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.
"Vaccine passports" are a system that requires proof of a COVID-19 vaccination as a condition of engaging in activities that pose a risk of transmitted SARS-CoV-2. Digital Health Passes (DHPs) are typically a smartphone application with a code that verifies whether someone has been vaccinated.
Vaccine passports could very much be in our future. Many businesses are implementing or planning to require proof of vaccination as a condition of returning to the workplace. Colleges and universities have announced vaccine requirements for students, staff, and faculty. It may not be long before the private sector requires a vaccination card or image to attend an entertainment or sporting event, to travel, or even to dine or shop indoors, at least in some venues.
But it's unlikely the federal government or the states will launch DHPs, at least not in the near-term. President Biden announced the White House has no intention of requiring proof of vaccination. While no state has mandated DHPs, New York is piloting its Excelsior Pass on a voluntary basis, partnering with IBM. Other nations are not so hesitant. Israel's "Green Pass" has gotten the nation back to normal in record time. And various countries and regions are planning DHPs, including the European Union and the United Kingdom. Foreign airlines are likely to require proof of vaccination as a condition of flying internationally.
DHPs could emerge as a way to get us back to normal more quickly, but are they ethical? Let's start with the law. The US Equal Opportunity Commission (EEOC) has specifically said that employers have the legal right to require proof of vaccination as a condition of returning to work. Colleges and universities already require several vaccines for students living in dorms. Hospitals and nursing homes often mandate influenza vaccinations. And, of course, all states require childhood vaccinations for school attendance. Vaccine passports are lawful but are they ethical? The short answer is "yes" but only if we ensure no one is left behind.
Vaccine passports "don't force anyone to be vaccinated against his or her will. They simply say to individuals that if you choose not to be vaccinated, you can't work or recreate in public spaces that risk transmission of the virus."
Why are vaccine passports ethical? Vaccines are a miracle of modern science, but they have become a political symbol, and a significant part of the population doesn't want to get a jab. The rare cases of blood clots associated with the Johnson & Johnson and AstraZeneca vaccines have only created more distrust.
Most opposition to vaccine passports hinges on the claim that they infringe personal autonomy and liberty. But this argument misses the point. Of course, every competent adult has the right to make decisions that affect his or her own health and safety. But no one has a right to infringe on the rights of others, such as by exposing them to a potentially serious or deadly infectious disease. An individual can't claim the right to attend a crowded event mask-less and unvaccinated. This was once accepted across the political spectrum. Conservative economists called it an "externality," that is a person has no right to harm others. The U.S. has lost the tradition of the common good. We have become so focused on our own individual rights that we forget about our ethical obligations to our neighbors and to our community.
In fact, DHPs actually don't force anyone to be vaccinated against his or her will. They simply say to individuals that if you choose not to be vaccinated, you can't work or recreate in public spaces that risk transmission of the virus.
DHPs also don't infringe on privacy. Again, everyone has the choice whether to show proof of vaccination. It isn't required. Moreover, DHPs may actually protect privacy because all they do is show whether or not you have been vaccinated. They don't disclose any other personal medical information. All of us actually have already had to show proof of vaccination as a condition of going to school. Thus, DHPs are well established in the United States.
But there is one ethical argument against DHPs that I find to be powerful, and that is equity. If we require proof of vaccination while doses are scarce, we will give the already privileged even more privilege. And that would be unconscionable. Thus, DHPs should not be implemented until everyone who wants a vaccine is able to get a vaccine. Equity isn't a side issue. It needs to be front and center.
As of today, all adults in the U.S. are eligible to get vaccinated, and President Biden has pledged that by the end of May there will be enough doses to vaccinate the entire U.S. population. It is a realistic promise. Once vaccines become plentiful, everyone should get their shot. All Food and Drug Administration authorized vaccines are highly safe and effective, even the Johnson & Johnson vaccine that the FDA has just put on pause.
Businesses have an economic incentive to require proof of vaccination. Very few of us would feel comfortable returning to our jobs, shops, theaters, or restaurants unless we feel safe. Businesses understand the duty to create safer places for work, recreation, and commerce.
One question has dominated national conversation since the pandemic began. "When will we get back to normal?" There is a deep human yearning to hug family and friends, see our work colleagues, recreate, and be entertained. One day we will have defeated this wily virus and get back to normal. But vaccine passports can help us get back to the things we love faster and more safely. As long as we don't leave anyone behind, using this miracle of modern science to make our lives better is both lawful and ethical.
Editor's Note: This op/ed is part of a "Big Question" series on the ethics of vaccine passports. Read the flip-side argument here.
The Pandemic Is Ushering in a More Modern—and Ethical—Way of Studying New Drugs and Diseases
Before the onset of the coronavirus pandemic, Dutch doctoral researcher Joep Beumer had used miniature lab-grown organs to study the human intestine as part of his PhD thesis. When lockdown hit, however, he was forced to delay his plans for graduation. Overwhelmed by a sense of boredom after the closure of his lab at the Hubrecht Institute, in the Netherlands, he began reading literature related to COVID-19.
"By February [2020], there were already reports on coronavirus symptoms in the intestinal tract," Beumer says, adding that this piqued his interest. He wondered if he could use his miniature models – called organoids -- to study how the coronavirus infects the intestines.
But he wasn't the only one to follow this train of thought. In the year since the pandemic began, many researchers have been using organoids to study how the coronavirus infects human cells, and find potential treatments. Beumer's pivot represents a remarkable and fast-emerging paradigm shift in how drugs and diseases will be studied in the coming decades. With future pandemics likely to be more frequent and deadlier, such a shift is necessary to reduce the average clinical development time of 5.9 years for antiviral agents.
Part of that shift means developing models that replicate human biology in the lab. Animal models, which are the current standard in biomedical research, fail to do so—96% of drugs that pass animal testing, for example, fail to make it to market. Injecting potentially toxic drugs into living creatures, before eventually slaughtering them, also raises ethical concerns for some. Organoids, on the other hand, respond to infectious diseases, or potential treatments, in a way that is relevant to humans, in addition to being slaughter-free.
Human intestinal organoids infected with SARS-CoV-2 (white).
Credit: Joep Beumer/Clevers group/Hubrecht Institute
Urgency Sparked Momentum
Though brain organoids were previously used to study the Zika virus during the 2015-16 epidemic, it wasn't until COVID-19 that the field really started to change. "The organoid field has advanced a lot in the last year. The speed at which it happened is crazy," says Shuibing Chen, an associate professor at Weill Cornell Medicine in New York. She adds that many federal and private funding agencies have now seen the benefits of organoids, and are starting to appreciate their potential in the biomedical field.
Last summer, the Organo-Strat (OS) network—a German network that uses human organoid models to study COVID-19's effects—received 3.2 million euros in funding from the German government. "When the pandemic started, we became aware that we didn't have the right models to immediately investigate the effects of the virus," says Andreas Hocke, professor of infectious diseases at the Charité Universitätsmedizin in Berlin, Germany, and coordinator of the OS network. Hocke explained that while the World Health Organization's animal models showed an "overlap of symptoms'' with humans, there was "no clear reflection" of the same disease.
"The network functions as a way of connecting organoid experts with infectious disease experts across Germany," Hocke continues. "Having organoid models on demand means we can understand how a virus infects human cells from the first moment it's isolated." Overall, OS aims to create infrastructure that could be applied to future pandemics. There are 28 sub-projects involved in the network, covering a wide assortment of individual organoids.
Cost, however, remains an obstacle to scaling up, says Chen. She says there is also a limit to what we can learn from organoids, given that they only represent a single organ. "We can add drugs to organoids to see how the cells respond, but these tests don't tell us anything about drug metabolism, for example," she explains.
A Related "Leaps" in Progress
One way to solve this issue is to use an organ-on-a-chip system. These are miniature chips containing a variety of human cells, as well as small channels along which functions like blood or air flow can be recreated. This allows scientists to perform more complex experiments, like studying drug metabolism, while producing results that are relevant to humans.
An organ-on-a-chip system.
Credit: Fraunhofer IGB
Such systems are also able to elicit an immune response. The FDA has even entered into an agreement with Wyss Institute spinoff Emulate to use their lung-on-a-chip system to test COVID-19 vaccines. Representing multiple organs in one system is also possible. Berlin-based TissUse are aiming to make a so-called 'human on a chip' system commercially available. But TissUse senior scientist Ilka Maschmeyer warns that there is a limit to how far the technology can go. "The system will not think or feel, so it wouldn't be possible to test for illnesses affecting these abilities," she says.
Some challenges also remain in the usability of organs-on-a-chip. "Specialized training is required to use them as they are so complex," says Peter Loskill, assistant professor and head of the organ-on-a-chip group at the University of Tübingen, Germany. Hocke agrees with this. "Cell culture scientists would easily understand how to use organoids in a lab, but when using a chip, you need additional biotechnology knowledge," he says.
One major advantage of both technologies is the possibility of personalized medicine: Cells can be taken from a patient and put onto a chip, for example, to test their individual response to a treatment. Loskill also says there are other uses outside of the biomedical field, such as cosmetic and chemical testing.
"Although these technologies offer a lot of possibilities, they need time to develop," Loskill continues. He stresses, however, that it's not just the technology that needs to change. "There's a lot of conservative thinking in biomedical research that says this is how we've always done things. To really study human biology means approaching research questions in a completely new way."
Even so, he thinks that the pandemic marked a shift in people's thinking—no one cared how the results were found, as long as it was done quickly. But Loskill adds that it's important to balance promise, potential, and expectations when it comes to these new models. "Maybe in 15 years' time we will have a limited number of animal models in comparison to now, but the timescale depends on many factors," he says.
Beumer, now a post-doc, was eventually allowed to return to the lab to develop his coronavirus model, and found working on it to be an eye-opening experience. He saw first-hand how his research could have an impact on something that was affecting the entire human race, as well as the pressure that comes with studying potential treatments. Though he doesn't see a future for himself in infectious diseases, he hopes to stick with organoids. "I've now gotten really excited about the prospect of using organoids for drug discovery," he says.
The coronavirus pandemic has slowed society down in many respects, but it has flung biomedical research into the future—from mRNA vaccines to healthcare models based on human biology. It may be difficult to fully eradicate animal models, but over the coming years, organoids and organs-on-a-chip may become the standard for the sake of efficacy -- and ethics.
Jack McGovan is a freelance science writer based in Berlin. His main interests center around sustainability, food, and the multitude of ways in which the human world intersects with animal life. Find him on Twitter @jack_mcgovan."