Sixty years ago, on April 12, 1955, in Ann Arbor, Michigan, the results of the largest clinical trial in history were announced. To the tremendous relief of a hopeful nation, Thomas Francis Jr., MD, revealed that the Salk inactivated poliomyelitis vaccine was “safe, effective, and potent” against paralytic polio.
The trial had begun in April 1954 when the first of about 1.8 million first- , second-, and third-graders began their participation as vaccine recipients (about 422,000), placebo recipients (about 201,000), observed control subjects (about 725,000), and non-injected second-graders (about 500,000) (see the official report on the trial for details on the study design). Injections, observations, and data collection continued through the spring, and then the information was handed over to Francis’s team for analysis.
Francis had been silent in the months leading up to the announcement about the results of the trial. Only he and his team knew that in the experimental arm of the trials, reductions in paralytic polio were incontrovertible when compared with both observed and injected controls.
The media fanfare was tremendous; television announcers and newspaper trumpeted the results. And the hope and celebration wasn’t just limited to the immediate problem of polio; the announcement seemed to signal the inevitability of future advancements. As the University of Michigan press release said, “There can be no doubt that humanity can pull itself up from its own bootstraps and protect its children from the insidious invasion of ultramicroscopic disease.”
April 12 1955 announcement from March of Dimes
In his book Polio: An American Story, David Oshinsky notes that the jubilant reaction to the trial result didn’t quite match the degree of effectiveness demonstrated in some aspects of the test. Specifically, while the vaccine was highly effective against paralytic disease caused by Types 2 and 3 polioviruses, the vaccine was only 60% to 70% effective against disease caused by Type 1 poliovirus. Salk alluded to this gap in his remarks that day, and claimed that the more recent version of the vaccine he’d been working on would be more effective, perhaps even 100% effective.
What Salk didn’t talk about that day was his simmering anger that NIH representatives on the trial design committee had successfully demanded that a preservative be added to the experimental vaccine to reduce the risk of bacterial contamination. Salk had opposed the addition on the grounds that the vaccine was to be used immediately, and so contamination wasn’t a threat. He warned that the vaccine might be weakened by the addition of the preservative. Indeed, this seemed to be the case: Salk himself tested several lots of the vaccine used in the trial and found that it lost potency. He thought this accounted for the lower effectiveness of the Type 1 vaccine. The vaccine released after the trial for general use — which was approved for licensure just two hours after the press conference — did not use the preservative Salk had objected to. Chapter 12 of Oshinky’s book provides an interesting depiction of this behind-the-scenes drama.
Of course, the next month brought news of a tragic failure — some lots of the vaccine were contaminated with live virus that the manufacturing methods failed to inactivate.
Over the past few years, scores of participants in the 1954 vaccine trials have posted comments on this blog. Many recall being afraid both of getting the shots and of getting polio, and many remember friends and family members who became ill with polio. Memory can be tricky: several people remembered getting the polio “drops” in this trial – though the oral vaccine, in liquid form, would not be used for several more years. They are most likely remembering being revaccinated with the oral vaccine later because of its better immunogenicity.
Most of the participants I’ve corresponded with take pride in their role in the trial. But some of them question the methods used to enroll children in the trial and remark on the changes we’ve seen since the 1950s in the ethical considerations that guide medical research.
Information on the Salk polio vaccine announcement is here.