Fever Therapy
The same year Lowell snapped from adolescence into a man of biology, a “brilliant but extremely difficult” psychiatrist by the name of Julius Wagner von Jauregg tried a memorable experiment that would soon transform the study of malaria.1
The experiment unfolded across the Atlantic Ocean, in the foothills of the Austrian Alps, while the Great War still raged. This difficult psychiatrist drew blood from a malaria-infected soldier just home from the Balkans and immediately injected the blood into the shoulder blade of another man. Jauregg’s stony face and fixed eyes remained unchanged as he pushed the entire contents into the bloodstream of the second man—a thirty-seven-year-old stage actor suffering from the shameful corkscrew bacteria of syphilis.2 The actor’s infection had reached his brain and turned him mad, so his family put him in Jauregg’s care. And Jauregg, by filling him with infected blood, hoped beyond all hope that this mental cripple—this babbling idiot prone to obscene acts and violent rants—would soon burn with fever. Then perhaps the madness would end.
The event took place back before Jauregg became the renowned grandfather of psychiatry. Before this tall, statuelike doctor became a Nobel laureate. And before he gave the world an excuse to use many thousands of syphilis patients in malaria experiments. This was back when he was just another man of medicine tied to psychiatry because he had failed to obtain the appointments necessary for internal medicine.3
The son of an Austro-Hungarian knight, Jauregg towered over his peers in personality and stature. All fell silent when he entered a room, “as if in the shadow of a titan.”4 His biographer traced this stern, authoritative persona to a once happy childhood gone bad after the untimely death of his mother from tuberculosis. When he was just ten, his two sisters were sent to convents and he and his brother moved with their father to Vienna, where they attended the city’s most renowned school for boys, with strict academic standards. Young Julius studied with sons of nobility and earned excellent grades in everything from Latin to the natural sciences, winning him entry into medical school, where he spent five years earning grades with distinction and studying under arrogant and undistinguished professors. He found his place in that sweet spot between intense competence and hard work, with an eye for brilliance in others. He resided where reason took precedence over sentiment, which made him somewhat caustic and short, but never overbearing and rarely wrong.
The famous scientist-turned-writer Paul de Kruif remembered Jauregg as a “piece of granite rock”; his biographer called him “gruff” but “generous,” with an “indestructible calmness”; assistants said he was “straight as a candle and as if chiseled in stone,” but kind and fatherly, with a “golden humor” and deep humanity.5 While his students called him a “wooden statue,” they attended his lectures in droves, and loved to see his eyes twinkle through that famously dour expression whenever he had cause to tell one of his many off-color jokes, which were always at the expense of Jews or degenerates.6
He wore his thick black hair neatly cropped and his handlebar mustache tightly curled and combed. He dressed conservatively in a pressed suit and crossed tie. High chiseled cheekbones framed a long, thin face that, with age, fell southward, creating a jowly, hound-dog effect. His striking appearance made a bold mark on the many medical meetings he attended, even among the famous, at large international conferences, which he called “church fairs.” He by far preferred small, productive gatherings of the Vienna Medical Society and other local medical organizations, where he often took charge of a discussion gone astray or gave sage insights during disputes.7 Everything about him showed off a man in control, but for the outsize mustache and bushy eyebrows, which hung like a shag rug over deep-set eyes.
In the thankless world of psychiatry he saw himself as a hybrid, a gentleman in the trenches—maybe like a pearl amid swine. He could have easily been like other psychiatrists: a man of medicine in title only, unable to practice his trade because scarcely any treatments improved mental illnesses. Psychiatry often meant life as an asylum superintendent, overseeing palliative care—a manager watching over the mentally afflicted until they finally passed away or hanged themselves. In the case of syphilis, death came soon after the bacteria entered the brain. No treatment could slow the progress, which made medical care perfunctory and meaningless.
But Jauregg, in his granite resolve, found this unacceptable. If psychiatry would be his profession, he would find a way to treat mental conditions, which he believed were caused by physiological functions gone awry—not emotional disturbances that could be cured by therapy.
He was among the first in his field to believe that infectious diseases caused, and could cure, different forms of mental illness. At night he went to the Vienna medical library to pore over international periodicals and study biological functions he suspected might be associated with cognitive failings. He conducted autopsies on the deceased to study their spinal fluid and nervous systems, looking for clues that might explain their conditions. He studied and wrote a paper on resuscitating patients who had attempted suicide by hanging, surmising that the convulsions and memory loss that followed probably stemmed from asphyxiation (not from emotional hysterics, as his peers believed). He also observed that the physical shock of being near death and then brought back to life appeared to have a positive effect on a patient’s mental state. He described one woman who had been melancholy and paranoid before she was cut down from the rope. After a few convulsions and some minor amnesia she was cured.8 To him, this was a physiological disturbance correcting another physiological disturbance. His patients weren’t crazy; they suffered from biological hiccups that led to mental catastrophes that were probably treatable, if enough study were dedicated to the effort.
For all these reasons, he took good care of his patients, and he even married one—a morphine addict.9 She was a degenerate by his definition, but still marriageable. This kind of hypocrisy seemed to make him whole. While he believed the insane should be sterilized so as not to procreate, he treated them well. While he told terrible jokes about Jews, he had many Jewish friends, assistants, and students. And while he made fun of the new psychoanalytical theories advanced by his Jewish friend Sigmund Freud, he respected and liked Freud and defended his theories, even as he disagreed with them. This may have been because Freud also showed uncommon respect for the mentally ill—something Jauregg valued above professional partisanship.
Only those who would disrespect patients felt his icy judgment.
One visitor to his clinic, according to his biographer, walked up to him as he towered over his ward wearing the usual white lab coat over a vest and cross-tie, and asked: “Excuse me, sir, where are the madmen?”
With his usual stone face, he pointed to the outside and said: “The madmen are out there,” then pointed to his ward and added, “In there are the sick men.”10
Their ailments humbled his sense of duty and challenged him to find novel treatments—including the use of malaria. He wasn’t just testing hunches on the insane because they were easy prey for medical experiments. He hoped to cure insanity. And he believed high fevers could do it.
This hypothesis was broadly shared. He and others had seen outbreaks of typhus, cholera, smallpox, and other fever-causing contagions burn through patients at their respective asylums, always leaving behind death and despair.11 But they also left some hope by turning one or two lunatics sane, sometimes for short periods, sometimes for good. Jauregg combined his own observations at the Asylum of Lower Austria in Vienna with those made by others at other asylums to write a “landmark” paper in 1887 that advanced the idea of inducing fevers as a possible cure for mental illness.12
In 1889, Jauregg tested this observed phenomenon by giving his patients streptococci erysipelas, which caused skin eruptions and high fevers. The results were unclear and he lacked adequate time to flesh out the possibilities. So he encouraged others to take up the cause. He lectured on it and implored colleagues to pitch in—hoping someone would find a reliable way to induce fevers. Then he grew discouraged when he learned that one psychiatrist had used a poisonous ointment on the skin of patients’ shaven heads, and left it there for weeks, until red-hot inflammation and oozing puss immunologically forced the onset of fevers. Jauregg openly objected to the method. Others implanted horsehairs under the skin to “provoke abscesses,” or applied mustard plasters or Spanish fly, which he called cruel.13Eventually he gave up on his fellow psychiatrists and drafted a new study design to try for himself.
But his next attempt didn’t set much of an example. He started it in 1890, when a research associate gave him a vial of tuberculin bacteria from Berlin.
Jauregg injected it into brain-damaged syphilis patients—a condition with many names but that was broadly referred to as general paresis, and the sufferers were called paretics. This type of neurosyphilis attacked the central nervous system and usually appeared ten to twenty years after exposure. Symptoms included decreased language and motor abilities, impaired judgment, hallucinations, delusions, violent mood swings, dementia, seizures, obscene behaviors, and muscle weakness that led to a telltale gait. Once these symptoms appeared, patients had two, maybe three years to live. Jauregg chose them as test subjects because of their dreaded condition. Why not use fevers to try to save them?
He infected sixty-nine so-called paretics with his vial of German TB and compared them to sixty-nine untreated paretics. Mental health improvements were observable in only those patients who reacted strongly—with particularly high fevers that raged for days. This suggested that intense fevers worked better than regular fevers.14
But Jauregg abandoned the project after he learned that patients he had sent home cured of syphilis and dementia later died of TB.15 Meanwhile, the ethical objections rolled in as “the entire Viennese press printed editorials caustically criticizing his work and holding him to be a potential murderer.”16 It didn’t matter that several of his colleagues repeated his experiments and produced the same promising results. If the scientific community saw his data as contaminated—because he mistreated patients—no one would publish his papers or advance his theories.
So he bided his time again. The TB work had narrowed the concept. He’d found his target group. Syphilitics became his cause, and he lectured cautiously about his discovery: “We cannot be reproached for using a procedure which is irrational. We have listened to nature; we have attempted to imitate the method by which nature itself produces cures.”17 He was sure of the concept, but the TB experiments instructed him to move forward gingerly, trying only dead bacillus and staphylococci, neither of which worked well because they failed to produce furnace-hot fevers for days on end.
For that, he theorized that malaria would work beautifully. And the infections could be easily controlled by quinine. His main problem was that Austria had no malaria and he didn’t know where to get it. Parasites that cause malaria couldn’t be grown or kept alive in petri dishes, so scientists couldn’t simply share vials of them.
He eventually moved to the Vienna General Hospital to run its Outpatient Department for Nervous Diseases—the first stop for patients with signs of late-stage syphilis, and usually a few short months before being committed to an asylum. There he continued testing his other theories, which included the use of iodine to prevent goiters and cretinism—work that led Austrian authorities to add iodine to salt.18He started treating battle-traumatized soldiers with electric shock therapy that involved strapping them down and sending a jolt of electricity through their brains—with the hope that it would snap them out of their emotional hysterics.
Jauregg was developing a mixed reputation. On the one hand, he showed flashes of brilliance in thinking through physiological aspects of mental conditions—as evidenced by his iodine work. Even his fever therapy, while dangerous, was innovative and thorough. But the shock treatment was different. Jauregg treated soldiers as he was expected to. It mattered little whether they saw horrifying deaths and bloody dismemberments in grenadelike flashbacks that shattered their sense of safety. They belonged to a war-focused culture that needed men to be strong for the war effort.19 Jauregg’s job was to straighten them out so they could return to the front lines and fight for the Fatherland. This mind-set was Austrian; it was nationalistic; and it put the country before the individual.20 It also foreshadowed Jauregg’s political leanings, which eventually led him to the Nazi party in its early years, before Hitler occupied Austria.21
One soldier sued Jauregg’s clinic because of his assistant’s actions. The suit brought Jauregg’s operation and his competence into question—an unbearable burden for a brilliant man who saw himself as cautious and fair-minded. At his trial, his old friend Sigmund Freud came to his defense.22 Freud testified that all medical psychiatrists had been pressured to act like “machine guns behind the front lines, driving back those who fled.” He argued that while Jauregg may have hurt soldiers, the torture was unintended; Jauregg had actually been trying to treat them. And with that, the charges were dropped.
But it left Jauregg shaken. He was no monster. He tried to do no harm.
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AMID the controversy, one of his medical colleagues reported that a soldier just admitted for minor nerve damage also shivered with vivax malaria.23 The doctor asked: “Shall I give him quinine?”
To which Jauregg replied, “No!”
Finally, he had a source of malaria.
On June 14, 1917, he drew the soldier’s blood and immediately injected it into his demented patient, the former actor.24 When the actor came down with malaria, Jauregg extracted his blood and injected it into another eight patients also with late-stage syphilis. Then he watched over them as they sweated through days of extreme fevers and shook with bone-cold chills.
One patient died; two worsened and were admitted to the asylum; four regained cognitive function but later relapsed. Only two appeared cured of dementia. One was a thirty-four-year-old man whose cognitive failings had only just begun that month. After eleven attacks of fever, he fully recovered and, at his own request, returned to his army regiment. The other was a thirty-nine-year-old man, also in the early stages of dementia. He suffered through ten attacks of fever before regaining cognitive function. And soon after, he returned to his job as a cleric.25 As for the actor—the first to receive the transfusion of infected blood—he, too, improved; he gave performances for patients at the asylum and was discharged. But Jauregg later received a letter from a Frankfurt doctor reporting that the patient had relapsed and had to be admitted to an asylum there.
The two patients Jauregg fully cured, however, made history.
* * *
SYPHILITICS filled asylums in the late nineteenth and early twentieth centuries, occupying an estimated 10 to 20 percent of beds.26 The disease first appeared in medical records as an epidemic that burned through Europe beginning in the early 1500s. People back then called it a “pox,” because after ulcers appeared on the genitals—today’s classic symptom—the sores spread to cover other parts of the body. Symptoms also included nerve damage that caused excruciating pain.27 People feared it was a new type of leprosy sent by God for man’s sexual liberties; others believed Columbus brought it back from the New World. Today, scientists believe syphilis grew from a skin disease called yaws—caused by the same bacterium as syphilis, called Treponema pallidum. The mutation from skin disease to venereal disease occurred just as Europe’s population had exploded, when there were more houses of prostitution, more sexual freedoms, and more warfare—with mass movement of armies and refugees to spread diseases.28 Over the next two centuries, severe symptoms of syphilis moderated, became less leprosylike, and therefore less terrifying and prophylactic. It had morphed into an annoyance that people could live with, which advanced its spread.
But then another mutation occurred, one that allowed the bacteria to cross the blood-brain barrier and infect the frontal lobe. Scientists now believe this happened somewhere around 1800, because within the next few decades physicians noticed a tangible increase in dementia among relatively young people. This new type of psychosis caused a somewhat sudden personality change that brought on wild mood swings followed by profanities, inappropriate sexual behavior, and muscle paralysis. Puritans blamed it on masturbation and alcoholism, while scientists tried to figure out the real cause. Meanwhile, those infected brought shame and disgrace on their families and were sent away to lunatic asylums, where they became wards of the state and a financial burden.
Finally, in the early twentieth century, the cause had been identified as untreated syphilis. It had burned through the middle classes at infection rates as high as 20 percent in Europe.29 So prevalent was syphilis that it spawned its own medical specialty, called syphilology. According to historian Joel T. Braslow, some European asylums reported that 45 percent of their male patients were there because of neurosyphilis. Percentages were much lower in the United States but still ran around 10 percent of male hospital patients.30
* * *
FINDING something even partially effective against this brain-destroying sexually transmitted disease earned Jauregg accolades and helped repair his damaged reputation.
To continue, he sought permission from a military hospital to take blood from a soldier just home from the fighting and sick with malaria. Jauregg didn’t examine the blood before injecting it into four of his syphilis patients. To his horror, the four infections spiraled out of control. Despite large doses of emergency-level intravenous quinine, one patient’s red blood cell count dropped precipitously. After thirty-one days of Jauregg trying frantically to control the malaria, the patient died. By that point, Jauregg knew he had accidentally used deadly falciparum. Two others also died. Only one patient survived after forty-five days of heavy intravenous quinine. Weeks passed before Jauregg saw the silver lining: his sole survivor had been fully cured of insanity.31
By now, Jauregg had grown old. At age sixty his tall, stiff build began to hunch. His stern, stony manner—once considered serious and erudite, forceful and commanding—now came off as grim and difficult. His face appeared longer than ever, drawn down by that thick handlebar mustache and topped by wiry gray shoots coming off his shaggy eyebrows. But those eyes, those sunken, beady eyes, must have lit up at the reality that he had discovered a cure for syphilis. He was right about malaria—it could cure this type of dementia, and maybe other types as well. He may have even bested Salvarsan, the great Paul Ehrlich’s magic bullet, which really poisoned more patients than it helped.
So while the falciparum fiasco shook him, he continued working with malaria.