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.
Shoot for the Moon: Its Surface Contains a Pot of Gold
Here's a riddle: What do the Moon, nuclear weapons, clean energy of the future, terrorism, and lung disease all have in common?
One goal of India's upcoming space probe is to locate deposits of helium-3 that are worth trillions of dollars.
The answer is helium-3, a gas that's extremely rare on Earth but 100 million times more abundant on the Moon. This past October, the Lockheed Martin corporation announced a concept for a lunar landing craft that may return humans to the Moon in the coming decade, and yesterday China successfully landed the Change-4 probe on the far side of the Moon. Landing inside the Moon's deepest crater, the Chinese achieved a first in space exploration history.
Meanwhile, later this month, India's Chandrayaan-2 space probe will also land on the lunar surface. One of its goals is to locate deposits of helium-3 that are worth trillions of dollars, because it could be a fuel for nuclear fusion energy to generate electricity or propel a rocket.
The standard way that nuclear engineers are trying to achieve sustainable fusion uses fuels that are more plentiful on Earth: deuterium and tritium. But MIT researchers have found that adding small amounts of helium-3 to the mix could make it much more efficient, and thus a viable energy source much sooner that once thought.
Even if fusion is proven practical tomorrow, any kind of nuclear energy involves long waits for power plant construction measured in decades. However, mining helium-3 could be useful now, because of its non-energy applications. A major one is its ability to detect neutrons coming from plutonium that could be used in terrorist attacks. Here's how it works: a small amount of helium-3 is contained within a forensic instrument. When a neutron hits an atom of helium-3, the reaction produces tritium, a proton, and an electrical charge, alerting investigators to the possibility that plutonium is nearby.
Ironically, as global concern about a potential for hidden nuclear material increased in the early 2000s, so did the supply of helium-3 on Earth. That's because helium-3 comes from the decay of tritium, used in thermonuclear warheads (H-bombs). Thousands of such weapons have been dismantled from U.S. and Russian arsenals, making helium-3 available for plutonium detection, research, and other applications--including in the world of healthcare.
Helium-3 can help doctors diagnose lung diseases, since it enables imaging of the lungs in real time.
Helium-3 dramatically improves the ability of doctors to image the lungs in a range of diseases including asthma, chronic obstructive pulmonary disease and emphysema, cystic fibrosis, and bronchopulmonary dysplasia, which happens particularly in premature infants. Specifically, helium-3 is useful in magnetic resonance imaging (MRI), a procedure that creates images from within the body for diagnostic purposes.
But while a standard MRI allows doctors to visualize parts of the body like the heart or brain, it's useless for seeing the lungs. Because lungs are filled with air, which is much less dense than water or fat, effectively no signals are produced that would enable imaging.
To compensate for this problem, a patient can inhale gas that is hyperpolarized –meaning enhanced with special procedures so that the magnetic resonance signals from the lungs are finally readable. This gas is safe to breathe when mixed with enough oxygen to support life. Helium-3 is one such gas that can be hyperpolarized; since it produces such a strong signal, the MRI can literally see the air inside the lungs and in all of the airways, revealing intricate details of the bronchopulmonary tree. And it can do this in real time
The capability to show anatomic details of the lungs and airways, and the ability to display functional imaging as a patient breathes, makes helium-3 MRI far better than the standard method of testing lung function. Called spirometry, this method tells physicians how the lungs function overall, but does not home in on particular areas that may be causing a problem. Plus, spirometry requires patients to follow instructions and hold their breath, so it is not great for testing young children with pulmonary disease.
In recent years, the cost of helium-3 on Earth has skyrocketed.
Over the past several years, researchers have been developing MRI for lung testing using other hyperpolarized gases. The main alternative to helium-3 is xenon-129. Over the years, researchers have learned to overcome certain disadvantages of the latter, such as its potential to put patients to sleep. Since helium-3 provides the strongest signal, though, it is still the best gas for MRI studies in many lung conditions.
But the supply of helium-3 on Earth has been decreasing in recent years, due to the declining rate of dismantling of warheads, just as the Department of Homeland Security has required more and more of the gas for neutron detection. As a result, the cost of the gas has skyrocketed. Less is available now for medical uses – unless, of course, we begin mining it on the moon.
The question is: Are the benefits worth the 239,000-mile trip?
Should Organ Donors Be Paid?
Deanna Santana had assumed that people on organ transplant lists received matches. She didn't know some died while waiting. But in May 2011, after her 17-year-old son, Scott, was killed in a car accident, she learned what a precious gift organ and tissue donation can be.
"I would estimate it cost our family about $4,000 for me to donate a kidney to a stranger."
His heart, lungs, kidneys, liver and pancreas saved five people. His corneas enabled two others to see. And his bones, connective tissues and veins helped 73 individuals.
The donation's impact had a profound effect on his mother as well. In September 2016, she agreed to donate a kidney in a paired exchange of four people making the same sacrifice for four compatible strangers.
She gave up two weeks' worth of paid vacation to recuperate and covered lodging costs for loved ones during her transplant. Eventually, she qualified for state disability for part of her leave, but the compensation was less than her salary as public education and relations manager at Sierra Donor Services, an organ procurement organization in West Sacramento, California.
"I would estimate it cost our family about $4,000 for me to donate a kidney to a stranger," says Santana, 51. Despite the monetary hardship, she "would do it again in a heartbeat."
While some contend it's exploitative to entice organ donors and their families with compensation, others maintain they should be rewarded for extending their generosity while risking complications and recovering from donation surgery. But many agree on one point: The focus should be less on paying donors and more on removing financial barriers that may discourage interested prospects from doing a good deed.
"There's significant potential risk associated with donating a kidney, some of which we're continuing to learn," says transplant surgeon Matthew Cooper, a board member of the National Kidney Foundation and co-chair of its Transplant Task Force.
Although most kidneys are removed laparoscopically, reducing hospitalization and recuperation time, complications can occur. The risks include wound and urinary tract infections, pneumonia, blood clots, injury to local nerves causing decreased sensation in the hip or thigh, acute blood loss requiring transfusion and even death, Cooper says.
"We think that donation is a cost-neutral opportunity. It, in fact, is not."
Meanwhile, from a financial standpoint, estimates have found it costs a kidney donor in the United States an average of $3,000 to navigate the entire transplant process, which may include time off from work, travel to and from the hospital, accommodations, food and child care expenses.
"We think that donation is a cost-neutral opportunity. It, in fact, is not," says Cooper, who is also Director of Kidney and Pancreas Transplantation at MedStar Georgetown Transplant Institute in Washington, D.C.
The National Organ Transplant Act of 1984 makes it illegal to sell human organs but did not prohibit payment for the donation of human plasma, sperm and egg cells.
Unlike plasma, sperm and eggs cells—which are "renewable resources"—a kidney is irreplaceable, says John J. Friedewald, a nephrologist who is medical director of kidney transplantation at Northwestern Memorial Hospital in Chicago.
Offering some sort of incentives could lessen the overall burden on donors while benefiting many more potential recipients. "We can eliminate the people waiting on the list and dying, at least for kidneys," Friedewald says.
On the other hand, incentives may influence an individual to the point that the donation is made purely for monetary gain. "It's a delicate balance," he explains, "because so much of the transplant system has been built on altruism."
That's where doing away with the "disincentives" comes into the equation. Compensating donors for the costs they endure would be a reasonable compromise, Friedewald says.
Depending on the state, living donors may deduct up to $10,000 from their adjusted gross income under the Organ Donation Tax Deduction Act for the year in which the transplantation occurs. "Human organ" applies to all or part of a liver, pancreas, kidney, intestine, lung or bone marrow. The subtracted modification may be claimed for only unreimbursed travel and lodging expenses and lost wages.
For some or many donors, the tax credit doesn't go far enough in offsetting their losses, but they often take it in stride, says Chaya Lipschutz, a Brooklyn, N.Y.-based matchmaker for donors and recipients, who launched the website KidneyMitzvah.com in 2009.
Seeking compensation for lost wages "is extremely rare" in her experience. "In all the years of doing this," she recalls, "I only had two people who donated a kidney who needed to get paid for lost wages." She finds it "pretty amazing that mostly all who contact don't ask."
Lipschutz, an Orthodox Jew, has walked in a donor's shoes. In September 2005, at age 48, she donated a kidney to a stranger after coming across an ad in a weekly Jewish newspaper. The ad stated: "Please help save a Jewish life—New Jersey mother of two in dire need of kidney—Whoever saves one life from Israel it is as if they saved an entire nation."
To make matches, Lipschutz posts in various online groups in the United States and Israel. Donors in Israel may receive "refunds" for loss of earnings, travel expenses, psychological treatment, recovery leave, and insurance. They also qualify for visits to national parks and nature reserves without entrance fees, Lipschutz says.
"There has been an attempt to figure out what would constitute fair compensation without the appearance that people are selling their organs or their loved ones' organs."
Kidneys can be procured from healthy living donors or patients who have undergone circulatory or brain death.
"The real dilemma arises with payment for living donation, which would favor poorer individuals to donate who would not necessarily do so," says Dr. Cheryl L. Kunis, a New York-based nephrologist whose practice consists primarily of kidney transplant recipients. "In addition, such payment for living donation has not demonstrated to improve a donor's socioeconomic status globally."
Living kidney donation has the highest success rate. But organs from young and previously healthy individuals who die in accidents or from overdoses, especially in the opioid epidemic, often work just as well as kidneys from cadaveric donors who succumb to trauma, Kunis says.
In these tragic circumstances, she notes that the decision to donate is often left to an individual's grieving family members when a living will isn't available. A payment toward funeral expenses, for instance, could tip their decision in favor of organ donation.
A similar scenario presents when a patient with a beating heart is on the verge of dying, and the family is unsure about consenting to organ donation, says Jonathan D. Moreno, a professor in the department of medical ethics and health policy at the University of Pennsylvania.
"There has been an attempt to figure out what would constitute fair compensation," he says, "without the appearance that people are selling their organs or their loved ones' organs."
The overarching concern remains the same: Compensating organ donors could lead to exploitation of socioeconomically disadvantaged groups. "What's likely to finally resolve" this bioethics debate, Moreno foresees, "is patient-compatible organs grown in pigs as the basic science of xenotransplants (between species) seems to be progressing."
Cooper, the transplant surgeon at Georgetown, believes more potential donors would come forward if financial barriers weren't an issue. Of the ones who end up giving a part of themselves, with or without reimbursement, "the overwhelming majority look back upon it as an extremely positive experience," he says. After all, "they're lifesavers. They should be celebrated."