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.
A Rare Disease Just "Messed with the Wrong Mother." Now She's Fighting to Beat It Once and For All.
Amber Freed felt she was the happiest mother on earth when she gave birth to twins in March 2017. But that euphoric feeling began to fade over the next few months, as she realized her son wasn't making the same developmental milestones as his sister. "I had a perfect benchmark because they were twins, and I saw that Maxwell was floppy—he didn't have muscle tone and couldn't hold his neck up," she recalls. At first doctors placated her with statements that boys sometimes develop slower than girls, but the difference was just too drastic. At 10 month old, Maxwell had never reached to grab a toy. In fact, he had never even used his hands.
Thinking that perhaps Maxwell couldn't see well, Freed took him to an ophthalmologist who was the first to confirm her worst fears. He didn't find Maxwell to have vision problems, but he thought there was something wrong with the boy's brain. He had seen similar cases before and they always turned out to be rare disorders, and always fatal. "Start preparing yourself for your child not to live," he had said.
Getting the diagnosis took months of painful, invasive procedures, as well as fighting with the health insurance to get the genetic testing approved. Finally, in June 2018, doctors at the Children's Hospital Colorado gave the Freeds their son's diagnosis—a genetic mutation so rare it didn't even have a name, just a bunch of letters jammed together into a word SLC6A1—same as the name of the mutated gene. The mutation, with only 40 cases known worldwide at the time, caused developmental disabilities, movement and speech disorders, and a debilitating form of epilepsy.
The doctors didn't know much about the disorder, but they said that Maxwell would also regress in his development when he turned three or four. They couldn't tell how long he would live. "Hopefully you would become an expert and educate us about it," they said, as they gave Freed a five-page paper on the SLC6A1 and told her to start calling scientists if she wanted to help her son in any way. When she Googled the name, nothing came up. She felt horrified. "Our disease was too rare to care."
Freed's husband, a 6'2'' college football player broke down in sobs and she realized that if anything could be done to help Maxwell, she'd have be the one to do it. "I understood that I had to fight like a mother," she says. "And a determined mother can do a lot of things."
The Freed family.
Courtesy Amber Freed
She quit her job as an equity analyst the day of the diagnosis and became a full-time SLC6A1 citizen scientist looking for researchers studying mutations of this gene. In the wee hours of the morning, she called scientists in Europe. As the day progressed, she called researchers on the East Coast, followed by the West in the afternoon. In the evening, she switched to Asia and Australia. She asked them the same question. "Can you help explain my gene and how do we fix it?"
Scientists need money to do research, so Freed launched Milestones for Maxwell fundraising campaign, and a SLC6A1 Connect patient advocacy nonprofit, dedicated to improving the lives of children and families battling this rare condition. And then it became clear that the mutation wasn't as rare as it seemed. As other parents began to discover her nonprofit, the number of known cases rose from 40 to 100, and later to 400, Freed says. "The disease is only rare until it messes with the wrong mother."
It took one mother to find another to start looking into what's happening inside Maxwell's brain. Freed came across Jeanne Paz, a Gladstone Institutes researcher who studies epilepsy with particular interest in absence or silent seizures—those that don't manifest by convulsions, but rather make patients absently stare into space—and that's one type of seizures Maxwell has. "It's like a brief period of silence in the brain during which the person doesn't pay attention to what's happening, and as soon as they come out of the seizure they are back to life," Paz explains. "It's like a pause button on consciousness." She was working to understand the underlying biology.
To understand how seizures begin, spread and stop, Paz uses optogenetics in mice. From words "genetic" and "optikós," which means visible in Greek, the optogenetics technique involves two steps. First, scientists introduce a light-sensitive gene into a specific brain cell type—for example into excitatory neurons that release glutamate, a neurotransmitter, which activates other cells in the brain. Then they implant a very thin optical fiber into the brain area where they forged these light-sensitive neurons. As they shine the light through the optical fiber, researchers can make excitatory neurons to release glutamate—or instead tell them to stop being active and "shut up". The ability to control what these neurons of interest do, quite literally sheds light onto where seizures start, how they propagate and what cells are involved in stopping them.
"Let's say a seizure started and we shine the light that reduces the activity of specific neurons," Paz explains. "If that stops the seizure, we know that activating those cells was necessary to maintain the seizure." Likewise, shutting down their activity will make the seizure stop.
Freed reached out to Paz in 2019 and the two women had an instant connection. They were both passionate about brain and seizures research, even if for different reasons. Freed asked Paz if she would study her son's seizures and Paz agreed.
To do that, Paz needed mice that carried the SLC6A1 mutation, so Freed found a company in China that created them to specs. The company replaced a mouse SLC6A1 gene with a human mutated one and shipped them over to Paz's lab. "We call them Maxwell mice," Paz says, "and we are now implanting electrodes into them to see which brain regions generate seizures." That would help them understand what goes wrong and what brain cells are malfunctioning in the SLC6A1 mice—and help scientists better understand what might cause seizures in children.
Bred to carry SLC6A1 mutation, these "Maxwell mice" will help better understand this debilitating genetic disease. (These mice are from Vanderbilt University, where researchers are also studying SLC6A1.)
Courtesy Amber Freed
This information—along with other research Amber is funding in other institutions—will inform the development of a novel genetic treatment, in which scientists would deploy a harmless virus to deliver a healthy, working copy of the SLC6A1 gene into the mice brains. They would likely deliver the therapeutic via a spinal tap infusion, and if it works and doesn't produce side effects in mice, the human trials will follow.
In the meantime, Freed is raising money to fund other research of various stop-gap measures. On April 22, 2021, she updated her Milestone for Maxwell page with a post that her nonprofit is funding yet another effort. It is a trial at Weill Cornell Medicine in New York City, in which doctors will use an already FDA-approved drug, which was recently repurposed for the SLC6A1 condition to treat epilepsy in these children. "It will buy us time," Freed says—while the gene therapy effort progresses.
Freed is determined to beat SLC6A1 before it beats down her family. She hopes to put an end to this disease—and similar genetic diseases—once and for all. Her goal is not only to have scientists create a remedy, but also to add the mutation to a newborn screening panel. That way, children born with this condition in the future would receive gene therapy before they even leave the hospital.
"I don't want there to be another Maxwell Freed," she says, "and that's why I am fighting like a mother." The gene therapy trial still might be a few years away, but the Weill Cornell one aims to launch very soon—possibly around Mother's Day. This is yet another milestone for Maxwell, another baby step forward—and the best gift a mother can get.
Lina Zeldovich has written about science, medicine and technology for Popular Science, Smithsonian, National Geographic, Scientific American, Reader’s Digest, the New York Times and other major national and international publications. A Columbia J-School alumna, she has won several awards for her stories, including the ASJA Crisis Coverage Award for Covid reporting, and has been a contributing editor at Nautilus Magazine. In 2021, Zeldovich released her first book, The Other Dark Matter, published by the University of Chicago Press, about the science and business of turning waste into wealth and health. You can find her on http://linazeldovich.com/ and @linazeldovich.
This virtual event convened leading scientific and medical experts to address the public's questions and concerns about Covid-19 vaccines in kids and teens. Highlight video below.
DATE:
Thursday, May 13th, 2021
12:30 p.m. - 1:45 p.m. EDT
Dr. H. Dele Davies, M.D., MHCM
Senior Vice Chancellor for Academic Affairs and Dean for Graduate Studies at the University of Nebraska Medical (UNMC). He is an internationally recognized expert in pediatric infectious diseases and a leader in community health.
Dr. Emily Oster, Ph.D.
Professor of Economics at Brown University. She is a best-selling author and parenting guru who has pioneered a method of assessing school safety.
Dr. Tina Q. Tan, M.D.
Professor of Pediatrics at the Feinberg School of Medicine, Northwestern University. She has been involved in several vaccine survey studies that examine the awareness, acceptance, barriers and utilization of recommended preventative vaccines.
Dr. Inci Yildirim, M.D., Ph.D., M.Sc.
Associate Professor of Pediatrics (Infectious Disease); Medical Director, Transplant Infectious Diseases at Yale School of Medicine; Associate Professor of Global Health, Yale Institute for Global Health. She is an investigator for the multi-institutional COVID-19 Prevention Network's (CoVPN) Moderna mRNA-1273 clinical trial for children 6 months to 12 years of age.
About the Event Series
This event is the second of a four-part series co-hosted by Leaps.org, the Aspen Institute Science & Society Program, and the Sabin–Aspen Vaccine Science & Policy Group, with generous support from the Gordon and Betty Moore Foundation and the Howard Hughes Medical Institute.
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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.