Editors’ Notes: Mabel Rosenheck sketches out the historical lineages of human challenge trials, such as those which might be conducted to find a COVID-19 vaccine.
In April, I expressed my willingness to be deliberately infected with the coronavirus as a participant in a human challenge trial (HCT) for a vaccine to COVID-19. I am one among tens of thousands who have done so. Rather than testing a vaccine under real world conditions where a participant may or may not contract the virus—and thus the treatment may or may not ever be tested—an HCT assures infection, speeding up and reducing the scale of the process. This could mean faster approval, manufacture, and distribution of a life-saving vaccine. Normally, medical ethics would argue that it is not ethical to risk someone’s life in this way without any benefit to them. Medical experiments should attempt to cure diseases, not cause them.
But what if the benefit to society at large is as big as this could be? What if consent is informed and the participant, rather than the researcher alone, has agency over their decision? What if participation is based on the altruism of the volunteer, rather than the self-interest of researchers? Might it be ethical then? Even more than being simply ethical, under these circumstances, a human challenge trial could represent selfless and compassionate voluntarism that contributes to individual and social well-being, as well as to science itself. Just as people might donate blood or give time and money during a crisis, so might we be allowed to give our health and our bodies.
From Informed Consent to Participation
The touchstone in medical ethics and the history of human testing is the Tuskegee Syphilis Experiment that operated from 1932-1972 in Macon County, Alabama at the Tuskegee Institute. That experiment was not a human challenge trial, but it did help establish the principles of medical ethics, power, and coercion which are central to the question of HCTs today. In brief, the Tuskegee Experiment was an observational, non-therapeutic study run by the US Public Health Service (PHS) to investigate the progression of syphilis among Black men. While the 600 research subjects were not intentionally infected with syphilis by the PHS, the PHS did lie to them about their status and about the purpose of the experiment. Then even once penicillin emerged as a reliable treatment for the disease, the men were denied the potentially lifesaving therapy.
Tuskegee is a landmark because of the scale of what took place, because it was so egregiously coercive, unethical, and racist, and because of the public response that emerged once medical professionals, activists, and the press uncovered the experiment in the 1960s. It is also a landmark because it catalyzed the formal regulation of human testing, experimentation, and clinical trials. By creating an ethical framework for even the most extreme forms of testing—like a COVID challenge trial—these regulations assure that medical research can be a form of service like blood or organ donation. However, there were debates about these issues earlier in the century. Medical historian Susan Lederer’s research demonstrates that many of those conversations in the United States were driven by anti-vivisection societies, as well as by concerns over whether it was ever ethical for children to be experimented on, even with the consent of their parents. Indeed, the language of the late 19th and early 20th century focused on whether such children could be considered “volunteers” for medical experiments.
In 1947 judges at the International Military Tribunal included a set of codes—now known as the Nuremberg Codes—in their verdict for the war crimes of doctors and others involved in medical experiments at Nazi concentration camps. That verdict coined the term “informed consent.” However, it wasn’t until the 1970s when Congress investigated the Tuskegee Experiment that ethical standards were formalized in the United States. Institutional Review Boards were established in 1974. Then in 1976, a division of the Department of Health, published the Belmont Report which formally outlined basic principles of respect, beneficence, and justice for all research subjects.
These principles, along with IRBs and mechanisms that assure informed consent and voluntary participation, are what make an ethical human challenge trial possible. The history of medical abuses like those at Tuskegee are reminders that medical research and the practice of human testing has deep ties to racism, injustice, and the continued mistrust of the healthcare industry, particularly among Black people. However, they are also reminders that because of the legislative reaction to the coercion involved in that experiment and others, including some funded by private philanthropy, we have a framework through which subjects can volunteer to participate in research in a just and equitable manner. We have a mechanism not just to check the ambitions of scientists, philanthropic foundations, drug companies, and the state, but also to enable volunteers to offer themselves in service of the greater good and the benefit of others.
The early history of the human challenge trial, at least in Europe and the United States, has a history more like that of Tuskegee than of modern clinical trials that obtain informed consent. In 1796, English physician Edward Jenner vaccinated his gardener’s son—an eight-year-old named James Phipps—and then deliberately infected him with smallpox to test the vaccine’s effectiveness. The child’s ability to consent is dubious both because of his age, a common concern in human testing, but also because of his father’s status as Jenner’s employee, which might have led the father to be reluctant to challenge his employer’s wishes.
In the United States, Thomas Jefferson recreated this experiment in 1801, vaccinating one of the Black people he enslaved, then infecting him with smallpox in order to prove that the treatment worked. Only after the experiment’s success did Jefferson perform the procedure on his family. This kind of infection and experimentation on another’s body is unquestionably a gross abuse of power that is tied to other acts like the medical dehumanization of Black people as at Tuskegee.
If the human challenge trial is tied to a history of racism, abuse, and objectification, it also embodies a white, Eurocentric history of medical innovation that celebrates elite, white male scientists and the heroic service of noble research subjects. Think of Jonas Salk and the “Polio Pioneers.” In 1954, the parents of two million American children signed them up to test the vaccine that they were told could save thousands of lives each year. Those children did not face the risk that comes with intentional infection, but they were celebrated by magazines like Time and Newsweek for their voluntary service. The press, with help from the marketing machinery of the March of Dimes, showed them doing their part and contributing to the scientific effort to eradicate a deadly disease. Even decades later, many recalled that contribution with pride. In many ways, this episode has more in common with emerging attitudes towards a COVID HCT—at least attitudes among potential volunteers—than does the longer history of human testing and its abuses. HCT volunteers today, much like the Polio Pioneers of 1954, combine voluntary service with optimism in the power of science and trust in the medical industry that are likely rooted in race and class privilege.
HCT volunteers also share something in common with others who are dedicated not just to public service, but to acting in service of science as a body of knowledge that will help save lives. When I think of my participation in an HCT, I think less of the parallel to organ donation or blood donation, though certainly as a way of acting in times of crisis, blood donation is a relevant practice. Instead, what I think of is those who “donate their bodies to science” after they die. I certainly think of helping thousands of people by accelerating development of a vaccine, but I also think of volunteering for an HCT as a contribution, a service, to scientific knowledge itself.
In this, I have something in common with doctors who use themselves for experimentation because they do not want to risk the lives of others until more is known. One well known example is that of the US Army Yellow Fever Commission—a research team, rather than one engaged in combat—led by Dr. Walter Reed. When stationed in Cuba in 1900, members of the Commission infected themselves with Yellow Fever to prove that mosquitoes were the intermediate host needed to cause the disease. Jesse William Lazear, one of the self-experimenters who later died of the infection, was described as a martyr by the surgeon general and as having “manly and fearless devotion to duty” by Reed himself.
Similarly, in Peru, Daniel Carrion is celebrated as a hero for having infected himself with verruga Peruana in 1885 to show that one kind of bacteria could cause two diseases. There is now a monument to him in Lima. Describing Carrion, Lawrence Altman, a physician and journalist, writes: “Once he had made the decision that experimentation on a human was necessary, he must have asked himself: On whom? Carrion answered that question in the only way his conscience would allow: Myself.” Jesse Lazear and Daniel Carrion seem to say: If I can take the risk for the benefit of others, I will do so in service of science and humanity. The same sentiment is echoed among volunteers for a COVID HCT.
These are some of the broader histories and big questions that elucidate the unique stakes of a human challenge trial, especially one for a COVID-19 vaccine. The stories of HCT volunteers today echo these narratives of risk and altruistic service. Today’s volunteers, people like me, want to help the global community, and we believe that our service to scientific research is worthwhile. If the history of a COVID vaccine and the history of a human challenge trial for it is ever written, our stories of service and sacrifice could be granted prominent positions—especially if the trial is successful. It will be especially true if we are white and if we fit ourselves into these pre-established narratives. Our racial privilege is key to our willingness to volunteer because most of us have been taught throughout our lives that we can trust the medical system and that we are included in the medical discourse that tells these heroic stories about itself. We are volunteering our service to a system designed to include us and to serve us and, I suspect, to tell our stories as noble ones, not ones of foolish risk or unknowing exploitation. Volunteering for an HCT does represent a risk, but it is a risk for a system we have faith in and that has faith in us.
Making this kind of service and its benefits accessible to all requires work to build trust among communities that have been harmed by science and medicine. However, in Medical Apartheid, a history of experimentation on Black Americans, Harriet Washington closes with optimism that some of the most egregious abuses of the past have incited change. She encourages more Black people to participate in medical research both for the benefit of medical treatment generally, and for the benefit of Black communities that have unique health care needs which are often the product of environmental racism and racism in health care. In theory, volunteering to be study subjects could force the medical field to recognize and address its structural biases. Similarly, in the book and film How to Survive a Plague, David France chronicles queer activism around participation in development, testing, and distribution of AIDS medication in the 1980s and 1990s, activism that led to real change in AIDS treatment, but also in the operation of the FDA and other institutions involved in medical research. An HCT is certainly different because of the risk involved in infection among otherwise healthy subjects—experimental AIDS treatments were often a last resort for dying men.
Yet the reasons people are volunteering and the ethics through which the voluntarism is justified provide discourses of medical and bodily agency that are useful in thinking more broadly about participation in science and medicine as an active subject, rather than as a passive object, in the health and health care of one’s community.
Mabel Rosenheck is a writer, lecturer, and public historian in Philadelphia. She can be found online at www.mabelrosenheck.com.
 Susan Reverby. Examining Tuskegee: The Infamous Syphilis Study and Its Legacy (Chapel Hill: University of North Carolina Press, 2009).
 Susan E. Lederer. Subjected to Science: Human Experimentation in America Before the Second World War. (Baltimore: Johns Hopkins University Press, 1995).
 Some of the other well-known experiments that investigated infectious diseases by intentionally infecting subjects were Dr. Mark Boyd’s malaria trials for the Rockefeller Institute in the 1930s, US Army experiments at Stateville Prison during World War II, the Public Health Service syphilis experiments in Guatemala in the 1940s, and the hepatitis studies at Willowbrook State Hospital in the 1950s. These, also, were not technically challenge trials because they were observational and not testing a treatment.
 Harriet A. Washington. Medical Apartheid (New York: Penguin Random House, 2017), 60-61.
 Rebecca Herzig. Suffering for Science: Reason and Sacrifice in Modern America (New Brunswick, NJ: Rutgers University Press, 2005).
 Lawrence K. Altman. Who Goes First?: The Story of Self-Experimentation in Medicine. (New York: Random House. 1987), 5.