An overview of vaccine development production trials to deliveries.
Illustration by Nan Lee

On the morning of April 12, 1955, an epidemiologist named Thomas Francis, Jr., took the stage of the Rackham Auditorium, at the University of Michigan, in Ann Arbor. Short and portly, in his mid-fifties, with a long face and a close-clipped mustache, Francis was there to deliver a ninety-minute lecture on the vaccine field trial he had just completed. The trial had evaluated the efficacy of the poliovirus vaccine developed by Jonas Salk, a former postdoc in Francis’s lab.

An influenza researcher, Francis was known among scientists for his deft direction of complex flu-vaccine trials during the Second World War. He had taught Salk the techniques necessary for developing “killed virus” vaccines—shots in which large quantities of a virus are disabled in a formaldehyde solution, then introduced to the human immune system in order to prompt the production of antibodies. Today, no bioethics panel would allow Francis to run a safety trial for a vaccine developed by someone he knew so well. But rules were more relaxed back then—and, in any case, Francis’s reputation was so sterling that, as the Salk biographer Jane S. Smith has written, “even the most dedicated opponent of the new vaccine could never say a trial supervised by Francis was political, biased, or incomplete.”

Francis’s lecture was awaited breathlessly by the American public. Few diseases have inspired more fear than polio. During the first half of the twentieth century, summertime polio epidemics left wakes of paralysis and death behind them, forcing summer camps, movie theatres, and public pools to close. Newspapers regularly featured horrific images of children struggling to walk or breathe. Adults also suffered: after contracting the virus in 1921, when he was thirty-nine, Franklin D. Roosevelt was forced to use a wheelchair or leg braces for the rest of his life.

Roosevelt desperately wanted to eliminate polio, and, in 1938, during his second term as President, he founded the National Foundation for Infantile Paralysis (N.I.F.P.), with the goal of developing a vaccine. The foundation convened a strategy meeting at M-G-M studios, where the radio star Eddie Cantor proposed that every major radio show spend thirty seconds asking listeners to “send their dimes directly to the President at the White House”; the campaign, Cantor said, could be called the “March of Dimes.” Polio became the first disease to be fought through advertising and the mass media. During the next decade and a half, urged on by celebrity spokespeople and by pictures of “poster children” trapped in iron lungs or braces, more than two-thirds of Americans made contributions to the vaccine effort, often by dropping coins into cannisters carried door to door.

Now a phalanx of bulky television cameras focussed on Francis as he prepared to report on the efficacy of the vaccine. He had good news to share: to cheers from the audience, he explained that the Salk vaccine was sixty to seventy per cent effective against the most prevalent strain of poliovirus, and ninety per cent effective against the other, less common strains. All this had been shown through what was, at that time, the largest vaccine trial ever conducted.

All afternoon and evening, church bells rang out across America. People flooded into the streets, kissing and embracing; parents hugged their kids with joy and relief. Salk became an instant national hero, turning down the offer of a ticker-tape parade in New York City; President Dwight D. Eisenhower invited him to the White House and, later, asked Congress to award him a Congressional Gold Medal. That night, from the kitchen of a colleague’s house, Salk—whose name was being touted in newspapers, magazines, radio reports, and television news broadcasts around the world—gave his first network-TV interview to Edward R. Murrow, whose show “See It Now” had exposed the tactics of Senator Joseph McCarthy a year earlier. Blushing in admiration, Murrow asked the doctor, “Who owns the patent on this vaccine?” “The people,” Salk said, nobly. “There is no patent. Could you patent the sun?”

In the days that followed, schoolchildren were instructed by their teachers to write thank-you notes to Salk. Universities lined up to offer him honorary degrees. Millions of American doctors, nurses, and parents got down to the serious business of vaccinating their children against polio, using a shot they’d been anticipating for seventeen years.

To compare the springs of 1955 and 2021 is to see our own moment a little more clearly. In terms of scale, impact, and complexity, the coronavirus pandemic has vastly exceeded just about every contagious calamity in recent history, and the vaccines that are bringing it to an end are, by any measure, more scientifically impressive than the vaccines of the past. And yet, for many of us, it’s hard to feel the momentousness of the season through which we’re now living. Americans in the nineteen-fifties were unabashedly jubilant about the vanquishing of polio. But we are strangely uncertain in our celebration of our vaccines.

There are many reasons for our reticence. Americans in Francis’s time had spent decades waiting for a cure for polio; by 1954, when Francis began his vaccine field trial, more people knew about the Salk vaccine than could recite the full name of President Eisenhower. The development of our vaccines, by contrast, has unfolded in the course of a single, confusing pandemic year, from which we’re still reeling.

The clinical trials for the covid-19 vaccines involved tens of thousands of participants, but occurred mostly out of public view, and were seen mainly as technical exercises. But the Francis trial, once it started, was a subject of sustained, detailed public attention, in large part because it centered on children. Two million families, living in two hundred and seventeen locales, signed their kids up to be “Polio Pioneers”; like the fund-raising done through the March of Dimes, the trial was a shared, nationwide effort. (In the end, six hundred and fifty thousand kids ended up getting the vaccine during the trial; more than a million got a placebo.)

In 1955, there was just one polio vaccine. Americans today are receiving one of three different covid-19 vaccines approved by the Food and Drug Administration. (More vaccines are being produced and tested in other countries.) The three vaccines on offer in the United States, manufactured by Pfizer, Moderna, and Johnson & Johnson, differ in how they are administered—one shot or two? Twenty-one or twenty-eight days apart?—and interested Americans find themselves examining the statistics for each, parsing the distinction between efficacy (a vaccine’s performance under ideal, experimental conditions) and effectiveness (its performance in the real world). People are asking themselves which one to take.

Just as there is no single vaccine, there is no singular medical hero to idolize. Anthony Fauci and others have done the important work of explaining the pandemic to the American people; Joe Biden has appointed a team of highly accomplished doctors, scientists, and administrators. But we have had no scientific figure along the lines of Jonas Salk to lead us forward; for the first year of the pandemic, the figure that loomed largest was Donald Trump. Trump’s primacy is emblematic of larger changes. In the nineteen-fifties, trust in science and political leadership was high, but our era is characterized by widespread distrust of government. Science is often seen as biased, and anti-vaxxers and political opportunists have turned vaccine hesitancy into a form of ideology.

Because of social distancing, there can be no parades to celebrate the covid-19 vaccines; we’re still waiting to embrace in the streets. The death toll continues to mount, and variants are spreading; many people, having spent a year inside, are living in a malaise of blunted feelings. These factors, too, dim our perception of the moment we’re experiencing.

None of this is to say that the story of the polio vaccine was all cheers and klieg lights. On the contrary, it was marred by two scandals. The first came immediately after Francis finished his remarks. Francis’s speech was the model of a major scientific announcement, but Salk, seated in the front row, was visibly unhappy. Forty years old, balding and bespectacled, he took the stage directly after Francis and set about arguing with the sixty, seventy, and ninety per cent efficacy rates that Francis had cited. The reason his vaccine wasn’t a hundred per cent effective against all three strains of poliovirus, Salk said, was that Merthiolate, a mercury-based preservative and antiseptic, had been added to it during the trial, against his wishes. Salk declared that the latest version of his new, Merthiolate-free vaccine “may lead to one hundred per cent protection from paralysis of all those vaccinated.”

Francis was furious. “What the hell did you have to say that for?” he bellowed, when Salk arrived backstage. “You’re in no position to claim one hundred per cent effectiveness.” Salk had speculated publicly about the efficacy of a version of the vaccine that hadn’t been tested; by criticizing Francis’s trial, he had also violated the rules of decorum that dominated science in the nineteen-fifties—he was seen as showboating. The anti-Semitism that was pervasive at that time may have contributed to the fact that many in the scientific establishment never forgave him. Although Salk was esteemed around the world—he would eventually run the Salk Institute for Biological Studies, situated on the cliffs of La Jolla, California—he never won the Nobel Prize and was never elected to the National Academy of Sciences. A decade after the event, he lamented, “I was not unscathed by Ann Arbor.”

The second scandal was far more alarming. The Eisenhower Administration allowed six pharmaceutical companies—Wyeth, Parke-Davis, Eli Lilly, Sharp & Dohme, Pitman-Moore, and Cutter Laboratories—to manufacture and profit from the Salk vaccine; to avoid shortages, these companies produced hundreds of millions of doses before the Francis trial was complete. In August, 1954, a vaccine scientist at the National Institutes of Health named Bernice Eddy reported several startling problems with the vaccines produced by Cutter Laboratories. One of Eddy’s chief tasks was injecting random samples of the vaccine into monkeys. “We started getting lots of paralyzed monkeys,” she said, of the Cutter vaccine. Eddy immediately reported the problem to her supervisor, but he failed to mention the report to anyone.

The next year, shortly after Francis’s Ann Arbor lecture, a biologist named Julius Youngner travelled to Berkeley, California, to inspect the Cutter plant. Youngner, who was Salk’s right-hand man, was astonished by how messy the labs were. Tanks containing live virus were kept in the same room as those containing inactive virus. When Youngner asked to review the company’s vaccine-production protocols, his request was denied, on the grounds that they were proprietary. (This was ironic, given that Youngner had helped to develop them.) Youngner explained the problems to Salk, who promised to inform the N.F.I.P. and N.I.H.; it’s unclear whether he did so.

In April, 1955, the Cutter vaccine was shipped out and injected into American children all over the Midwest. Within days, about seventy thousand of them developed mild polio. Two hundred were permanently paralyzed, and ten died. They were later found to have received vaccine doses that contained live poliovirus. In a subsequent class-action lawsuit, Cutter Laboratories was found financially liable but not negligent. In retrospect, the horrifying oversights at Cutter were equalled by the failures of communication among government officials and scientists. After a careful field trial, a hurried manufacturing and distribution process had turned out to be its own source of danger. A warning of sorts had been stencilled in block letters on every crate of polio vaccine manufactured by Cutter: “rush.”

In May, the polio vaccination drive was temporarily suspended. Leonard Scheele, the U.S. Surgeon General, inspected the facilities of all six vaccine companies and fired the government officials he considered to be culpable; the director of the N.I.H. and the Secretary of Health voluntarily resigned. New safety procedures were developed, including an improved means of filtering the viral mix just before the formaldehyde was added. Better tests were developed to detect live virus, and stricter record-keeping was instituted. The incident could have created a vaccine-hesitancy crisis. But, incredibly, the American public readily accepted the medical establishment’s explanation for the failure, and its pledges to right the situation. The nation’s trust in medical progress and in Dr. Salk was so resolute that, when it was announced that a new, safe polio vaccine was available, parents pushed their children back to the head of the line. It’s hard to imagine such an outcome today.

In early January, I received an e-mail informing me that, as a professor at the University of Michigan Medical School, I was deemed “essential” and was eligible to receive Pfizer’s two-dose vaccine. As a sixty-year-old man with many of the attendant health problems age confers, I felt as if I had won the lottery. When the appointed day came, I ventured out into the cold Ann Arbor morning and drove to the university’s football stadium, which is just a ten-minute walk from where Francis gave his 1955 talk.

After dousing my hands with liquid soap, I signed onto the vaccine line with my iPhone. As I waited, standing six feet from the person in front of me, I looked out through the windows of the skyboxes. The football field was covered in deep snow, obscuring the green carpet beneath it. The jumbotron scoreboard kept track of how many people had been vaccinated inside: I was number 13,863. As the line of masked people inched forward, I could barely contain my glee. During my career as a pediatrician, I had poked many children with needles; unlike them, I looked forward to getting the vaccine, and to getting on with life.

After the head nurse signed my official vaccination card, I was ushered into the area where the injections were given. Outside, the streets were empty, but everyone in that room—from the patients to the people administering the shots—was in a good mood and eager to partake of the wonders of modern science. The oddly festive occasion reminded me of the spring of 1963, when I was a three-year old toddler. I have the faintest memory of a day when my mother took me and my sister to the largest shopping mall in Detroit, where we could receive the Sabin oral polio vaccine. The Sabin vaccine was far more intricate and elegant than the Salk shot, and had taken another eight years to develop; it used a live-attenuated virus—a strain of poliovirus raised through multiple generations until it no longer caused disease—was easier to administer, and conferred lasting immunity. After a lengthy wait, I remember being given a little white cup containing a sugar cube with a greenish-brown liquid squirted onto it.

That cup was the best “shot” of my life, until I was injected with one of the new covid-19 vaccines, on January 8th. For more than four decades, I have been a medical historian and practiced pediatrics with a love for all things infectious. That moment—sitting in a skybox in an empty football stadium, feeling the sharp needle glide its way through my skin and into my muscle—was a high point of my life in medicine.

Especially for the unvaccinated and vulnerable, going out still isn’t a good idea. Until we reach herd immunity, the new, highly contagious viral variants make social distancing even more important. It’s hard, in short, to celebrate the covid-19 vaccines when we are still in the middle of a pandemic. But I hope that, week by week, as more and more people roll up their sleeves and get vaccinated, we will begin to believe in the reality of our generation’s medical miracle, which is ending a deadly pandemic that has gripped the world. It exceeds the one announced in the spring of 1955. Our church bells should ring out, too.