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.
Researchers advance drugs that treat pain without addiction
Opioids are one of the most common ways to treat pain. They can be effective but are also highly addictive, an issue that has fueled the ongoing opioid crisis. In 2020, an estimated 2.3 million Americans were dependent on prescription opioids.
Opioids bind to receptors at the end of nerve cells in the brain and body to prevent pain signals. In the process, they trigger endorphins, so the brain constantly craves more. There is a huge risk of addiction in patients using opioids for chronic long-term pain. Even patients using the drugs for acute short-term pain can become dependent on them.
Scientists have been looking for non-addictive drugs to target pain for over 30 years, but their attempts have been largely ineffective. “We desperately need alternatives for pain management,” says Stephen E. Nadeau, a professor of neurology at the University of Florida.
A “dimmer switch” for pain
Paul Blum is a professor of biological sciences at the University of Nebraska. He and his team at Neurocarrus have created a drug called N-001 for acute short-term pain. N-001 is made up of specially engineered bacterial proteins that target the body’s sensory neurons, which send pain signals to the brain. The proteins in N-001 turn down pain signals, but they’re too large to cross the blood-brain barrier, so they don’t trigger the release of endorphins. There is no chance of addiction.
When sensory neurons detect pain, they become overactive and send pain signals to the brain. “We wanted a way to tone down sensory neurons but not turn them off completely,” Blum reveals. The proteins in N-001 act “like a dimmer switch, and that's key because pain is sensation overstimulated.”
Blum spent six years developing the drug. He finally managed to identify two proteins that form what’s called a C2C complex that changes the structure of a subunit of axons, the parts of neurons that transmit electrical signals of pain. Changing the structure reduces pain signaling.
“It will be a long path to get to a successful clinical trial in humans," says Stephen E. Nadeau, professor of neurology at the University of Florida. "But it presents a very novel approach to pain reduction.”
Blum is currently focusing on pain after knee and ankle surgery. Typically, patients are treated with anesthetics for a short time after surgery. But anesthetics usually only last for 4 to 6 hours, and long-term use is toxic. For some, the pain subsides. Others continue to suffer after the anesthetics have worn off and start taking opioids.
N-001 numbs sensation. It lasts for up to 7 days, much longer than any anesthetic. “Our goal is to prolong the time before patients have to start opioids,” Blum says. “The hope is that they can switch from an anesthetic to our drug and thereby decrease the likelihood they're going to take the opioid in the first place.”
Their latest animal trial showed promising results. In mice, N-001 reduced pain-like behaviour by 90 percent compared to the control group. One dose became effective in two hours and lasted a week. A high dose had pain-relieving effects similar to an opioid.
Professor Stephen P. Cohen, director of pain operations at John Hopkins, believes the Neurocarrus approach has potential but highlights the need to go beyond animal testing. “While I think it's promising, it's an uphill battle,” he says. “They have shown some efficacy comparable to opioids, but animal studies don't translate well to people.”
Nadeau, the University of Florida neurologist, agrees. “It will be a long path to get to a successful clinical trial in humans. But it presents a very novel approach to pain reduction.”
Blum is now awaiting approval for phase I clinical trials for acute pain. He also hopes to start testing the drug's effect on chronic pain.
Learning from people who feel no pain
Like Blum, a pharmaceutical company called Vertex is focusing on treating acute pain after surgery. But they’re doing this in a different way, by targeting a sodium channel that plays a critical role in transmitting pain signals.
In 2004, Stephen Waxman, a neurology professor at Yale, led a search for genetic pain anomalies and found that biologically related people who felt no pain despite fractures, burns and even childbirth had mutations in the Nav1.7 sodium channel. Further studies in other families who experienced no pain showed similar mutations in the Nav1.8 sodium channel.
Scientists set out to modify these channels. Many unsuccessful efforts followed, but Vertex has now developed VX-548, a medicine to inhibit Nav1.8. Typically, sodium ions flow through sodium channels to generate rapid changes in voltage which create electrical pulses. When pain is detected, these pulses in the Nav1.8 channel transmit pain signals. VX-548 uses small molecules to inhibit the channel from opening. This blocks the flow of sodium ions and the pain signal. Because Nav1.8 operates only in peripheral nerves, located outside the brain, VX-548 can relieve pain without any risk of addiction.
"Frankly we need drugs for chronic pain more than acute pain," says Waxman.
The team just finished phase II clinical trials for patients following abdominoplasty surgery and bunionectomy surgery.
After abdominoplasty surgery, 76 patients were treated with a high dose of VX-548. Researchers then measured its effectiveness in reducing pain over 48 hours, using the SPID48 scale, in which higher scores are desirable. The score for Vertex’s drug was 110.5 compared to 72.7 in the placebo group, whereas the score for patients taking an opioid was 85.2. The study involving bunionectomy surgery showed positive results as well.
Waxman, who has been at the forefront of studies into Nav1.7 and Nav1.8, believes that Vertex's results are promising, though he highlights the need for further clinical trials.
“Blocking Nav1.8 is an attractive target,” he says. “[Vertex is] studying pain that is relatively simple and uniform, and that's key to having a drug trial that is informative. But the study needs to be replicated and frankly we need drugs for chronic pain more than acute pain. If this is borne out by additional studies, it's one important step in a journey.”
Vertex will be launching phase III trials later this year.
Finding just the right amount of Nerve Growth Factor
Whereas Neurocarrus and Vertex are targeting short-term pain, a company called Levicept is concentrating on relieving chronic osteoarthritis pain. Around 32.5 million Americans suffer from osteoarthritis. Patients commonly take NSAIDs, or non-steroidal anti-inflammatory drugs, but they cannot be taken long-term. Some take opioids but they aren't very effective.
Levicept’s drug, Levi-04, is designed to modify a signaling pathway associated with pain. Nerve Growth Factor (NGF) is a neurotrophin: it’s involved in nerve growth and function. NGF signals by attaching to receptors. In pain there are excess neurotrophins attaching to receptors and activating pain signals.
“What Levi-04 does is it returns the natural equilibrium of neurotrophins,” says Simon Westbrook, the CEO and founder of Levicept. It stabilizes excess neurotrophins so that the NGF pathway does not signal pain. Levi-04 isn't addictive since it works within joints and in nerves outside the brain.
Westbrook was initially involved in creating an anti-NGF molecule for Pfizer called Tanezumab. At first, Tanezumab seemed effective in clinical trials and other companies even started developing their own versions. However, a problem emerged. Tanezumab caused rapidly progressive osteoarthritis, or RPOA, in some patients because it completely removed NGF from the system. NGF is not just involved in pain signalling, it’s also involved in bone growth and maintenance.
Levicept has found a way to modify the NGF pathway without completely removing NGF. They have now finished a small-scale phase I trial mainly designed to test safety rather than efficacy. “We demonstrated that Levi-04 is safe and that it bound to its target, NGF,” says Westbrook. It has not caused RPOA.
Professor Philip Conaghan, director of the Leeds Institute of Rheumatic and Musculoskeletal Medicine, believes that Levi-04 has potential but urges the need for caution. “At this early stage of development, their molecule looks promising for osteoarthritis pain,” he says. “They will have to watch out for RPOA which is a potential problem.”
Westbrook starts phase II trials with 500 patients this summer to check for potential side effects and test the drug’s efficacy.
There is a real push to find an effective alternative to opioids. “We have a lot of work to do,” says Professor Waxman. “But I am confident that we will be able to develop new, much more effective pain therapies.”
In the 1990s, a mysterious virus spread throughout the Massachusetts Institute of Technology Artificial Intelligence Lab—or that’s what the scientists who worked there thought. More of them rubbed their aching forearms and massaged their cricked necks as new computers were introduced to the AI Lab on a floor-by-floor basis. They realized their musculoskeletal issues coincided with the arrival of these new computers—some of which were mounted high up on lab benches in awkward positions—and the hours spent typing on them.
Today, these injuries have become more common in a society awash with smart devices, sleek computers, and other gadgets. And we don’t just get hurt from typing on desktop computers; we’re massaging our sore wrists from hours of texting and Facetiming on phones, especially as they get bigger in size.
In 2007, the first iPhone measured 3.5-inches diagonally, a measurement known as the display size. That’s been nearly doubled by the newest iPhone 13 Pro, which has a 6.7-inch display. Other phones, too, like the Google Pixel 6 and the Samsung Galaxy S22, have bigger screens than their predecessors. Physical therapists and orthopedic surgeons have had to come up with names for a variety of new conditions: selfie elbow, tech neck, texting thumb. Orthopedic surgeon Sonya Sloan says she sees selfie elbow in younger kids and in women more often than men. She hears complaints related to technology once or twice a day.
The addictive quality of smartphones and social media means that people spend more time on their devices, which exacerbates injuries. According to Statista, 68 percent of those surveyed spent over three hours a day on their phone, and almost half spent five to six hours a day. Another report showed that people dedicate a third of their day to checking their phones, while the Media Effects Research Laboratory at Pennsylvania State University has found that bigger screens, ideal for entertainment purposes, immerse their users more than smaller screens. Oversized screens also provide easier navigation and more space for those with bigger hands or trouble seeing.
But others with conditions like arthritis can benefit from smaller phones. In March of 2016, Apple released the iPhone SE with a display size of 4.7 inches—an inch smaller than the iPhone 7, released that September. Apple has since come out with two more versions of the diminutive iPhone SE, one in 2020 and another in 2022.
These devices are now an inextricable part of our lives. So where does the burden of responsibility lie? Is it with consumers to adjust body positioning, get ergonomic workstations, and change habits to abate tech-related pain? Or should tech companies be held accountable?
Kavin Senapathy, a freelance science journalist, has the Google Pixel 6. She was drawn to the phone because Google marketed the Pixel 6’s camera as better at capturing different skin tones. But this phone boasts one of the largest display sizes on the market: 6.4 inches.
Senapathy was diagnosed with carpal and cubital tunnel syndromes in 2017 and fibromyalgia in 2019. She has had to create a curated ergonomic workplace setup, otherwise her wrists and hands get weak and tingly, and she’s had to adjust how she holds her phone to prevent pain flares.
Recently, Senapathy underwent an electromyography, or an EMG, in which doctors insert electrodes into muscles to measure their electrical activity. The electrical response of the muscles tells doctors whether the nerve cells and muscles are successfully communicating. Depending on her results, steroid shots and even surgery might be required. Senapathy wants to stick with her Pixel 6, but the pain she’s experiencing may push her to buy a smaller phone. Unfortunately, options for these modestly sized phones are more limited.
These devices are now an inextricable part of our lives. So where does the burden of responsibility lie? Is it with consumers like Senapathy to adjust body positioning, get ergonomic workstations, and change habits to abate tech-related pain? Or should tech companies be held accountable for creating addictive devices that lead to musculoskeletal injury?
Kavin Senapathy, a freelance journalist, bought the Google Pixel 6 because of its high-quality camera, but she’s had to adjust how she holds the oversized phone to prevent pain flares.
Kavin Senapathy
A one-size-fits-all mentality for smartphones will continue to lead to injuries because every user has different wants and needs. S. Shyam Sundar, the founder of Penn State’s lab on media effects and a communications professor, says the needs for mobility and portability conflict with the desire for greater visibility. “The best thing a company can do is offer different sizes,” he says.
Joanna Bryson, an AI ethics expert and professor at The Hertie School of Governance in Berlin, Germany, echoed these sentiments. “A lot of the lack of choice we see comes from the fact that the markets have consolidated so much,” she says. “We want to make sure there’s sufficient diversity [of products].”
Consumers can still maintain some control despite the ubiquity of tech. Sloan, the orthopedic surgeon, has to pester her son to change his body positioning when using his tablet. Our heads get heavier as they bend forward: at rest, they weigh 12 pounds, but bent 60 degrees, they weigh 60. “I have to tell him, ‘Raise your head, son!’” she says. It’s important, Sloan explains, to consider that growth and development will affect ligaments and bones in the neck, potentially making kids even more vulnerable to injuries from misusing gadgets. She recommends that parents limit their kids’ tech time to alleviate strain. She also suggested that tech companies implement a timer to remind us to change our body positioning.
In 2017, Nan-Wei Gong, a former contractor for Google, founded Figur8, which uses wearable trackers to measure muscle function and joint movement. It’s like physical therapy with biofeedback. “Each unique injury has a different biomarker,” says Gong. “With Figur8, you are comparing yourself to yourself.” This allows an individual to self-monitor for wear and tear and strengthen an injury in a way that’s efficient and designed for their body. Gong noticed that the work-from-home model during the COVID-19 pandemic created a new set of ergonomic problems that resulted in injuries. Figur8 provides real-time data for these injuries because “behavioral change requires feedback.”
Gong worked on a project called Jacquard while at Google. Textile experts weave conductive thread into their fabric, and the result is a patch of the fabric—like the cuff of a Levi’s jacket—that responds to commands on your smartphone. One swipe can call your partner or check the weather. It was designed with cyclists in mind who can’t easily check their phones, and it’s part of a growing movement in the tech industry to deliver creative, hands-free design. Gong thinks that engineers at large corporations like Google have accessibility in mind; it’s part of what drives their decisions for new products.
Display sizes of iPhones have become larger over time.
Sourced from Screenrant https://screenrant.com/iphone-apple-release-chronological-order-smartphone/ and Apple Tech Specs: https://www.apple.com/iphone-se/specs/
Back in Germany, Joanna Bryson reminds us that products like smartphones should adhere to best practices. These rules may be especially important for phones and other products with AI that are addictive. Disclosure, accountability, and regulation are important for AI, she says. “The correct balance will keep changing. But we have responsibilities and obligations to each other.” She was on an AI Ethics Council at Google, but the committee was disbanded after only one week due to issues with one of their members.
Bryson was upset about the Council’s dissolution but has faith that other regulatory bodies will prevail. OECD.AI, and international nonprofit, has drafted policies to regulate AI, which countries can sign and implement. “As of July 2021, 46 governments have adhered to the AI principles,” their website reads.
Sundar, the media effects professor, also directs Penn State’s Center for Socially Responsible AI. He says that inclusivity is a crucial aspect of social responsibility and how devices using AI are designed. “We have to go beyond first designing technologies and then making them accessible,” he says. “Instead, we should be considering the issues potentially faced by all different kinds of users before even designing them.”