Update: This article has been updated to clarify that the Tuskegee patients were not infected with syphilis by the researchers; they were, though, denied the standard treatment for the disease.
Tuskegee, Ala., will long be synonymous with unethical research practices after hundreds of African Americans there with syphilis were denied care over a period of 40 years so that researchers could study the progression of the disease. In October 2010, Wellesley College's Susan Reverby discovered that some of those same investigators performed similar work in Guatemala, deliberately infecting 1,300 soldiers, prisoners, and mental patients with syphilis, gonorrhea, or chancroid in experiments — conducted between 1946 and 1948 — that had been paid for in part with US federal research funds.
Reverby was researching the work of John Cutler, a Public Health Service and Tuskegee investigator, when, rather than finding more about his studies in Alabama, she discovered evidence of similar experiments in Guatemala. National Institutes of Health Director Francis Collins and Centers for Disease Control and Prevention Director Thomas Frieden later published an article in the Journal of the American Medical Association about the ethical violations that marked the Guatemalan experiments. The researchers failed to obtain valid informed consent from the participants, they intentionally infected people with a dangerous pathogen, and they deliberately deceived the participants about the research aim, Collins and Frieden wrote. The authors also alleged that Cutler and his colleagues knew what they were doing was unethical.
"While effective protections against unethical research continue to evolve across the world, the past exploitations of vulnerable populations, including the subjects of the study in Guatemala in the 1940s, are regrettable and deeply saddening," Collins and Frieden wrote. "The 1946 to 1948 inoculation study should never have happened, and nothing like it should ever happen again."
US President Barack Obama apologized to Guatemalan President Álvaro Colom for the experiments, and set the Presidential Commission for the Study of Bioethical Issues to the task of figuring out what went wrong and how to prevent the same thing from happening again. The commission published a preliminary report in September, calling the experiments "clearly and grievously wrong."
A compensation plan
Aside from simply finding that Cutler's work was unethical, the panel also made a recommendation that reawakened a debate about how research participants should be -treated. During a two-day public meeting held after the report's release, the panel recommended that the US create a system through which people harmed while participating in scientific research might be compensated for such. Many other countries have such systems, the panel pointed out, while the US leaves those who feel they've been victimized to file lawsuits, and relies on the tort system to compensate people.
The commission's recommendation is hardly new, says Robert Cook-Deegan, director of the Center for Genomics, Ethics, Law & Policy at Duke University. Going back to the mid-1970s, the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research — which was formed in the aftermath of the Tuskegee scandal — was the first bioethics commission to recommend that human -research participants be compensated for -injuries incurred during scientific research, he says. Since then, several different presidential commissions has, at some point or another, made the same recommendation to create a compensation system, though none has been implemented.
"It makes no sense that we haven't done something about it," Cook-Deegan says. "It's partly because it would require some appropriations, and you would have to put some money into a box — into a pot that doesn't have a constituency, because these are future victims — and so it never seems like it's an important enough thing to getting around to writing the legislation and setting aside some money." Although he says such a system is needed in the US, Cook-Deegan adds that it is unlikely anything will be done now, even with the new report out. "Probably every three or four years, someone pays attention to this, realizes there are these reports that have been accumulating dust and unimplemented recommendations, and they say, 'We should do something about it this time.' And then nothing happens," he says. "So I don't see why this would play out any differently, given the money this time would be trading off against very real needs that are very immediate, and against cuts in other agencies." Lawsuits are fine for partial recompense, but aren't always fair, he adds.
Parsing the issues
The issue may not be as simple as recompensing obvious victims of unethical experiments, like those in Tuskegee or Guatemala, however. Karen Maschke, a research scholar at the Hastings Center, says there are two compensation issues that need to be addressed if a reparations system is to be created: Victims such as those in Guatemala would fall in one category, and people who have sustained injuries during the course of ethically conducted research would be in another.
"I have mixed feelings about [a compensation system] because it's hard to separate, for me, the issue of someone saying at some point, 'These studies were unethical and therefore people should be compensated,' and is it just because it was unethical or because they were harmed, and then what was the nature of the harm?" Maschke says. "How would you separate that from someone who is in a clinical trial, who claims that the interventional drug or device that was used severely damaged or injured her — that, to me, is just as important in terms of compensation." Even if it's decided that both people harmed during clinical trials and victims of unethical scientific research should be compensated, the issue is going to be whether that should be done through a national system or specifically by the research sponsor, she adds.
In addition, Maschke says that "it's always going to come down to what's going to be the basic criteria for establishing that the trial actually caused some harm." Some argue that there isn't any empirical evidence to show that people are being harmed during clinical trials, Maschke says, and it would be hard to differentiate between harm from an experimental drug or device and the effects of a disease. "How do you separate out if you already have a horrible disease or end-stage cancer and you take an experimental drug, how can you argue that it was the drug that made you sicker or killed you?" Maschke says. "It's really hard to tease that out. So that's probably another reason why there hasn't been support for a compensation system."
In the meantime
Though it's unlikely that a national compensation system will be created in the near future, Maschke says a potential compromise is plausible. Study sponsors could be required to directly compensate people who claim they've been injured. However, that would still require some regulatory actions — such an -approach would require an objective, evidence-based way to determine whether avoidable harms have occurred as a result of an ethical lapse. "Probably what will happen is that there will be these ad hoc, every-now-and-then instances that will arise, like the Guatemalan studies," she adds. "I think for the large-scale ones it certainly makes sense to have to, at minimum, consider compensation and what that would look like. But the larger issue of compensation, particularly for genetic research, is the more challenging one. And that might come up in the future if people are in these highly innovative genetic studies. It's going to be interesting to see what happens."
Obama's bioethics commission is expected to release a full report on its findings and recommendations next month.