Trading syphilis for malaria: How doctors treated one deadly disease by infecting patients with another
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.
"Making Sense of Science" is a monthly podcast that features interviews with leading medical and scientific experts about the latest developments and the big ethical and societal questions they raise. This episode is hosted by science and biotech journalist Emily Mullin, summer editor of the award-winning science outlet Leaps.org.
Listen to the episode:
Meet the Psychologist Using Psychedelics to Treat Racial Trauma
Monnica Williams was stuck. The veteran psychologist wanted to conduct a study using psychedelics, but her university told her they didn't have the expertise to evaluate it via an institutional review board, which is responsible for providing ethical and regulatory oversight for research that involves human participants. Instead, they directed her to a hospital, whose reviewers turned it down, citing research of a banned substance as unethical.
"I said, 'We're not using illegal psilocybin, we're going through Health Canada,'" Williams said. Psilocybin was banned in Canada in 1974, but can now be obtained with an exemption from Health Canada, the federal government's health policy department. After learning this, the hospital review board told Williams they couldn't review her proposal because she's not affiliated with the hospital, after all.
It's all part of balancing bureaucracy with research goals for Williams, a leading expert on racial trauma and psychedelic medicine, as well as obsessive compulsive disorder (OCD), at the University of Ottawa. She's exploring the use of hallucinogenic substances like MDMA and psilocybin — commonly known as ecstasy and magic mushrooms, respectively — to help people of color address the psychological impacts of systemic racism. A prolific researcher, Williams also works as an expert witness, offering clinical evaluations for racial trauma cases.
Scientists have long known that psychedelics produce an altered state of consciousness and openness to new perspectives. For people with mental health conditions who haven't benefited from traditional therapy, psychedelics may be able to help them discover what's causing their pain or trauma, including racial trauma—the mental and emotional injury spurred by racial bias.
"Using psychedelics can not only bring these pain points to the surface for healing, but can reduce the anxiety or response to these memories and allow them to speak openly about them without the pain they bring," Williams says. Her research harnesses the potential of psychedelics to increase neuroplasticity, which includes the brain's ability to build new pathways.
"People of color are dealing with racism all the time, in large and small ways, and even dealing with racism in healthcare, even dealing with racism in therapy."
But she says therapists of color aren't automatically equipped to treat racial trauma. First, she notes, people of color are "vastly underrepresented in the mental health workforce." This is doubly true in psychedelic-assisted psychotherapy, in which a person is guided through a psychedelic session by a therapist or team of therapists, then processes the experience in subsequent therapy sessions.
"On top of that, the therapists of color are getting the same training that the white therapists are getting, so it's not even really guaranteed that they're going to be any better at helping a person that may have racial trauma emerging as part of their experience," she says.
In her own training to become a clinical psychologist at the University of Virginia, Williams says she was taught "how to be a great psychologist for white people." Yet even people of color, she argues, need specialized training to work with marginalized groups, particularly when it comes to MDMA, psilocybin and other psychedelics. Because these drugs can lower natural psychological defense mechanisms, Williams says, it's important for providers to be specially trained.
"People of color are dealing with racism all the time, in large and small ways, and even dealing with racism in healthcare, even dealing with racism in therapy. So [they] generally develop a lot of defenses and coping strategies to ward off racism so that they can function." she says. This is particularly true with psychedelic-assisted psychotherapy: "One possibility is that you're going to be stripped of your defenses, you're going to be vulnerable. And so you have to work with a therapist who is going to understand that and not enact more racism in their work with you."
Williams has struggled to find funding and institutional approval for research involving psychedelics, or funding for investigations into racial trauma or the impacts of conditions like OCD and post-traumatic stress disorder (PTSD) in people of color. With the bulk of her work focusing on OCD, she hoped to focus on people of color, but found there was little funding for that type of research. In 2020, that started to change as structural racism garnered more media attention.
After the killing of George Floyd, a 46-year-old Black man, by a white police officer in May 2020, Williams was flooded with media requests. "Usually, when something like that happens, I get contacted a lot for a couple of weeks, and it dies off. But after George Floyd, it just never did."
Monnica Williams, clinical psychologist at the University of Ottawa
Williams was no stranger to the questions that soon blazed across headlines: How can we mitigate microaggressions? How do race and ethnicity impact mental health? What terms should we use to discuss racial issues? What constitutes an ally, and why aren't there more of them? Why aren't there more people of color in academia, and so many other fields?
Now, she's hoping that the increased attention on racial justice will mean more acceptance for the kind of research she's doing.
In fact, Williams herself has used psychedelics in order to gain a better understanding of how to use them to treat racial trauma. In a study published in January, she and two other Black female psychotherapists took MDMA in a supervised setting, guided by a team of mental health practitioners who helped them process issues that came up as the session progressed. Williams, who was also the study's lead author, found that participants' experiences centered around processing and finding release from racial identities, and, in one case, of simply feeling wholly human without the burden of racial identity for the first time.
The purpose of the study was twofold: to understand how Black women react to psychedelics and to provide safe, firsthand, psychedelic experiences to Black mental health practitioners. One of the other study participants has since gone on to offer psychedelic-assisted psychotherapy to her own patients.
Psychedelic research, and psilocybin in particular, has become a hot topic of late, particularly after Oregon became the first state to legalize it for therapeutic use last November. A survey-based, observational study with 313 participants, published in 2020, paved the way for Williams' more recent MDMA experiments by describing improvements in depression, anxiety and racial trauma among people of color who had used LSD, psilocybin or MDMA in a non-research setting.
Williams and her team included only respondents who reported a moderate to strong psychoactive effect of past psychedelic consumption and believed these experiences provided "relief from the challenging effects of ethnic discrimination." Participants reported a memorable psychedelic experience as well as its acute and lasting effects, completing assessments of psychological insight, mystical experience and emotional challenges experienced during psychedelic experience, then describing their mental health — including depression, anxiety and trauma symptoms — before and after that experience.
Still, Williams says addressing racism is much more complex than treating racial trauma. "One of the questions I get asked a lot is, 'How can Black people cope with racism?' And I don't really like that question," she says. "I think it's important and I don't mind answering it, but I think the more important question is, how can we end racism? What can Black people do to stop racism that's happening to them and what can we do as a society to stop racism? And people aren't really asking this question."