Trading syphilis for malaria: How doctors treated one deadly disease by infecting patients with another
In the 1920s, doctors induced a high fever in patients - so called "fever therapy" - as a way to help them recover from syphilis, though it involved ethical problems.
If you had lived one hundred years ago, syphilis – a bacterial infection spread by sexual contact – would likely have been one of your worst nightmares. Even though syphilis still exists, it can now be detected early and cured quickly with a course of antibiotics. Back then, however, before antibiotics and without an easy way to detect the disease, syphilis was very often a death sentence.
To understand how feared syphilis once was, it’s important to understand exactly what it does if it’s allowed to progress: the infections start off as small, painless sores or even a single sore near the vagina, penis, anus, or mouth. The sores disappear around three to six weeks after the initial infection – but untreated, syphilis moves into a secondary stage, often presenting as a mild rash in various areas of the body (such as the palms of a person’s hands) or through other minor symptoms. The disease progresses from there, often quietly and without noticeable symptoms, sometimes for decades before it reaches its final stages, where it can cause blindness, organ damage, and even dementia. Research indicates, in fact, that as much as 10 percent of psychiatric admissions in the early 20th century were due to dementia caused by syphilis, also known as neurosyphilis.
Like any bacterial disease, syphilis can affect kids, too. Though it’s spread primarily through sexual contact, it can also be transmitted from mother to child during birth, causing lifelong disability.
The poet-physician Aldabert Bettman, who wrote fictionalized poems based on his experiences as a doctor in the 1930s, described the effect syphilis could have on an infant in his poem Daniel Healy:
I always got away clean
when I went out
With the boys.
The night before
I was married
I went out,—But was not so fortunate;
And I infected
My bride.
When little Daniel
Was born
His eyes discharged;
And I dared not tell
That because
I had seen too much
Little Daniel sees not at all
Given the horrors of untreated syphilis, it’s maybe not surprising that people would go to extremes to try and treat it. One of the earliest remedies for syphilis, dating back to 15th century Naples, was using mercury – either rubbing it on the skin where blisters appeared, or breathing it in as a vapor. (Not surprisingly, many people who underwent this type of “treatment” died of mercury poisoning.)
Other primitive treatments included using tinctures made of a flowering plant called guaiacum, as well as inducing “sweat baths” to eliminate the syphilitic toxins. In 1910, an arsenic-based drug called Salvarsan hit the market and was hailed as a “magic bullet” for its ability to target and destroy the syphilis-causing bacteria without harming the patient. However, while Salvarsan was effective in treating early-stage syphilis, it was largely ineffective by the time the infection progressed beyond the second stage. Tens of thousands of people each year continued to die of syphilis or were otherwise shipped off to psychiatric wards due to neurosyphilis.
It was in one of these psychiatric units in the early 20th century that Dr. Julius Wagner-Juaregg got the idea for a potential cure.
Wagner-Juaregg was an Austrian-born physician trained in “experimental pathology” at the University of Vienna. Wagner-Juaregg started his medical career conducting lab experiments on animals and then moved on to work at different psychiatric clinics in Vienna, despite having no training in psychiatry or neurology.
Wagner-Juaregg’s work was controversial to say the least. At the time, medicine – particularly psychiatric medicine – did not have anywhere near the same rigorous ethical standards that doctors, researchers, and other scientists are bound to today. Wagner-Juaregg would devise wild theories about the cause of their psychiatric ailments and then perform experimental procedures in an attempt to cure them. (As just one example, Wagner-Juaregg would sterilize his adolescent male patients, thinking “excessive masturbation” was the cause of their schizophrenia.)
But sometimes these wild theories paid off. In 1883, during his residency, Wagner-Juaregg noted that a female patient with mental illness who had contracted a skin infection and suffered a high fever experienced a sudden (and seemingly miraculous) remission from her psychosis symptoms after the fever had cleared. Wagner-Juaregg theorized that inducing a high fever in his patients with neurosyphilis could help them recover as well.
Eventually, Wagner-Juaregg was able to put his theory to the test. Around 1890, Wagner-Juaregg got his hands on something called tuberculin, a therapeutic treatment created by the German microbiologist Robert Koch in order to cure tuberculosis. Tuberculin would later turn out to be completely ineffective for treating tuberculosis, often creating severe immune responses in patients – but for a short time, Wagner-Juaregg had some success in using tuberculin to help his dementia patients. Giving his patients tuberculin resulted in a high fever – and after completing the treatment, Wagner-Jauregg reported that his patient’s dementia was completely halted. The success was short-lived, however: Wagner-Juaregg eventually had to discontinue tuberculin as a treatment, as it began to be considered too toxic.
By 1917, Wagner-Juaregg’s theory about syphilis and fevers was becoming more credible – and one day a new opportunity presented itself when a wounded soldier, stricken with malaria and a related fever, was accidentally admitted to his psychiatric unit.
When his findings were published in 1918, Wagner-Juaregg’s so-called “fever therapy” swept the globe.
What Wagner-Juaregg did next was ethically deplorable by any standard: Before he allowed the soldier any quinine (the standard treatment for malaria at the time), Wagner-Juaregg took a small sample of the soldier’s blood and inoculated three syphilis patients with the sample, rubbing the blood on their open syphilitic blisters.
It’s unclear how well the malaria treatment worked for those three specific patients – but Wagner-Juaregg’s records show that in the span of one year, he inoculated a total of nine patients with malaria, for the sole purpose of inducing fevers, and six of them made a full recovery. Wagner-Juaregg’s treatment was so successful, in fact, that one of his inoculated patients, an actor who was unable to work due to his dementia, was eventually able to find work again and return to the stage. Two additional patients – a military officer and a clerk – recovered from their once-terminal illnesses and returned to their former careers as well.
When his findings were published in 1918, Wagner-Juaregg’s so-called “fever therapy” swept the globe. The treatment was hailed as a breakthrough – but it still had risks. Malaria itself had a mortality rate of about 15 percent at the time. Many people considered that to be a gamble worth taking, compared to dying a painful, protracted death from syphilis.
Malaria could also be effectively treated much of the time with quinine, whereas other fever-causing illnesses were not so easily treated. Triggering a fever by way of malaria specifically, therefore, became the standard of care.
Tens of thousands of people with syphilitic dementia would go on to be treated with fever therapy until the early 1940s, when a combination of Salvarsan and penicillin caused syphilis infections to decline. Eventually, neurosyphilis became rare, and then nearly unheard of.
Despite his contributions to medicine, it’s important to note that Wagner-Juaregg was most definitely not a person to idolize. In fact, he was an outspoken anti-Semite and proponent of eugenics, arguing that Jews were more prone to mental illness and that people who were mentally ill should be forcibly sterilized. (Wagner-Juaregg later became a Nazi sympathizer during Hitler’s rise to power even though, bizarrely, his first wife was Jewish.) Another problematic issue was that his fever therapy involved experimental treatments on many who, due to their cognitive issues, could not give informed consent.
Lack of consent was also a fundamental problem with the syphilis study at Tuskegee, appalling research that began just 14 years after Wagner-Juaregg published his “fever therapy” findings.
Still, despite his outrageous views, Wagner-Juaregg was awarded the Nobel Prize in Medicine or Physiology in 1927 – and despite some egregious human rights abuses, the miraculous “fever therapy” was partly responsible for taming one of the deadliest plagues in human history.
Nicole Gularte in Feb 2019 at her three-month follow up visit after her successful CAR T-cell therapy last fall at Penn.
[Editor's Note: This is the final video of a five-part series titled "The Future Is Now: The Revolutionary Power of Stem Cell Research." Produced in partnership with the Regenerative Medicine Foundation, and filmed at the annual 2019 World Stem Cell Summit, this series illustrates how stem cell research will profoundly impact human life.]
Kira Peikoff was the editor-in-chief of Leaps.org from 2017 to 2021. As a journalist, her work has appeared in The New York Times, Newsweek, Nautilus, Popular Mechanics, The New York Academy of Sciences, and other outlets. She is also the author of four suspense novels that explore controversial issues arising from scientific innovation: Living Proof, No Time to Die, Die Again Tomorrow, and Mother Knows Best. Peikoff holds a B.A. in Journalism from New York University and an M.S. in Bioethics from Columbia University. She lives in New Jersey with her husband and two young sons. Follow her on Twitter @KiraPeikoff.
The Troubling Reason I Obsessively Researched My Pregnancy
A pregnant woman in her third trimester.
At the end of my second trimester of pregnancy, I answered a call from an unknown number.
To be pregnant is to exist on a never-ending receiving line of advice, whether we want it or not.
"I know your due date is approaching," said a stranger at the other end of the line, completely freaking me out. She identified herself as being from Natera, a company that my doctor had used for genetic testing I had consented to months ago.
"Excuse me?" I said.
"Have you considered cord-blood banking?" she said.
"No, I'm not doing that," I said. I had read enough about cord-blood banking, the process of saving stem cell-containing blood from your baby's umbilical cord, to understand that my family was in the vast majority of those that would with extremely high likelihood derive no medical benefit from it. Of course, in the societally sanctioned spending spree that accompanies new parenthood, plenty of companies are happy to charge anyone hundreds if not thousands of dollars plus annual storage fees to collect and manage your cord blood.
"Why not? Have you considered all the bene—"
"I'm not doing it and I don't want to explain my decision," I said before hanging up. I would later learn I neglected to check a miniscule box on my testing consent forms at the doctor to opt out of solicitations. Still, I was angry that I was being telemarketed unnecessary and costly medical services by someone who had been trained to immediately call my judgment into question. I was annoyed that my doctor's office would allow such intrusions at all. When I asked my OB about it at my next visit, she told me there's no way Natera would have gotten my information from them. Apparently even she didn't realize what was on those forms.
The incident with Natera did nothing to heighten my trust of the medical establishment during my pregnancy. I was hardly alone. Almost every mom I knew had expressed a similar sentiment.
"I don't trust doctors," read the text of a loved one when I told her I would probably get an epidural after my doctor recommended getting one because, she said, it can help relax the pelvic muscles during labor. But this friend, a highly educated woman who had had done her research and had two unmedicated births, believed firmly otherwise. "Look it up," she said. Thus commenced more of the furious Googling I found myself doing multiple times a day since deciding I wanted to become pregnant.
To be pregnant is to exist on a never-ending receiving line of advice, whether we want it or not. Information presents to us from Google's never-out-of-reach search bar, friends and family eager to use our pregnancies as an excuse to recall their own, and the doctor's office, where the wisdom of medical professionals neatly comingles with brochures and free samples from myriad companies that would really, really like our business as new moms. Separating the "good" advice from the rest is a Herculean task that many pregnant women manage only with vigorous fact-finding missions of their own.
The medical community in America is poorly equipped to help women navigate the enormous pressures that come with birth and transitioning to motherhood.
Doing my research during pregnancy felt like a defense against the scary unknowns, overabundance of opinions, and disturbing marketing schemes that come with entering parenthood. The medical community in America is poorly equipped to help women navigate the enormous emotional and societal pressures that come with birth and transitioning to motherhood. Too much of what pregnant women experience at the doctor has to do with dated ideas about our care, mandated by tradition or a fear of being sued rather than medical necessity. These practices, like weigh-ins at every appointment or medically unnecessary C-sections (which are estimated to account, horrifically, for almost 50 percent of all C-sections performed in the U.S.), only heighten anxiety.
Meanwhile, things that might alleviate stress – like having thorough discussions about the kinds of interventions we might be asked to accept at the hospital during labor and delivery – are left to outside educators and doulas that insurance plans typically don't cover. The net effect isn't better health outcomes for mom and baby, but rather a normalized sense of distrust many American women feel toward their OBGYNs, and the burden of going to every appointment and the delivery room on the defensive. Instead of being wed to dated medical practices and tangled in America's new motherhood industrial complex, shouldn't our doctors, of all people, be our biggest advocates?
As soon as I found out I was pregnant, I devoured Expecting Better, by Emily Oster, an economist who embarked on her own fact-finding mission during her first pregnancy, predicated on the belief that the advice OBGYNs have been giving pregnant women for decades is out of date and unnecessarily restrictive. The book includes controversial stances, like that having small amounts of alcohol while pregnant is OK. (More recent research has called this view into question.) Oster writes that for the vast majority of pregnant women, it's perfectly fine to lie on your back, do sit-ups, and eat Brie — all things I was relieved to learn I wouldn't have to give up for nine months, despite the traditional advice, which my doctor also gave to me.
Oster recommends hiring a doula, based both on research and personal experience. It's a worthwhile investment for those who can afford it: according to one study, 20.4 percent of laboring women with doulas had C-sections compared with 34.2 percent of women without them. A doula can do many things for a pregnant client, including helping her write a birth plan, massaging her back in labor, and cheering her on, which is especially useful for women who plan to labor without pain medication. Use of doulas is on the rise; according to DONA International, the world's largest and oldest doula association, the number of doulas who have been certified to date is over 12,000, up from 2,000 in 2002.
But the most significant role a doula plays is that of patient advocate in the hospital. This is a profound commentary on the way the medical establishment handles childbirth, a medical event that 86 percent of women aged 40 to 44 had gone through as of 2016. Recognizing the maternal mortality crisis in the U.S., where women are far more likely to die as a result of childbirth than anywhere else in the developed world and black women are three times more likely to die in childbirth than white women, a few states now allow Medicaid to cover doulas. Can you imagine feeling the need to hire an independent non-medical care provider to help you run interference with your doctors and nurses for something like an appendectomy?
I wouldn't have been aware of all the imminent interventions during my labor if my doula hadn't told me about them. Things happen fast in the hospital and doctors and nurses may rush patients to consent before proceeding with things like breaking their water or hooking them up to an IV of Pitocin. Only because my husband and I had spent six hours in birth class — a suggestion by my doula — did I realize that I was empowered to say "no" to such procedures.
Expecting more trustworthy advice to come from my doctor than books or Google or even a doula hardly seems unreasonable.
Of course, we all feel immense pressure to become good parents, and questioning conventional medical wisdom is a natural response to that pressure. "Looking around at the world and saying, who am I as a parent? What is important to me? Who are the wise people? What do I think wisdom is? What is a good decision? If you're a certain type of introspective person, if you're really asking those questions, that's going to include like taking a second look at things that doctors, for example, say," says Koyuki Smith, a doula and birth educator.
Expecting more trustworthy advice to come from my doctor than books or Google or even a doula hardly seems unreasonable. Yet my doctor's office seemed more concerned with checking off a list of boxes rather than providing me with personalized care that might have relieved my understandable anxiety about my first birth. When I still hadn't gone into labor around the time of my due date, my doctor encouraged me to be induced because my baby appeared to be large. I declined but scheduled an induction to "hold my spot" around the 42-week mark.
When I asked what medication would be used for an induction if I had one and she said Cytotec, I told her I had read that drug could cause serious complications, but she dismissed my concerns after I told her they stemmed from a book I read on natural childbirth. The FDA's page on Cytotec isn't exactly reassuring.
The nurse who took me in triage after I went into labor a week past my due date practically scolded me for waiting to go into labor naturally instead of opting for induction sooner. My doula told her while I was struggling to speak through labor pains to get off my case about it. I hadn't even become a mom and I was already doing so many things "wrong." Because I had done my own reading, I felt confident that my choices weren't harming my baby or me.
Becoming a mom would be less daunting if the medical community found a way to help women navigate the pressures of motherhood instead of adding to them. "Our culture at large doesn't support women enough in the complicated emotions that are a part of this process," said Alexandra Saks, a reproductive psychologist and author of What No One Tells You: A Guide to Your Emotions From Pregnancy to Motherhood. "I hope that every practitioner that works with women around reproductive health prioritizes her emotions around her experience."
For many of us, that will mean doctors who help us understand the pros and cons of conventional advice, don't use their offices as marketing channels, and don't pressure women into medically unnecessary inductions. Moms should also receive more attention after delivery both in the hospital and after they get home; a single, quick postpartum visit at six weeks is not an adequate way to care for women recovering from the trauma of childbirth, nor is it an adequate way to ensure women are emotionally supported during the transition. While several people interrogated me about my mental health at the hospital and my doctor's office just before and after birth, if I had been concerned about postpartum depression, I can't imagine feeling comfortable enough in those moments to tell strangers filling out obligatory worksheets.
It also means figuring out how to talk to patients who are prone to Googling their pregnancies with gusto every single day. It would be impossible for many women to shun independent research during pregnancy altogether. But it would also be nice if our doctors didn't add to our impulse to do it.