HENRY COTTON’S EXPERIMENTS were part of a broader pattern of new treatments aimed at mental patients’ bodies that marked the first four decades of the twentieth century. Some might argue that the psychopharmacological revolution that began in the early 1950s represented an extension of that pattern of cavalier experimentation. Be that as it may, a remarkable array of somatic treatments emerged in the 1920s and 1930s and, with a single notable exception, subsequently vanished from the scene.
Once biology had come to seem a route to cures, rather than a reason for pessimism, the search was on for novel approaches. One of the discoveries that helped persuade Henry Cotton of the infectious origins of mental illness was the series of studies that had shown the syphilitic origins of General Paralysis of the Insane (GPI). Almost contemporaneously with Cotton’s early experiments with “surgical bacteriology,” a Viennese physician, Julius Wagner-Jauregg, had begun treating patients with GPI by infecting them with malaria.
Wagner-Jauregg entered psychiatry as a young man after failing to secure a post in internal medicine. As early as the 1880s, he had begun to speculate that fever might prove therapeutic in some cases of psychosis, having observed temporary improvement in febrile patients. At first, his junior status stood in the way of implementing his hypothesis, but following his appointment to a chair in psychiatry at Graz in 1889, he began experimenting with Robert Koch’s newly discovered tuberculin to induce fever, choosing to inject those with GPI, “because a favourable result cannot be so easily regarded as fortuitous as in other psychoses.”1 Adverse reactions forced him to stop, but following his appointment as the professor of psychiatry at the University of Vienna in 1902, he experimented with a variety of other means of inducing fevers. The most common of these were injections of streptococcus pyogenes, the cause of the disease erysipelas, popularly known as St. Anthony’s Fire, which was characterized by a rapidly developing skin disorder accompanied by shivering, pain, fever, and chills. But this was a dangerous technique in a pre-antibiotic era. It could leave patients with lymphatic damage or even result in death. Besides, patients stubbornly failed to improve.
Then, on June 14, 1917, Wagner-Jauregg came upon an Italian prisoner of war suffering from tertian malaria.2 Here was a novel febrile agent, and Wagner-Jauregg at once extracted some of the man’s blood, which he then injected into two psychiatric patients afflicted with GPI. These patients in turn supplied malarial blood to treat another small group of patients. Within about a week, all developed malaria, and they proceeded to have between seven and twelve attacks each. Three of those he had treated, by his account, soon showed signs of improvement and were subsequently able to return to work. Unlike erysipelas, for which no treatment existed, the high spiking fever associated with malaria could (usually) be curtailed by administering quinine. Here, perhaps, was the febrile cure that Wagner-Jauregg had long sought. If so, it would surely secure his fame.
Within a matter of months, the Great War was over. Wagner-Jauregg found himself on the losing side and was soon arraigned on charges of war crimes. Industrialized warfare had created hundreds of thousands of psychiatric casualties, those whom the British and Americans called victims of shell shock, and the Central Powers termed sufferers from die Kriegneurose. On both sides, treatment was often brutal. British or French, German or Austrian, it made little difference: psychiatrists often resorted to using powerful electrical currents to inflict great pain on soldiers who were mute or claimed to be paralyzed. The French neuropsychiatrist Clovis Vincent called the process torpillage. Attaching electrodes to tongues and genitals, he administered powerful jolts of faradic electricity, persisting until the soldier spoke (if mute) or moved arms and legs (if paralyzed). As one of his assistants, Andre Gilles, put it, “These pseudo-impotents of the voice, the arms, or the legs, are really only impotents of the will; it is the doctor’s job to will on their behalf.”3 At Queen Square Hospital in London, Lewis Yealland and Edgar Adrian (who would later win a Nobel Prize) pursued almost identical tactics. In Germany, this approach was nicknamed the “Kaufmann cure,” and Fritz Kaufmann added shouted military commands to the electrical “treatment.”4
Wagner-Jauregg had supervised and directed similar tactics on Austrian troops in Vienna. After the defeat, angry veterans demanded that he be held accountable for visiting torture on them, and forced a trial. Aided in part by testimony from Sigmund Freud and bolstered by his own testimony that he had been motivated only by a genuine desire to cure, he secured an acquittal.5 The cloud apparently lifted, he returned to his chair at the university.
News of his malaria treatment spread rapidly. He presented a paper on his approach at the 1920 meeting of the German Psychiatric Society in Hamburg, and two years later, a translated version appeared in the Journal of Nervous and Mental Disease. American psychiatrists, like their European counterparts, responded enthusiastically to his work. Trials were soon under way at the New York State Psychiatric Institute and at the Manhattan State Hospital. George Kirby, head of the institute, reported a 34.9 percent remission rate among the 106 cases he had treated, and by 1926, mental hospitals throughout the New York State system were employing fever therapy.6 Wagner-Jauregg had pointed out that ”when one has once inoculated a paretic one can inoculate other paretics from him and so establish a malarial stock and further cultivate it.”7 It was an approach the American psychiatrist William Alanson White, superintendent of the St. Elizabeths Mental Hospital in Washington, DC, was fiercely critical of, for, as he pointed out, the diagnostic tests for syphilis were far from foolproof, and a misdiagnosed patient receiving malarial blood might simultaneously contract syphilis.8
Most mental hospitals ignored this concern, and thermos flasks of malarial blood soon passed through the mails. Some psychiatrists preferred a more “natural” method of transmission, encouraging mosquitos to bite infected patients, and then placing those they wanted to “treat,” confined in straitjackets, into rooms occupied by the insects and waiting for nature to take its course.9 The treatment, when it was not fatal, produced savage symptoms: high spiking fevers and chills that resembled a near-death experience. Nor were doses of quinine always sufficient to terminate the process. Still, since the alternative was a lingering death, bedridden, afflicted with “gangrenous trophic ulcers, total incontinence, and profound dementia,” and victims of syphilis were destined in many cases to die choking on their own vomit, both patients and their families were driven to seek the new cure.10 Curiously, as Joel Braslow has shown using California clinical records, one unintended side effect was to reduce some of the double stigma that GPI patients had traditionally faced, as both mad and damned for engaging in illicit sex.11 Psychiatrists who had previously viewed their patients as “hopeless,” “immoral,” and “stupid”—objects to be acted upon and people who were sinful and depraved—now reacted much more empathically and positively toward their patients, who were allowed to become active participants in their treatment. Patients with syphilis voluntarily sought admissions to asylums they had previously shunned, and they began to see asylums as places of treatment rather than confinement. Whatever else it accomplished, malaria therapy did succeed in producing powerful shifts in the perceptions of both doctors and patients.
The 1920s and 1930s were a period of experimentation with other mechanisms for inducing fever. Some tried injecting horse serum into patients’ spinal canals, thereby producing meningitis.12 Injections of the organisms that caused rat-bite fever were tried, as were injections of killed typhoid bacilli and colloidal sulphur, a technique that by design led to the formation of abscesses. Alternatively, efforts were made to employ sweat boxes (or diathermy machines, to use the preferred term) to break down the body’s ability to maintain a steady temperature.13 Like malaria therapy, diathermy machines were not without their hazards. After his first attempt to use the technique, the superintendent of Arizona State Hospital reported to Winfred Overholser, the influential superintendent of St. Elizabeths Hospital in Washington, DC, that he had been forced to resume using malaria to induce fever because “as sometimes happens, the first patient treated in the new-fangled [machine] had died. Since that time the few graduate nurses we have have refused to operate the cabinet and I am in no position to force them to do so.”14 Some psychiatrists experimented with fever as a treatment for other forms of serious mental disorder, schizophrenia in particular.15
The consensus was clear: none of the alternative febrile agents were as convenient or effective as malaria. And other forms of psychosis were unaffected by fever. That the original malarial treatment produced a substantial number of remissions in cases of GPI was widely, though not universally, believed, and as the progenitor of this breakthrough, Wagner-Jauregg was rewarded with the 1927 Nobel Prize in medicine (one of only two psychiatric interventions to achieve this distinction).16
Did the treatment work? Certainly, many psychiatrists at the time were convinced that it did. What had been a uniformly fatal disease now seemed somewhat treatable, with one 1926 examination of the published data on a collection of 2,336 cases claiming that 27.5 percent of them were greatly improved and another quarter moderately improved.17 Some historians seem inclined to accept these data, but others have been more skeptical, perhaps remembering that for many centuries, physicians were convinced by their clinical experience that blood-letting, purges, and vomits were sovereign remedies in the treatment of a host of diseases. In the words of Gerald Grob, “The evidence to support the alleged effectiveness of fever therapy was extraordinarily weak. The criteria to judge either remission or improvement was vague, and the fact that the psychiatric therapist was also the evaluator vitiated the results still further.”18
In this connection, it is worth recalling that Wagner-Jauregg’s initial claims about the efficacy of his approach rested on nine cases he had treated in 1917. On his account, six of the nine improved after undergoing a series of malaria treatments and were subsequently discharged. If these statistics are taken at face value, this would seem a remarkable turn of events, even though one of the patients died in the course of his treatment. Those initial optimistic statistics, however, belie what we now know about the actual fate of the remaining eight patients. Two of them, a tram conductor and a clerical worker, returned to work and we know no more of their fates, so being generous one may presume (though we cannot be certain) that they were successes. Four others are a different matter. We know that in two cases, a sergeant-major and a woman cleaner, the remission lasted barely a few months—and it was not uncommon for there to be some temporary remission of symptoms in cases of GPI. A third patient, a railway worker, committed suicide following his discharge. Finally, there was a thirty-seven-year-old actor who had been admitted “suffering from loss of memory and epileptic fits due to suspected paralysis.”19
Audiences found this case to be particularly telling evidence of malaria’s efficacy, for on Wagner-Jauregg’s account, within two months of his treatment he was able to give readings for his fellow patients, and after his discharge, he was able to resume his career on the stage. Well and good, except for the inconvenient postscript Wagner-Jauregg neglected to add until 1936: within months he had learned from another psychiatrist, Dr. Raphael Weichbrodt of the Frankfurt-am-Main Asylum, that the patient had relapsed and been rehospitalized.20 To these four we can add the remaining three cases, who were acknowledged at the time not to have responded to the malarial treatment. So, to review what we now know of the results in these nine cases: two appear to have recovered, though we cannot know for certain as they disappeared after their release; four had brief remissions; three did not even briefly improve; and one died as a direct result of the treatment.
There are many troubling issues surrounding the statistics on treatment for GPI. For example, the notion that all these patients were definitively suffering from tertiary syphilis rests upon the twin assumptions that all had serological tests for the disease and that those Wasserman tests never produced false positives. Both assumptions are false, and at least some of the cases diagnosed with GPI may in fact have not been suffering from this disease. Just how careless Wagner-Jauregg was with his serological technique is demonstrated by what happened a few months after he had treated his first group of patients. Seeking to treat another patient but not having malarial blood available, he approached an internal medicine specialist at a nearby hospital for some blood he could use. Not pausing to run a serological test to ensure that the sample was of the relatively benign tertian form of malaria, he injected the blood into one patient and, when that patient exhibited symptoms of the disease, drew blood from him and injected it into three more patients. When he attempted to short-circuit the fever with large doses of quinine, following his usual procedure, the intervention was a failure. He had, it turned out, infected these poor creatures with the malignant variant of malaria tropica. Three of the four patients were dead within a matter of weeks, their white blood cells having disappeared, and their red corpuscles declined massively. It was an incident that gave Wagner-Jauregg pause, and it was a year before he resumed malaria therapy. This incident remained hidden until the posthumous publication of his memoirs.21
Perhaps a Scottish verdict of “not proven” on malaria therapy might be in order. The advent of penicillin in the 1940s (which was a real magic bullet when used to treat syphilis) eventually led to the demise of the malaria treatment without its ever being put to a controlled test. But in certain respects, to debate this question is to miss the point: what mattered at the time was the widespread acceptance of the claim that a biological treatment for a major form of mental illness had been discovered—one that, as crude as it was, seemed to improve the fate of at least a fraction of the afflicted. Still more crucially, these claims had been validated by the award of a Nobel Prize—an accolade no other psychiatric therapy would achieve until Egas Moniz won the same award in 1949 for inventing the lobotomy. Perhaps at last psychiatry’s claims to be more than the custodian of the crazy would have some substance, and its isolation from the rest of medicine might begin to diminish. And perhaps other treatments directed at the body might now emerge.
Wagner-Jauregg had speculated that “the brutalities of war” may have allowed him to avoid “possible censure for experimentally infecting sick people with a new disease.”22 The example of Henry Cotton and his “surgical bacteriology” raises some doubts on this score. Shut up in every sense of the term, deprived of all legal rights, stigmatized as barely human, and seen as an immense burden on the public purse, the mentally ill were uniquely vulnerable to therapeutic experimentation, and experiments there most certainly were.
IN FACT, within three years of Wagner-Jauregg’s first experiments in Vienna, a Swiss psychiatrist at the famous Burghölzli Asylum in Zurich, Jakob Kläsi, suggested a possible way to intervene in the apparently hopeless course of another form of psychosis: schizophrenia. Nineteenth-century psychiatrists had long relied on a variety of hypnotics to keep many patients sedated. From opium and morphine, they had gravitated to new classes of drugs, including paraldehyde, chloral hydrate, and the bromides. There were no claims that these drugs were therapeutic, but they did make the management of asylums (and the calming of manic patients) somewhat easier. The bromides, in particular, were highly toxic, and these medications often gave rise to psychiatric side effects, but in a general climate of therapeutic hopelessness, their sedative properties were too useful to ignore. From 1904 onward, when the Bayer company in Germany began to market the first barbiturate, these drugs too came to be widely employed in asylums.23
In 1920, Kläsi proposed that barbiturates might be used not just as a symptomatic treatment, but as a curative therapy. He termed the approach Dauernarkose, or, as it became known in the English-speaking world, prolonged sleep therapy. Kläsi believed that his preferred barbiturate, Somnifen, was completely harmless, especially with respect to heart and lung functions.24 He had found that using it to produce prolonged sleep could reduce manic excitation, both psychic and physical, and, by increasing the patient’s dependence on the physician, it might create the possibility of increased contact with his doctor.25 Patients undergoing the treatment had to be periodically awakened to eat and drink and to excrete. Otherwise, intravenous doses of barbiturates were used to keep them unconscious, sometimes for as long as eleven days.
Three of Kläsi’s first twenty-six patients died in the course of treatment, something he neglected to mention in his first report on his work.26 Instead, he emphasized that between a quarter and a third of those he had treated had recovered sufficiently to be discharged from the asylum. (The deaths had resulted from bronchial pneumonia and hemorrhages in the heart muscle.) As with Cotton’s reports of his surgical interventions and Wagner-Jauregg’s of fever therapy, these results seem to have been accepted completely uncritically, and the treatment spread rapidly, with many others reporting on their use of this novel approach. A number of these reports mentioned the heightened risk of death among those being treated, as well as a host of other complications: high fever, vomiting, lowered blood pressure, rapid breathing, cyanosis, and symptoms of the general collapse of various critical bodily functions.27 Recoveries, however defined, were few and far between, though the treating psychiatrists often concluded that there was some degree of symptomatic improvement. Even at Kläsi’s own institution, Burghölzli, increasing doubts were expressed about the dangerous side effects of Somnifen, and efforts were made to find an alternative compound, to which drugs designed to prevent collapse of the circulatory system were added. To little avail: life-threatening complications persisted, often forcing the early termination of the treatment. And yet, as one scholar put it, “in the face of equivocal evidence in regard to its effectiveness, but with ample evidence of complications and mortality,” the Burghölzli and other institutions persisted in using deep sleep therapy into the mid-1930s.28
ONE OF THE GREAT DISCOVERIES of Western medicine in the 1920s was insulin. Until then, what at the time was called juvenile diabetes had had a uniformly fatal course. Doses of the newly discovered hormone suddenly transformed that situation. Excessive doses of insulin, however, could produce hypoglycemia and, in extreme cases, unconsciousness or even death. It was this property that led the Polish physician Manfred Sakel to suggest that insulin might have a role in the treatment of schizophrenia and, having developed a technique for inducing comas, to proclaim that he had discovered a remarkably effective new therapy.
Sakel had first encountered insulin when he worked at a private clinic, the Lichterfelder Hospital just outside Berlin, which specialized in treating morphine addicts. One of the techniques used to manage patients’ withdrawal symptoms had been to administer insulin to put them into a semicomatose state. At some point in the early 1930s, Sakel began to play with the idea of extending the use of insulin to the treatment of schizophrenia. Convinced he had discovered a valuable new approach, he moved to Vienna in 1933 and continued his experiments at the University Clinic.29
If Kläsi’s deep-sleep therapy had rendered his patients unconscious for hours at a time, Sakel’s approach went further still. By injecting his patients with steadily increasing doses of insulin, he eventually produced a sufficiently severe state of hypoglycemia that they lapsed into a coma. The consequences could be dire, and those undergoing the treatment required constant nursing and medical attention, lest they slip into irreversible unconsciousness or simply expire. Even after the comas had been terminated by the administration of glucose, there were risks of hypoglycemic “aftershocks,” so close medical supervision remained vital. The comas were induced five or six times a week, and a course of treatment often consisted of sixty or more such comas before it ceased.
As one observer recorded, “Shortly after an injection, the patients became quiet as the insulin began to lower blood sugar and deprive the brain of energy.… By the end of the first hour, the patients who had higher insulin doses had lapsed into a coma; many were tossing, rolling, and moaning, their muscles starting to twitch; and some had tremors and spasms. Here and there an arm would shoot up uncontrollably. Some of the patients began to grasp the air, reflexively … [and there were] other ‘primitive movements,’ including rapid licking of the lips.”30
Isabel Wilson, who visited Sakel’s clinic on behalf of the Board of Control, the body that supervised England’s mental hospitals, added her own observations of the treatment. She noted that before lapsing into a coma, the patient “may indeed look very ill, groan or shriek, grind his teeth, twitch or splutter or make snorting or rasping noises.… There can be no doubt that the treatment is unpleasant for the patient … the feeling of anxiety, confusion, and distress in the process of waking are obvious to the onlooker.” She attempted to minimize these problems in her report with the claim that, “fortunately, the patient himself is usually left with an amnesia for most of this period.” But this contention was somewhat undermined by her simultaneous acknowledgment that “insulin therapy, with all its consequences, was carried out in full sight and hearing of every patient within range in any given dormitory.”31
During the comas, patients sweated profusely. Their reflex responses declined nearly to the vanishing point. Not infrequently, their stupor was interrupted by a series of convulsions. As two experienced observers noted, during this phase, “the face is now pale and sunken. The pupils gradually contract to pinpoints and light reaction is lost.… [T]he greatest depth of the insulin effect consistent with safety has been reached. Beyond this point, the changes are likely to be irreversible, and protracted coma with central pulse and respiratory difficulties may be expected.”32 In the immediate aftermath of their comas, patients were often described as calmer and briefly less delusional. The influential Philadelphia psychiatrist Earl Bond rhapsodized about the lucid period that could occur: “From an aloof, withdrawn, bizarre and suspicious individual,” he and a colleague noted, “the schizophrenic is momentarily transformed into a warm, friendly, responsive, and lucid person whose symptoms are either absent or greatly diminished in intensity.”33 Unfortunately, such improvements usually proved evanescent, but the hope was that with time, the lucid periods would become more extensive and perhaps permanent. Hence the fifty or sixty comas or more to which many patients were subjected.
Sakel referred to the preconvulsive comas as “wet shock” and the convulsions, should they occur, as “dry shock.” He concluded that these seizures were beneficial and, in later years, deliberately added intravenous doses of a drug that produced convulsions to ensure the proper therapeutic effect. As he put it, “The mode of action of the epileptic seizure is on the one hand like a battering ram which breaks through the barriers in resistant cases, so that the ‘regular troops’ of hypoglycemia can march through.” Secondarily, “The epileptic seizure also affects the psychosis … by means of the retrograde amnesia it produces.” Only such risky and radical measures could hope “to break through the fixated and petrified psychotic processes and to devitalize them.”34
Between 1934 and 1935, Sakel published thirteen reports on his work in the Wiener Medizinische Wochenschrift. Henry Cotton had claimed his treatment of focal sepsis had cured 80 percent of those he operated on. Sakel was bolder yet: he maintained that 88 percent of his schizophrenic patients had improved.35 An American researcher who visited his clinic wrote back to his colleagues at Bellevue, in New York, that the therapy was one of the most remarkable things he had seen, and in an article in the Journal of the American Medical Association in 1936, his fellow New York psychiatrist Bernard Glueck informed his readers that if the improvements he had witnessed proved permanent, Sakel’s work would constitute “one of the greatest achievements of medicine.”36
News of these remarkable results was sufficient to induce the commissioner of mental health for New York State to issue an invitation for Sakel to come to America at the department’s expense to demonstrate his approach. Sakel’s lecture at the Harlem River State Hospital in 1936 was attended by twenty-five psychiatrists from throughout the state, and it led to the rapid spread of insulin shock units, first in New York and then in many other states. As a Jew, Sakel had endured vicious antisemitism in Vienna, and he gratefully accepted a visiting appointment at Harlem River State Hospital. He spent the rest of his career in the United States. At the invitation of the New York Academy of Medicine, he delivered a lecture on his work in January 1937, based on what he claimed were 300 cases of schizophrenia. In his first one hundred recent cases (ill for less than six months), he claimed that he had completely cured 70 percent, leaving them symptom-free, and had greatly improved the condition of 19 percent more.37 Soon he was being feted in the popular press. The Reader’s Digest spoke of a “Bedside Miracle,” and that other oracle of middle-class America, Time, informed its readers that “Sakel has cured hundreds of cases of schizophrenia at his Vienna clinic by means of insulin injections.”38 With powerful endorsements like these, Sakel proceeded to make a fortune in private practice.39
The psychiatric profession was almost equally enthusiastic. The American Journal of Psychiatry devoted an entire issue in 1937 to insulin shock. Subsequently the journal published a special supplement reprinting papers from the Swiss Psychiatric Society devoted to the new shock therapies—a highly unusual move for a profession that was generally insular and unconcerned with developments elsewhere in the world. Professional enthusiasm for insulin coma therapy rested on more than just anecdote. Benjamin Malzberg, a statistician employed by the New York State mental hospital system, wrote an influential study of 1,039 patients treated with insulin comas, and compared them with a “historical” control group of nontreated patients admitted to the same hospitals in 1935 and 1936. The results, though far from the “cures” Sakel had claimed for his treatment, seemed promising to most psychiatrists who encountered them. Malzberg reported that some degree of improvement was evident in 65 percent of those given insulin, as compared with 22 percent among the control group, and that 37.6 percent of the treated group were much improved compared with only 14.7 percent of the control group.40
Aaron Rosenoff, overseeing California’s sizable state hospital system, used the enthusiasm for insulin coma therapy to extract $2 million from a previously dubious state legislature in 1939 to construct an acute care psychiatric facility, the Langley Porter Clinic in San Francisco. He estimated that employing insulin treatment there would save the state $2 million each year.41 And where New York and California led, the rest of the country soon followed. A federal survey undertaken just before the United States entered the Second World War found that 72 percent of the 305 public and private mental hospitals included in the study were using insulin coma treatment.42
In reality, Malzberg’s “controls” were nothing of the sort. He relied on the assessments of the psychiatrists employing the treatment, and there was no indication (or likelihood) that the same standards were used to measure the two groups, since there was no systematic guideline establishing how to proceed, and different psychiatrists made the assessments. Nor did the two groups form a meaningful comparison in any case. Those subjected to the insulin treatment were “carefully selected with regard to their physical status” and likely for their potential treatability, whereas many of the “controls” were in far poorer physical and mental condition—a discrepancy that showed up in the dramatic differences in their death rates, which were almost four times higher among the so-called controls than among those being treated.43 For the most part, however, these difficulties were ignored at the time by a profession unused to the notion of controls and impressed by any sort of comparison between treated and untreated patients.
Even a handful of studies reporting negative results had no discernible effects on enthusiasm for the treatment.44 Just as Cotton had dismissed those who attempted to replicate his findings as having failed because they had not been ruthless enough, so Sakel and his allies contended that the poor results some reported simply reflected poor technique. Managing the comas and knowing when to terminate them was, they contended, a delicate art, not reducible to a formula, and deeply dependent on clinical skill and experience. Those who reported failures simply were incompetent practitioners or had been insufficiently aggressive in their treatment.45
Those employing insulin could see themselves as using one of the great advances of twentieth-century medicine in order to rescue an otherwise hopeless victim of schizophrenia. The sense of intoxication, power, and psychiatric heroism was nicely captured by Charles Burlingame, whose Institute for Living attracted some of the most affluent patients in America:
There are few scenes that can match the dramatic intensity of the insulin treatment room in a modern psychiatric center. Here, each day, the patient is brought to the very fringe of life and allowed to hover there for several hours; sometimes he even starts to slide across the border, and only heroic measures, applied without delay, bring him back. Only the immeasurable reward of a mind restored could possibly justify the extremity of the method. From the moment the insulin is injected into the muscle of the patient he is under the most careful scrutiny. A special nurse is assigned to him. Pulse and temperature are taken every few minutes, and the physician is constantly nearby, ready to go into action at any sign of danger. The nurse looks up from her patient: “Doctor, I can detect no respiration.” The doctor moves to the side of the patient and speaks sharply in an attempt to rouse him. There is no response, nor is there any visible sign of breathing; a few minutes ago the breathing was stertorous, but now the patient is silent and limp. Meanwhile, artificial respiration is being given. It is a matter of seconds before the sterilized needle is injected. Breathing follows almost instantly. Then follows the administration of sugar. The effect is quick. In five minutes the patient is sitting up in bed, smiling and, fortunately, remembers nothing of what has taken place. So it goes, this skillful sparring with death, where a few moments of neglect, inattention or inadvertence may cost a life.46
What could be more at odds with the conventional image of the psychiatrist as a curator of a museum of madness, a mere boarding housekeeper? Here was active treatment with a vengeance.
Not everyone was as sanguine about insulin coma therapy. Its dramatic effects led some to recoil and a number of doctors to raise questions about employing so savage a treatment. “The neurological and psychiatric phenomena suggest an extensive disintegration of cerebral function,” one University of Minnesota physician noted in 1939. “The profound clinical manifestations make one wonder how these patients are able to withstand such severe reactions without some ill effect upon the nervous system.”47
Stanley Cobb, professor of psychiatry at Harvard, was one of the principal skeptics. In 1937 and 1938 he cited a variety of animal experiments to show that brain damage followed the administration of insulin (and metrazol, a treatment we shall turn to next). “Such evidence,” he complained, “makes me believe that the therapeutic effect of insulin and metrazol may be due to the destruction of great numbers of nerve cells in the cerebral cortex. The destruction is irreparable.… [T]he physician recommending these radical measures should do so with his eyes open to the fact that he may be removing the symptoms by practically destroying the most highly organized part of the brain. The use of these measures in the treatment of psychoses and neuroses from which recovery may occur seems to me entirely unjustifiable.”48 A letter in the New England Journal of Medicine elaborated on his concerns. Two recent “authoritative” studies reporting on autopsies of patients who had died during the course of insulin coma treatment had shown “petechial hemorrhages in the brains of [those] who died of hypoglycemia” and “widespread devastation” of their brains. “In certain devastated areas no nerve cells remained.” Animal experiments had shown similar results. In the face of the extraordinary claims, “one is obliged to be skeptical. One suspects that the treatment is merely palliative and is carried out at the risk of permanent damage to the brain.”49
Cobb’s leading position in the still-tiny field of academic psychiatry ensured that he had a prominent platform from which to promulgate his views. Most notably, he wrote an annual assessment of the state of neurology and psychiatry for the Archives of Internal Medicine, and these essays provided a forum for his firmly held doubts about the shock therapies, insulin prominent among them. He complained repeatedly that the public was being led astray by misleading press reports, pointing out that the patients most likely to recover were being chosen for the treatment and that “remission is not cure.” Citing Cotton’s colectomies, he pointed out that “it has long been known that any situation that brings a schizophrenic patient near to death may rid him temporarily of his symptoms.” And he returned again to the physical consequences of the comas: “It is now demonstrated beyond reasonable doubt that repeated insulin shock destroys nerve cells in the brain. It is probably that the mechanism is asphyxia, resulting from hypoglycemia.” Optimistically, he proclaimed that “the tide of enthusiasm [that rose to a flood … now has ebbed.”50
Cobb’s concerns about the damaging effects of hypoglycemia on the brain were echoed in a whole series of studies published in the late 1930s in Science, the American Journal of Psychiatry, the Archives of Neurology and Psychiatry, and other publications.51 Contrary to Cobb’s expectations, however, these findings did not seem to diminish most psychiatrists’ enthusiasm for the procedure, as Lawrence Kolb’s survey for the American Public Health Service showed.52 The press, which routinely seems to be willing to hype the latest medical breakthrough, took this as their cue to continue to praise Sakel’s treatment, and the public, eager for some solution to the plague of mental illness, had little reason to dissent.
Sakel had developed insulin coma therapy purely serendipitously, without any theory to explain why it might work. Under some pressure to develop an explanation after the fact, he had first proffered the notion that neurons were like engines suffering from an oversupply of fuel and that insulin diminished this oversupply. Alternatively, he suggested that somehow overactive adrenal glands caused schizophrenia, and that insulin “opposes the action of the products of the adrenal system, so that excessive stimuli are muffled, and the cells kept relatively quiescent, to the benefit of the individual.”53 Rather than being discomforted by the evidence that hypoglycemia was producing brain damage, some suggested that “these very alterations may be responsible for the favorable transformation of the morbid psychic picture of schizophrenia.”54
Sakel was increasingly inclining to the view that brain damage was central to insulin’s therapeutic effect. Hans Hoff, who worked closely with him, noted that “Dr. Sakel’s working theory held that under the influence of shock treatments, sick and defective cell connections in the brain would be separated.”55 The resulting brain damage selectively killed “psychotically functioning nerve cells which, because of their hyperactivity, were more sensitive to the hypoglycemic blockade than normal ones.”56 Accepting the notion that insulin (and its contemporary rival, metrazol) worked by producing anoxia and thus selective cell death in the brain, Harold Himwich and his colleagues experimented with a different approach that they thought might produce the same result: they argued that nitrogen might be used as a “safer and more controllable” way to starve the brain of oxygen. They boasted that “unlike previous attempts of other workers, the anoxia was intense. At the height of the bout the patient was respiring almost pure nitrogen.” They observed “respiratory stimulation, tachycardia, cyanosis, spasms, and convulsive jerkings”—and no cures.57
Many were unimpressed by these attempts to provide a rationale for the comas and accentuate the effects. As one Chicago psychiatrist commented, “Obviously this ‘theory’ does not deserve serious physiologic consideration, since it is based on concepts having no scientific foundation.”58 This criticism seems not to have bothered Sakel. “The mistakes in theory,” he said, “should not be counted against the treatment itself, which seems to be accomplishing more than the theory.”59 Pragmatically, American psychiatrists seem to have concurred.
The fact that insulin coma treatment required such an enormous and ongoing commitment of medical and nursing resources and entailed considerable costs to set up and run the specialized units used for treatment meant that its practical application was always limited. In some respects, it functioned more as a symbolic gesture toward a curative psychiatry than an intervention routinely employed on large numbers of patients. During the Second World War, the shortages of trained personnel added to these problems. The British, short of sugar as well, improvised and tried to use a slurry of potatoes administered through a gastric tube to bring patients out of their comas. Yet once the war ended, the treatment was readopted widely in many mental hospitals, and leading psychiatric texts continued to proclaim that it was the single most effective treatment for schizophrenia. Lothar Kalinowsky and Paul Hoch’s textbook, Shock Treatments and Other Somatic Procedures in Psychiatry, which first appeared in 1946 and was published in successive editions through 1961, endorsed the procedure. Similarly, Arthur Noyes’s Modern Clinical Psychiatry, the standard American textbook that passed through a multitude of editions, first published in 1935 and continuously in print for nearly forty years, continued to give prominent place to insulin coma therapy. Leading figures in British medicine had dubbed Henry Cotton “the Lister of psychiatry.” As late as 1943, the science reporter for the New York Times thought the inventor of insulin coma therapy stood comparison to an even greater figure in the history of medicine: Manfred Sakel, he announced, was “the Pasteur of Psychiatry.”60
INSULIN COMA THERAPY’S DEATH came slowly and stealthily. In 1953, a young British psychiatrist, Harold Bourne, published a paper in the Lancet decrying “The Insulin Myth.” He pointed out that patients given the treatment “are given, at a conservative estimate, 50–100 times as much medical and nursing care, measured by the clock, as non-insulin treated patients.” Beyond this, they were carefully selected recent cases, judged particularly likely to recover anyway. Surveying the existing literature, he found that the reported success rates were inflated and based on research so riddled with methodological flaws as to be useless, with no common diagnostic standards, and no clear criteria of what constituted “improvements.” “It is clear,” he concluded, “that … insulin offers the schizophrenic no long term benefits [and that] insulin has no place in [the treatment of] chronic schizophrenia.”61
The response from senior members of the psychiatric establishment was swift and scathing. Bourne was an inexperienced junior doctor who had selectively examined the literature, and he was an example of clinical ignorance and youthful intemperance. Such prominent figures as Willy Mayer-Gross, Richard Hunter, Linford Rees, and William Sargant marshalled their years of clinical experience and professional standing to squash the young upstart.62
The following year, the American psychiatrist Henry David echoed Bourne’s complaints in the pages of the American Journal of Psychiatry. Notwithstanding the ubiquity of insulin coma units in mental hospitals, and the evident conviction among his fellow psychiatrists of the value of the treatment, the fact remained that “in twenty years of work with IST [insulin shock treatment], there has been only one controlled study reported in the literature”—and that controlled study had found no significant differences in outcome between cases of schizophrenia treated with insulin, brief psychotherapy, or electroshock treatment. Moreover, the range and extent of the flaws in the research made it unsafe to draw any conclusions about the value of the treatment.63
Three years on, the Lancet published a controlled study in which patients were rendered unconscious using either insulin or barbiturates. Commenting on the existing literature, the authors noted that “despite the claims of enthusiastic supporters, and despite the vigorous protestations of Sakel himself, the evidence for the value of insulin remains far from convincing.” Their study compared randomly assigned groups of first-break schizophrenics who had been ill for less than a year and showed as yet no signs or recovery. Each got daily treatment five times a week and were subjected to thirty-five or forty comas before being assessed by psychiatrists who were not aware which patients had been treated with insulin and which with barbiturates. Those assessments took place at the end of the treatment, six months later, and then annually. There were no significant differences between the two groups, prompting the authors to comment that “insulin is not the specific therapeutic agent of the coma regime as has so often been claimed.”64
One might be tempted to conclude that science ultimately triumphed, that after two decades, carefully controlled work debunked the insulin myth. In reality, the picture was more complicated. The use of insulin comas had begun to decline three years before the study appeared, the consequence of the emergence of an alternative, far cheaper, and much more readily administered form of treatment, one that far more closely resembled the approach to disease employed by mainstream medicine: the first antipsychotic drugs, which appeared on the market in 1954.
Nor did the publication of findings that undermined the claims about insulin’s therapeutic properties bring about the demise of the therapy in any simple fashion. To be sure, insulin therapy continued its slow decline in the late 1950s and early 1960s—lamented though it was by its supporters, who continued to claim that it constituted a “pivotal advance in the treatment of the mentally sick” and “THE ONLY SUCCESSFUL BIOLOGICAL TREATMENT OF OUR TIME.”65 Far from being deterred as they learned more about the brain damage insulin comas inflicted on mental patients, the treatment’s advocates insisted that this damage constituted its singular merit: “The objective of IST is the destruction of brain cells, in other words, the production of a controlled brain lesion,” O. H. Arnold proudly announced at the conference held in 1958 to honor Sakel’s legacy, and “in many such cases we have to risk considerable organic brain damage.”66 Hoch, who had been head of the department of experimental psychiatry at the prestigious New York Psychiatric Institute and from 1955 was commissioner of mental health for the State of New York, hastened to add his endorsement of Arnold’s claims. If the treatment of schizophrenia were to succeed, “cells which are sick have to be destroyed. Otherwise relapses will come. That means that one of the most important things is to see that really every cell which is affected is really destroyed.”67 The British psychiatrist D. N. Parfitt had previously suggested that the appropriate analogy was to psychosurgery, contending that the effects of insulin coma therapy could “most easily be understood in terms of a physiological rather than anatomical lobotomy and generally this physiological lobotomy is of better quality”—a sort of “bloodless operation.”68
Three years later, the future Nobel Prize winner John Nash, who had been diagnosed as schizophrenic, was admitted to Trenton State Hospital. There he underwent a lengthy course of insulin coma therapy—to no avail. At what cost no one can say.69