Viruses are rarely mentioned in Intermediate Physics for Medicine and Biology. We do discuss them in the very first section of the book, when we talk about distances and scales. Perhaps we should say more, because viruses and their vaccines are such a hot topic today. Unfortunately, vaccines have become politically controversial. The science often seems to play a secondary role to politics.
Given the current controversy (justified or not) about the safety of vaccines, I thought it would be useful to consider one of the most famous and successful clinical trials: The 1954 trial of Jonas Salk’s polio vaccine. I base this discussion largely on Liza Dawson’s article “The Salk polio vaccine trial of 1954: Risks, randomization and public involvement in research” (Clinical Trials, 1:122–130, 2004).
This was a huge clinical trial, involving over a million children in 44 states. There were essentially two parts, or arms, in the trial. In one arm about 400,000 children in second grade were injected with either the vaccine or a placebo. This part was randomized and double-blind (neither the children, their parents, nor their doctors knew if they received the vaccine or a placebo). In the other arm, about a quarter million second graders received the vaccine, and their results were compared to about three quarters of a million “observed controls” in first and third grades who did not receive an injection.
The trial design had many controversies. First, Salk’s vaccine was based on a virus killed using chemicals. A competing virologist, Albert Sabin, created a vaccine based on an attenuated but live virus. Many medical doctors had concerns about safety, especially with a live virus. Although the implications of contracting polio were terrible, often leading to paralysis or life spent breathing in an iron lung, the incidence of polio in the general population was low. In that case, the safety of the vaccine must be extraordinarily high in order to justify its use. Moreover, the trial needed to be huge in order to have enough statistical power to provide reliable results. Salk had enough confidence in his initial results that he wondered if the use of a placebo was even ethical (an issue often raised today among vaccine advocates and opponents). However, most virologists (including Thomas Francis of the University of Michigan, who was recruited to oversee the study) insisted that at least part of the study include a placebo injection. There were three different strains of polio virus, and the vaccine had to protect against all three. Many epidemiologists worried about bias influencing the “controlled observation” arm of the study. This part was not randomized, and parents consenting to have the vaccine may have represented a subset of families with a different economic or educational background compared to the controls, which could be a confounding factor influencing the results. Above all, the trial would be conducted on children, heightening any ethical concerns.
Given the distrust of scientists and doctors that many have today, I was impressed by the public support for this trial. The number of polio cases was at its peak in the early 1950s,
and parents were terrified of the disease and desperate to
slow its spread. The trial was conducted with funding from the National Foundation for Infantile Paralysis (commonly known as the “March of Dimes”). Thousands of volunteers went door to door to raise over $40 million dollars, with the average donation being 27 cents. More than 200,000 lay volunteers helped with the trial, along with 60,000 doctors and nurses and 64,000 teachers and school principals. The study had no difficulty finding parents willing to sign up their children; about two thirds of the parents chose to have their kids participate. There was truly a national ownership of the trial. It was a time, unlike our own, when scientists and medical doctors were held in high regard.
Children received their vaccines between April 26 and June 15, 1954. Blood samples were taken from 40,000 children after inoculation to check for the production of antibodies. On April 12, 1955 the results were announced at the University of Michigan. The overall trial results were clearly positive for all three strains of polio. In the placebo part of the trial, about 200,000 children received the vaccine and another 200,000 the placebo, and roughly twice as many unvaccinated children contracted polio compared to vaccinated children (80 versus 160). A nationwide vaccination program began two weeks later. Within a decade, the number of deaths per year in the United States from polio dropped from about 1000 per year to about 10 per year. Now polio is nearly eradicated from the USA. Let’s do our best to keep it that way.
Celebrating 70 years of the Salk polio vaccine
