Crammed into a corner on the highest floor, the sixth, is a tiny square of space with a single caged bulb screwed into the buckling ceiling, the damp dirt floor beneath it clawed by who knows how many hands. This could well have been the “quiet room,” where patients were sent when their behaviors could no longer be controlled. Down below me, and beyond the fields that surround the structure, the city streets thrum. Through one of the dirt-speckled windows I can just make out a pair of women pushing strollers. A man walks by with a baguette tucked under his arm as vendors hawk their wares beneath bright umbrellas striped and swirled and dotted—a picture of perfection that serves only to deepen the gloom of this building soon to be razed, sent tumbling into a heap of broken brick by the crane’s wrecking ball.
Founded in 1833, this state hospital was once a bustling institution, forty miles west of Boston. In the 1920s, ’30s, and ’40s, this hospital, like a host of other mental hospitals (called then insane asylums) scattered around our country and abroad, was a place to send the crazed and “idiotic,” a place equipped with what today seem like terribly primitive tools to handle the screaming, sweaty bodies of men and women hounded by hallucinations in an era long before managed care and medication. A hundred years ago, even eighty years ago, very few people were confident that chemicals could mend the mind, which as recently as the nineteenth century was believed to dwell not in the brain but somewhere in a spirit or soul immune to chemical intervention. Those afflicted with serious mental illnesses—schizophrenia, bipolar disorder, severe depression, and autism—often lived out their lives between the walls of hospitals just like this one, undergoing questionable cures that, while never intended to harm, rarely worked.
In 1991, more than 150 years after it first opened, this hospital at last closed its doors, meeting the same fate that had already befallen many other such mental hospitals in the decades following the deinstitutionalization movement that gathered momentum in the 1960s, when President Kennedy, whose sister Rosemary had been the victim of an early and failed prefrontal lobotomy, provided funding for community mental health centers, a move that was further encouraged by the passage of President Johnson’s Medicaid and Medicare bills. In 1955, at their peak, American mental hospitals held 560,000 patients nationwide, double the number at the turn of the twentieth century. By 1988, three decades later, that figure had fallen to 120,000.
One of the phenomena that truly made this sea change viable—allowing patients to be treated in the least restrictive setting possible, whether that was in a community health center or at home with their families—was the discovery, in the early 1950s, of a blockbuster drug called chlorpromazine. When branded and marketed as Thorazine in this country and Largactil in Europe, this new drug stabilized untold thousands of schizophrenic, psychotic, and otherwise mentally ill patients and eventually brought about a sustained exodus from mental hospitals in the United States and abroad.
Great and Desperate Cures
One way of grasping the meaning of Thorazine is to know the types of treatments that preceded it, treatments which the former University of Michigan psychologist Elliot Valenstein has called “great and desperate cures.” There was, for instance, insulin coma therapy, first used by Austrian psychiatrist Manfred Sakel in 1927, in an attempt to treat opiate addicts in withdrawal with small doses of insulin. Some of these patients, however, slipped into hypoglycemic comas, and when they awoke, following an emergency administration of glucose, their personalities seemed altered. Addicts who had been defensive, angry, difficult were now “tranquil and more responsive.” This led Sakel to wonder whether deliberately inducing comas in schizophrenic patients might produce a similar recovery. He set about trying this and claimed miraculous results after inducing comas, sometimes as many as sixty times in a two-month period, in his schizophrenic patients. Perhaps unsurprisingly, patients emerging from these comas did appear more docile, but the treatment carried severe risk—including death and irreversible coma.
Convulsive therapies were also popular during the first half of the last century. Before electroconvulsive treatment (ECT) was developed, convulsions were brought on by injecting patients with drugs. Ladislas Meduna, a psychiatrist working in Budapest, noted that epileptics who also had schizophrenia appeared to have fewer seizures and that, conversely, schizophrenics who suffered from epilepsy would often have spontaneous remissions of their psychoses after a seizure. Meduna chose first camphor and then metrazol, a white crystalline drug employed as a respiratory or circulatory stimulant, to induce seizures in schizophrenic patients. Afterward, his first test subjects rose from their beds and asked, in perfectly lucid ways, when they could go home. “I felt elated and I knew I had discovered a new treatment,” Meduna said. “I felt happy beyond words.”
What was the operating theory behind metrazol therapy? Some claimed that it gave the mentally ill a near-death experience that set them straight once the seizures were over. Instead of scaring schizophrenics to death, the thinking went, it scared them back to life. Patients coming out of metrazol shock often called for their mothers, or begged the nurses to hold them, childlike behavior which their physicians considered proof that the seizure had altered their personalities for the better. No longer raucous or caught up in the clutch of hallucinations, metrazol patients were frequently friendly and cooperative, and this led doctors to believe that with enough treatments, the positive behavior would become habitual.
Metrazol therapy, however, had a host of thorny problems. When asylum physicians beyond Meduna tried it on their patients, the seizures the drug caused were horrific. The treatments filled their patients with dread, and they begged to be spared the injections, which caused their whole bodies to writhe and spasm in convulsions of such ferocity that they frequently suffered fractures: dislocated shoulders, broken femurs, clavicles, scapulae. One patient compared it to being “roasted alive in a white-hot furnace.” And yet it was not uncommon for patients to have as many as forty metrazol injections.
Other treatments, some of which caused patients degrees of discomfort we can only imagine, since seemingly they left behind no record of their experiences, involved the injection of animal blood and castor oil and massive doses of caffeine. For quite some time, sleep therapy became a popular intervention in the treatment of schizophrenia—a kinder although no less dangerous undertaking. Patients were fed a cocktail of tranquilizing tonics and drugs meant to send them into slumbers that, in some cases, lasted as long as two or three weeks. The rationale: in states of deep rest the nervous system might find its precarious balance again. It’s true that some schizophrenics were actually helped by sleep therapy, but there were a number of fatalities as well. Patients’ lungs filled with fluid, pneumonias developed, or vomit was aspirated—all in a time before penicillin.
In 1938, Italian psychiatrist Lucio Bini discovered that he could cause convulsions in mental patients using electricity instead of drugs. Bini tried his new therapy on catatonic patients, some of whom were helped by this charge to their systems, as they emerged from their catatonia and began conversing with those around them. Others, however, as they lay on the table, seized to no effect at all, the voltage so high they flopped like fish, again and again, as the body was charged and changed, in a mode of treatment that seems barbaric to the modern mentality. (Electroconvulsive therapy, which actually can be extremely effective in severe depression that has failed to respond to antidepressant medications, is still used today, the theory being that the electrical current “resets” the brain. But the voltage is much lower, the treatment is typically used on only one hemisphere, and patients are given muscle relaxants so they do not have violent seizures.) Other hospital-based therapies of the time included ice wraps, freezing baths, or just plain old restraints, with the patient simply tied to a chair while his dreams and demons wafted.
Were the lengths to which these psychiatrists went to calm the mad mind heroic, or simply cruel? Canadian doctor Heinz Lehmann, for instance, noting that the psyches of his s
chizophrenic patients seemed much clearer when they were felled by high fevers, sought out ways of inducing in his patients the most extreme temperatures he could, going so far as to inject turpentine into the abdominal wall of one female patient in the hope that the infected abscess formed in the wake of such a procedure would cause a fever high enough to quell her hallucinations. Some have criticized Lehmann for what they consider cruelty, but it’s more likely that this doctor, who would later become one of the first North American prescribers of Thorazine, had the best of intentions, so driven was he to find ways of suppressing psychosis.
The zenith—or, depending upon your outlook, the nadir—of these fervent efforts to cure, or at least subjugate, the mentally ill was the 1936 development, by Portuguese doctor Egas Moniz, of psychosurgery. At its best, psychosurgery was a vanguard technique that—though we are now loath to admit it—healed some patients, allowing many to be released back into the community. For instance, there is the case of the physician, decimated by depression, who, after psychosurgery, reestablished a medical practice with nine other colleagues—and became a pilot to boot. There is also the case of a former virtuoso violinist, unable to play anything but her jangling, screeching nerves once her schizophrenia set in, so much so that she set the instrument aside for a dozen years. She too submitted to the destruction of her frontal lobes and found, afterward, that she could make music again, such that music was still her livelihood almost twenty years later. At its worst, however, psychosurgery was an ice pick thrust carelessly through the orbit of the eye. Indeed, the very first transorbital lobotomy in the United States was performed by the notorious Walter Freeman on a housewife in Washington, D.C., using an ice pick from his own kitchen drawer.
What this string of experimental treatments reveals is that while we tend to think of the last century and the centuries before it as eras when there were few or no viable biological therapies available to mental patients, this is at best half true. Yes, there was a period when psychoanalysis and its psychodynamic offshoots did grip the American imagination, assuming preeminence over medication in the 1950s, ’60s, and even the ’70s, but both here and in Europe we have never been without biological treatments for those suffering from mental disease or distress. Equally significant, some of these biological treatments were actually effective, even if only briefly and for uncertain reasons. For the deeply disturbed there was insulin, camphor, electricity, enemas, ice, and ice picks, and for the walking wounded, from antiquity on, there were all manner of tonics and brews, this in a period when whatever medication was available was easy to procure, before pharmacies controlled the flow of chemicals.
In the early twentieth century, for instance, opiates were widely used for all sorts of ills, even sold in syrup to calm colicky babies. Lithium baths prospered—vats of cool bubbling water said to soothe the troubled soul. Extract of conium, either on its own or coupled with iron, quinine, or Fowler’s solution, was used to treat depression, as was the plant extract nux vomica. Hyoscyamus, from the passionflower, was used to diminish sleeplessness or extreme excitement. There were tinctures of veratrine and belladonna and stimulants such as ammonia, lytta, and all kinds of aromatics in small amber jars you held just below the nostrils, sniffing in comforting drafts of lavender, rosemary, or cinnamon. So prevalent were and are attempts at biological cures, and so available for such a great span of time, that nonphysical therapies, such as psychoanalysis and other “talking cures,” are in fact the real oddity, a brief blip in what has otherwise been a mostly somatic approach to the treatment of human suffering in all its manifestations.
But despite the steady and ongoing reliance on brews, tonics, leechings, electrical current, ice baths, and lithium waters, on aromatics and extracts made from the garden’s crushed stamens and leaves, on convulsions and comas and high-flying fevers, prior to the development of Thorazine no one had ever really conceived of a drug to help heal serious mental illness. The tonics and brews of yesteryear were for the most part intended merely to manage the most severe symptoms. And while barbiturates were synthesized as early as 1903 and brought to market in 1904, and opium even earlier, these were used mostly as sedatives, to send patients into states of slumber so that doctors could attempt deep-sleep therapy. No one was trying to develop a pill that might somehow steady the brain, because the notion of such a thing lay outside the imagination, seemingly beyond conception.
The mind, back then, was mythic. It was a vast and uncharted territory, an Antarctica, unreachable, unfathomable, arising not from neurotransmission and chemical signaling but from, it was believed, electrical impulses impossible to decode, or, still more abstract, from one’s singular and God-given spirit. Very little was known about neurotransmitters, the chemical messengers that convey nerve impulses across a synapse, because while the neurotransmitter acetylcholine had been discovered in 1921, it was the only one researchers knew of, and it would be decades before they began to understand how or why it worked. Serotonin, norepinephrine, endorphins, and complex chemical cascades—these all lay far in the future, yet to be uncovered in laboratory experiments.
Thus while the emphasis on biological cures was not at all new, before Thorazine and then a second antipsychotic, reserpine, these biological treatments were largely contradictory, even paradoxical, given that measurable materials were being used to treat what many saw as the immeasurable soul. Had anyone in the nineteenth or even the early twentieth century suggested that schizophrenia arose from an “imbalance” of chemicals in the brain, that person would have been seen as speaking nonsense, because schizophrenia arose, in the popular imagination, from the twisted soul, and, in the medical imagination, from either a fixed and ill-fated inheritance, meaning a bad bloodline passed from person to person, or from humors—blood, bile, phlegm—gone wildly out of whack. When we finally did discover antipsychotics in the 1950s, we discovered much more than drugs. We discovered, along with capsules containing crushed and potent powders, the three-pound mass of matter between our ears which, we now believe, serves as the seat of our humanity. For many people, this was a brand-new belief.
Brilliant Colors
Thorazine was a long time coming. In fact it took almost a century to finally become what it was, a chemical called chlorpromazine, made by chlorinating the antihistamine promazine in a laboratory at Rhône-Poulenc, a French pharmaceutical company which, from the 1930s to the 1950s, specialized in antihistamines. But although Rhône-Poulenc and the pharmacists working under its roof can be credited with creating, in 1950, the drug that came to be known as Thorazine, its existence really began in the mid-nineteenth century, when organic chemists discovered that, by distilling coal tars, they could make brilliant colors, which they sold as dyes.
One of these dyes, named methylene blue, turned out to contain medicinal properties (and, in fact, is still today included on the World Health Organization’s list of essential medicines, being used as an affordable antimalarial drug and also showing promise for the treatment of Alzheimer’s). In 1886, in the process of researching a cure for malaria, against which the dye did prove to be effective, German scientist and eventual Nobel laureate Paul Ehrlich discovered that this strange and potent blue liquid would selectively stain the nerve cells of the frogs he dissected, and thus seemed to have an affinity for nerves, the highways and byways of everything we feel and are. Ehrlich, observing how the blue dye sank into and saturated only the frogs’ nerve cells, leaving the rest of the dissected animal untouched, thought to treat neuralgia with methylene blue; it didn’t work, but more than a decade later, in 1899, an Italian physician named Pietro Bodoni, aware of Ehrlich’s research, used it to treat manic excitation in psychotic patients with good, even grand, success, calming their fevered fears and rat-a-tat agitations. This makes sense in hindsight, because of all the dyes discovered in the heyday of organic chemistry, it was methylene blue that would eventually be transformed—distilled and finally synthesized—into chlorpromazine, otherwise known as Thorazine, fifty years after
Bodoni first tried the dye on the deeply distressed of Genoa.
Despite the success methylene blue had in calming manic excitation in psychotic patients, the dye never quite had a chance to come into widespread use, thanks to the introduction of barbiturates, in 1904, just five years after Bodoni’s initial treatments in Genoa. Barbiturates were faster acting and cast a wider net, their highly sedative effects able to calm virtually any kind of patient with any kind of mental illness diagnosis, and to do so more effectively than methylene blue, which was not a sedative. Methylene blue, in addition, could not be used in deep-sleep therapy, while the barbiturates could.
It is common, or even fashionable, for people to think that prior to Thorazine and the drugs that followed, psychiatrists were operating in the Dark Ages, using these “great and desperate cures” in ways often painted as almost, if not outright, barbaric. The real story, however, is much more nuanced. Without doubt the large asylums of the past could be gruesome places, but the doctors and their proffered treatments must be seen as separate from the settings in which they practiced. In addition to the successes of psychosurgery, with patients such as the physician-cum-pilot and the violinist, there are similar stories about patients who underwent insulin coma therapies, electroconvulsive therapies, and sleep therapy, and achieved happy outcomes.
Our predecessors, then, were not practicing in the Dark Ages any more than we are practicing in an Enlightenment. There has always been consistent confusion, a range of questionable cures, and then the occasional home run. This is the case today as much as it was back then. Methylene blue was a kind of home run that disappeared from psychiatric use not because it was ineffective or barbaric but because, according to British psychopharmacologist David Healy, “patents had been obtained on newer agents and no drug company would market an old drug even if it worked.” In the case of methylene blue, then, “there were competing therapies or interest groups likely to make more money out of other therapies than they would from methylene blue.” In the 1970s, methylene blue reemerged as a means of treating manic depression, for which it was highly effective, but ultimately corporate profit-seeking interests rather than therapeutic outcomes won the day.
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