Here's What Happens When You Try to Scale Up Vaccine Production Too Quickly
WHY YOU SHOULD CARE
Jonas Salk's invention was a miracle. But it didn't go off without a hitch.
By Virat Markandeya
When Vladimir Putin announced that his own daughter had received what he touted as a functional COVID-19 vaccine (despite the skepticism of most of the rest of the world), it was seen as a sign of his confidence in the treatment. But he wasn’t the first person to use his family to instill confidence in a new, swiftly created vaccine’s audience. On April 12, 1955, when 40-year-old Jonas Salk — who admittedly was not an authoritarian leader but a respected scientist and future Presidential Medal of Freedom winner — took center stage at the University of Michigan to triumphantly declare that his vaccine’s trials had been successful, his young sons were in the audience. And, as newsreels of the day made clear, they’d all been early test subjects for the inoculation.
While polio had been the cause of multiple 20th century epidemics, Salk’s development process — just six years from lab discoveries to mass manufacture — was among the fastest in history.
In many ways, the polio vaccine effort of the 1950s was Warp Speed 1, says Paul Offit, a professor of vaccinology at the University of Pennsylvania, referring to the Trump administration’s initiative to produce a COVID-19 vaccine today.
Polio, caused by a virus, was a seasonal scourge that spawned a U.S. epidemic in 1952. There were roughly 57,000 cases, of which about 5 percent died and more than a third of the sufferers were paralyzed. The vaccine trial was managed by the National Foundation for Infantile Paralysis, which had been founded 15 years earlier by President Franklin D. Roosevelt, who himself suffered from polio.
That afternoon of April 12, licenses to commercially produce the vaccine were recommended for six companies: Eli Lilly, Parke-Davis, Wyeth, Pitman-Moore, Sharp & Dohme and Cutter Laboratories. Of these, Eli Lilly and Parke-Davis had already been manufacturing the vaccine for the trial of over 1.8 million children, of which several hundred thousand received the polio vaccine in a placebo-controlled, double-blind study. The licensing process, as Offit wrote in a commentary for the New England Journal of Medicine in 2005, only took two-and-a-half hours. The vaccine had been produced at risk by the companies, in anticipation of a successful vaccine trial. Even before the vaccine was approved, the Foundation had ordered $9 million worth in order to have enough ready to go by the 1956 polio season.
The Salk vaccine was what’s known as an inactivated vaccine, which means it used an effectively dead version of the poliovirus to induce an appropriate immune response — technology still used today in shots for rabies and flu, and currently being tested in at least one coronavirus vaccine candidate undergoing phase three trials. The Salk vaccine used three types of poliovirus, including the Mahoney strain, known to be particularly deadly but it also produced the strongest immune response. As long as the virus used in the vaccine was dead, it wouldn’t matter.
But just weeks later, reports of paralytic polio in children who’d received the inoculations began trickling in. On April 26, the director of the government’s Laboratory of Biologics Control, William Workman, received calls about five California children whose arms had become paralyzed — an indication that the vaccine was responsible, since paralysis of the legs is more common in polio victims. The vaccine at fault had been made by Cutter Laboratories, which had already administered 380,000 doses to first- and second-graders.
The next day, U.S. Surgeon General Leonard Scheele told Cutter Laboratories to recall its vaccine, which it did. On April 30, California suspended its polio vaccination program altogether, and by May 7 all polio vaccinations had been paused for a week by recommendation of the surgeon general. After that, the vaccine was gradually released during the spring, but confusion and fear caused inoculation rates to drop — adults could choose not to be vaccinated, and parents could opt out of having their kids inoculated — even in places where it was available and where Cutter vaccines weren’t used.
Eventually, what became known as the Cutter Incident caused 260 symptomatic cases of polio and 11 deaths. While the bulk of the blame went to Cutter, there were deaths connected to vaccine lots from Wyeth as well. The government report on the Cutter Incident that came out in August that year did not get to the bottom of what went wrong, and even concealed specifics of Cutter’s production process as “trade secrets.”
In retrospect, “it was obviously not just the Cutter Incident, it was the scale-up incident,” says Offit, who wrote The Cutter Incident: How America’s First Polio Vaccine Led to the Growing Vaccine Crisis. All the companies had trouble scaling up their manufacturing, though these problems were exacerbated at Cutter. Cutter did not abide by protocols on how long to treat the polio virus with formaldehyde to inactivate it based on Salk’s instruction, and concealed the fact that it had been unable to produce consistent lots of inactivated vaccine from both the government and other polio researchers. Because it used a less optimal filtration technique and the government safety tests were insufficiently rigorous, the situation was made worse.
Immediately following the Cutter Incident, a Poliomyelitis Surveillance Unit was set up in Atlanta, Georgia. The next month, the minimal requirements for manufacturing the polio vaccine were amended and continued to be updated as the science advanced. A permanent advisory group was also set up by the surgeon general to provide guidance in vaccine production and testing. The Laboratory of Biologics Control was reorganized, now coming under the National Institutes of Health.
“It was really the birth of vaccine regulation in the United States,” says Offit. “I think it was a seminal moment.”
After the Cutter Incident, 400 million doses of inactivated polio vaccine were distributed between 1955 and 1961 in the United States. None are known to have caused polio.
As multiple companies and governments rush toward a coronavirus vaccine, the difficulties of even a phase three trial have become apparent. AstraZeneca temporarily suspended its U.K. trial after a participant became ill. Other companies, like U.S. front-runner Moderna, rely on promising but untested vaccine technology called mRNA vaccines. For the Russian vaccine, Sputnik V, preliminary data has been questioned. But as the Cutter Incident shows, even after a successful phase three trial, there is reason to be cautious.
Offit is concerned about what the rush for a coronavirus vaccine will mean from a regulatory standpoint. The clearance for a vaccine in the United States will likely be through the Emergency Use Authorization Act, which raises new questions. “In that case, does the FDA have a lighter touch? Are they less rigorous in terms of their regulation?” he asks. “I don’t know, and I guess we’re going to find out. I hope we don’t find out the hard way.”
- Virat Markandeya, OZY AuthorContact Virat Markandeya