It was 60 years ago yesterday that the nation heaved an enormous collective sigh of relief. The largest clinical trial for a vaccine in history had concluded, the data had been collected and analyzed, and the results were announced on April 12, 1955, coincidentally the ten-year anniversary of polio sufferer Franklin D. Roosevelt’s death: Jonas Salk‘s inactivated polio vaccine was “safe, effective and potent.”
“People were hugging in the streets, kids were let out of school, Salk was invited to the White House where Eisenhower broke down in tears thanking him – it was really this shining moment of great faith in science and in medical research,” said David Oshinsky, the director of the Division of Medical Humanities at NYU Langone Medical Center and the Pulitzer-prize winning author of Polio: An American Story. “The nation went into this extraordinary, almost unprecedented celebration short of anything but the end of the world war.”
Later that afternoon, the federal government licensed the vaccine for use – the very same day the trial’s conclusions were announced.
“There was great pressure because the polio season was at hand,” Salk’s son, Peter Salk, M.D., president of the Jonas Salk Legacy Foundation, told me. Polio season generally started in May and ran through the summer. “People were terrified. This disease struck without warning, and there was no way of predicting who was going to get it and who wasn’t. The predominant effect of this announcement was a lifting of fear. It was seen as an absolute miracle and blessing.”
What many may not realize is that the polio vaccine was not Salk’s first. He was inspired to invent a vaccine with an inactivated virus, as opposed to a weakened, or attenuated, live virus, when he heard in a lecture during medical training that it couldn’t be done. “That was the dogma of the time,” his son said. But with his colleague Thomas Francis, Salk proved that dogma wrong by inventing the first inactivated viral vaccine – the influenza vaccine, the same one that gave rise to all of today’s inactivated flu vaccines. Then shortly after Salk took a position at the University of Pittsburgh, the March of Dimes approached him about beginning research on polio.
Salk began that research in 1948, discovered there were three strains, and had an experimental trivalent solution by 1952. During the first safety trials from May 1953 through March 1954, Salk administered the vaccine to more than 5,300 individuals, including himself, his wife and his three sons. No one experienced bad side effects, and blood tests revealed antibodies against the disease. The massive field trial began the following month with more than 1.8 million first, second and third graders – “Polio Pioneers” – in 44 states and well over a quarter million field volunteers. At an estimated cost of $7.5 million, the field trial was bankrolled by the March of Dimes with thousands of individual donations. (You might call it the first crowd-funded vaccine trial.)
Until the morning of April 12, Salk himself did not know the trial’s results, which his colleague Francis had completed and kept secret. Salk was nervous, his son said. “There had been a lot of pressure from the March of Dimes to make this a reality because it was such a hugely frightening disease,” Peter Salk explained. Among almost 52,000 cases in 1952, for example, 21,000 resulted in paralysis. In addition, the U.S. government had recommended at the last minute before the trial that Merthiolate be added to the vaccine. Popularly called “monkey blood” back then, this deep red liquid was a mercury and sodium tincture used by moms and grandmothers everywhere to kill bacteria on cuts and scrapes. Adding it to the vaccine would kill any bacteria or fungi in the vials. Today, this preservative is better known by its generic name, thimerosal. Salk had not had time to test the vaccine’s effectiveness with the preservative and worried about whether it would decrease the formulation’s immunogenicity, the ability to induce an immune response.
It turned out he had no cause for concern. Where the vaccine was compared against no vaccine, it was 60 to 80 percent effective against paralytic polio. When compared to the placebo (Medium 199, the solution used to grow the virus), the vaccine was 80 to 90 percent effective. No polio cases or fatal side effects occurred, and only a few allergic reactions occurred. Just six years later, the rate of polio had dropped 96 percent.
Dr. Jonas Salk is shown holding two bottles containing a culture used to grow the polio vaccines, in the 1950s. (AP Photo)
The incongruity between then and now is difficult to ignore.
“I think my father’s head would be spinning,” Salk said about some attitudes toward vaccines today. “Back then, people looked to science and scientists to be helping and creating things that we needed and wanted. The advent of the vaccine against polio was greeted with such relief, and the contrast couldn’t be greater with the way people are viewing vaccines today. To think of vaccines as being an intrusion instead of a blessing just wouldn’t be on par with the thinking those decades ago.”
Similarly, the idea that the FDA would license a vaccine on the very day its effectiveness and safety were announced is inconceivable today.
“You have to put it in historical context – suddenly there’s a vaccine that’s going to save tens of thousands of lives, and every parent wanted it now,” Oshinsky said. “They didn’t want to wait until another polio season – they wanted it now.” But rushing had its consequences. The high level of quality control Salk maintained when supervising production of the trial’s batches did not carry over to all six manufacturers licensed to make the vaccine: Eli Lilly, Parke-Davis, Pitman-Moore, Wyeth Laboratories and, infamously, Cutter Laboratories. At Cutter, Salk’s strict instructions regarding temperature, acidity in the medium for growing the virus, the amount of formaldehyde to neutralize the virus and other particulars were not followed. The field trial required 11 straight batches manufactured without a single live virus, but at Cutter, employees simply tossed in the trash any batches they suspected contained live viruses and hoped they caught them all. They didn’t.
The largest pharmaceutical disaster in history, the Cutter incident led to 120,000 doses inoculations containing a live polio virus. Five children died, 56 were paralyzed, and in the resulting outbreaks that occurred, another five died and 112 were paralyzed. Secretary of the U.S. Department of Health, Education and Welfare, Oveta Culp Hobby, and the director of the National Institutes of Health, William Sebrell, stepped down. The silver lining was in how quickly the federal government acted and in subsequently implemented safeguards. Cutter withdrew the vaccine April 27, weeks after its licensure, and multiple levels of government oversight still in place today were put into effect. “Since Cutter, we haven’t had a single case of contaminated polio vaccine,” Oshinsky said. “You needed a bureaucracy; you needed researchers to test these drugs more carefully during manufacturing.”
But the incident didn’t much dent Americans’ enthusiasm for the vaccine. “I think the disconnect now between some of the public and the medical community is much greater than it was then,” Oshinsky said. Particularly after Watergate and Vietnam, Americans lost faith in the government. That distrust has spread to medical authorities perceived as conspiring with pharmaceutical companies, Oshinsky said, and the Internet now offers hundreds of sites filled with misinformation about vaccines and other medical interventions.
Then, there is the success of the vaccine itself and others like it, leading to a loss of cultural memory, Peter Salk said. “Most of the people who are parents now didn’t go through that fear,” he said. “They don’t know firsthand what the world was like when these diseases were rampant.”
It’s that distrust of medical authorities that has made the home stretch of worldwide polio eradication challenging. Pockets of resistance in places like Pakistan and Nigeria, where some health workers have even been murdered, have held up the WHO’s eradication goals. Unlike smallpox symptoms, those of polio are not always visible in everyone carrying the virus, which means every person needs to be vaccinated. Then there is the decision about which vaccine to use – Salk’s inactivated (and safer) one (used in the U.S. and all high-income countries), or Albert Sabin‘s later live virus oral vaccine, which can be more effective at the population level but carries a risk of paralytic polio in about one of every 2.7 million doses. We are just at the tipping point where the number of vaccine-caused polio cases in the world is about on par with the number of wild virus polio cases.
“The time has come to make a change,” Peter Salk said. “Ultimately the oral [live] vaccine is going to have to be stopped if the virus is going to be eradicated.”
Until then, a simultaneous concern is that polio might ever return to countries where it has already been eliminated, as happened to Syria during its civil war. “On the one hand, I think Jonas Salk would be thrilled that the number of polio cases has dropped from 50,000 in the U.S. and untold numbers in the world to fewer than 1,000 in the world today,” Oshinsky said. “He has saved countless lives, and what could make a researcher prouder than that.”
On the other hand, Oshinsky added, he would probably be “astonished” that a parent would withhold something like a measles vaccine from their child. “I think he would be a little taken aback by the anti-vaccine movement and the damage it’s doing when we have all these vaccines to prevent childhood diseases,” he said. “I think he’d be worried, as many of us are, if herd immunity drops below a certain level, that polio could come back again.”