How thousands of first- and second-graders saved the world from a deadly disease
Exactly 67 years ago, in 1955, a group of scientists and reporters gathered at the University of Michigan and waited with bated breath for Dr. Thomas Francis Jr., director of the school’s Poliomyelitis Vaccine Evaluation Center, to approach the podium. The group had gathered to hear the news that seemingly everyone in the country had been anticipating for the past two years – whether the vaccine for poliomyelitis, developed by Francis’s former student Jonas Salk, was effective in preventing the disease.
Polio, at that point, had become a household name. As the highly contagious virus swept through the United States, cities closed their schools, movie theaters, swimming pools, and even churches to stop the spread. For most, polio presented as a mild illness, and was usually completely asymptomatic – but for an unlucky few, the virus took hold of the central nervous system and caused permanent paralysis of muscles in the legs, arms, and even people’s diaphragms, rendering the person unable to walk and breathe. It wasn’t uncommon to hear reports of people – mostly children – who fell sick with a flu-like virus and then, just days later, were relegated to spend the rest of their lives in an iron lung.
For two years, researchers had been testing a vaccine that would hopefully be able to stop the spread of the virus and prevent the 45,000 infections each year that were keeping the nation in a chokehold. At the podium, Francis greeted the crowd and then proceeded to change the course of human history: The vaccine, he reported, was “safe, effective, and potent.” Widespread vaccination could begin in just a few weeks. The nightmare was over.
The road to success
Jonas Salk, a medical researcher and virologist who developed the vaccine with his own research team, would rightfully go down in history as the man who eradicated polio. (Today, wild poliovirus circulates in just two countries, Afghanistan and Pakistan – with only 140 cases reported in 2020.) But many people today forget that the widespread vaccination campaign that effectively ended wild polio across the globe would have never been possible without the human clinical trials that preceded it.
As with the COVID-19 vaccine, skepticism and misinformation around the polio vaccine abounded. But even more pervasive than the skepticism was fear. The consequences of polio had arguably never been more visible.
The road to human clinical trials – and the resulting vaccine – was a long one. In 1938, President Franklin Delano Roosevelt launched the National Foundation for Infantile Paralysis in order to raise funding for research and development of a polio vaccine. (Today, we know this organization as the March of Dimes.) A polio survivor himself, Roosevelt elevated awareness and prevention into the national spotlight, even more so than it had been previously. Raising funds for a safe and effective polio vaccine became a cornerstone of his presidency – and the funds raked in by his foundation went primarily to Salk to fund his research.
The Trials Begin
Salk’s vaccine, which included an inactivated (killed) polio virus, was promising – but now the researchers needed test subjects to make global vaccination a possibility. Because the aim of the vaccine was to prevent paralytic polio, researchers decided that they had to test the vaccine in the population that was most vulnerable to paralysis – young children. And, because the rate of paralysis was so low even among children, the team required many children to collect enough data. Francis, who led the trial to evaluate Salk’s vaccine, began the process of recruiting more than one million school-aged children between the ages of six and nine in 272 counties that had the highest incidence of the disease. The participants were nicknamed the “Polio Pioneers.”
Double-blind, placebo-based trials were considered the “gold standard” of epidemiological research back in Francis's day - and they remain the best approach we have today. These rigorous scientific studies are designed with two participant groups in mind. One group, called the test group, receives the experimental treatment (such as a vaccine); the other group, called the control, receives an inactive treatment known as a placebo. The researchers then compare the effects of the active treatment against the effects of the placebo, and every researcher is “blinded” as to which participants receive what treatment. That way, the results aren’t tainted by any possible biases.
But the study was controversial in that only some of the individual field trials at the county and state levels had a placebo group. Researchers described this as a “calculated risk,” meaning that while there were risks involved in giving the vaccine to a large number of children, the bigger risk was the potential paralysis or death that could come with being infected by polio. In all, just 200,000 children across the US received a placebo treatment, while an additional 725,000 children acted as observational controls – in other words, researchers monitored them for signs of infection, but did not give them any treatment.
As with the COVID-19 vaccine, skepticism and misinformation around the polio vaccine abounded. But even more pervasive than the skepticism was fear. President Roosevelt, who had made many public and televised appearances in a wheelchair, served as a perpetual reminder of the consequences of polio, as an infection at age 39 had rendered him permanently unable to walk. The consequences of polio had arguably never been more visible, and parents signed up their children in droves to participate in the study and offer them protection.
The Polio Pioneer Legacy
In a little less than a year, roughly half a million children received a dose of Salk’s polio vaccine. While plenty of children were hesitant to get the shot, many former participants still remember the fear surrounding the disease. One former participant, a Polio Pioneer named Debbie LaCrosse, writes of her experience: “There was no discussion, no listing of pros and cons. No amount of concern over possible side effects or other unknowns associated with a new vaccine could compare to the terrifying threat of polio.” For their participation, each kid received a certificate – and sometimes a pin – with the words “Polio Pioneer” emblazoned across the front.
When Francis announced the results of the trial on April 12, 1955, people did more than just breathe a sigh of relief – they openly celebrated, ringing church bells and flooding into the streets to embrace. Salk, who had become the face of the vaccine at that point, was instantly hailed as a national hero – and teachers around the country had their students to write him ‘thank you’ notes for his years of diligent work.
But while Salk went on to win national acclaim – even accepting the Presidential Medal of Freedom for his work on the polio vaccine in 1977 – his success was due in no small part to the children (and their parents) who took a risk in order to advance medical science. And that risk paid off: By the early 1960s, the yearly cases of polio in the United States had gone down to just 910. Where before the vaccine polio had caused around 15,000 cases of paralysis each year, only ten cases of paralysis were recorded in the entire country throughout the 1970s. And in 1979, the virus that once shuttered entire towns was declared officially eradicated in this country. Thanks to the efforts of these brave pioneers, the nation – along with the majority of the world – remains free of polio even today.
The "Making Sense of Science" podcast features interviews with leading medical and scientific experts about the latest developments and the big ethical and societal questions they raise. This monthly podcast is hosted by journalist Kira Peikoff, founding editor of the award-winning science outlet Leaps.org.
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Kira Peikoff was the editor-in-chief of Leaps.org from 2017 to 2021. As a journalist, her work has appeared in The New York Times, Newsweek, Nautilus, Popular Mechanics, The New York Academy of Sciences, and other outlets. She is also the author of four suspense novels that explore controversial issues arising from scientific innovation: Living Proof, No Time to Die, Die Again Tomorrow, and Mother Knows Best. Peikoff holds a B.A. in Journalism from New York University and an M.S. in Bioethics from Columbia University. She lives in New Jersey with her husband and two young sons. Follow her on Twitter @KiraPeikoff.
Man Who Got the First Fecal Transplant to Cure Melanoma Shares His Surprising Experience
Jamie Rettinger was still in his thirties when he first noticed a tiny streak of brown running through the thumbnail of his right hand. It slowly grew wider and the skin underneath began to deteriorate before he went to a local dermatologist in 2013. The doctor thought it was a wart and tried scooping it out, treating the affected area for three years before finally removing the nail bed and sending it off to a pathology lab for analysis.
I have some bad news for you; what we removed was a five-millimeter melanoma, a cancerous tumor that often spreads, Jamie recalls being told on his return visit. "I'd never heard of cancer coming through a thumbnail," he says. None of his doctors had ever mentioned it either. "I just thought I was being treated for a wart." But nothing was healing and it continued to bleed.
A few months later a surgeon amputated the top half of his thumb. Lymph node biopsy tested negative for spread of the cancer and when the bandages finally came off, Jamie thought his medical issues were resolved.
Melanoma is the deadliest form of skin cancer. About 85,000 people are diagnosed with it each year in the U.S. and more than 8,000 die of the cancer when it spreads to other parts of the body, according to the Centers for Disease Control and Prevention (CDC).
There are two peaks in diagnosis of melanoma; one is in younger women ages 30-40 and often is tied to past use of tanning beds; the second is older men 60+ and is related to outdoor activity from farming to sports. Light-skinned people have a twenty-times greater risk of melanoma than do people with dark skin.
"It was pretty weird, I was totally blasted away. Who had thought of this?"
Jamie had a follow up PET scan about six months after his surgery. A suspicious spot on his lung led to a biopsy that came back positive for melanoma. The cancer had spread. Treatment with a monoclonal antibody (nivolumab/Opdivo®) didn't prove effective and he was referred to the UPMC Hillman Cancer Center in Pittsburgh, a four-hour drive from his home in western Ohio.
An alternative monoclonal antibody treatment brought on such bad side effects, diarrhea as often as 15 times a day, that it took more than a week of hospitalization to stabilize his condition. The only options left were experimental approaches in clinical trials.
Early Research
"When I graduated from medical school, in 2005, melanoma was a death sentence" with a cure rate in the single digits, says Dr. Diwakar Davar, 39, an oncologist at UPMC Hillman Cancer Center who specializes in skin cancer. That began to change in 2010 with introduction of the first immunotherapies, monoclonal antibodies, to treat cancer. The antibodies attach to PD-1, a receptor on the surface of T cells of the immune system and on cancer cells. Antibody treatment boosted the melanoma cure rate to about 30 percent. The search was on to understand why some people responded to these drugs and others did not.
At the same time, there was a growing understanding of the role that bacteria in the gut, the gut microbiome, plays in helping to train and maintain the function of the body's various immune cells. Perhaps the bacteria also plays a role in shaping the immune response to cancer therapy.
One clue came from genetically identical mice. Animals ordered from different suppliers sometimes responded differently to the experiments being performed. That difference was traced to different compositions of their gut microbiome; transferring the microbiome from one animal to another in a process known as fecal transplant (FMT) could change their responses to disease or treatment.
When researchers looked at humans, they found that the patients who responded well to immunotherapies had a gut microbiome that looked like healthy normal folks, but patients who didn't respond had missing or reduced strains of bacteria.
Davar and his team knew that FMT had a very successful cure rate in treating the gut dysbiosis of C. difficile infection and they wondered if a fecal transplant from a patient who had responded well to cancer immunotherapy treatment might improve the cure rate of patients who did not originally respond to immunotherapies for melanoma.
Clinical Trial
"It was pretty weird, I was totally blasted away. Who had thought of this?" Jamie first thought when the hypothesis was explained to him. But Davar's explanation that the procedure might restore some of the beneficial bacterial his gut was lacking, convinced him to try. He quickly signed on in October 2018 to be the first person in the clinical trial.
Fecal donations go through the same safety procedures of screening for and inactivating diseases that are used in processing blood donations to make them safe for transfusion. The procedure itself uses a standard hollow colonoscope designed to screen for colon cancer and remove polyps. The transplant is inserted through the center of the flexible tube.
Most patients are sedated for procedures that use a colonoscope but Jamie doesn't respond to those drugs: "You can't knock me out. I was watching them on the TV going up my own butt. It was kind of unreal at that point," he says. "There were about twelve people in there watching because no one had seen this done before."
A test two weeks after the procedure showed that the FMT had engrafted and the once-missing bacteria were thriving in his gut. More importantly, his body was responding to another monoclonal antibody (pembrolizumab/Keytruda®) and signs of melanoma began to shrink. Every three months he made the four-hour drive from home to Pittsburgh for six rounds of treatment with the antibody drug.
"We were very, very lucky that the first patient had a great response," says Davar. "It allowed us to believe that even though we failed with the next six, we were on the right track. We just needed to tweak the [fecal] cocktail a little better" and enroll patients in the study who had less aggressive tumor growth and were likely to live long enough to complete the extensive rounds of therapy. Six of 15 patients responded positively in the pilot clinical trial that was published in the journal Science.
Davar believes they are beginning to understand the biological mechanisms of why some patients initially do not respond to immunotherapy but later can with a FMT. It is tied to the background level of inflammation produced by the interaction between the microbiome and the immune system. That paper is not yet published.
Surviving Cancer
It has been almost a year since the last in his series of cancer treatments and Jamie has no measurable disease. He is cautiously optimistic that his cancer is not simply in remission but is gone for good. "I'm still scared every time I get my scans, because you don't know whether it is going to come back or not. And to realize that it is something that is totally out of my control."
"It was hard for me to regain trust" after being misdiagnosed and mistreated by several doctors he says. But his experience at Hillman helped to restore that trust "because they were interested in me, not just fixing the problem."
He is grateful for the support provided by family and friends over the last eight years. After a pause and a sigh, the ruggedly built 47-year-old says, "If everyone else was dead in my family, I probably wouldn't have been able to do it."
"I never hesitated to ask a question and I never hesitated to get a second opinion." But Jamie acknowledges the experience has made him more aware of the need for regular preventive medical care and a primary care physician. That person might have caught his melanoma at an earlier stage when it was easier to treat.
Davar continues to work on clinical studies to optimize this treatment approach. Perhaps down the road, screening the microbiome will be standard for melanoma and other cancers prior to using immunotherapies, and the FMT will be as simple as swallowing a handful of freeze-dried capsules off the shelf rather than through a colonoscopy.