How thousands of first- and second-graders saved the world from a deadly disease
Although Jonas Salk has gone down in history for helping rid the world (almost) of polio, his revolutionary vaccine wouldn't have been possible without the world’s largest clinical trial – and the bravery of thousands of kids.
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.
While lab-grown meat is not yet ready to crisis-proof the food supply chain, it offers key benefits that could make it an important solution beyond this pandemic.
The coronavirus pandemic exposed significant weaknesses in the country's food supply chain. Grocery store meat counters were bare. Transportation interruptions influenced supply. Finding beef, poultry, and pork at the store has been, in some places, as challenging as finding toilet paper.
In traditional agriculture models, it takes at least three months to raise chicken, six to nine months for pigs, and 18 months for cattle.
It wasn't a lack of supply -- millions of animals were in the pipeline.
"There's certainly enough food out there, but it can't get anywhere because of the way our system is set up," said Amy Rowat, an associate professor of integrative biology and physiology at UCLA. "Having a more self-contained, self-sufficient way to produce meat could make the supply chain more robust."
Cultured meat could be one way of making the meat supply chain more resilient despite disruptions due to pandemics such as COVID-19. But is the country ready to embrace lab-grown food?
According to a Good Food Institute study, GenZ is almost twice as likely to embrace meat alternatives for reasons related to social and environmental awareness, even prior to the pandemic. That's because this group wants food choices that reflect their values around food justice, equity, and animal welfare.
Largely, the interest in protein alternatives has been plant-based foods. However, factors directly related to COVID-19 may accelerate consumer interest in the scaling up of cell-grown products, according to Liz Specht, the associate director of science and technology at The Good Food Institute. The latter is a nonprofit organization that supports scientists, investors, and entrepreneurs working to develop food alternatives to conventional animal products.
While lab-grown food isn't ready yet to definitively crisis-proof the food supply chain, experts say it offers promise.
Matching Supply and Demand
Companies developing cell-grown meat claim it can take as few as two months to develop a cell into an edible product, according to Anthony Chow, CFA at Agronomics Limited, an investment company focused on meat alternatives. Tissue is taken from an animal and placed in a culture that contains nutrients and proteins the cells need to grow and expand. He cites a Good Food Institute report that claims a 2.5-millimeter sample can grow three and a half tons of meat in 40 days, allowing for exponential growth when needed.
In traditional agriculture models, it takes at least three months to raise chicken, six to nine months for pigs, and 18 months for cattle. To keep enough maturing animals in the pipeline, farms must plan the number of animals to raise months -- even years -- in advance. Lab-grown meat advocates say that because cultured meat supplies can be flexible, it theoretically allows for scaling up or down in significantly less time.
"Supply and demand has drastically changed in some way around the world and cultivated meat processing would be able to adapt much quicker than conventional farming," Chow said.
Scaling Up
Lab-grown meat may provide an eventual solution, but not in the immediate future, said Paul Mozdziak, a professor of physiology at North Carolina State University who researches animal cell culture techniques, transgenic animal production, and muscle biology.
"The challenge is in culture media," he said. "It's going to take some innovation to get the cells to grow at quantities that are going to be similar to what you can get from an animal. These are questions that everybody in the space is working on."
Chow says some of the most advanced cultured meat companies, such as BlueNal, anticipate introducing products to the market midway through next year. However, he thinks COVID-19 has slowed the process. Once introduced, they will be at a premium price, most likely available at restaurants before they hit grocery store shelves.
"I think in five years' time it will be in a different place," he said. "I don't think that this will have relevance for this pandemic, but certainly beyond that."
"Plant-based meats may be perceived as 'alternatives' to meat, whereas lab-grown meat is producing the same meat, just in a much more efficient manner, without the environmental implications."
Of course, all the technological solutions in the world won't solve the problem unless people are open-minded about embracing them. At least for now, a lab-grown burger or bluefin tuna might still be too strange for many people, especially in the U.S.
For instance, a 2019 article published by "Frontiers in Sustainable Food Systems" reflects results from a study of 3,030 consumers showing that 29 percent of U.S. customers, 59 percent of Chinese consumers, and 56 percent of Indian consumers were either 'very' or 'extremely likely' to try cultivated meat.
"Lab-grown meat is genuine meat, at the cellular level, and therefore will match conventional meat with regard to its nutritional content and overall sensory experience. It could be argued that plant-based meat will never be able to achieve this," says Laura Turner, who works with Chow at Agronomics Limited. "Plant-based meats may be perceived as 'alternatives' to meat, whereas lab-grown meat is producing the same meat, just in a much more efficient manner, without the environmental implications."
A Solution Beyond This Pandemic
The coronavirus has done more than raise awareness of the fragility of food supply chains. It has also been a wakeup call for consumers and policy makers that it is time to radically rethink our meat, Specht says. Those factors have elevated the profile of lab-grown meat.
"I think the economy is getting a little bit more steam and if I was an investor, I would be getting excited about it," adds Mozdziak.
Beyond crises, Mozdziak explains that as affluence continues to increase globally, meat consumption increases exponentially. Yet farm animals can only grow so quickly and traditional farming won't be able to keep up.
"Even Tyson is saying that by 2050, there's not going to be enough capacity in the animal meat space to meet demand," he notes. "If we don't look at some innovative technologies, how are we going to overcome that?"
A COVID-19 moonshot program challenged chemists around the world to submit ideas for how best to design a drug to target the virus.
By mid-March, Alpha Lee was growing restless. A pioneer of AI-driven drug discovery, Lee leads a team of researchers at the University of Cambridge, but his lab had been closed amidst the government-initiated lockdowns spreading inexorably across Europe.
If the Moonshot proves successful, they hope it could serve as a future benchmark for finding new medicines for chronic diseases.
Having spoken to his collaborators across the globe – many of whom were seeing their own experiments and research projects postponed indefinitely due to the pandemic – he noticed a similar sense of frustration and helplessness in the face of COVID-19.
While there was talk of finding a novel treatment for the virus, Lee was well aware the process was likely to be long and laborious. Traditional methods of drug discovery risked suffering the same fate as the efforts to find a cure for SARS in the early 2000, which took years and were ultimately abandoned long before a drug ever reached the market.
To avoid such an outcome, Lee was convinced that global collaboration was required. Together with a collection of scientists in the UK, US and Israel, he launched the 'COVID Moonshot' – a project which encouraged chemists worldwide to share their ideas for potential drug designs. If the Moonshot proves successful, they hope it could serve as a future benchmark for finding new medicines for chronic diseases.
Solving a Complex Jigsaw
In February, ShanghaiTech University published the first detailed snapshots of the SARS-CoV-2 coronavirus's proteins using a technique called X-ray crystallography. In particular, they revealed a high-resolution profile of the virus's main protease – the part of its structure that enables it to replicate inside a host – and the main drug target. The images were tantalizing.
"We could see all the tiny pieces sitting in the structure like pieces of a jigsaw," said Lee. "All we needed was for someone to come up with the best idea of joining these pieces together with a drug. Then you'd be left with a strong molecule which sits in the protease, and stops it from working, killing the virus in the process."
Normally, ideas for how best to design such a drug would be kept as carefully guarded secrets within individual labs and companies due to their potential value. But as a result, the steady process of trial and error to reach an optimum design can take years to come to fruition.
However, given the scale of the global emergency, Lee felt that the scientific community would be open to collective brainstorming on a mass scale. "Big Pharma usually wouldn't necessarily do this, but time is of the essence here," he said. "It was a case of, 'Let's just rethink every drug discovery stage to see -- ok, how can we go as fast as we can?'"
On March 13, he launched the COVID moonshot, calling for chemists around the globe to come up with the most creative ideas they could think of, on their laptops at home. No design was too weird or wacky to be considered, and crucially nothing would be patented. The entire project would be done on a not-for-profit basis, meaning that any drug that makes it to market will have been created simply for the good of humanity.
It caught fire: Within just two weeks, more than 2,300 potential drug designs had been submitted. By the middle of July, over 10,000 had been received from scientists around the globe.
The Road Toward Clinical Trials
With so many designs to choose from, the team has been attempting to whittle them down to a shortlist of the most promising. Computational drug discovery experts at Diamond and the Weizmann Institute of Science in Rehovot, Israel, have enabled the Moonshot team to develop algorithms for predicting how quick and easy each design would be to make, and to predict how well each proposed drug might bind to the virus in real life.
The latter is an approach known as computational covalent docking and has previously been used in cancer research. "This was becoming more popular even before COVID-19, with several covalent drugs approved by the FDA in recent years," said Nir London, professor of organic chemistry at the Weizmann Institute, and one of the Moonshot team members. "However, all of these were for oncology. A covalent drug against SARS-CoV-2 will certainly highlight covalent drug-discovery as a viable option."
Through this approach, the team have selected 850 compounds to date, which they have manufactured and tested in various preclinical trials already. Fifty of these compounds - which appear to be especially promising when it comes to killing the virus in a test tube – are now being optimized further.
Lee is hoping that at least one of these potential drugs will be shown to be effective in curing animals of COVID-19 within the next six months, a step that would allow the Moonshot team to reach out to potential pharmaceutical partners to test their compounds in humans.
Future Implications
If the project does succeed, some believe it could open the door to scientific crowdsourcing as a future means of generating novel medicine ideas for other diseases. Frank von Delft, professor of protein science and structural biology at the University of Oxford's Nuffield Department of Medicine, described it as a new form of 'citizen science.'
"There's a vast resource of expertise and imagination that is simply dying to be tapped into," he said.
Others are slightly more skeptical, pointing out that the uniqueness of the current crisis has meant that many scientists were willing to contribute ideas without expecting any future compensation in return. This meant that it was easy to circumvent the traditional hurdles that prevent large-scale global collaborations from happening – namely how to decide who will profit from the final product and who will hold the intellectual property (IP) rights.
"I think it is too early to judge if this is a viable model for future drug discovery," says London. "I am not sure that without the existential threat we would have seen so many contributions, and so many people and institutions willing to waive compensation and future royalties. Many scientists found themselves at home, frustrated that they don't have a way to contribute to the fight against COVID-19, and this project gave them an opportunity. Plus many can get behind the fact that this project has no associated IP and no one will get rich off of this effort. This breaks down a lot of the typical barriers and red-tape for wider collaboration."
"If a drug would sprout from one of these crowdsourced ideas, it would serve as a very powerful argument to consider this mode of drug discovery further in the future."
However the Moonshot team believes that if they can succeed, it will at the very least send a strong statement to policy makers and the scientific community that greater efforts should be made to make such large-scale collaborations more feasible.
"All across the scientific world, we've seen unprecedented adoption of open-science, collaboration and collegiality during this crisis, perhaps recognizing that only a coordinated global effort could address this global challenge," says London. "If a drug would sprout from one of these crowdsourced ideas, it would serve as a very powerful argument to consider this mode of drug discovery further in the future."
[An earlier version of this article was published on June 8th, 2020 as part of a standalone magazine called GOOD10: The Pandemic Issue. Produced as a partnership among LeapsMag, The Aspen Institute, and GOOD, the magazine is available for free online.]