, a substance that transmits nerve impulses, in the brain centers that coordinate movement. Biochemical and electrophysiological studies have shown that chlorpromazine and haloperidol block the action of dopamine. Thus brain researchers suspect that schizophrenia results, at least in part, from an excess of dopamine.

Another clue to schizophrenia, says Dr. Seymour Kety, chief of the psychiatric research laboratories at Massachusetts General Hospital, lies in the discovery of an enzyme in the brains of both animals and man that can convert normal brain chemicals like tryptamine to dimethyltryptamine, a well-known hallucinogen. Kety and other scientists speculate that in schizophrenics such a process may be out of control.

DEPRESSION. Some severe psychiatric illnesses can now be controlled chemically. Researchers have theorized that depression may result when certain brain substances called monoamines are either lacking or are broken.down too quickly. A new class of drugs neutralizes monoamine oxidase (MAO), the enzyme that destroys these substances. The drugs, known as MAO inhibitors, thus prolong the useful life of the monoamines in the brain. The drugs by themselves are not considered a cure for depression, but they can give relief to the victim of acute depression while psychotherapy attempts to get at the root of his problem.

PARKINSON'S DISEASE, which afflicts over a million Americans, could once be relieved only by severing certain nerve pathways deep in the cerebrum. While the operation relieved the tremors and rigidity of the disease, patients could suffer partial paralysis and loss of speech. Now, most Parkinson's victims can be relieved by a drug known as levodihydroxyphenylalanine, or L-dopa. First used successfully by George Cotzias of the Brookhaven National Laboratory, L-dopa provides a classic example of molecular chemistry at work. Normal movement depends in large part upon the action of dopamine, one of the brain's most important chemical transmitters. Parkinson's disease results from a degeneration of the cells that help produce this chemical. By boosting the level of dopamine in the brain, L-dopa helps to prevent the palsy associated with the disease.

The drug is also enabling doctors to take some tentative yet encouraging steps toward treating Huntington's chorea, a genetically-determined degenerative nerve disease that strikes its vic tims at about the age of 40 and kills them within 15 years. A group headed by Dr. Leslie Iverson, 36, of the British Medical Research Council's Division of Neurochemical Pharmacology, has been studying the chemical changes in brains of Huntington's victims. The team has found that victims of the disease have lower-than-normal quantities of the transmitter gamma amino butyric acid (GABA) and occasionally-elevated amounts of dopamine. They are now trying to develop drugs that will restore the balance between these chemicals.

EPILEPSY, which affects one person out of every 100 is caused by clusters of brain cells, or foci, that discharge electrical impulses paroxysmally. It produces violent seizures resulting in convulsions and unconsciousness, brief staring spells or episodes of uncontrollable rage. Researchers have discovered that most epileptic conditions can be controlled by a drug called Dilantin, which Dr. Frank Morrell, 47, of Chicago's Rush Medical College, believes prevents epileptic discharges from spreading to neighboring neurons.

A technique for relieving cases of epilepsy that resist treatment by drugs has been devised by Dr. Irving Cooper, 51, of St. Barnabas Hospital in New York. Cooper has found that stimulating the cerebellum electrically apparently increases its inhibitory action on the cerebrum. Cooper has implanted electronic "pacemakers" upon the cerebellums of several epileptics, as well as patients suffering from stroke-caused paralysis, cerebral palsy and from dystonia, a neuromuscular defect in which permanently flexed muscles twist and distort the limbs. The device, which stimulates the cerebellum with low-voltage jolts, has produced relief in most of the 70 cases in which it has been used. One muscular 26-year-old man suffered from daily epileptic seizures before he came to Cooper for a pacemaker. Since the machine was implanted a year ago, the man has been free of major seizures.

There are other areas in which neuroscientific research is paying dividends:

RELIEVING PAIN. Doctors are still not sure how the brain perceives pain, but some neurosurgeons have found ways of relieving the chronic and acute discomfort associated with terminal cancer and other diseases. Dr. William Sweet, chief of neurosurgery at Massachusetts General Hospital, has found that by destroying small clusters of cells in different parts of the brain, either by freezing or by electric current, he can relieve pain without producing the degrading effects of the old-style prefrontal lobotomy, which often produced antisocial behavior and, eventually, mental deterioration. He has also found a way of dealing with tic douloureux, an excruciatingly painful nervous disorder involving the trigeminal nerve of the face. With his patient sedated but conscious, Sweet places electrodes in the face and destroys certain small nerve fibers that transmit pain without harming those larger fibers involved in perceiving touch.

REDUCING VIOLENCE. Building on his earlier work, Sweet and others have also discovered that they can calm the violent outbursts of rage often associated with psychomotor epilepsy by destroying or partially removing the amygdala, an almond-shaped body in the limbic system of the brain. Sweet's onetime student, Dr. Vernon Mark, has performed amygdalectomies on 13 patients who exhibited violent behavior associated with a rare form of epilepsy. The operations reduced the frequency of their seizures and their aggressive outbursts. But the surgery produced no significant effects on their intelligence or ability to think.

BIOFEEDBACK CONTROL. A handful of yoga and Zen masters have known for centuries how to control such autonomic or involuntary nervous functions as heart and respiratory rates. Rockefeller University Psychologist Neal Miller has found ways to help those with a less spiritual outlook to achieve the same kind of control. Using devices that enable patients to monitor various body functions like blood circulation and heartbeat, Miller and other researchers have trained them to raise and lower their blood pressure and hand temperatures. The phenomenon, he explains, is basically no different from other forms of learning. All learning depends on some sort of feedback to the brain --from eyes, hand or other sources --that tells the student whether he is succeeding or failing in what he is trying to do. Biofeedback-monitoring devices simply enable the patient to tell when he is consciously controlling his involuntary functions. Miller's work has been capitalized upon by charlatans and mystics who insist that biofeedback can bring a kind of instant satori to those willing to spend money for lessons and equipment. But many legitimate researchers also believe that biofeedback may prove valuable in controlling moods and dealing with certain illnesses.

While neuroscientists look forward eagerly to the day when they will under stand how the brain works, some people feel that they have already gone too far. There are those who fear that new drugs and surgical techniques could be used to impose a form of "mind control" on nonconformists, tranquilize prisoners or inmates of mental hospitals, and tame those whose behavior or ideas society finds troubling. They note that psychosurgery is being widely used in Japan to calm down hyperactive children. They also observe with alarm the tendency of some school physicians to recommend drug treatment for these schoolchildren. Others, on a more philosophical level, are concerned lest the neurosciences succeed in erasing the factitious Line between "mind" and "brain" and reduce man to a collection of neurons.

Neuroscientists generally appreciate their concern. "It is a measure of the distrust with which science is now viewed that people automatically think first of the evil that scientific knowledge can bring," says M.I.T.'s Teuber. "It's as if we're suffering from some sort of Manhattan Project complex."

Most neuroscientists agree that their science can be abused but doubt that it will be. Schmitt, for example, feels that fear of thought control is unreasonable. "When it comes to thought control," he says, "politicians and journalists do a better job than neuroscientists." Instead, the brain researchers stress that the benefits resulting from their research would far outweigh the dangers. An understanding of how the brain works could lead to treatments for some forms of mental retardation. A greater knowledge of what takes place during learning could result in improvement in teaching techniques. Even human intelligence might be increased as a result.

A breakthrough could also lead to the kind of social evolution that might help prevent the conflicts that now set man against man and nation against nation. "Most of our evolution has been somatic," says Schmitt. "We've changed our shape. But if we could really understand ourselves and by extension each other, we could evolve socially as well." That kind of evolution, Schmitt contends, may well be necessary for the continuation of the species. "Armies aren't the key to man's survival," he says. "Governments are not enough. Treaties are not enough. Only self-knowledge will help man to survive."

The ocean that separates man from this self-knowledge remains to be charted. Crossing it will require money, dedication, ingenuity and the development of a whole new field of science and technology. The explorers of the brain have embarked on a journey even more significant than the voyage of Columbus in 1492. Columbus discovered a new continent. The explorers of the brain may well discover a new world.

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