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.
Is Carbon Dioxide the New Black? Yes, If These Fabric-Designing Scientists Have Their Way
Each year the world releases around 33 billion tons of carbon dioxide into the atmosphere. What if we could use this waste carbon dioxide to make shirts, dresses and hats? It sounds unbelievable. But two innovators are trying to tackle climate change in this truly unique way.
Chemist Tawfiq Nasr Allah set up Fairbrics with material scientist Benoît Illy in 2019. They're using waste carbon dioxide from industrial fumes as a raw material to create polyester, identical to the everyday polyester we use now. They want to take a new and very different approach to make the fashion industry more sustainable.
The Dark Side of Fast Fashion
The fashion industry is responsible for around 4% of global emissions. In a 2015 report, the MIT Materials Systems Laboratory predicted that the global impact of polyester fabric will grow from around 880 billion kg of CO2 in 2015 to 1.5 trillion kg of CO2 by 2030.
Professor Greg Peters, an expert in environmental science and sustainability, highlights the wide-ranging difficulties caused by the production of polyester. "Because it is made from petrochemical crude oil there is no real limit on how much polyester can be produced...You have to consider the ecological damage (oil spills, fracking etc.) caused by the oil and gas industry."
Many big-name brands have pledged to become carbon neutral by 2050. But nothing has really changed in the way polyester is produced.
Some companies are recycling plastic bottles into polyester. The plastic is melted into ultra-fine strands and then spun to create polyester. However, only a limited number of bottles are available. New materials must be added because of the amount of plastic degradation that takes place. Ultimately, recycling accounts for only a small percentage of the total amount of polyester produced.
Nasr Allah and Illy hope they can offer the solution the fashion industry is looking for. They are not just reducing the carbon emissions that are conventionally produced by making polyester. Their process actually goes much further. It's carbon negative and works by using up emissions from other industries.
"In a sense we imitate what nature does so well: plants capture CO2 and turn it into natural fibers using sunlight, we capture CO2 and turn it into synthetic fibers using electricity."
Experts in the field see a lot of promise. Dr Phil de Luna is an expert in carbon valorization -- the process of converting carbon dioxide into high-value chemicals. He leads a $57-million research program developing the technology to decarbonize Canada.
"I think the approach is great," he says. "Being able to take CO2 and then convert it into polymers or polyester is an excellent way to think about utilizing waste emissions and replacing fossil fuel-based materials. That is overall a net negative as compared to making polyester from fossil fuels."
From Harmful Waste to Useful Raw Material
It all started with Nasr Allah's academic research, primarily at the French Alternative Energies and Atomic Energy Commission (CEA). He spent almost 5 years investigating CO2 valorization. In essence, this involves breaking the bonds between the carbon and oxygen atoms in CO2 to create bonds with other elements.
Recycling carbon dioxide in this way requires extremely high temperatures and pressures. Catalysts are needed to break the strong bonds between the atoms. However, these are toxic, volatile and quickly lose their effectiveness over time. So, directly converting carbon dioxide into the raw material for making polyester fibers is very difficult.
Nasr Allah developed a process involving multiple simpler stages. His innovative approach involves converting carbon dioxide to intermediate chemicals. These chemicals can then be transformed into the raw material which is used in the production of polyester. After many experiments, Nasr Allah developed new processes and new catalysts that worked more effectively.
"We use a catalyst to transform CO2 into the chemicals that are used for polyester manufacturing," Illy says. "In a sense we imitate what nature does so well: plants capture CO2 and turn it into natural fibers using sunlight, we capture CO2 and turn it into synthetic fibers using electricity."
The Challenges Ahead
Nasr Allah met material scientist Illy through Entrepreneur First, a programme which pairs individuals looking to form technical start-ups. Together they set up Fairbrics and worked on converting Nasr Allah's lab findings into commercial applications and industrial success.
"The main challenge we faced was to scale up the process," Illy reveals. "[It had to be] consistent and safe to be carried out by a trained technician, not a specialist PhD as was the case in the beginning."
They recruited a team of scientists to help them develop a more effective and robust manufacturing process. Together, the team gained a more detailed theoretical understanding about what was happening at each stage of the chemical reactions. Eventually, they were able to fine tune the process and produce consistent batches of polyester.
They're making significant progress. They've produced their first samples and signed their first commercial contract to make polyester, which will then be both fabricated into clothes and sold by partner companies.
Currently, one of the largest challenges is financial. "We need to raise a fair amount to buy the equipment we need to produce at a large scale," Illy explains.
How to Power the Process?
At the moment, their main scientific focus is getting the process working reliably so they can begin commercialization. In order to remain sustainable and economically viable once they start producing polyester on a large scale, they need to consider the amount of energy they use for carbon valorization and the emissions they produce.
The more they optimize the way their catalyst works, the easier it will be to transform the CO2. The whole process can then become more cost effective and energy efficient.
De Luna explains: "My concern is...whether their process will be economical at scale. The problem is the energy cost to take carbon dioxide and transform it into these other products and that's where the science and innovation has to happen. [Whether they can scale up economically] depends on the performance of their catalyst."
They don't just need to think about the amount of energy they use to produce polyester; they also have to consider where this energy comes from.
"They need access to cheap renewable energy," De Luna says, "...so they're not using or emitting CO2 to do the conversion." If the energy they use to transform CO2 into polyester actually ends up producing more CO2, this will end up cancelling out their positive environmental impact.
Based in France, they're well located to address this issue. France has a clean electricity system, with only about 10% of their electric power coming from fossil fuels due to their reliance on nuclear energy and renewables.
Where Do They Get the Carbon Dioxide?
As they scale up, they also need to be able to access a source of CO2. They intend to obtain this from the steel industry, the cement industry, and hydrogen production.
The technology to purify and capture waste carbon dioxide from these industries is available on a large scale. However, there are only around 20 commercial operations in the world. The high cost of carbon capture means that development continues to be slow. There are a growing number of startups capturing carbon dioxide straight from the air, but this is even more costly.
One major problem is that storing captured carbon dioxide is expensive. "There are somewhat limited options for permanently storing captured CO2, so innovations like this are important,'' says T. Reed Miller, a researcher at the Yale University Center for Industrial Ecology.
Illy says: "The challenge is now to decrease the cost [of carbon capture]. By using CO2 as a raw material, we can try to increase the number of industries that capture CO2. Our goal is to turn CO2 from a waste into a valuable product."
Beyond Fashion
For Nasr Allah and Illy, fashion is just the beginning. There are many markets they can potentially break into. Next, they hope to use the polyester they've created in the packaging industry. Today, a lot of polyester is consumed to make bottles and jars. Illy believes that eventually they can produce many different chemicals from CO2. These chemicals could then be used to make paints, adhesives, and even plastics.
The Fairbrics scientists are providing a vital alternative to fossil fuels and showcasing the real potential of carbon dioxide to become a worthy resource instead of a harmful polluter.
Illy believes they can make a real difference through innovation: "We can have a significant impact in reducing climate change."
Vaccines are one of the greatest public health accomplishments of all time. For centuries, public health has relied on vaccinations to prevent and control disease outbreaks for a plethora of infectious scourges, with our crowning achievement being the successful eradication of smallpox.
The purpose of vaccine documentation is to provide proof of an individual's protection from either becoming infected or transmitting a vaccine-preventable disease. Vouching for these protections requires a firm knowledge about the epidemiology of the disease, as well as scientific knowledge concerning the efficacy of the vaccine. The vaccines we currently require be documented have met these tests; the vaccine for COVID-19 has not yet been proven to do so.
Let's acknowledge that the term "vaccine passport" is a poor choice of words. Passports are a legal travel document created by nations and governed by law for identification of the bearer to control entry and exit from nation states. They often serve as legal forms of identification and as a record of international travel. They are generally very sophisticated documents that have been created in a secure manner and may include a range of electronic and, in some cases, biometric measures such as fingerprints to ensure the holder is indeed who they say they are. Vaccine passports are medical documents used to document the vaccination status of an individual. They do not undergo the same level of administrative scrutiny and cannot be used to verify that the presenter is indeed the vaccinated individual. Some companies do have electronic methods to address concerns about verification; however, most people currently have paper records that can be easily falsified.
"Vaccine passports" as currently proposed risk giving people a false sense of security.
Successful disease control from vaccination programs relies on the ability to vaccinate at a level that prevents large-scale disease spread and the ability to rapidly identify the presence of disease outbreaks. It requires reliable, safe, and effective vaccines that are easily delivered in clinical and nonclinical settings. Keeping vaccination information as a part of the medical record, and even having a separate specialized vaccine record for personal use, is a time-honored tradition.
Keeping a vaccination record provides a method to keep track of the many shots one receives and serves as a visual reminder to help ensure the appropriate vaccine shot schedule is maintained for vaccines requiring multiple doses. The vaccine record, when combined with vaccine safety monitoring systems, serves as a mechanism to track adverse events to monitor and ensure the safety of vaccines as a consumer product. The record also serves as the official record of vaccination when required for administrative or legally prescribed purposes.
"Vaccine passports" as currently proposed risk giving people a false sense of security. In the case of the COVID-19 vaccines currently approved for use, many of the essential questions remain unanswered. While we do know the current three vaccines are highly protective against severe disease and death, and there is some evidence that these vaccinations do reduce infections and virus transmission of SARS-CoV-2, we do not yet know the full degree to which this occurs.
For example, we know there have been some cases of people that have been infected in close proximity to getting their full vaccination and rare cases of breakthrough reinfections. A breakthrough infection in a restaurant is a challenge for contact tracing, but an outbreak from a movie theater exposure or a baseball game could spark a major outbreak at our current level of vaccination. Current CDC guidance recommends continued mask wearing in order to address these concerns.
We also do not yet know how long the protections will last and if or when a booster or revaccination is required. In effect, it is too soon to know. Should an annual booster shot be required, then a vaccine passport would require annual updating, a process more frequent than renewal of a driver's license.
We also know that the current SARS-CoV-2 virus is mutating briskly. While the current approved vaccines have remained effective overall, there is evidence of some degree of degradation in vaccine effectiveness against some of the circulating strains. We also have sparse data on many of the other emerging strains of concern because we have not had the surveillance capacity in the U.S. to gain an adequate sense of how the virus is changing to fully align vaccine effectiveness with viral capabilities.
The risk of people misusing these "passports" is troubling. The potential for using these documents for hiring, firing or job limitation is a serious concern. Unvaccinated workers are at risk of this form of discrimination even from well-meaning employers or supervisors. Health insurers are prohibited by the Affordable Care Act from discriminating based on preexisting conditions, but they could probably charge a higher premium for unvaccinated individuals. There also is a risk of stigmatizing individuals who are not vaccinated or have left their vaccine documentation at home. Another concern: the opportunity to discriminate based on race, gender, sexual orientation, or religion, using one's vaccination status as an excuse.
These "passports" are being discussed as a "ticket verification" for entry to many activities, including dining at restaurants, flying domestically and/or internationally, going to movie theaters and sporting events, etc. These are all activities we already are doing at reduced levels and for which wearing a mask, hand hygiene and physical distancing are effective disease control practices. COVID-19 vaccines are indeed the measure that will make the ability to totally reopen our society complete, but we are not there yet. Documentation of one's COVID-19 vaccine status may be useful in selected situations in the future. That remains to be seen.
Finally, inadequate vaccine supply and disparities in vaccine delivery have created enormous challenges in providing equal access to vaccination. Also, the amount of misinformation, disinformation, and lingering vaccine hesitancy continue to limit the speed at which we will reach the level of vaccination of the population that would make this documentation meaningful. The requirement for "vaccine passports" is already alienating people who are opposed to vaccinations for a variety of reasons, paradoxically risking reduced vaccine uptake. This politicization of the vaccination effort is of concern. There are indeed people who, due to medical contraindications or legal exemptions, will not be vaccinated, and we do not yet have a national framework on how to address this.
Vaccine passports are not the solution for reopening our society — a robust vaccination program is. The requirement to document one's vaccination status for COVID-19 may one day have its place. For now, it is an idea whose time has not yet come.
Editor's Note: This op/ed is part of a "Big Question" series on the ethics of vaccine passports. Read the flip side argument here.