Episode 31: Malariotherapy

 in Podcasts  tagged ethics / history / malaria / malariotherapy / nazi / nobel / psychiatry / syphilis by

Malariotherapy — infecting comatose syphilis patients with malaria to cure them of the disease — was once the cutting edge of medicine, and earned its inventor, Julius Wagner-Jauregg, the Nobel Prize in Medicine or Physiology in 1927. In this episode, we’re going to talk about the fascinating story behind this remarkable treatment, from the murky beginnings of syphilis through its sordid sexual connotations, to the birth of modern psychiatry and Nazi experiments. Plus, there’s a brand new #AdamAnswers about whether or not ancient doctors thought hair served to store semen (seriously).  Listen to all this and more in Episode 31 of Bedside Rounds, a tiny podcast about fascinating stories in clinical medicine.

Sources:

  • Crellato E et al, “The Hippocratic treatise ‘On glands’: the first document on lymphoid tissue on lymph nodes,” Leukemia. Retrieved online at https://www.nature.com/articles/2404618
  • Farhi D, Dupin N, Origins of syphilis and management in the
    immunocompetent patient: Facts and controversies. Clinics in Dermatology (2010) 28, 533–538
  • Frith J, “Syphilis – Its early history and Treatment until Penicillin and the Debate on its Origins,” Journal of Military and Veterans’ Health, 20(4), retrieved online at: http://jmvh.org/article/syphilis-its-early-history-and-treatment-until-penicillin-and-the-debate-on-its-origins/
  • Gelder MG, “Biological Psychiatry in Perspective,” British Medical Bulletin. 1996;2 (No. 3H01-4G7)
  • Howes OD et al, “Julius Wagner-Jauregg, 1857-1940,” American Journal of Psychiatry, April 2009 Volume 166 Number 4, Volume 166, Issue 4, April, 2009, pp. 409-409.
  • Karamanou M et al, “Julius Wagner-Jauregg (1857-1940): Introducing fever therapy in the treatment of neurosyphilis.” Psychiatriki. 2013 Jul-Sep;24(3):208-12.
  • Kent, ME and Romanelli F. Reexamining Syphilis: An Update on Epidemiology, Clinical
    Manifestations, and Management, The Annals of Pharmacotherapy. 2008 February, Volume 42
  • Kreston R, “Pyromania! On Neurosyphilis and Fighting Fire with Fire,” Body Horrors blog on Discover. Retrieved online at: http://blogs.discovermagazine.com/bodyhorrors/2014/05/31/pyromania-syphilis-malaria/#.WnTvHKinE2x
  • Martin TW, “Paul’s argument from Nature for the Veil in 1 Corinthians 11:13-15: A Testicle Instead of a Head Covering,” Journal of Biblical Literature, Vol. 123, No. 1 pp 75-84.
  • Rothschild, BM, “History of Syphilis Clinical Infectious Diseases.” 2005; 40:1454–63
  • Simpson WM, “Artificial fever therapy of syphilis,” JAMA. 1935;105(26):2132-2140.
  • Tampa M et al, “Brief History of Syphilis.” J Med Life. 2014 Mar 15; 7(1): 4–10.
  • Tsay CJ, “Julius Wagner-Jauregg and the Legacy of Malarial Therapy for the Treatment of General Paresis of the Insane,” Yale J Biol Med. 2013;86(2): 245–254
  • Wagner-Jauregg J, “The history of malaria treatment of general paralysis.” Am J Psychiatry. 1946;02: 577-582

Transcript

Hey guys, we’ve got a lot of new listeners, so before the episode starts I have a favor to ask. If you like Bedside Rounds, please rate and review us on iTunes, Stitcher, or whatever podcasting service you use. Or even better, tell a friend! It’s one of the best ways there is to get the word out about the show. Okay, enough of that.

 

This is Adam Rodman, and you’re listening to Bedside Rounds, a tiny podcast about fascinating stories in clinical medicine. This episode is called Malariotherapy and it’s about how Julius Wagner-Jauregg, an Austrian psychiatrist, won the 1927 Nobel Prize in physiology or medicine for infecting comatose syphilis patients with malaria.  But it’s about so much more than that — I’m going to talk about the murky beginnings of syphilis, the sordid sexual associations, the birth of modern psychiatry, Nazi medical experiments, and a discovery that laudits a Nobel Prize gets more of less forgotten in just a few decades. So let’s get started.  

 

Julius Wagner-Jauregg is one of the most influential and prominent psychiatrists of the early twentieth century. But a cursory — and very unscientific — poll on my Twitter suggests that you’ve never heard of him. So we should start with a refresher on what he did. 

 

It’s 1917, and Wagner-Jauregg is already a prominent psychiatrist famous for his research into biological causes of psychiatric diseases, and the Chief and Director of the First Asylum of the University of Vienna. World War I rages on, and every medical facility is doing what they can to support the war effort. A young soldier stricken with malaria, returning from the Balkans, is accidentally sent to his asylum. So I’ll quote from Wagner-Jauregg himself, writing two decades later, on what happened next:

 

“Should he be given quinine?” [my assistant Dr. Alfred Fuchs] asked. I immediately said: “No.” This I regarded as a sign of destiny. Because soldiers with malaria were usually not admitted to my wards, which accepted only cases suffering from a psychosis or patients with injuries to the central nervous system … I obtained during a paroxysm a small sample of the soldier’s blood, and I inoculated 3 general paralytic patients by rubbing a few drops into several superficial scarifications of the skin. Then the malaria of the soldier was stopped with quinine

 

He then inoculated this malaria-filled sample into 9 patients suffering from general paralysis of the insane, the final paralytic phase of syphilis that was invariably fatal. And yes, it’s still called general paralysis of the insane, or GPI, today. The results were dramatic — one patient died and two remained paralyzed. However, six showed considerable improvement. Three of these patients fully recovered — a paralyzed actor soon returned to the theater, as did a clerk and a military officer.

 

Over the next decade, this cure for GPI had been subject to hundreds of experiments confirming his results, and anopheles mosquitoes were being cultivated across the world to serve as a new reservoir for this so-called “malaria therapy”. By 1927, he would win the Nobel Prize in Physiology or Medicine, the first and only psychiatrist to win this award. And now you’ve never heard of him. Why?

 

One of my favorite Carl Sagan quotes is (https://www.youtube.com/watch?v=7s664NsLeFM) if you want to make an apple pie from scratch, you must first invent the universe. I’m not that ambitious,  but to really understand the impact of Wagner-Jauregg’s discovery we have to start quite a bit earlier. 

 

So let’s start by talking about syphilis. Syphilis was a common disease in the pre-antibiotic area, and it was widely known that any physician worth his salt would be familiar with its many permutations. William Osler himself wrote, “I often tell my students that it is the only disease which they require to know thoroughly.  Know syphilis in all its manifestations and relations, and all other things clinical will be added unto you.” Today it’s far rarer, though on the rise in the United States. It’s caused by a corkscrew-shaped bacteria called treponema pallidum, and the only known reservoir is people. It’s first and foremost a sexually transmitted disease — the bacteria enter easily through mucosal surfaces, meaning that it can be transmitted not only through the genitals, but also through oral sex, or even just kissing near a lesion. Less commonly, it’s transmitted between mother in child, both via blood and during birth. Initially, you’d get a bump at the site the bacteria entered, often the genitals, that would transform into a painless, clean-based ulcer. This is called a chancre, and is the classic finding in what we now call primary syphilis. This chancre would resolve, and then after a few months you’d develop a rash, classically on the palms and soles, flu-like symptoms, and hair loss. This is secondary syphilis, as the disease replicates through your body. After about a year, you’d develop growths called gumma would form over your body — on your skin, in your bones, in your blood vessels, especially the aorta, and in your internal organs. Your spinal column might be affected, and you’d find it hard to walk. You’d become more and more confused. And at the very end, you would slip into a deep coma — the dreaded general paralysis of the insane — from which you’d never wake. 

 

These dreaded effects of tertiary syphilis were not uncommon. The 20th century saw two longitudinal studies of syphilis patients — and yes, one of them was the infamous Tuskeegee syphilis study, which is an unfortunate story for another time. But essentially, they confirmed that up to 15% of patients with syphilis died of the disease, and about ⅓ of them would develop these feared late complications of syphilis. And no wonder Osler felt that syphilis was so essential to know inside and out — it was considered the “great imitator”, since the gummas of tertiary syphilis could appear like pretty much any other disease.

 

So many of the diseases that have plagued humanity — smallpox, tuberculosis, malaria — their origins are lost in the deep past. Syphilis is ancient too, but it’s appearance to physicians in the West can be dated to a single year: 1495. I don’t truly understand the politics of the situation, but in 1494, the Pope invited Charles VIII of France to lead an army of 25,000 mercenaries from across Europe, including Spanish mercenaries who had just returned from Columbus’ trip to the New World, into Italy to collect a debt from the Prince of Naples. Numerous camp followers, including sex workers, were in tow. The troops first stopped in Rome, where they apparently lived a life of debauchery for about a month, before marching towards Naples. They took the city with little resistance, since it was only defended by about 1,000 mercenaries, who certainly did not relish 25 to 1 odds.  Charles’ mercenaries did little to endear themselves to the population, with accounts of rape, theft, and general depravity. In response, neighboring Italian princes joined together and defeated the French army. And what they found in the newly liberated city, and on the French soldiers’ bodies, was horrifying.

 

A new disease had cursed the soldiers, and the people of Naples. Genital ulcers would appear, and soon after a high fever, rash, and muscle pains. Within a few weeks, the body would erupt with open sores and abscesses. These sores would eat into the bones, destroy noses, and in many cases cause death. If this sounds more severe than the modern description on syphilis, it’s because it likely was — we can estimate by contemporaneous engravings and descriptions of physicians in Italy that this iteration of syphilis was far more morbid than the disease we know today. I’ve posted some of these engravings to Twitter if you’re curious. As Charles’ defeated mercenaries disbanded, they took the disease back to their home countries with them. As the ever-quotable Voltaire would later write: 

 

‘On their flippant way through Italy, the French carelessly picked up Genoa, Naples and syphilis. Then they were thrown out and deprived of Naples and Genoa. But they did not lose everything – syphilis went with them.

 

By the next year, doctors across Europe had described this mysterious new disease — accurately describing the primary chancre, followed by the secondary fevers, ulcers, and pustules, and also noted that it was sexually-transmitted in nature. By the 1520s, doctors had also described the third stage of the disease, including bone destruction, and ulcers (gumma) throughout the organs of the body. And most notably — all these doctors agreed that this was something new, not known to the ancients.

 

And what to call this new disease? One term was the “great pox,” to differentiate it from smallpox. But syphilis was quickly tied up in politics of sex, shame, and blame. Morbus gallicum, or the French disease, was the preferred name, especially to German- and English-speakers, though the French preferred to cast the blame on the people of Naples — the Neopolitan disease. Not to be outdone, the Dutch and the Ottomans called it the Spanish Sickness, the Poles called it the German Sickness, and the Japanese called it the Canton rash or the Chinese ulcer. By 1527, Jacques de Bethencourt suggested that nations should not cast the blame on each other, but on the true culprit — sex, and particularly illicit sex. He proposed the term “morbus venerus,” the disease of venus, known in English as venereal disease. 

 

I should have an aside here about the sexual connotations of syphilis. Gonorrhea and chlamydia are likely far older than syphilis, though it took until the nineteenth century until physicians had accurately differentiated the diseases. Syphilis therefore presented a literal punishment from god for sex, and especially sex outside of marriage, that people had not seen before. The same year the disease emerged, the Holy Roman Emperor issued an edict that syphilis was a punishment from god for sins — especially those of a sexual nature. People with disfiguring gummas were ostracized like lepers. And these disfiguring sins were visible for all to see — on your neighbor, your local priest — even on a  pope. Since they had sinned, doctors reasoned that only harsh treatments could cure the disease. That is, if they were even worthy of treatment at all; it was a common view that patients with syphilis should be simply allowed to die, a popular enough opinion that the famous physician Thomas Sydenham wrote an opposing viewpoint that physicians should treat all without judgement. Unexpectedly, rulers used this to crack down on brothels and sexual encounters outside of marriage, as well as clamping down on mixed bathing.

 

This sort of steamy association has lasted until today, and is repeated in our medical education. Find a medical student and ask him what the Argyll Robertson pupil is. So, what it actually is is a very specific sign of neurosyphilis — the patient’s pupils will contract to an object near them (accomodation), but not to a light shown in their eyes. You can also see it in diabetic eye disease, but in an era with far more prevalent syphilis, this finding was more or less pathognomonic for neurosyphilis.

 

Medical students, at least most of them, do not know that. I know because I like to ask them. What they remember is a smirking older physician telling them that it’s called the “whore’s pupils”, because they accommodate but do not react. That’s an incredibly gross pun, if you can even call it that, and my skin kind of crawls just remembering when I was taught that. I know I’m not the only one who was taught that particularly useless piece of trivia, just because of its sordid association.

 

So one kind final aside in the name of syphilis — well, why is it called syphilis? That name actually comes from an Italian poet-physician who wrote a pseudo-Ancient poem about a shepherd named Syphilis, who led his people to blaspheme against the Sun God, who punished syphilis by cursing him with a new disease of pustules, which he was condemned to spread throughout his people. This faux-Greek name slowly caught on, though it wasn’t until the mid-nineteenth century that syphilis fully supplanted the French disease, or French pox, in the English-speaking world.

 

The popularity of the name also likely came from the context — the people of Europe were left wondering just where this horrifying disease had come from. There have been three major theories on the origin of syphilis, and there used to be quite the controversy about its mysterious origin, and while a consensus has emerged, there might still be a paleopathologist or two willing to throw down over the subject.

 

So the first theory was what was suspected by doctors living in the time of the great outbreak — what is now called the Columbian hypothesis. That is, syphilis is a disease of the New World, and then Columbus and his crew landed on the Island on Hispaniola, they contracted the disease and brought it back to Spain. Some of these men would later serve as Charles’ mercenaries during the siege of Naples. The rest, they say, is history. This account is actually backed up by one of the expedition’s physicians, who wrote in the 1520s that he treated Columbus’ men with the same disease that he now saw spreading in Spain. 

 

This view was mostly universally accepted by the medical community until the late 19th century, with the advent of modern anthropology. Syphilis leaves telltale markers of its destruction in the bones of the dead, and anthropologists started to notice these in pre-Contact Europeans. Paleopathologists also analyzed some of the writings of the ancients, and found descriptions that could be consistent with syphilis. Perhaps syphilis had always been among Europeans, and it was a mutation that caused the especially violent strain in 1495? This is called the Pre-Columbian Hypothesis. 

 

Before I describe the final theory, I should mention that syphilis is not the only disease caused by treponema pallidum; there’s also yaws, and bejel. Both also cause bony changes, but are far less destructive. Which brings us to the final theory, the so-called Unitarian hypothesis, that all treponemal diseases are caused by the same organism, and local factors cause the different symptoms. This has been definitively disproved by DNA analysis, which identifies these different diseases as evolutionarily different subspecies, so I don’t really have anymore to say about it.

 

So throughout the 20th century there has been, shall we say, spirited debate about the origin of syphilis. However, and I don’t want to make more controversy here, but the debate has largely been settled on the side of the Columbians. I’ve linked the meta-analysis in the show notes if you’re curious, but Dr. Rothschild developed a so-called osteotype of specific bone findings found in syphilis, but not in other diseases — saber shins and gummas, which are only found in syphilis and nothing else. He then analyzed all the Old World findings that had been published, and not a single one had this osteotype; rather, they had non-specific findings that could be explained by syphilis, sure, but also by other boney diseases. Contrarily, looking at New World bones, the syhpilis osteotype was very common, and in fact could be dated as the disease traveled down the Americas. Furthermore, bones dating to the time Columbus landed on Hispaniola also suggest that syphilis was prevalent on the island at that time. Taken together with modern DNA evidence, this all strongly suggests that syphilis is an Old World disease, transplanted back to Europe by Columbus in his men. This would also explain why the initial outbreak was so severe — Europeans had no natural immunity to the disease. In this sense, syphilis served as a counterpoint to the introduction of the smallpox in the new world,  a disease from sin — not sexual in nature, but the sin of imperialism and genocide.

 

So by the sixteenth century, physicians had largely accurately described syphilis. But how to treat it was an open question. One of the first proposed therapies was guiacum, an herb from the New World commonly called Holy Wood. However, the imported herb was expensive, and ineffective, so an old staple came to become the treatment of choice — mercury. Guiacum was likely useless, but mercury was deadly. A typical treatment would put the patient in a sauna, with a mercury ointment massaged into the skin several times a day. They would breath deeply and inhale these toxic vapors. If mercury wasn’t available, vitriol, the old name for sulfuric acid, or arsenic could be used as well. The principle isn’t actually bad — mercury and other heavy metals are toxic to bacteria, syphilis included, and this principle would actually lead to the first effective syphilis treatment in the 20th century. Of course, they’re also toxic to people. Patients unsurprisingly suffered the effects of heavy metal poisoning — kidney failure, anemia, neuropathy, and non-healing ulcers. 


Many recognized that the treatment might be worse than the disease, and a common saying was, “A night with venus, then a lifetime with Mercury”. As the 20th century approached, doctors continued to learn about syphilis — it was now recognized that syphilis and gonorrhea were two different diseases, neurosyphilis, including general paralysis of the insane, was fully described, and in 1905, the organism itself was identified under a dark field microscope. But mercury remained the mainstay of treatment until 1910 — and was on the national formulary of Australia as recently as 1955. Everything changed with Ehrlich and Hata’s discovery of Salvarsan, or Compound 606. This story is fascinating, but for another podcast — briefly, they were systematically trying to make an arsenic compound that would be toxic against syphilis, but not humans. In any event, this was the first chemotherapeutic agent, and the first truly effective medicine against syphilis. It was capable of curing both the primary and secondary forms of the disease, though with considerable side effects. Alas, neurosyphilis, and especially general paralysis of the insane, were untouched by the compound. 

 

So there’s your background on syphilis. Now we have to talk briefly about the psychiatric milieu that Wagner-Jauregg was trained in. For millennia, the Four Humours had informed medical beliefs about what we would now call psychiatry — that imbalances in the body’s four constituent fluids caused all sorts of pathologies. I’m actually working on a podcast on this incredibly influential idea, so stay tuned. By the 19th century, humoral theory was on its last legs. Neurology had shown that some diseases that had previously been thought to have been psychiatric in nature — stroke and epilepsy most notably — were in fact caused by lesions in the brain. A group of physicians in Germany and Austria therefore posited that in fact all psychiatric disease must be caused by some sort of physical pathology in the body. They also felt that by treating these diseases, they could empty the asylums which had been filling up in the countryside by returning people to their lives. Ultimately, this movement failed to catch on — they were only able to classify a small number of diseases, and ultimately couldn’t offer any effective treatments.

 

But in any event, Wagner-Jauregg studied medicine in the late 19th century, and came of age in this heady period. He initially wanted to study internal medicine, but couldn’t secure a position so chose psychiatry instead, “which neither harmed myself nor psychiatry” as he would later quip. He quickly became an enthusiastic supporter of this new biological view of psychiatry. This views were crystallized by a remarkable case he witnessed early in his career, in 1887. A woman was admitted to his asylum with psychosis, and developed a nasty case of erysipelas, a rapidly-spreading skin infection caused by streptococcus. She developed a high fever, and then general skin desquamation — that is, the top layers of her skin actually came off. She survived — and was completely cured of her psychosis, being discharged home after her recovery. Wagner-Jauregg began to read extensively on the topic. This observation — that fever could ease madness, or even cure it, was actually ancient in origin. Hippocrates and Galen had reported that tertian fever, with was likely malaria, could cure other illnesses. He was also aware of the experiments of a Dr. Rosenblum in Russia. Rosenblum had purposefully infected a number of comatose patients with various relapsing fevers in his sanitarium. His intention, however, was not to cure them — rather, they were to serve as human petri dishes for microbiological experiments. But much to his surprise, half of these patients improved. 

 

Germ theory was new, and Wagner-Jauregg was an eager convert, and he set about attempting to craft a cure to psychosis. Remembering his first patient, he tried to use streptococcus to cause erysipelas. He found a woman with metastatic breast cancer, and inoculated her wound into several patients, but the infection wouldn’t take. With public opinion turning against experimenting on humans, he moved onto the new field of vaccination, which had only recently spread beyond smallpox.  He first tried tuberculin, a sterile protein from tuberculosis which would cause a fever, and he had some success. He noted that the response was most dramatic in patients with the end stage of syphilis, general paralysis of the insane, GPI. And there would have been plenty of neurosyphilis patients. Up to 15 percent of patients in asylums had the disease, and it was invariably fatal within just a few years. Wagner-Jauregg therefore designed a remarkable controlled trial — he identified 129 patients with GPI. 69 of them, he gave tuberculin, plus the standard of care, mercury injections. The other 60 received mercury injections only. He then followed then up for four years. At the end of four years, patients treated with tuberculin plus mercury had a longer life, as well as more and better quality transmissions. Despite this, tuberculin never really caught on. He repeated the experiments with new typhus and typhoid vaccines, seeing some success. And then finally, it was 1917, the day a poor soldier returning from the Balkans was accidentally admitted to a psych ward with malaria. After this experiment, he continued his research, getting fresh malarial blood from a nearby military hospital. Initially the experiments were a disaster — he inoculated four patients with “malignant tertian malaria”, which we know now was the more deadly plasmodium falciparum, and three of them died. But eventually he cultivated “benign” malaria — we now know as vivax and ovale — and went on to perform chain infection for 16 years. At long last, psychiatry had a silver bullet — not only a biological explanation, but an ability to actually get patients back to their lives.  Physicians all over the world rushed to repeat the experiment, and within a few years malaria therapy had become the standard of care. A protocol was slowly developed. Patients would be observed in the hospital and either inoculated with malarial blood, or in the United States, introduced with malaria-containing mosquitoes. At the same time, they would be given neosalvarsan, which had now replaced mercury, to treat syphilis. Then, under medical monitoring, the patient would be allowed to undergo 10-12 cycles of fevers before they were given quinine to treat the malaria. 

 

The effects were dramatic — in 1926, a review was performed of 35 different studies which showed that 28% of patients had a full remission and 27% had a partial remission that allowed them to leave the asylum. That’s not to say there weren’t risks involved. Anywhere between 2-15% of patients died from the therapy. By 1927, he was accepting the Nobel Prize in Medicine, the first (and only) ever awarded to a psychiatrist. By this time, thousands of patients around the world had been cured of a previously uncurable disease.

 

Believe it or not, we don’t actually know quite how malariotherapy worked. The presumption was that the fever itself caused the relief, and soon malariotherapy was part of a larger group of treatments called pyrotherapy with included heating blankets and medications to raise the body temperature. But none of them worked nearly as well as malaria. With our modern understanding of syphilis, it seems unlikely that the fever itself would work — T. pallidum can survive temperatures as high as 41 degrees centigrade for six hours, far too high for any human to survive. Ultimately, we’ll have to be satisfied with the idea that somehow malaria attacked not only the blood cells of the host, but also syphilis bacteria itself.

 

I think it’s telling that pretty much everyone has heard of Sigmund Freud, but not his friend and contemporary Julius Wagner-Jauregg. Undoubtedly psychoanalysis has had a massive impact on modern psychiatry, but malariotherapy, and more generally, biological treatments for psychiatric diseases — and treating previously intractable mentally illnesses so patients can return to their lives — is now the mainstay of psychiatry. So why have we forgotten him?

 

I think there are a few main reasons. The first is that medicine moved on — penicillin was invented, and by 1943 had been demonstrated to be curative in syphilis, including neurosyphilis and GPI. Penicillin today remains the standard of care for the condition.  In this sense, we don’t talk about malariotherapy for the same reason we don’t talk about neosalvarsan anymore.

 

And the second is even more understandable — the specter of the Nazis. Ethical objections to Wagner-Jauregg’s work had flared prior to the war; in fact, he was considerably delayed in receiving his Nobel because B. Gadelius, a Swedish psychiatrist on the committee, refused to give a Novel to “a physician who injected malaria into a paralytic, because he was in his eyes a criminal.” But after the horrors of Nazi medical experimentation were revealed during the Nuremburg trials, injecting malarial blood into non-consenting adults made you a persona non grata. And it didn’t help that Wagner-Jauregg was himself a Nazi. He was an anti-Semite (despite his first wife being Jewish), enthusiastically joined the Nazi party, and towards the end of his life dabbled in eugenics research. That he stood up for the mentally ill, and died in 1940 before the worst horrors of the Nazis did little to redeem him against a world recoiling in horror.

 

I’d point out that the de-Nazification of medicine is still reasonably recent, and we had forgotten Wagner-Jauregg well before this. I’m not a psychiatrist, but it seems like there has been a bit of professional embarrassment about malariotherapy. It was the first in a line of so-called stress therapies, which involved brutal treatments for psychiatric illness, including electric shock, lobotomies, inducing hypoglycemic seizures with insulin, and using chemotherapeutic drugs to bring on fevers. This have been rightly vilified — think Nurse Ratchett in One Flew Over the Cuckoo’s Nest, so much so that the relatively benign and effective electro-consulsive therapy for depression is still a tough sell today. In an era of pharmaceuticals for psychiatry, Wagner-Jauregg is a particularly embarrassing Nazi uncle.

 

This strange, brief foray into using malaria as a medical treatment still has repercussions today. Stocks of malaria-infected anopheles mosquitoes were kept throughout the world for a malaria source, and researchers experiences with these helped to illuminate the life cycle of malaria, and identify a new species — plasmodium ovale. Many of the new malarial drugs, some of which are in use today, were tested on patients undergoing malaria therapy. And the impact on psychiatry was considerable — a psychiatric disease was for the first time treatable with a biological agent. The generation raised with the knowledge of malariotherapy would go on to develop antipsychotics, and continue the mission of getting psychiatric patients back to their lives. Malariotherapy even had a brief resurgence in the 80s and 90s — first proposed as a treatment for Lyme disease, and then a very ethically murky and bizarre trial by Dr. Heimlich — yes, the guy who invented the anti-choking maneuver — on HIV patients in the late 90s in China.  But probably the most impactful legacy was that thousands of patients who would have died of GPI were cured, and thousands more had their lives improved. 


Before I went down the malariotherapy rabbit hole, I had assumed Wagner-Jauregg’s experiments and Nobel were an amusing side show to the development of modern medicine. But now my thinking has evolved. The man did many laudable things for medicine. He was inspired by his care of patients at the bedside, by careful observation, and he tested his methods by crafting scientific trials. In an era that was content to throw people with mental illness into asylums located in the countryside, far from population centers, he dreamed of a world where his patients could return to society — and accomplished it to a degree. And we always have to remember, the invention of penicillin was not a foregone conclusion — germ theory opened an opportunity to finally fight infectious diseases, and malariotherapy was one of the more promising inventions. It’s hard to admire a man who experimented on non-consenting patients, an anti-Semite, a Nazi — but it’s also hard to deny his contributions to medicine.

 

Well, that’s it for the show! But wait — it’s time for #AdamAnswers. So this question comes from Zach Lawson via twitter:

 

@AdamRodmanMD I have a weird NSFW #AdamAnswers: A (non-medical) peer-reviewed paper I read claims Hippocrates & contemporaries believed hair primarily served to absorb semen. 1) lol really? 2) how do we establish consensus of ancient medical community vs what some rando thought?

 

This is an amazing set of questions, and I’m going to do my best to answer both — but I have to give a brutal caveat. I don’t get ancient medicine, and most of my contact with it comes through mediaries, in particular the excellent if dense textbook “Ancient Medicine” by Vivian Nutton. I’m not sure why, but the ancients don’t speak to me yet like early modern doctors; I “get” Wagner-Jauregg, I get Thomas Sydenham. When I’ve read the Hippocratic corpus, I don’t yet feel like I’m having a conversation with a physician in the past, and I don’t have enough to really put this all in context.

 

So to address your first question — did Hippocrates and the contemporaries believe that hair existed to absorb semen? 

 

So the quote your friend showed you is from a piece of Christian apologetics in the Journal of Biblical Literature called “Paul’s argument from nature for the veil in 1 Corinthians 11;13-15: A testicle instead of a head covering”. The gist of the argument is, and this is a direct quote, “Paul appropriately instructs women in the service of God to cover their hair since it is part of the female genitalia.” Now, I admittedly don’t know anything about Christian apologetics, nor have I read Corinthians in over a decade, and I’m therefore completely incapable of judging the article on the merits the author intended. The quotes that your friend noted referencing semen-containing hair are real. Many of the quotes defending his hypothesis from from a remarkable little treatise of the Hippocratic Corpus, called “On Glands.” This short work is the first discussion of the lymphatic system in history. The description is remarkably modern — he describes the arrangement of the lymph nodes, the involvement of the spleen, how they can form abscesses, the swelling in response to illness. Their purpose, according to the author, is to drain fluid — which, of course is accurate, and a brilliant observation for 2000 years ago, though the author refers to of course the four humors, rather than chylous material as we know today. He hypothesizes that these glands are connected by thin, hollow structures — which of course they are — and posits that hair might in fact be part of the same overall system, which we now know it  is not. 

 

And now we have to talk about about the ancient conception of, well,  conception. The Hippocratic school believed that both men and women created semen, which was made in the head, and would migrate down the body during sex. In the woman’s body, the two would mix in the womb, where a new life would be created. Semen was a fluid, and created in the head, which was attached to a number of glands — wouldn’t it make some sense that it might be stored there?

 

So that answer to your first question is, yes, really. Now on the to the second. How do we establish a consensus about what the ancients really thought?

 

The answer, of course, is that we don’t. There was a huge variety of opinions in ancient medicine, and most of the writings have not been saved. Sometimes we get tantalizing glimpses, usually through Galen disagreeing with someone. For example, we know about three active medical sects in Rome during Galen’s time — the Dogmatists, the Empiricists, and the Rationalists. It’s all very philosophical about how we come to know medical knowledge. But that’s not the point. We don’t hear from these doctors themselves; their thoughts have been lost, like tears in the rain. We only know about them because Galen has been preserved. Similarly with humorism — we have tantalizing glimpses of an atomist version of medicine, not based on the four humors. But these authors’ works did not survive.

 

In many ways, what has been preserved says more about the values of Arab scholars and monks in the Middle Ages than it does about the ancients’ themselves. We know that Galen and Hippocrates were no “randos” — their work was preserved for a reason, and they are referring glowingly by contemporaries. But we don’t have a good sense of what, if any, consensus existed, and what discussions were ongoing. 

 

So Zach, wonderful question — I’m glad I got to do some research into semen storage in hair, which is not reading I thought I’d ever be doing. Sorry that I don’t know more. And dear listeners, if any of YOU want to be disappointed by my lackluster answers, Tweet a question to me @AdamRodmanMD!

 

So that’s actually it for the show. Exciting — and disruptive — things are happening in my life. After about 10 years or so of bouncing around the country and the world, my wife and I are finally setting down for a breather — meaning that we literally just bought a house. I’m recording this literally surrounded boxes, so this will be the last podcast recorded in my old place. I don’t expect any imminent changes to the show, but I’ll be setting up a recording studio of sorts in our new place, which is cool.   I’m also going to have some bonus content later this week — I’m interviewing the author of a great article on Julius Wagner-Jauregg, Cynthia Tsay, so expect that soon.  You can listen to all my episodes on the website at www.bedside-rounds.org, or on Apple Podcasts, Stitcher, or the podcast retrieval method of your choice. I’m on facebook at /BedsideRounds, or on Twitter @AdamRodmanMD. I love to hear from listeners, and I’ve learned a lot from you guys — so come and say hi!

 

All the sources are in the shownotes.

 

And finally, while I am actually a doctor and I don’t just play one on the internet, this podcast is intended to be purely for entertainment and informational purposes, and should not be construed as medical advice. If you have any medical concerns, please see your primary care provider.