History Lesson: Vaccine Trials in the Classroom

One of the indelible images from the 1954 Jonas Salk polio vaccine trials is that of smiling, middle-class American schoolchildren eagerly lining up to be inoculated. Did these students’ families realize that the safety of the vaccine they were about to receive had been questioned by some of the country’s leading experts? The history of how schools have been used for vaccine trials goes well beyond polio and raises important questions about the evolution of research ethics. This month’s feature in a Public Health Then and Now by Schupmann (p. 1015), explores this story in depth, tracing it backward to diphtheria and forward to measles.

Historical discussions of research ethics raise three sets of questions. The easiest is that of whether the ethics of a particular trial in the past would pass by today’s standards (spoiler alert—the answer is always “no”). The second and third questions are more intriguing. Can a past clinical trial be judged as unethical by the standards of its own day? And how does knowing this history speak to research ethics today?

MEET TODAY’S STANDARDS?

From todays’ ethical standpoint, it can be argued that 20th century school-based vaccine trials targeting diphtheria, polio, and measles were relatively benign compared with the widespread practice at the time of carrying out research among institutionalized children.¹ Each of these examples followed initial (and certainly riskier) studies exploring efficacy and safety among just such vulnerable populations. Moreover, written consent was obtained from parents—something not to be assumed before the 1960s.

Nonetheless, as this article makes clear, the kind of consent described in these trials certainly took place in a setting of subtle but powerful forms of potential coercion. They occurred in the mid-20th century, when public health authorities were turning away from the strategy of compulsion (as had been the case with smallpox) to persuasion and mass immunization campaigns.² William Park found the cooperation of principals and teachers to be essential for recruiting families to his diphtheria vaccine studies. He was tapping into the well-established authority established by schools for monitoring and promoting health.³ The media excitement surrounding the Salk vaccine infused the 1954 field trials with the energy of a religious revival. This generated tremendous pressure on individual families to participate. There was no real effort to create a barrier between the consent process and these powerful influences. The consent forms were perfunctory and made little mention of potential risks. Such practices fall far short of today’s standards.

UNETHICAL BY THE STANDARDS OF ITS OWN DAY?

How ethical were these studies as judged by contemporary standards? Although legal standards guiding research ethics were essentially nonexistent at the time, sociologist Sydney Halpern has persuasively argued that early 20th century researchers worked within a framework of accepted moral norms and conventions.⁴ The foremost of these she calls the “lesser harms” tradition. An application of the ethical principal of beneficence to research, this condoned human experimentation when the likely benefit of preventing or treating a disease exceeded anticipated risks to the participants. Other common norms included the affirmation that experimentation needed to begin with animal models whenever possible and then be extended to humans through well-designed studies. These norms could be enforced by scientist-led moratoria. An example of this was virologist Simon Flexner’s promotion of a moratorium on polio vaccine research that effectively barred any clinical trials of polio vaccine (with two notable exceptions) for most of the first half of the 20th century.

Despite what we would consider shortcomings in obtaining consent, one suspects that Park and Salk considered the school-based clinical trials of their vaccines morally justifiable from this “lesser harms” vantage point. These trials addressed widely feared illnesses, using interventions that had been demonstrated to have raised no significant safety concerns in previous trials that used institutionalized children. Their study designs were within the wide range of what was accepted at the time.

Still, these risk–benefit assumptions were not beyond challenge. Diphtheria in the 1920s was indeed a deadly disease, but Park himself acknowledged that 80% to 85% of its mortality took place in the preschool period.⁵ It was simply much harder to conduct a large study among this population. In 1954, some of the leading polio experts in the country (notably Albert Sabin and John Enders) questioned the efficacy of Salk’s inactivation process and the decision of the March of Dimes to move from small studies to the inoculation of more than 600 000 schoolchildren in one year without addressing these concerns. ⁶ These fears proved to be justified when more than 200 children contracted polio from vaccine containing live virus in 1956, an incident blamed at the time on Cutter Pharmaceuticals, but eventually traced to Salk’s own inactivation process.⁷

HOW CAN THIS HISTORY SPEAK TO US?

Today’s emphasis on informed consent arose largely in response to abuses involving institutionalized and vulnerable populations. The ethical questions raised by the school vaccination trials of the mid-20th century were substantially different, and yet raise questions that remain troublesome. Put simply, it is not completely clear whether the public understood these projects to be experimental trials or community immunization campaigns. They had features of both. Indeed, it is not certain that investigators always understood the distinction. One senses that both Park and Salk had already been convinced that their new vaccines were safe and effective before their use in large school trials. That made it easy to justify consent processes that emphasized potential benefits over risks. And such optimism made it easy to see principals and media as allies who could recruit parents to their cause, rather than act as advocates for their students as human participants.

We now recognize the flaw in safeguarding the patient by relying solely upon the individual investigator’s commitment to beneficence. Federal law has responded by making informed consent the central pillar of human participant protection. Yet, as this article reminds us, informed consent always takes place in a context. Patients derive information from many sources—friends, physicians, teachers, principals, and, increasingly, pharmaceutical companies. Whether it is really possible to insulate a research participant from all outside influences may be doubted. Nor does a 20-page consent form necessarily lead to a better-informed patient. Informed consent is but one of the pillars of human participant protection, along with the others such as peer review and the integrity of the investigator. Balancing the goals of offering research participants opportunities while protecting them from harm requires strengthening all of these approaches and, indeed, developing new ones.