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.
Is a Successful HIV Vaccine Finally on the Horizon?
Few vaccines have been as complicated—and filled with false starts and crushed hopes—as the development of an HIV vaccine.
While antivirals help HIV-positive patients live longer and reduce viral transmission to virtually nil, these medications must be taken for life, and preventative medications like pre-exposure prophylaxis, known as PrEP, need to be taken every day to be effective. Vaccines, even if they need boosters, would make prevention much easier.
In August, Moderna began human trials for two HIV vaccine candidates based on messenger RNA.
As they have with the Covid-19 pandemic, mRNA vaccines could change the game. The technology could be applied for gene editing therapy, cancer, other infectious diseases—even a universal influenza vaccine.
In the past, three other mRNA vaccines completed phase-2 trials without success. But the easily customizable platforms mean the vaccines can be tweaked better to target HIV as researchers learn more.
Ever since HIV was discovered as the virus causing AIDS, researchers have been searching for a vaccine. But the decades-long journey has so far been fruitless; while some vaccine candidates showed promise in early trials, none of them have worked well among later-stage clinical trials.
There are two main reasons for this: HIV evolves incredibly quickly, and the structure of the virus makes it very difficult to neutralize with antibodies.
"We in HIV medicine have been desperate to find a vaccine that has effectiveness, but this goal has been elusive so far."
"You know the panic that goes on when a new coronavirus variant surfaces?" asked John Moore, professor of microbiology and immunology at Weill Cornell Medicine who has researched HIV vaccines for 25 years. "With HIV, that kind of variation [happens] pretty much every day in everybody who's infected. It's just orders of magnitude more variable a virus."
Vaccines like these usually work by imitating the outer layer of a virus to teach cells how to recognize and fight off the real thing off before it enters the cell. "If you can prevent landing, you can essentially keep the virus out of the cell," said Larry Corey, the former president and director of the Fred Hutchinson Cancer Research Center who helped run a recent trial of a Johnson & Johnson HIV vaccine candidate, which failed its first efficacy trial.
Like the coronavirus, HIV also has a spike protein with a receptor-binding domain—what Moore calls "the notorious RBD"—that could be neutralized with antibodies. But while that target sticks out like a sore thumb in a virus like SARS-CoV-2, in HIV it's buried under a dense shield. That's not the only target for neutralizing the virus, but all of the targets evolve rapidly and are difficult to reach.
"We understand these targets. We know where they are. But it's still proving incredibly difficult to raise antibodies against them by vaccination," Moore said.
In fact, mRNA vaccines for HIV have been under development for years. The Covid vaccines were built on decades of that research. But it's not as simple as building on this momentum, because of how much more complicated HIV is than SARS-CoV-2, researchers said.
"They haven't succeeded because they were not designed appropriately and haven't been able to induce what is necessary for them to induce," Moore said. "The mRNA technology will enable you to produce a lot of antibodies to the HIV envelope, but if they're the wrong antibodies that doesn't solve the problem."
Part of the problem is that the HIV vaccines have to perform better than our own immune systems. Many vaccines are created by imitating how our bodies overcome an infection, but that doesn't happen with HIV. Once you have the virus, you can't fight it off on your own.
"The human immune system actually does not know how to innately cure HIV," Corey said. "We needed to improve upon the human immune system to make it quicker… with Covid. But we have to actually be better than the human immune system" with HIV.
But in the past few years, there have been impressive leaps in understanding how an HIV vaccine might work. Scientists have known for decades that neutralizing antibodies are key for a vaccine. But in 2010 or so, they were able to mimic the HIV spike and understand how antibodies need to disable the virus. "It helps us understand the nature of the problem, but doesn't instantly solve the problem," Moore said. "Without neutralizing antibodies, you don't have a chance."
Because the vaccines need to induce broadly neutralizing antibodies, and because it's very difficult to neutralize the highly variable HIV, any vaccine will likely be a series of shots that teach the immune system to be on the lookout for a variety of potential attacks.
"Each dose is going to have to have a different purpose," Corey said. "And we hope by the end of the third or fourth dose, we will achieve the level of neutralization that we want."
That's not ideal, because each individual component has to be made and tested—and four shots make the vaccine harder to administer.
"You wouldn't even be going down that route, if there was a better alternative," Moore said. "But there isn't a better alternative."
The mRNA platform is exciting because it is easily customizable, which is especially important in fighting against a shapeshifting, complicated virus. And the mRNA platform has shown itself, in the Covid pandemic, to be safe and quick to make. Effective Covid vaccines were comparatively easy to develop, since the coronavirus is easier to battle than HIV. But companies like Moderna are capitalizing on their success to launch other mRNA therapeutics and vaccines, including the HIV trial.
"You can make the vaccine in two months, three months, in a research lab, and not a year—and the cost of that is really less," Corey said. "It gives us a chance to try many more options, if we've got a good response."
In a trial on macaque monkeys, the Moderna vaccine reduced the chances of infection by 85 percent. "The mRNA platform represents a very promising approach for the development of an HIV vaccine in the future," said Dr. Peng Zhang, who is helping lead the trial at the National Institute of Allergy and Infectious Diseases.
Moderna's trial in humans represents "a very exciting possibility for the prevention of HIV infection," Dr. Monica Gandhi, director of the UCSF-Gladstone Center for AIDS Research, said in an email. "We in HIV medicine have been desperate to find a vaccine that has effectiveness, but this goal has been elusive so far."
If a successful HIV vaccine is developed, the series of shots could include an mRNA shot that primes the immune system, followed by protein subunits that generate the necessary antibodies, Moore said.
"I think it's the only thing that's worth doing," he said. "Without something complicated like that, you have no chance of inducing broadly neutralizing antibodies."
"I can't guarantee you that's going to work," Moore added. "It may completely fail. But at least it's got some science behind it."
New Podcast: The Lead Scientist for the NASA Mission to Venus
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.
This month, our guest is JPL's Dr. Suzanne Smrekar, who will be pushing the boundaries of knowledge about the planet Venus during the upcoming VERITAS mission set to launch in 2028. Why did Earth's twin planet develop so differently than our own? Could Venus ever have hosted life? What is the bigger purpose for humanity in studying the solar system -- is it purely scientific, or is it also a matter of art and philosophy? Hear Dr. Smrekar discuss all this and more on the latest episode.
Watch the 30-Second Trailer:
Listen to the Episode:
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.