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.
I'll never forget the experience of having a child in the neonatal intensive care unit (NICU).
Now more than ever, we're working to remove the barriers between new parents and their infants.
It was another layer of uncertainty that filtered into my experience of being a first-time parent. There was so much I didn't know, and the wires attached to my son's small body for the first week of his life were a reminder of that.
I wanted to be the best mother possible. I deeply desired to bring my son home to start our lives. More than anything, I longed for a wireless baby whom I could hold and love freely without limitations.
The wires suggested my baby was fragile and it left me feeling severely unprepared, anxious, and depressed.
In recent years, research has documented the ways that NICU experiences take a toll on parents' mental health. But thankfully, medical technology is rapidly being developed to help reduce the emotional fallout of the NICU. Now more than ever, we're working to remove the barriers between new parents and their infants. The latest example is the first ever wireless monitoring system that was recently developed by a team at Northwestern University.
After listening to the needs of parents and medical staff, Debra Weese-Mayer, M.D., a professor of pediatric autonomic medicine at Feinberg School of Medicine, along with a team of materials scientists, engineers, dermatologists and pediatricians, set out to develop this potentially life-changing technology. Weese-Mayer believes wireless monitoring will have a significant impact for people on all sides of the NICU experience.
"With elimination of the cumbersome wires," she says, "the parents will find their infant more approachable/less intimidating and have improved access to their long-awaited but delivered-too-early infant, allowing them to begin skin-to-skin contact and holding with reduced concern for dislodging wires."
So how does the new system work?
Very thin "skin like" patches made of silicon rubber are placed on the surface of the skin to monitor vitals like heart rate, respiration rate, and body temperature. One patch is placed on the chest or back and the other is placed on the foot.
These patches are safer on the skin than previously used adhesives, reducing the cuts and infections associated with past methods. Finally, an antenna continuously delivers power, often from under the mattress.
The data collected from the patches stream from the body to a tablet or computer.
New wireless sensor technology is being studied to replace wired monitoring in NICUs in the coming years.
(Northwestern University)
Weese-Mayer hopes that wireless systems will be standard soon, but first they must undergo more thorough testing. "I would hope that in the next five years, wireless monitoring will be the standard in NICUs, but there are many essential validation steps before this technology will be embraced nationally," she says.
Until the new systems are ready, parents will be left struggling with the obstacles that wired monitoring presents.
Physical intimacy, for example, appears to have pain-reducing qualities -- something that is particularly important for babies who are battling serious illness. But wires make those cuddles more challenging.
There's also been minimal discussion about how wired monitoring can be particularly limiting for parents with disabilities and mobility aids, or even C-sections.
"When he was first born and I was recovering from my c-section, I couldn't deal with keeping the wires untangled while trying to sit down without hurting myself," says Rhiannon Giles, a writer from North Carolina, who delivered her son at just over 31 weeks after suffering from severe preeclampsia.
"The wires were awful," she remembers. "They fell off constantly when I shifted positions or he kicked a leg, which meant the monitors would alarm. It felt like an intrusion into the quiet little world I was trying to mentally create for us."
Over the last few years, researchers have begun to dive deeper into the literal and metaphorical challenges of wired monitoring.
For many parents, the wires prompt anxiety that worsens an already tense and vulnerable time.
I'll never forget the first time I got to hold my son without wires. It was the first time that motherhood felt manageable.
"Seeing my five-pound-babies covered in wires from head to toe rendered me completely overwhelmed," recalls Caila Smith, a mom of five from Indiana, whose NICU experience began when her twins were born pre-term. "The nurses seemed to handle them perfectly, but I was scared to touch them while they appeared so medically frail."
During the nine days it took for both twins to come home, the limited access she had to her babies started to impact her mental health. "If we would've had wireless sensors and monitors, it would've given us a much greater sense of freedom and confidence when snuggling our newborns," Smith says.
Besides enabling more natural interactions, wireless monitoring would make basic caregiving tasks much easier, like putting on a onesie.
"One thing I noticed is that many preemie outfits are made with zippers," points out Giles, "which just don't work well when your baby has wires coming off of them, head to toe."
Wired systems can pose issues for medical staff as well as parents.
"The main concern regarding wired systems is that they restrict access to the baby and often get tangled with other equipment, like IV lines," says Lamia Soghier, Medical Director of the Neonatal Intensive Care Unit at Children's National in Washington, D.C , who was also a NICU parent herself. "The nurses have to untangle the wires, which takes time, before handing the baby to the family."
I'll never forget the first time I got to hold my son without wires. It was the first time that motherhood felt manageable, and I couldn't stop myself from crying. Suddenly, anything felt possible and all the limitations from that first week of life seemed to fade away. The rise of wired-free monitoring will make some of the stressors that accompany NICU stays a thing of the past.
There's a quiet revolution going on in medicine. It's driven by artificial intelligence, but paradoxically, new technology may put a more human face on healthcare.
AI's usefulness in healthcare ranges far and wide.
Artificial intelligence is software that can process massive amounts of information and learn over time, arriving at decisions with striking accuracy and efficiency. It offers greater accuracy in diagnosis, exponentially faster genome sequencing, the mining of medical literature and patient records at breathtaking speed, a dramatic reduction in administrative bureaucracy, personalized medicine, and even the democratization of healthcare.
The algorithms that bring these advantages won't replace doctors; rather, by offloading some of the most time-consuming tasks in healthcare, providers will be able to focus on personal interactions with patients—listening, empathizing, educating and generally putting the care back in healthcare. The relationship can focus on the alleviation of suffering, both the physical and emotional kind.
Challenges of Getting AI Up and Running
The AI revolution, still in its early phase in medicine, is already spurring some amazing advances, despite the fact that some experts say it has been overhyped. IBM's Watson Health program is a case in point. IBM capitalized on Watson's ability to process natural language by designing algorithms that devour data like medical articles and analyze images like MRIs and medical slides. The algorithms help diagnose diseases and recommend treatment strategies.
But Technology Review reported that a heavily hyped partnership with the MD Anderson Cancer Center in Houston fell apart in 2017 because of a lack of data in the proper format. The data existed, just not in a way that the voraciously data-hungry AI could use to train itself.
The hiccup certainly hasn't dampened the enthusiasm for medical AI among other tech giants, including Google and Apple, both of which have invested billions in their own healthcare projects. At this point, the main challenge is the need for algorithms to interpret a huge diversity of data mined from medical records. This can include everything from CT scans, MRIs, electrocardiograms, x-rays, and medical slides, to millions of pages of medical literature, physician's notes, and patient histories. It can even include data from implantables and wearables such as the Apple Watch and blood sugar monitors.
None of this information is in anything resembling a standard format across and even within hospitals, clinics, and diagnostic centers. Once the algorithms are trained, however, they can crunch massive amounts of data at blinding speed, with an accuracy that matches and sometimes even exceeds that of highly experienced doctors.
Genome sequencing, for example, took years to accomplish as recently as the early 2000s. The Human Genome Project, the first sequencing of the human genome, was an international effort that took 13 years to complete. In April of this year, Rady Children's Institute for Genomic Medicine in San Diego used an AI-powered genome sequencing algorithm to diagnose rare genetic diseases in infants in about 20 hours, according to ScienceDaily.
"Patient care will always begin and end with the doctor."
Dr. Stephen Kingsmore, the lead author of an article published in Science Translational Medicine, emphasized that even though the algorithm helped guide the treatment strategies of neonatal intensive care physicians, the doctor was still an indispensable link in the chain. "Some people call this artificial intelligence, we call it augmented intelligence," he says. "Patient care will always begin and end with the doctor."
One existing trend is helping to supply a great amount of valuable data to algorithms—the electronic health record. Initially blamed for exacerbating the already crushing workload of many physicians, the EHR is emerging as a boon for algorithms because it consolidates all of a patient's data in one record.
Examples of AI in Action Around the Globe
If you're a parent who has ever taken a child to the doctor with flulike symptoms, you know the anxiety of wondering if the symptoms signal something serious. Kang Zhang, M.D., Ph.D., the founding director of the Institute for Genomic Medicine at the University of California at San Diego, and colleagues developed an AI natural language processing model that used deep learning to analyze the EHRs of 1.3 million pediatric visits to a clinic in Guanzhou, China.
The AI identified common childhood diseases with about the same accuracy as human doctors, and it was even able to split the diagnoses into two categories—common conditions such as flu, and serious, life-threatening conditions like meningitis. Zhang has emphasized that the algorithm didn't replace the human doctor, but it did streamline the diagnostic process and could be used in a triage capacity when emergency room personnel need to prioritize the seriously ill over those suffering from common, less dangerous ailments.
AI's usefulness in healthcare ranges far and wide. In Uganda and several other African nations, AI is bringing modern diagnostics to remote villages that have no access to traditional technologies such as x-rays. The New York Times recently reported that there, doctors are using a pocket-sized, hand-held ultrasound machine that works in concert with a cell phone to image and diagnose everything from pneumonia (a common killer of children) to cancerous tumors.
The beauty of the highly portable, battery-powered device is that ultrasound images can be uploaded on computers so that physicians anywhere in the world can review them and weigh in with their advice. And the images are instantly incorporated into the patient's EHR.
Jonathan Rothberg, the founder of Butterfly Network, the Connecticut company that makes the device, told The New York Times that "Two thirds of the world's population gets no imaging at all. When you put something on a chip, the price goes down and you democratize it." The Butterfly ultrasound machine, which sells for $2,000, promises to be a game-changer in remote areas of Africa, South America, and Asia, as well as at the bedsides of patients in developed countries.
AI algorithms are rapidly emerging in healthcare across the U.S. and the world. China has become a major international player, set to surpass the U.S. this year in AI capital investment, the translation of AI research into marketable products, and even the number of often-cited research papers on AI. So far the U.S. is still the leader, but some experts describe the relationship between the U.S. and China as an AI cold war.
"The future of machine learning isn't sentient killer robots. It's longer human lives."
The U.S. Food and Drug Administration expanded its approval of medical algorithms from two in all of 2017 to about two per month throughout 2018. One of the first fields to be impacted is ophthalmology.
One algorithm, developed by the British AI company DeepMind (owned by Alphabet, the parent company of Google), instantly scans patients' retinas and is able to diagnose diabetic retinopathy without needing an ophthalmologist to interpret the scans. This means diabetics can get the test every year from their family physician without having to see a specialist. The Financial Times reported in March that the technology is now being used in clinics throughout Europe.
In Copenhagen, emergency service dispatchers are using a new voice-processing AI called Corti to analyze the conversations in emergency phone calls. The algorithm analyzes the verbal cues of callers, searches its huge database of medical information, and provides dispatchers with onscreen diagnostic information. Freddy Lippert, the CEO of EMS Copenhagen, notes that the algorithm has already saved lives by expediting accurate diagnoses in high-pressure situations where time is of the essence.
Researchers at the University of Nottingham in the UK have even developed a deep learning algorithm that predicts death more accurately than human clinicians. The algorithm incorporates data from a huge range of factors in a chronically ill population, including how many fruits and vegetables a patient eats on a daily basis. Dr. Stephen Weng, lead author of the study, published in PLOS ONE, said in a press release, "We found machine learning algorithms were significantly more accurate in predicting death than the standard prediction models developed by a human expert."
New digital technologies are allowing patients to participate in their healthcare as never before. A feature of the new Apple Watch is an app that detects cardiac arrhythmias and even produces an electrocardiogram if an abnormality is detected. The technology, approved by the FDA, is helping cardiologists monitor heart patients and design interventions for those who may be at higher risk of a cardiac event like a stroke.
If having an algorithm predict your death sends a shiver down your spine, consider that algorithms may keep you alive longer. In 2018, technology reporter Tristan Greene wrote for Medium that "…despite the unending deluge of panic-ridden articles declaring AI the path to apocalypse, we're now living in a world where algorithms save lives every day. The future of machine learning isn't sentient killer robots. It's longer human lives."
The Risks of AI Compiling Your Data
To be sure, the advent of AI-infused medical technology is not without its risks. One risk is that the use of AI wearables constantly monitoring our vital signs could turn us into a nation of hypochondriacs, racing to our doctors every time there's a blip in some vital sign. Such a development could stress an already overburdened system that suffers from, among other things, a shortage of doctors and nurses. Another risk has to do with the privacy protections on the massive repository of intimately personal information that AI will have on us.
In an article recently published in the Journal of the American Medical Association, Australian researcher Kit Huckvale and colleagues examined the handling of data by 36 smartphone apps that assisted people with either depression or smoking cessation, two areas that could lend themselves to stigmatization if they fell into the wrong hands.
Out of the 36 apps, 33 shared their data with third parties, despite the fact that just 25 of those apps had a privacy policy at all and out of those, only 23 stated that data would be shared with third parties. The recipients of all that data? It went almost exclusively to Facebook and Google, to be used for advertising and marketing purposes. But there's nothing to stop it from ending up in the hands of insurers, background databases, or any other entity.
Even when data isn't voluntarily shared, any digital information can be hacked. EHRs and even wearable devices share the same vulnerability as any other digital record or device. Still, the promise of AI to radically improve efficiency and accuracy in healthcare is hard to ignore.
AI Can Help Restore Humanity to Medicine
Eric Topol, director of the Scripps Research Translational Institute and author of the new book Deep Medicine, says that AI gives doctors and nurses the most precious gift of all: time.
Topol welcomes his patients' use of the Apple Watch cardiac feature and is optimistic about the ways that AI is revolutionizing medicine. He says that the watch helps doctors monitor how well medications are working and has already helped to prevent strokes. But in addition to that, AI will help bring the humanity back to a profession that has become as cold and hard as a stainless steel dissection table.
"When I graduated from medical school in the 1970s," he says, "you had a really intimate relationship with your doctor." Over the decades, he has seen that relationship steadily erode as medical organizations demanded that doctors see more and more patients within ever-shrinking time windows.
"Doctors have no time to think, to communicate. We need to restore the mission in medicine."
In addition to that, EHRs have meant that doctors and nurses are getting buried in paperwork and administrative tasks. This is no doubt one reason why a recent study by the World Health Organization showed that worldwide, about 50 percent of doctors suffer from burnout. People who are utterly exhausted make more mistakes, and medical clinicians are no different from the rest of us. Only medical mistakes have unacceptably high stakes. According to its website, Johns Hopkins University recently announced that in the U.S. alone, 250,000 people die from medical mistakes each year.
"Doctors have no time to think, to communicate," says Topol. "We need to restore the mission in medicine." AI is giving doctors more time to devote to the thing that attracted them to medicine in the first place—connecting deeply with patients.
There is a real danger at this juncture, though, that administrators aware of the time-saving aspects of AI will simply push doctors to see more patients, read more tests, and embrace an even more crushing workload.
"We can't leave it to the administrators to just make things worse," says Topol. "Now is the time for doctors to advocate for a restoration of the human touch. We need to stand up for patients and for the patient-doctor relationship."
AI could indeed be a game changer, he says, but rather than squander the huge benefits of more time, "We need a new equation going forward."