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.
Life is Emerging: Review of Siddhartha Mukherjee’s Song of the Cell
The DNA double helix is often the image spiraling at the center of 21st century advances in biomedicine and the growing bioeconomy. And yet, DNA is molecularly inert. DNA, the code for genes, is not alive and is not strictly necessary for life. Ought life be at the center of our communication of living systems? Is not the Cell a superior symbol of life and our manipulation of living systems?
A code for life isn’t a code without the life that instantiates it. A code for life must be translated. The cell is the basic unit of that translation. The cell is the minimal viable package of life as we know it. Therefore, cell biology is at the center of biomedicine’s greatest transformations, suggests Pulitzer-winning physician-scientist Siddhartha Mukherjee in his latest book, The Song of the Cell: The Exploration of Medicine and the New Human.
The Song of the Cell begins with the discovery of cells and of germ theory, featuring characters such as Louis Pasteur and Robert Koch, who brought the cell “into intimate contact with pathology and medicine.” This intercourse would transform biomedicine, leading to the insight that we can treat disease by thinking at the cellular level. The slightest rearrangement of sick cells might be the path toward alleviating suffering for the organism: eroding the cell walls of a bacterium while sparing our human cells; inventing a medium that coaxes sperm and egg to dance into cellular union for in vitro fertilization (IVF); designing molecular missiles that home to the receptors decorating the exterior of cancer cells; teaching adult skin cells to remember their embryonic state for regenerative medicines.
Mukherjee uses the bulk of the book to elucidate key cell types in the human body, along with their “connective relationships” that enable key organs and organ systems to function. This includes the immune system, the heart, the brain, and so on. Mukherjee’s distinctive style features compelling anecdotes and human stories that animate the scientific (and unscientific) processes that have led to our current state of understanding. In his chapter on neurons and the brain, for example, he integrates Santiago Ramon y Cajal’s meticulous black ink sketches of neurons into Mukherjee’s own personal encounter with clinical depression. In one lucid section, he interviews Dr. Helen Mayberg, a pioneering neurologist who takes seriously the descriptive power of her patients’ metaphors, as they suffer from “caves,” “holes,” “voids,” and “force fields” that render their lives gray. Dr. Mayberg aims to stimulate patients’ neuronal cells in a manner that brings back the color.
Beyond exposing the insight and inventiveness that has arisen out of cell-based thinking, it seems that Mukherjee’s bigger project is an epistemological one. The early chapters of The Song of the Cell continually hint at the potential for redefining the basic unit of biology as the cell rather than the gene. The choice to center biomedicine around cells is, above all, a conspicuous choice not to center it around genes (the subject of Mukherjee’s previous book, The Gene), because genes dominate popular science communication.
This choice of cells over genes is most welcome. Cells are alive. Genes are not. Letters—such as the As, Cs, Gs, and Ts that represent the nucleotides of DNA, which make up our genes—must be synthesized into a word or poem or song that offers a glimpse into deeper truths. A key idea embedded in this thinking is that of emergence. Whether in ancient myth or modern art, creation tends to be an emergent process, not a linearly coded script. The cell is our current best guess for the basic unit of life’s emergence, turning a finite set of chemical building blocks—nucleic acids, proteins, sugars, fats—into a replicative, evolving system for fighting stasis and entropy. The cell’s song is one for our times, for it is the song of biology’s emergence out of chemistry and physics, into the “frenetically active process” of homeostasis.
Re-centering our view of biology has practical consequences, too, for how we think about diagnosing and treating disease, and for inventing new medicines. Centering cells presents a challenge: which type of cell to place at the center? Rather than default to the apparent simplicity of DNA as a symbol because it represents the one master code for life, the tension in defining the diversity of cells—a mapping process still far from complete in cutting-edge biology laboratories—can help to create a more thoughtful library of cellular metaphors to shape both the practice and communication of biology.
Further, effective problem solving is often about operating at the right level, or the right scale. The cell feels like appropriate level at which to interrogate many of the diseases that ail us, because the senses that guide our own perceptions of sickness and health—the smoldering pain of inflammation, the tunnel vision of a migraine, the dizziness of a fluttering heart—are emergent.
This, unfortunately, is sort of where Mukherjee leaves the reader, under-exploring the consequences of a biology of emergence. Many practical and profound questions have to do with the ways that each scale of life feeds back on the others. In a tome on Cells and “the future human” I wished that Mukherjee had created more space for seeking the ways that cells will shape and be shaped by the future, of humanity and otherwise.
We are entering a phase of real-world bioengineering that features the modularization of cellular parts within cells, of cells within organs, of organs within bodies, and of bodies within ecosystems. In this reality, we would be unwise to assume that any whole is the mere sum of its parts.
For example, when discussing the regenerative power of pluripotent stem cells, Mukherjee raises the philosophical thought experiment of the Delphic boat, also known as the Ship of Theseus. The boat is made of many pieces of wood, each of which is replaced for repairs over the years, with the boat’s structure unchanged. Eventually none of the boat’s original wood remains: Is it the same boat?
Mukherjee raises the Delphic boat in one paragraph at the end of the chapter on stem cells, as a metaphor related to the possibility of stem cell-enabled regeneration in perpetuity. He does not follow any of the threads of potential answers. Given the current state of cellular engineering, about which Mukherjee is a world expert from his work as a physician-scientist, this book could have used an entire section dedicated to probing this question and, importantly, the ways this thought experiment falls apart.
We are entering a phase of real-world bioengineering that features the modularization of cellular parts within cells, of cells within organs, of organs within bodies, and of bodies within ecosystems. In this reality, we would be unwise to assume that any whole is the mere sum of its parts. Wholeness at any one of these scales of life—organelle, cell, organ, body, ecosystem—is what is at stake if we allow biological reductionism to assume away the relation between those scales.
In other words, Mukherjee succeeds in providing a masterful and compelling narrative of the lives of many of the cells that emerge to enliven us. Like his previous books, it is a worthwhile read for anyone curious about the role of cells in disease and in health. And yet, he fails to offer the broader context of The Song of the Cell.
As leading agronomist and essayist Wes Jackson has written, “The sequence of amino acids that is at home in the human cell, when produced inside the bacterial cell, does not fold quite right. Something about the E. coli internal environment affects the tertiary structure of the protein and makes it inactive. The whole in this case, the E. coli cell, affects the part—the newly made protein. Where is the priority of part now?” [1]
Beyond the ways that different kingdoms of life translate the same genetic code, the practical situation for humanity today relates to the ways that the different disciplines of modern life use values and culture to influence our genes, cells, bodies, and environment. It may be that humans will soon become a bit like the Delphic boat, infused with the buzz of fresh cells to repopulate different niches within our bodies, for healthier, longer lives. But in biology, as in writing, a mixed metaphor can cause something of a cacophony. For we are not boats with parts to be replaced piecemeal. And nor are whales, nor alpine forests, nor topsoil. Life isn’t a sum of parts, and neither is a song that rings true.
[1] Wes Jackson, "Visions and Assumptions," in Nature as Measure (p. 52-53).
Twice a day, morning and night, I use a neti pot to send a warm saltwater solution coursing through one nostril and out the other to flush out debris and pathogens. I started many years ago because of sinus congestion and infections and it has greatly reduced those problems. Along with vaccination when it became available, it seems to have helped with protecting me from developing Covid-19 symptoms despite being of an age and weight that puts me squarely at risk.
Now that supposition of protection has been backed up with evidence from a solidly designed randomized clinical trial. It found that irrigating your sinuses twice a day with a simple saltwater solution can lead to an 8.5-fold reduction in hospitalization from Covid-19. The study is another example of recent research that points to easy and inexpensive ways to help protect yourself and help control the epidemic.
Amy Baxter, the physician researcher behind the study at Augusta University, Medical College of Georgia, began the study in 2020, before a vaccine or monoclonal antibodies became available to counter the virus. She wanted to be able to offer another line of defense for people with limited access to healthcare.
The nasal cavity is the front door that the SARS-CoV-2 virus typically uses to enter the body, latching on to the ACE2 receptors on cells lining those tissue compartments to establish infection. Once the virus replicates here, infection spreads into the lungs and often other parts of the body, including the brain and gut. Some studies have shown that a mouthwash could reduce the viral load, but any effect on disease progression was less clear. Baxter reasoned that reducing the amount of virus in the nose might give the immune system a better chance to react and control that growth before it got out of hand.
She decided to test this approach in patients who had just tested positive for Covid-19, were over 55 years of age, and often had other risk factors for developing serious symptoms. It was the quickest and easiest way to get results. A traditional prevention study would have required many more volunteers, taken a longer period of follow up, and cost money she did not have.
The trial enrolled 79 participants within 24 hours of testing positive for Covid-19, and they agreed to follow the regimen of twice daily nasal irrigation. They were followed for 28 days. One patient was hospitalized; a 1.27% rate compared with 11% in a national sample control group of similar age people who tested positive for Covid-19. Patients who strictly adhered to nasal irrigation had fewer, shorter and less severe symptoms than people in the study who missed some of their saline rinses.
Baxter initially made the results of her clinical trial available as a preprint in the summer of 2021 and was dismayed when many of the comments were from anti-vaxxers who argued this was a reason why you did not need to get vaccinated. That was not her intent.
There are several mechanisms that explain why warm saltwater is so effective. First and most obvious is the physical force of the water that sweeps away debris just as a rainstorm sends trash into a street gutter and down a storm drain. It also lubricates the cilia, small hair-like structures whose job it is to move detritus away from cells for expulsion. Cilia are rich in ACE2 receptors and keeping them moving makes it harder for the virus to latch on to the receptors.
It turns out the saline has a direct effect on the virus itself. SARS-CoV-2 becomes activated when an enzyme called furin snips off part of its molecular structure, which allows the virus to grab on to the ACE2 receptor, but saline inhibits this process. Once inside a cell the virus replicates best in a low salt environment, but nasal cells absorb salt from the irrigation, which further slows viral replication, says Baxter.
Finally, “salt improves the jellification of liquid, it makes better and stickier mucus so that you can get those virus out,” she explains, lamenting, “Nobody cares about snot. I do now.”
She initially made the results of her clinical trial available as a preprint in the summer of 2021 and was dismayed when many of the comments were from anti-vaxxers who argued this was a reason why you did not need to get vaccinated. That was not her intent. Two journals rejected the paper, and Baxter believes getting caught up in the polarizing politics of Covid-19 was an important part of the reason why. She says that editors “didn't want to be associated with something that was being used by anti-vaxxers.” She strongly supports vaccination but realizes that additional and alternative approaches also are needed.
Premeasured packets of saline are inexpensive and can be purchased at any drug store. They are safe to use several times a day. Say you’re vaccinated but were in a situation where you fear you might have been exposed to SARS-CoV-2; an extra irrigation will clear out your sinuses and may reduce the risk of that possible exposure.
Baxter plans no further study in this area. She is returning to her primary research focus, which is pain control and reducing opioid use, but she hopes that others will expand on what she had done.