Her name here can be Joan. She lives in a world that sometimes becomes agonizing, even terrifying. There are moments when she hears strange voices, sees haunting shapes. Recurrently the black moods of depression descend upon her and often then at night she is shaken by fits of irrational crying. Sometimes, without warning, moods of sudden fury appear, and, full of fear that she is loosing control of herself, it is all that she can do not to smash her TV set or a chair or a shelf of dishes.
     Yet much of the time she manages on the surface to appear self-possessed -- though strange. Strange because she is so withdraw, keeps so much to herself. She has a job, maintains a small apartment, comes and goes quietly, and says hello if a neighbor says it first. At 25 she is unmarried. She was once engaged, but nothing came of that. She isn't sure why. Nor does she know why she is totally unable to relate to other people, why her world so often is such an explosive, tormenting one. She has consulted doctors about her headaches, sleeping difficulties, fatigue. But she hasn't mentioned the other troubles. Appraised of them all, given the complete picture, a doctor could have suspected what is really wrong. For Joan is a victim of schizophrenia.
     The chances are that almost all of us know at least one schizophrenic---though we may not realize it.
     Schizophrenia affects some two million people in the United States and Canada -- one of every 100 people in the world. It is the major mental disorder. It fills more than half of all hospital beds. Moreover, many of its victims -- like Joan -- are unknowing victims. They have milder yet hampering forms that may never have been diagnosed, let alone treated. "For every hospital case," observed a late Dr. Paul Hoch, commissioner of mental health in New York State, "there are probably several in the community, usually less severe but nevertheless emotionally sick, a problem to themselves and to others."
     It is hardly a wonder that schizophrenia has long loomed as one of medicine's greatest challenges. Few, if any, disorders are more damaging and more enigmatic.
     Those whom schizophrenia strikes usually have been relatively normal before. It may strike at any time - but most often makes it appearance in young adults, 16 to 30 years old. It may appear suddenly, overpoweringly - or it may develop slowly, almost imperceptibly. And it may last a few days or a lifetime. It's no respecter of social class, wealth, or talent. It has affected many distinguished artists, writers, scientists, statesmen. Abraham Lincoln suffered a schizophrenic breakdown as a young man and recovered.
     The manifestations of schizophrenia can be almost infinitely varied so that no two victims share the exact same set of them. But all experience to some degree disturbances of two kinds -- of perception, for one, and, for another, of thought, mood and behavior.
     To the schizophrenic the world may appear distorted -- objects flat instead of three-dimensional, colors more or less brilliant than they really are. The shapes of people may change. Sounds may seem louder than they are, music deafening. Odor perception may be distorted.
     Some schizophrenics complain of bizarre sensations -- worms crawling under the skin. For some, food tastes strange, and they may believe that they are deliberately being poisoned. Often there are illusions -- garments hanging in a closet suddenly turn into fanciful animals, people into chess pieces.
     For some victims thinking slows to the point where it becomes difficult to think at all; for others it so speeds up that they complain their thoughts are running away from them. Depression is common and often is accompanied by crippling fatigue and apathy. Many schizophrenics develop irrational fears. Some suffer from inner tension so severe they feel they are about to explode. Some have physical disturbances -- headaches, darkening of skin, offensive body odor.
     More than half a century ago psychiatrists classified schizophrenia into four major subtypes:
     1) Simple schizophrenia is characterized by apathy, withdrawal, and confusion.
     2) Hebephrenic schizophrenia is is a strange mixture of hypochondria and silliness, with delight in childish pranks and the wearing of bizarre adornments.
     3) Catatonic schizophrenia leads to muteness, stupor. Its victims often seem inanimate as they huddle in stiff grotesque positions and refuse to move to take food or even to satisfy calls of nature.
     4) Paranoid schizophrenia is characterized by suspiciousness, bitterness, feelings of persecution. To a paranoid schizophrenic everything may have a sinister aspect so that the most casual gesture of another person may appear to be a threat.
     What conceivably could be responsible for such a tragic disorder?
     The long-prevailing theory holds schizophrenia to be a personality-environment disorder. The basis is laid through some failure in the mother-child relationship. The child grows up with a personality weakness that leaves him or her vulnerable so that in some point in life when a crisis arises -- marital, financial, social -- a breakdown follows.
     More recently there has been some broadening of the theory. Many investigators now believe that the role of the father is no less significant than that of the early mother-child relationship. Some suggest that the relationship between the parents themselves also helps to determine whether a child has a healthy emotional environment.
     Today there is, however, heavy emphasis on research to find a physical basis for schizophrenia. One of the spurs was the discovery that heredity may be a factor.
     Twenty years ago Dr. Franz J. Kallman of Columbia University made a significant study with identical twins in which he was able to show that if one of a pair is in a state hospital suffering from schizophrenia, there is an 85% likelihood that the other twin will be found to have the same disorder.
     Other heredity investigations followed. One, made three years ago at the National Institute of Mental Health, dealt with the first recorded case of quadruple schizophrenia - four young women, identical quadruplets, all with the disorder. When 60 investigators studied the rare case, the found evidence of a faulty gene that could have transmitted a tendency toward schizophrenic breakdown; they found a similar pattern of abnormal brain waves in the four girls and their father and a history of mental illness in the father's family. At the same time they uncovered environmental problems in the girls' family.
     In their report the investigators concluded: "In most cases, an inherited factor needs to be present for schizophrenia to develop. However, without severe environmental stresses, the illness may not appear in those who have a predisposition to it."
     The fact is that often when an inherited, or genetic, abnormality is present, so is an abnormality of body chemistry. Some of the most important breakthroughs in medicine have stemmed from discoveries of such genetically induced biochemical abnormalities.
     On top of the work in heredity has come another development that gives impetus to the search for physical factors in schizophrenia. This was the discovery of the mind-affecting qualities of the drug LSD. LSD can produce hallucinations and other disturbances much like those of schizophrenia. But the startling fact is that so little of it -- less than a 70-millionth of a man's body weight -- can do so.
     If such a minute LSD dosage can have such vast repercussions in the mind, it seemed likely that some chemical in the body also could have such effects -- and that the tiny quantity involved could easily escape detection.
     Very soon after LSD became available, Dr. D. W. Wooley of the Rockefeller Institute for Medical Research, in New York, carried out a study with it.
     Dr. Wooley was able to show that LSD and serotonin -- a body chemical believed to be a nerve and brain hormone -- are antagonistic. When LSD was applied to a strip of animal muscle, the muscle contracted violently. When serotonin was applied, it kept the muscle calm, uncontracted. Possibly, Dr. Wooley suggested, the hallucinations and other disturbances produced by LSD result from the drugs's interference with normal serotonin work in the nervous system. And schizophrenia might be the result of some fault in body metabolism, in the handling of chemicals, that similarly disturbed serotonin activity.
     In 1957, Dr. Robert Heath and a team of Tulane University investigators reported the discovery in the blood of schizophrenics of a strange substance to which they gave the name taraxein. Injected into monkeys, taraxein produced brain-wave changes similar to those in chronic schizophrenics. Given to normal human volunteers, it induced temporary schizophrenic-like behavior.
     Because the exact nature of taraxein was not known and the substance had not been isolated in pure form but remained bound up with a fraction of blood called globulin, there was a problem. Dr. Heath and his co-workers went on to try to purify taraxein and to learn more about it.
     Meanwhile Dr. Jacques Gottlieb and Dr. Charles Frohman at the Lafayette Clinic, in Detroit, were also working with a blood-fraction material that might have contained taraxein. In 1962 the Detroit physicians reported they had found the material could alter the processes by which energy is released from sugars in the body. Conceivably, if such alterations took place in the nervous system, affecting the transmission of messages to the brain, they might account for the altered perceptions and thinking in schizophrenia.
     At another laboratory, the Worcester (Massachusetts) Foundation for Experimental Biology, researchers also studied a suspected material in the blood of schizophrenics. When this material was injected into rats trained to climb ropes, the rats became greatly confused, and their climbing slowed markedly.
     When, too, researchers at other institutions turned up what seemed to be an abnormal substance. In schizophrenic urine, the Worcester workers tried it on their trained rats and found it disturbed their performance as much as did the blood substance.
     Some of the body's most most potent chemicals are classified, because of their structure, as amines. Adrenaline from the adrenal gland is, for example, an amine. Not long ago the Worcester researchers reported evidence that the factor in schizophrenic blood that disturbed the rats may be an amine. And there are indications that the urine factor also is an amine -- one related to adrenaline.
     Could a disturbance in adrenaline functioning be involved in schizophrenia? In Canada, at the University of Saskatchewan, Dr. Abram Hoffer and Dr. Humphry Osmond had begun to consider that possibility in the early 1950's. For one thing, the drug mescaline, derived from a cactus plant and long known to produce hallucinations, has a chemical structure much like that of adrenaline. One investigator, after trying mescaline, had observed that the "schizophrenic is like a man permanently under the influence of mescaline." And when the Canadian doctors studied the effects of mescaline in volunteers, they were impressed by the schizophrenic-like reactions it produces. They were impressed also when one of their own co-workers, a severe asthmatic, observing the reactions, remarked that sometimes, when he took large doses of adrenaline for an acute asthma episode, the effects were much like those in the mescaline-taking volunteers, though milder.
     There was another clue. In Canada, during World War II, supplies of fresh adrenaline sometimes ran short. In emergencies, when some patients had to be given adrenaline from old stock -- adrenaline that had turned slightly pink -- they had experienced temporary hallucinations.
     What was the hallucinogen in pink adrenaline? It might, the researchers decided, be adrenochrome, a chemical formed during an intermediate stage in adrenaline decomposition. Possibly in the normal body adrenaline proceeds rapidly through the adrenochrome stage. But I the schizophrenic, because of some chemical deficiency, adrenochrome may remain for longer periods, causing trouble.
     Adrenochrome could indeed cause trouble, the doctors found when they used themselves as guinea pigs. After taking injections of it, they experienced visual distortions and had difficulty relating distances and time. In volunteers, large doses led to hallucinations and thought disturbances.
     If adrenochrome plays a role in schizophrenia, what could be done to counteract it? One possibility, Dr. Hoffer and Dr. Osmond decided, might be to try to slow down adrenaline production. For adrenaline formation, certain chemical constituents -- methyl groups -- are needed. If large amounts of these could be removed from circulation, adrenaline production would be reduced and, as a consequence, so would adrenochrome production.
     There is a vitamin -- B3 (also known as niacin, nicotinic acid, and nicotinamide) -- that can sop up chemicals of the methyl groups in the body. The Canadian investigators decided to try it.
     Their first patient was a young man who had become acutely schizophrenic a few months earlier. Hospitalized and given shock treatment, he had failed to respond. On huge daily doses of niacin (B3) -- several hundred times normal daily requirements -- he showed improvement and could be discharged.
     Encouraged, Dr. Hoffer and Dr. Osmond began to use the vitamin treatment in other patients. Over the past 13 years they have used it on hundreds of patients, they report, and three of every four have responded. Ordinarily half of the schizophrenic patients treated in Saskatchewan without the vitamin required rehospitalization with in a five-year period; only one in six of the vitamin-treated patients has had to be rehospitalized.
     B-3 treatment took time -- often months -- before it produced benefits. It was most effective with early schizophrenics -- those treated within a year after onset. In cases of longer duration, it sometimes helped when combined with other treatment(sic), including electroshock.
     Then, late in 1965, Dr. Hoffer began to work with a new chemical, NAD, a derivative of nicotinic acid. Produced as an experimental drug, it seemed to do everything the vitamin did -- but in days.
     Early in 1966, at a New York medical meeting, after three months of trials with NAD, Dr. Hoffer made a preliminary report. Of 17 patients treated, 13 had shown dramatic improvement. A woman hospitalized for eight years seemed almost completely recovered three days after NAD treatment began.
     It seemed to Dr. Hoffer that NAD was the active form of nicotinic acid; that in normal circumstances, the body converted nicotinic acid from food into NAD but that in the schizophrenic the conversion couldn't take place, with the result that large amounts of adrenaline were turned into adrenochrome.
     There will be further studies to clarify the NAD question. The possibilities in B-3 treatment also are now getting increased attention. Meanwhile other work is going on to try to fit together the pieces of the great schizophrenic puzzle.
     Some investigators recently have reported evidence that the taraxein of Dr. Heath may sensitize to substances like adrenochrome. Animals that receive taraxein in amounts too small to produce any effects show marked behavior changes when very low doses of adrenochrome then are given. The presence of taraxein thus might make schizophrenic patients particularly sensitive to quantities of adrenochrome that otherwise might not have been dangerous.
     Even more recently, in January 1967, Dr. Heath himself had a new report to make about taraxein. After many years of quiet work he had succeeded in finding ways ways to purify the substance further. And he found that taraxein appears to act like an antibody in the brain.
     Antibodies are part of the body's protective mechanisms. Normally they are formed to combat specific invading disease organisms. And the basis of all protective vaccines is the use of incapacitated organisms to trigger the body to make antibodies that will be waiting and ready to stop any actual invasion by the real virulent organism.
     But the protective mechanism can go wrong. It does in allergic people who form antibodies -- useless and irritating -- to materials their bodies mistake for enemies. And it may do so in a growing list of diseases that are called auto immune diseases and are believed to result when the body somehow is fooled into producing antibodies against its own tissues.
     Schizophrenia, Dr. Heath's latest work suggests, may be an immune disease in which the body produces taraxein as an antibody directed against the brain. If this can be confirmed, it may be possible to develop substances that could combat schizophrenia by neutralizing the schizophrenia antibodies.
     Much remains to be learned about the chemistry of schizophrenia. Meanwhile, there is much that can be done right now for victims of the disorder.
     Only recently has it become clear that among the drugs loosely lumped together under the term 'tranquilizers' are some that do far more than tranquilize. These belong to a specific class of compounds, the phenothiazines -- and it's a growing class.
     The first phenothiazine -- chlorpromazine -- led to dramatic changes in mental institutions when it first came into use in the mid-'50s. It calmed patients, made them manageable. Schizophrenics previously beyond communication became reachable. Various forms of psychotherapy could be tried, where before it had often been hopeless even to try.
     But the full value of chlorpromazine and newer drugs in the same class remained to be established.
     Less than three years ago, after a three-year investigation, a nine-hospital study group under the auspices of the National Institute of Mental Health made a significant report. Of 400 acute schizophrenic patients treated with phenothiazines, almost 95% improved. "More significantly," the report announced, "the effects of phenothiazine therapy are not only quantitative in that a large percentage of patients improved; they are also qualitative in that a wide range of schizophrenic symptoms and behavior is favorably altered."
     The report went on to say that, although the phenothiazines have been thought of largely as just tranquilizers for reducing anxiety, "evidence from this study confirms the generalized effect of phenothiazines. Almost all symptoms and manifestations characteristic of schizophrenia improved with drug therapy, suggesting that the phenothiazines should be regarded as 'antischzophrenic' in the broad sense. In fact, it is questionable whether the term 'tranquilizer' should be retained."
     Even more important, possibly, are the many recent reports of how effectively phenothiazines can be used to keep patients from entering institutions and to keep others, discharged form hospitals free of relapse and the need for rehospitalization. Records of a New York program show that more than 90% of patients can be kept from needing rehospitalization and also that the majority can return to former occupations; the medication does not interfere with work capacity of learning ability when patients want to acquire new skills or more formal education.
     Certainly schizophrenia is not yet a solved problem. But present-day drugs are potent if not curative -- new knowledge about how to use them effectively and new facilities for making their use conveniently available can offer hope now that most victims can lead nearly normal, and many of them completely normal, useful lives.
     And there is added comfort for both victims and family in the fact that some of the best scientific researchers are convinced that schizophrenia is as much a physically caused disorder as is diabetes or pneumonia, that its cause is as likely to be discoverable, and that once the basic cause is known, schizophrenia may become an erasable -- and possibly even a preventable -- disorder.