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.
Harvard Researchers Are Using a Breakthrough Tool to Find the Antibodies That Best Knock Out the Coronavirus
To find a cure for a deadly infectious disease in the 1995 medical thriller Outbreak, scientists extract the virus's antibodies from its original host—an African monkey.
"When a person is infected, the immune system makes antibodies kind of blindly."
The antibodies prevent the monkeys from getting sick, so doctors use these antibodies to make the therapeutic serum for humans. With SARS-CoV-2, the original hosts might be bats or pangolins, but scientists don't have access to either, so they are turning to the humans who beat the virus.
Patients who recovered from COVID-19 are valuable reservoirs of viral antibodies and may help scientists develop efficient therapeutics, says Stephen J. Elledge, professor of genetics and medicine at Harvard Medical School in Boston. Studying the structure of the antibodies floating in their blood can help understand what their immune systems did right to kill the pathogen.
When viruses invade the body, the immune system builds antibodies against them. The antibodies work like Velcro strips—they use special spots on their surface called paratopes to cling to the specific spots on the viral shell called epitopes. Once the antibodies circulating in the blood find their "match," they cling on to the virus and deactivate it.
But that process is far from simple. The epitopes and paratopes are built of various peptides that have complex shapes, are folded in specific ways, and may carry an electrical charge that repels certain molecules. Only when all of these parameters match, an antibody can get close enough to a viral particle—and shut it out.
So the immune system forges many different antibodies with varied parameters in hopes that some will work. "When a person is infected, the immune system makes antibodies kind of blindly," Elledge says. "It's doing a shotgun approach. It's not sure which ones will work, but it knows once it's made a good one that works."
Elledge and his team want to take the guessing out of the process. They are using their home-built tool VirScan to comb through the blood samples of the recovered COVID-19 patients to see what parameters the efficient antibodies should have. First developed in 2015, the VirScan has a library of epitopes found on the shells of viruses known to afflict humans, akin to a database of criminals' mug shots maintained by the police.
Originally, VirScan was meant to reveal which pathogens a person overcame throughout a lifetime, and could identify over 1,000 different strains of viruses and bacteria. When the team ran blood samples against the VirScan's library, the tool would pick out all the "usual suspects." And unlike traditional blood tests called ELISA, which can only detect one pathogen at a time, VirScan can detect all of them at once. Now, the team has updated VirScan with the SARS-CoV-2 "mug shot" and is beginning to test which antibodies from the recovered patients' blood will bind to them.
Knowing which antibodies bind best can also help fine-tune vaccines.
Obtaining blood samples was a challenge that caused some delays. "So far most of the recovered patients have been in China and those samples are hard to get," Elledge says. It also takes a person five to 10 days to develop antibodies, so the blood must be drawn at the right time during the illness. If a person is asymptomatic, it's hard to pinpoint the right moment. "We just got a couple of blood samples so we are testing now," he said. The team hopes to get some results very soon.
Elucidating the structure of efficient antibodies can help create therapeutics for COVID-19. "VirScan is a powerful technology to study antibody responses," says Harvard Medical School professor Dan Barouch, who also directs the Center for Virology and Vaccine Research. "A detailed understanding of the antibody responses to COVID-19 will help guide the design of next-generation vaccines and therapeutics."
For example, scientists can synthesize antibodies to specs and give them to patients as medicine. Once vaccines are designed, medics can use VirScan to see if those vaccinated again COVID-19 generate the necessary antibodies.
Knowing which antibodies bind best can also help fine-tune vaccines. Sometimes, viruses cause the immune system to generate antibodies that don't deactivate it. "We think the virus is trying to confuse the immune system; it is its business plan," Elledge says—so those unhelpful antibodies shouldn't be included in vaccines.
More importantly, VirScan can also tell which people have developed immunity to SARS-CoV-2 and can return to their workplaces and businesses, which is crucial to restoring the economy. Knowing one's immunity status is especially important for doctors working on the frontlines, Elledge notes. "The resistant ones can intubate the sick."
Lina Zeldovich has written about science, medicine and technology for Popular Science, Smithsonian, National Geographic, Scientific American, Reader’s Digest, the New York Times and other major national and international publications. A Columbia J-School alumna, she has won several awards for her stories, including the ASJA Crisis Coverage Award for Covid reporting, and has been a contributing editor at Nautilus Magazine. In 2021, Zeldovich released her first book, The Other Dark Matter, published by the University of Chicago Press, about the science and business of turning waste into wealth and health. You can find her on http://linazeldovich.com/ and @linazeldovich.
As countries around the world combat the coronavirus outbreak, governments that already operated sophisticated surveillance programs are ramping up the tracking of their citizens.
"The potential for invasions of privacy, abuse, and stigmatization is enormous."
Countries like China, South Korea, Israel, Singapore and others are closely monitoring citizens to track the spread of the virus and prevent further infections, and policymakers in the United States have proposed similar steps. These shifts in policy have civil liberties defenders alarmed, as history has shown increases in surveillance tend to stick around after an emergency is over.
In China, where the virus originated and surveillance is already ubiquitous, the government has taken measures like having people scan a QR code and answer questions about their health and travel history to enter their apartment building. The country has also increased the tracking of cell phones, encouraged citizens to report people who appear to be sick, utilized surveillance drones, and developed facial recognition that can identify someone even if they're wearing a mask.
In Israel, the government has begun tracking people's cell phones without a court order under a program that was initially meant to counter terrorism. Singapore has also been closely tracking people's movements using cell phone data. In South Korea, the government has been monitoring citizens' credit card and cell phone data and has heavily utilized facial recognition to combat the spread of the coronavirus.
Here at home, the United States government and state governments have been using cell phone data to determine where people are congregating. White House senior adviser Jared Kushner's task force to combat the coronavirus outbreak has proposed using cell phone data to track coronavirus patients. Cities around the nation are also using surveillance drones to maintain social distancing orders. Companies like Apple and Google that work closely with the federal government are currently developing systems to track Americans' cell phones.
All of this might sound acceptable if you're worried about containing the outbreak and getting back to normal life, but as we saw when the Patriot Act was passed in 2001 in the wake of the 9/11 terrorist attacks, expansions of the surveillance state can persist long after the emergency that seemed to justify them.
Jay Stanley, senior policy analyst with the ACLU Speech, Privacy, and Technology Project, says that this public health emergency requires bold action, but he worries that actions may be taken that will infringe on our privacy rights.
"This is an extraordinary crisis that justifies things that would not be justified in ordinary times, but we, of course, worry that any such things would be made permanent," Stanley says.
Stanley notes that the 9/11 situation was different from this current situation because we still face the threat of terrorism today, and we always will. The Patriot Act was a response to that threat, even if it was an extreme response. With this pandemic, it's quite possible we won't face something like this again for some time.
"We know that for the last seven or eight decades, we haven't seen a microbe this dangerous become a pandemic, and it's reasonable to expect it's not going to be happening for a while afterward," Stanley says. "We do know that when a vaccine is produced and is produced widely enough, the COVID crisis will be over. This does, unlike 9/11, have a definitive ending."
The ACLU released a white paper last week outlining the problems with using location data from cell phones and how policymakers should proceed when they discuss the usage of surveillance to combat the outbreak.
"Location data contains an enormously invasive and personal set of information about each of us, with the potential to reveal such things as people's social, sexual, religious, and political associations," they wrote. "The potential for invasions of privacy, abuse, and stigmatization is enormous. Any uses of such data should be temporary, restricted to public health agencies and purposes, and should make the greatest possible use of available techniques that allow for privacy and anonymity to be protected, even as the data is used."
"The first thing you need to combat pervasive surveillance is to know that it's occurring."
Sara Collins, policy counsel at the digital rights organization Public Knowledge, says that one of the problems with the current administration is that there's not much transparency, so she worries surveillance could be increased without the public realizing it.
"You'll often see the White House come out with something—that they're going to take this action or an agency just says they're going to take this action—and there's no congressional authorization," Collins says. "There's no regulation. There's nothing there for the public discourse."
Collins says it's almost impossible to protect against infringements on people's privacy rights if you don't actually know what kind of surveillance is being done and at what scale.
"I think that's very concerning when there's no accountability and no way to understand what's actually happening," Collins says. "The first thing you need to combat pervasive surveillance is to know that it's occurring."
We should also be worried about corporate surveillance, Collins says, because the tech companies that keep track of our data work closely with the government and do not have a good track record when it comes to protecting people's privacy. She suspects these companies could use the coronavirus outbreak to defend the kind of data collection they've been engaging in for years.
Collins stresses that any increase in surveillance should be transparent and short-lived, and that there should be a limit on how long people's data can be kept. Otherwise, she says, we're risking an indefinite infringement on privacy rights. Her organization will be keeping tabs as the crisis progresses.
It's not that we shouldn't avail ourselves of modern technology to fight the pandemic. Indeed, once lockdown restrictions are gradually lifted, public health officials must increase their ability to isolate new cases and trace, test, and quarantine contacts.
But tracking the entire populace "Big Brother"-style is not the ideal way out of the crisis. Last week, for instance, a group of policy experts -- including former FDA Commissioner Scott Gottlieb -- published recommendations for how to achieve containment. They emphasized the need for widespread diagnostic and serologic testing as well as rapid case-based interventions, among other measures -- and they, too, were wary of pervasive measures to follow citizens.
The group wrote: "Improved capacity [for timely contact tracing] will be most effective if coordinated with health care providers, health systems, and health plans and supported by timely electronic data sharing. Cell phone-based apps recording proximity events between individuals are unlikely to have adequate discriminating ability or adoption to achieve public health utility, while introducing serious privacy, security, and logistical concerns."
The bottom line: Any broad increases in surveillance should be carefully considered before we go along with them out of fear. The Founders knew that privacy is integral to freedom; that's why they wrote the Fourth Amendment to protect it, and that right shouldn't be thrown away because we're in an emergency. Once you lose a right, you don't tend to get it back.