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.
Brittany Barreto first got the idea to make a DNA-based dating platform nearly 10 years ago when she was in a college seminar on genetics. She joked that it would be called GeneHarmony.com.
Pheramor and startups, like DNA Romance and Instant Chemistry, both based in Canada, claim to match you to a romantic partner based on your genetics.
The idea stuck with her while she was getting her PhD in genetics at Baylor College of Medicine, and in March 2018, she launched Pheramor, a dating app that measures compatibility based on physical chemistry and what the company calls "social alignment."
"I wanted to use genetics and science to help people connect more. Our world is so hungry for connection," says Barreto, who serves as Pheramor's CEO.
With the direct-to-consumer genetic testing market booming, more and more companies are looking to capitalize on the promise of DNA-based services. Pheramor and startups, like DNA Romance and Instant Chemistry, both based in Canada, claim to match you to a romantic partner based on your genetics. It's an intriguing alternative to swiping left or right in hopes of finding someone you're not only physically attracted to but actually want to date. Experts say the science behind such apps isn't settled though.
For $40, Pheramor sends you a DNA kit to swab the inside of your cheek. After you mail in your sample, Pheramor analyzes your saliva for 11 different HLA genes, a fraction of the more than 200 genes that are thought to make up the human HLA complex. These genes make proteins that regulate the immune system by helping protect against invading pathogens.
It takes three to four weeks to get the results backs. In the meantime, users can still download the app and start using it before their DNA results are ready. The app asks users to link their social media accounts, which are fed into an algorithm that calculates a "social alignment." The algorithm takes into account the hashtags you use, your likes, check-ins, posts, and accounts you follow on Facebook, Twitter, and Instagram.
The DNA test results and social alignment algorithm are used to calculate a compatibility percentage between zero and 100. Barreto said she couldn't comment on how much of that score is influenced by the algorithm and how much comes from what the company calls genetic attraction. "DNA is not destiny," she says. "It's not like you're going to swab and I'll send you your soulmate."
Despite its name, Pheramor doesn't actually measure pheromones, chemicals released by animals that affect the behavior of others of the same species. That's because human pheromones have yet to be identified, though they've been discovered throughout the animal kingdom in moths, mice, rabbits, pigs, and many other insects and mammals. The HLA genes Pheramor analyzes instead are the human version of the major histocompatibility complex (MHC), a gene group found in many species.
The connection between HLA type and attraction goes back to the 1970s, when researchers found that inbred male mice preferred to mate with female mice with a different MHC rather than inbred female mice with similar immune system genes. The researchers concluded that this mating preference was linked to smell. The idea is that choosing a mate with different MHC genes gives animals an evolutionary advantage in terms of immune system defense.
The couples who had more dissimilar HLA types reported a more satisfied sex life and satisfied partnership, but it was a small effect.
In the 1990s, Swiss scientists wanted to see if body odor also had an effect on human attraction. In a famous experiment known as the "sweaty T-shirt study", they recruited 49 women to sniff sweaty, unwashed T-shirts from 44 men and put each in a box with a smelling hole and describe the odors of every shirt. The study found that women preferred the scents of T-shirts worn by men who were immunologically different from them compared to men whose HLA genes were similar to their own.
"The idea is, if you are very similar with your partner in HLA type then your offspring is similar in terms of HLA. This reduces your resistance against pathogens," says Illona Croy, a psychologist at the Technical University of Dresden who has studied HLA type in relation to sexual attraction in humans.
In a 2016 study Pheramor cites on its website, Croy and her colleagues tested the HLA types of 250 couples—all of them university students—and asked them how satisfied they were with their partnerships, with their sex lives, and with the odors of their partners. The couples who had more dissimilar HLA types reported a more satisfied sex life and satisfied partnership, but Croy cautions that it was a small effect. "It's not like they were super satisfied or not satisfied at all. It's a slight difference," she says.
Croy says we're much more likely to choose a partner based on appearance, sense of humor, intelligence and common interests.
Other studies have reported no preference for HLA difference in sexual attraction. Tristram Wyatt, a zoologist at the University of Oxford in the U.K. who studies animal pheromones, says it's been difficult to replicate the original T-shirt study. And one of the caveats of the original study is that women who were taking birth control pills preferred men who were more immunologically similar.
"Certainly, we learn to really like the smell of our partners," Wyatt says. "Whether it's the reason for choosing them in the first place, we really don't know."
Wyatt says he's skeptical of DNA-based dating apps because there are many subtypes of HLA genes, meaning there's a fairly low chance that your HLA type and your romantic partner's would be an exact match, anyway. It's why finding a suitable match for a bone marrow transplant is difficult; a donor's HLA type has to be the same as the recipient's.
"What it means is that since we're all different, it's hard statistically to say who the best match will be," he says.
DNA-based dating apps haven't yet gone mainstream, but some people seem willing to give them a try. Since Pheramor's launch a little over a year ago, about 10,000 people have signed up to use the app, about half of which have taken the DNA test, Barreto says. By comparison, an estimated 50 million people use Tinder, which has been around since 2012, and about 40 million people are on Bumble, which was released in 2014.
In April, Barreto launched a second service, this one for couples, called WeHaveChemistry.com. A $139 kit includes two genetic tests, one for you and your partner, and a detailed DNA report on your sexual compatibility.
Unlike the Phermor app, WeHaveChemistry doesn't provide users with a numeric combability score but instead makes personalized recommendations based on your genetic results. For instance, if the DNA test shows that your HLA genes are similar, Barreto says, "We might recommend pheromone colognes, working out together, or not showering before bed to get your juices running."
Despite her own research on HLA and sexual compatibility, Croy isn't sure how knowing HLA type will help couples. However, some researchers are doing studies on whether HLA types are related to certain cases of infertility, and this is where a genetic test might be very useful, says Croy.
"Otherwise, I think it doesn't matter whether we're HLA compatible or not," she says. "It might give you one possible explanation about why your sexual life isn't as satisfactory as it could be, but there are many other factors that play a role."
Between the ever-growing Great Pacific Garbage Patch, the news that over 90% of plastic isn't recycled, and the likely state of your personal trash can, it's clear that the world has a plastic problem.
Scientists around the world have continued to discover different types of fungus that can degrade specific types of plastic.
We now have 150 million tons of plastic in our oceans, according to estimates; by 2050, there could be more plastic than fish. And every new batch of trash compounds the issue: Plastic is notorious for its longevity and resistance to natural degradation.
The Lowdown
Enter the humble mushroom. In 2011, Yale students made headlines with the discovery of a fungus in Ecuador, Pestalotiopsis microspora, that has the ability to digest and break down polyurethane plastic, even in an air-free (anaerobic) environment—which might even make it effective at the bottom of landfills. Although the professor who led the research trip cautioned for moderate expectations, there's an undeniable appeal to the idea of a speedier, cleaner, side effect-free, and natural method of disposing of plastic.
A few years later, this particular application for fungus got a jolt of publicity from designer Katharina Unger, of LIVIN Studio, when she collaborated with the microbiology faculty at Utrecht University to create a project called the Fungi Mutarium. They used the mycelium—which is the threadlike, vegetative part of a mushroom—of two very common types of edible mushrooms, Pleurotus ostreatus (Oyster mushrooms) and Schizophyllum commune (Split gill mushrooms). Over the course of a few months, the fungi fully degraded small pieces of plastic while growing around pods of edible agar. The result? In place of plastic, a small mycelium snack.
Other researchers have continued to tackle the subject. In 2017, scientist Sehroon Khan and his research team at the World Agroforestry Centre in Kunming, China discovered another biodegrading fungus in a landfill in Islamabad, Pakistan: Aspergillus tubingensis, which turns out to be capable of colonizing polyester polyurethane (PU) and breaking it down it into smaller pieces within the span of two months. (PU often shows up in the form of packing foam—the kind of thing you might find cushioning a microwave or a new TV.)
Next Up
Utrecht University has continued its research, and scientists around the world have continued to discover different types of fungus that can degrade different, specific types of plastic. Khan and his team alone have discovered around 50 more species since 2017. They are currently working on finding the optimal conditions of temperature and environment for each strain of fungus to do its work.
Their biggest problem is perhaps the most common obstacle in innovative scientific research: Cash. "We are developing these things for large-scale," Khan says. "But [it] needs a lot of funding to get to the real application of plastic waste." They plan to apply for a patent soon and to publish three new articles about their most recent research, which might help boost interest and secure more grants.
Is there a way to get the fungi to work faster and to process bigger batches?
Khan's team is working on the breakdown process at this point, but researchers who want to continue in Unger's model of an edible end product also need to figure out how to efficiently and properly prepare the plastic input. "The fungi is sensitive to infection from bacteria," Unger says—which could turn it into a destructive mold. "This is a challenge for industrialization—[the] sterilization of the materials, and making the fungi resistant, strong, and faster-growing, to allow for a commercial process."
Open Questions
Whether it's Khan's polyurethane-chomping fungus or the edible agar pods from the Fungi Mutarium, the biggest question is still about scale. Both projects took several months to fully degrade a small amount of plastic. That's much shorter than plastic's normal lifespan, but still won't be enough to keep up with the global production of plastic. Is there a way to get the fungi to work faster and to process bigger batches?
We'd also need to figure out where these plastic recyclers would live. Could individuals keep a small compost-like heap, feeding in their own plastic and harvesting the mushrooms? Or could this be a replacement for local recycling centers?
There are still only these few small experiments for reference. But taken together, they suggest a fascinating future for waste disposal: An army of mycelium chewing quietly and methodically through our plastic bags and foam coffee cups—and potentially even creating a new food source along the way. We could have our trash and eat it, too.