Early results of the Covid-19 vaccine trials sponsored by Pfizer, Moderna, and AstraZeneca are welcome news. We appreciate the urgency of getting these newly developed coronavirus vaccines out to millions of Americans and potentially billions of people around the world.
We also know all too well the tragic story of a rushed polio vaccine.
We know this story because of our personal connections with Paul Meier, a young statistician at Johns Hopkins in the 1950s who studied the polio vaccine program of 1955 and its aftermath. He was the father of one of the authors (D.E.M.), father-in-law of another (R.S.M.), and mentor of another (C.B.).
The missteps that resulted in 40,000 unnecessary vaccine-induced polio infections are being repeated today. Failure to invest in safety and quality as well as speed has the potential to harm many people and further erode the nation’s faith in science and public health.
Meier, who died in 2011, was the chair of statistics at the University of Chicago and later at Columbia University. He was one of the first and most vocal proponents of what is today the gold standard for studies of new drugs and vaccines, the now-ubiquitous randomized controlled trial. Working with mathematician Edward Kaplan, they developed the Kaplan-Meier estimator, which is now used throughout medicine to estimate patient survival.
By the early 1950s, polio paralyzed 13,000 to 20,000 children every year. Pressure for a vaccine was overwhelming. Virologist Jonas Salk began work on a vaccine in 1953 under the assumption that if the body was presented with a vaccine containing “killed” polio virus, it would create antibodies protecting it from live polio virus. The trick was to inactivate the live virus just enough so it could not cause infection, but not so much as to destroy its structure and prevent antibody production. Within two years, Salk’s vaccine went from development to field testing in nearly 2 million children.
On April 12, 1955, Salk’s vaccine was declared to be safe and effective. Within three hours of this announcement, the federal government granted licenses to five pharmaceutical companies to begin producing the vaccine. Thanks to political pressure, mass vaccine production, dissemination, and inoculation began on April 13.
Within days there were reports of post-vaccine paralysis. Even as the number of children who developed polio after getting the vaccine grew, repeated assurances of safety by the vaccine developers combined with minimal federal oversight allowed polio vaccination to continue for an additional three weeks.
When the surgeon general finally stopped vaccinations on May 6, 1955, 40,000 children had developed vaccine-induced polio, 200 were paralyzed, and 10 had died. Salk’s inactivation method had been used incorrectly by several manufacturers, and 200,000 children had received vaccines containing live poliovirus.
Meier’s analysis of the vaccine program’s failure is a cautionary tale for coronavirus. Writing in Science magazine in May 1957, he noted that government leadership accepted without question the Salk laboratory’s assertion that the vaccine was “absolute[ly] safe.” He critiqued the elimination of safeguards in the rush to fast-track production. He uncovered the fact that a vaccine manufacturer hid relevant safety data from the public. He concluded that if an independent monitoring program had existed, the manufacturing flaws might have been identified before distribution or, at worst, the program could have been halted when the first cases of vaccine-induced polio were reported.
Mounting pressures to rapidly deliver coronavirus vaccines could overwhelm the steps required to ensure their safety. We need to ensure that the procedures that had been skipped in 1955, leading to 40,000 children developing polio, do not happen with Covid-19 vaccines.
How to make sure that doesn’t happen? The original data from the ongoing Covid-19 vaccine trials should be verified by independent experts. The FDA must have oversight and testing of the manufacturing processes. The FDA must not, as currently planned, eliminate inspections of manufacturing plants before issuing a vaccine emergency use authorization — exactly what Pfizer and Moderna are planning to request. Once vaccine distribution begins, there must be rigorous monitoring and side effect reporting, since vaccine trials, even those as large as Moderna’s and Pfizer’s, can never be large enough to identify all rare side effects. The National Vaccine Program Office, which once provided this oversight, was dismantled by the Trump administration last year. It needs to be reinstated.
Vaccines work only if people agree to get them. Acceptance of Covid-19 vaccines requires the public to trust the assurances of scientists, physicians, and governments that they are safe. In 1955, the public lost faith both in the polio vaccine and in those who had assured them of its safety and effectiveness. This public distrust of science and vaccinations persist to this day. Our ability to control the Covid-19 pandemic depends upon safe and effective vaccines and preventing further erosion of this trust.
Paul Meier knew the consequences of bad science and failed oversight. He also knew that when science is done correctly, the outcomes can be transformative. Polio vaccine research and production reopened with the much stronger safety regulations and scientific oversight that he had advocated for. When Diane was old enough for her vaccine, her father walked her to school to get one of the first doses of the recently released Sabin “live” oral polio vaccine. They stood in line in the school cafeteria for her vaccine sugar cube, a daughter trusting her father, her father trusting in science.
Polio is a thing of the past.
Diane E. Meier is professor and R. Sean Morrison is professor and chair of the department of geriatrics and palliative medicine at the Icahn School of Medicine at Mount Sinai in New York. Chris Barker is a statistician and former student of Paul Meier.