Unethical Guatemalan study may undermine recruitment, trust

'For people who are skeptical, this [could] turn them further away'

Research sites that work with minority, international, or vulnerable populations should be particularly sensitive to continuing fall-out from recent revelations of strikingly unethical behavior by U.S. researchers in Guatemala in the 1940s.

The research world was rattled in October by the announcement that the U.S. Public Health System sponsored a study, from 1946 to 1948, where investigators purposely infected Guatemalans with sexually-transmitted diseases (STDs) and hid the research's true knowledge from them.

This latest chapter in the world's dark history of unethical research projects raises issues that are relevant in today's globalized clinical trial world, experts say.

"When I first heard the news of the Guatemalan study I felt that I wished I had been more surprised," says James Lavery, MSc, PhD, research scientist at St. Michael's Hospital in Toronto, Canada.

"Surely we've made progress over all these years, but have we really come to a clear understanding of what it means to be respectful of the communities we do research on?" Lavery says. "I'm not convinced that we have."

For instance, when western researchers conduct trials that involve the collection and use of human tissue in a developing part of the world, they often make decisions about how this will be done based on input from the local community's authorities and ministries of health, rather than talking to people in the community, he explains.

"The communities try to be polite and are good hosts, but they don't voice their concerns enough," Lavery says. "And when the trial is over, what is left is a residual distrust in a community; people are unhappy and believe the researchers' actions were disrespectful."

Global researchers likely will encounter some skepticism or questions about the Guatemalan study as they pursue trials in resource-poor areas. But the key will be to educate the public about the protections put into place.

The IRB system was established in 1974 by Congress with the National Research Act, and federal human subjects research regulations followed in the early 1980s, says Robert J. Levine, MD, professor of medicine and a lecturer in pharmacology at the Yale University School of Medicine in New Haven, CT. Levine also is a senior fellow in bioethics at the Yale Interdisciplinary Center for Bioethics, which he co-founded.

Both safeguards have been enormously successful in preventing research abuses as grievous as what occurred in the 1960s and earlier, Levine says.

"Since that time, all of our major news stories about unethical incidents in research have been about studies from the distant past," he adds.

"The Advisory Commission on Atomic Radiation Experiments reviewed the whole field and found nothing that looked bad that occurred after 1974, which was the year Congress established the IRB system," he explains.

Tuskegee parallels

The Guatemalan study has several parallels to the 40-year Tuskegee syphilis study, including the fact that the two studies shared at least one investigator, John Charles Cutler, MD, who was a central figure in both. Cutler died in 2003.

In the Tuskegee research, African American men were not told what the study was for or that they had been diagnosed with syphilis. When the study began in 1932, there were no accepted treatments of the disease. But the research continued well past 1947 when clinicians were using antibiotics to cure syphilis. The Tuskegee researchers did not offer any treatment to the men enrolled in the study, even as late as 1972 when national media reports caused public outcry and forced federal officials to close the study.

In the Guatemalan study, prisoners, soldiers, people with mental illness, and other marginalized members of the community were unknowingly infected with syphilis and other STDs for the purpose of studying whether antibiotics could prevent infection. The study never answered the question and might have remained buried and hidden from public view if it had not been for the work of Wellesley College historian Susan Reverby who discovered the archives and brought them to public attention. Top officials with President Barack Obama's administration quickly denounced the research and apologized to the Guatemalan people.

One of the ironies of the recent disclosure is that for decades there has been distrust among some members of the African American community toward researchers, particularly in light of the Tuskegee experiment. And one of the undercurrents of that distrust has been the circulation of rumors that U.S. Public Health officials intentionally infected the Tuskegee men with syphilis, says Alex Capron, a professor at the University of Southern California in Los Angeles, CA. Capron also is a professor of law and medicine at the Keck School of Medicine, and he's the Scott H. Bice Chair in Healthcare Law, Policy and Ethics and co-director of the Pacific Center for Health Policy and Ethics.

"And now we know that Dr. Cutler was intentionally infecting people in Guatemala," Capron says. "So the main effect of the Guatemalan study might be that we see a conflation of those two things in people's minds."

The revelation might revive the Tuskegee rumors and increase concern among potential research subjects, he adds.

"The fact that as soon as this was discovered and revealed it was denounced by the president and Secretary of Health and Human Services and the Secretary of State with official apologies being made will differentiate it from the Tuskegee situation which took a long time before the government actually apologized to the victims," Capron says. "Those actions make it less of a festering situation."

American subjects infected

Observers looking at Guatemalan study revelation have speculated that researchers went outside the United States to avoid scrutiny of their research practices. But the cold truth is that U.S. investigators had been injecting American subjects with diseases for years, Levine says.

"Researchers induced malaria by injecting malaria parasites into our prisoners," he says. "There was great justification for this during World War II when our enemies took over places where natural anti-malarial agents were grown and we had to develop synthetic anti-malarials."

The researchers chose Guatemala more for the country's lax attitude toward letting sex workers visit prisoners, an environmental condition they thought would make it easier to study STD transmission, he adds.

The United States research community's history of using human subjects in these ways is a source of shame, but it wasn't limited to international studies, he says.

"The current stories of what happened in Guatemala don't have historical perspective," Levine adds.

So the key way to handle any anticipated fallout from the news is to educate communities – both domestic and international – about how federal regulations and local IRBs have been very effective in preventing these types of research abuses for 30-plus years.

Still, it's possible that American Hispanics will find news about the Guatemalan experiment relevant toward their attitudes about health care and research.

"I don't know if this will have an impact on current patient willingness to be a research participant," says Scott J. Lipkin, DPM, CIP, an associate vice president of research for LeHigh Valley Health Network in Allentown, PA.

"Perhaps for people who are skeptical, this will turn them further away from research," Lipkin adds. "But most people are intelligent enough to understand that this happened a long time ago, and there have been a lot of changes since it happened."