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.
Growing Human Organs Inside Pigs Could Save Lives, But the U.S. Won't Fund the Research
Pigs in a barn.
The shortage of organs is a public health menace. Approximately 120,000 people in the U.S. need a lifesaving organ transplant. Of those, approximately 75,000 patients are on the active waiting list. Every day, nearly 20 individuals die from the shortage of organs in the United States.
Ethical concerns about human-animal chimera research might be dramatically overblown.
Scientists worldwide are developing new methods with potential to save countless patients in need of organs. Such approaches have tremendous potential, if only ethical and regulatory challenges could be overcome first.
One way that scientists are proposing to increase the number of transplantable organs is to produce organs from patient stem cells. Owed to their ability to grow limitlessly in the lab and form all tissue types, pluripotent stem cells from patients, in principle, could supply an infinite amount of cells that could potentially be transplanted back into patients. Unfortunately, all efforts to generate organs that can be transplanted into patients from stem cells to date have been unsuccessful.
A different encouraging approach is to generate patient organs inside livestock species, such as pigs. In the latest methods, interspecies chimeras – animals containing cells from both humans and animals – are generated by introducing human stem cells into early-stage animal embryos. Key genes essential for organ formation are disabled, allowing the introduced human stem cells to fill the empty space. In theory, this strategy will produce a human organ inside pigs or sheep.
Creating chimeras is not new in biology. Chimeras, or animals comprised of tissues from two different individuals, have already been deployed in research. Mouse chimeras are routinely used to create genetically engineered mice to study genes. The concept of generating human organs inside pigs or sheep comes from previous studies involving interspecies chimeras generated between mice and rats. Past experiments have demonstrated that it is possible to generate a rat pancreas inside a mouse.
Scientific and Ethical Obstacles
Unfortunately, chimera research has faced hurdles that have impeded progress. Of note, attempts to generate interspecies chimeras by several groups have failed. The results of these studies indicate that human cells appear unable to grow inside mouse embryos. The levels of human chimerism – the number of human cells inside the host animal embryo – appear too low to support any human organ generation.
Another obstacle is that chimera generation is ethically controversial. Some question the moral status of an animal that is comprised of human and animal cells. The most concerning question is whether human cells will contribute to the host animal's brain, potentially altering the cognition of the animal. These issues have prompted scientists to proceed very cautiously with chimera experiments. However, such concerns might be dramatically overblown. This is because the levels of human chimerism are too low to cause any significant change in animal brain function.
The ethical controversy has affected research policy in the United States. In the United States, the National Institutes of Health (NIH), the major funding body of biomedical research, blocked funding for chimera research while ethical questions were considered. Later, it was proposed that a new review process would be instated for chimera research. However, no change in policy has actually happened. The restrictive NIH policy is a major barrier to chimera research progress because laboratories around the United States cannot obtain funding for it. Lifting the restrictions on NIH funding for chimera research would dramatically accelerate chimera research.
Nonetheless, despite the past and current hurdles that chimera research has faced, new advances are changing the landscape of chimera research.
It is time to lift restrictions on chimera research so that its promise can be fully realized.
Progress on the Horizon
Scientists are developing improved strategies to increase the numbers of cells in animal embryos to the point where it might be possible to generate a human organ in an animal. For example, it has been suggested that the human stem cells researchers have been using cannot grow in animals. Scientists have made advances in generating new types of human stem cells that might have an improved ability to form chimeras.
Additionally, scientists have identified some barriers responsible for the failure to generate chimeras. For example, preventing cell death and enhancing the ability of stem cells to compete with host animal tissues also improves the numbers of human cells to the point where human organs can be generated inside an animal.
Finally, a relaxation of regulatory hurdles in other countries has created a more permissive environment for human-animal interspecies chimera research. In March, the Japanese government approved the first such experiments that could comprise a new way of generating organs from patients for transplantation.
Additionally, in spite of the somewhat negative attention that chimera generation has received, the International Society for Stem Cell Research (ISSCR) supports the new Japanese policies allowing chimera experiments. The ISSCR maintains that research involving the generation of chimeras should be permitted, as long as rigorous oversight and ethics review occur.
Chimera research has the potential to transform medicine. Of all the impediments, the NIH restrictions on funding remain the single most significant barrier. It is time to lift restrictions on chimera research so that its promise can be fully realized. One day, it might be possible to grow patient-specific organs inside of livestock animals such as pigs and sheep, saving thousands of human lives. But to change our current policy, the public, scientists, and bioethicists must first agree that this critical cause is worth fighting for.
In China, Prisoners of Conscience Are Being Murdered for Their Organs to Fuel Transplant Tourism
A somber photo of the Great Wall of China.
Organ transplantation can dramatically improve or save lives. A heart transplant can literally give a person a new lease of life, while a kidney transplant frees the recipient from lengthy spells on dialysis.
A people's tribunal in London has recently found that in China, organs are sourced from prisoners of conscience who are killed on demand to fuel the lucrative organ transplantation market.
To protect the integrity of organ transplantation, there are strict ethical guidelines. When organs are sourced from deceased persons, the donation must be voluntary, donors must die naturally before any organs are taken, and death must not be hastened to provide organs. These ethical guidelines protect donors and provide assurance to transplant recipients that their organs have been sourced ethically.
However, not all countries follow these ethical guidelines. A people's tribunal in London has recently found that in China, organs are sourced from prisoners of conscience who are killed on demand to fuel the lucrative organ transplantation market. This conclusion, reported at the United Nations Human Rights Council on September 24, was not reached lightly.
The independent China Tribunal, made up of four human rights lawyers, one surgeon with transplant experience, an academic who specialises in China studies and a businessman with human rights interests, spent over a year looking at written materials and heard evidence from over 50 witnesses in five days of hearings. Their grim conclusion, that prisoners of conscience are murdered for their organs, confirms the findings of earlier investigations.
Questions first arose over China's transplant system when the numbers of transplants rose dramatically after 2000. Transplant capacity rapidly increased; new infrastructure was built and staff were trained. Hospital websites offered livers, hearts and kidneys available in a matter of days or weeks, for a price. Foreigners were encouraged to come to China to avoid lengthy transplant waiting lists in their home countries.
At the time, it was a mystery as to how China had a ready supply of organs, despite having no volunteer donation system. Eventually, in 2006, the Chinese government stated that organs were removed from prisoners who had been found guilty and sentenced to the death penalty. But this explanation did not ring true. Death row prisoners often have poor health, including high rates of infectious diseases, making them poor candidates for donation. By contrast, the organs offered for sale were promised to be healthy.
In 2006, the first clues about the source of the organs emerged. A woman called Annie reported that her surgeon husband had been present during organ removal from Falun Gong practitioners who were still breathing as the scalpels cut into them. A subsequent investigation by two Canadian human rights lawyers examined multiple sources of evidence, concluding that murdered Falun Gong practitioners were indeed the source of the organs.
The evidence included testimony from practitioners who had been imprisoned, tortured, and later released. During imprisonment, many practitioners reported blood and other medical tests examining the health of their organs—tests that were not performed on any other prisoners. Phone calls made to Chinese hospitals by investigators posing as patients were offered rapid access to fresh organs from Falun Gong practitioners. The organs were guaranteed to be healthy, as the practice forbids smoking tobacco and drinking alcohol.
Since 2006, evidence has continued to accumulate. China has a huge transplant industry and no plausible source of voluntary organ donations. Unlike the rest of the world, Chinese waiting times remain very short. Foreigners continue to come to China to avoid lengthy waiting lists. Prisoners of conscience, including Tibetans and Uyghurs as well as Falun Gong practitioners, are still being imprisoned and medically tested.
The Chinese government continues to deny these crimes, claiming that there is a volunteer donor system in place.
The China Tribunal heard from Uyghur witnesses who had recently been inside the notorious labour camps (also called "re-education" centers) in Xin Xiang. The witnesses reported terrible conditions, including overcrowding and torture, and were forced to have medical examinations. They saw other prisoners disappear without explanation following similar medical tests. As recently as 2018, doctors in Chinese hospitals were promising potential patients healthy Falun Gong organs in taped phone calls.
The Chinese government continues to deny these crimes, claiming that there is a volunteer donor system in place. In the Chinese system, prisoners are counted as volunteers.
China's forced organ harvesting from prisoners of conscience has international implications. A recent study found that most published Chinese transplant research is based on organs sourced from prisoners. International ethical guidance prohibits taking organs from prisoners and prohibits publication of research based on transplanted material from prisoners. The authors of that study called for retractions of the papers, some of which are in well-known scientific journals. So far Transplantation and PLOS One are among the journals that have already retracted over twenty articles in response. On questioning from the editors, the authors of the papers failed to respond or could not verify that the organs in the transplant research came from volunteers.
The international community has a moral obligation to act together to stop forced organ harvesting in China.
The China Tribunal concluded that forced organ harvesting remains China's main source of transplant organs. In their view, the commission of Crimes Against Humanity against the Uyghurs and Falun Gong has been proved beyond reasonable doubt. By their actions, the Chinese government has turned a life-saving altruistic practice into our worst nightmare. The international community has a moral obligation to act together to stop forced organ harvesting in China, and end these crimes against humanity.