Guatemalan research travesty raises new questions for IRBs

'Worse than Tuskegee — these people were deliberately infected'

The recent shocking disclosure that U.S. public health officials sanctioned a study in Guatemala 64 years ago in which people were deliberately infected with sexually-transmitted diseases (STDs) for research purposes has brought home the message to IRBs that transparency is absolutely critical in human subjects research.

Top U.S. officials were quick to offer public apologies to Guatemala in October, 2010, after an historian found evidence that the U.S. Public Health Service was involved in experiments between 1946 and 1948 in which Guatemalan men and women were infected with syphilis or other STDs without their knowledge.

The shocking disclosure was eerily reminiscent of the Tuskegee syphilis study, and even more alarming was the announcement that one of the Guatemala study's investigators, John Charles Cutler, MD, was also involved in the Tuskegee research. Cutler died in 2003.

"The real issue here is that these communities were not treated as people in their own right," says James Lavery, MSc, PhD, a research scientist at St. Michael's Hospital in Toronto, Canada.

IRB and research officials find news of the Guatemalan study particularly disturbing because of its focus on using vulnerable populations without any sort of informed consent during an experiment in which they were deliberately and covertly infected.

"One of the sentinel events in the human subjects research history was the Tuskegee study, and this one seems worse than Tuskegee because these people were deliberately infected," says Brenda L. Ruotolo, CIP, associate director of the Columbia University IRB office in New York, NY.

"We went outside our country to find a convenient sample of people who were not capable of providing consent," she adds. "They were educationally-disadvantaged and more vulnerable than the average person."

Tuskegee parallels

The U.S. Public Health Service studied the effects of syphilis on African-American men from 1932 to 1972 at Macon County, AL, near Tuskegee. The men were examined regularly as part of the study, but they were never given treatment, even after 1947 when penicillin was widely accepted as a cure for the disease. In 1972, media reports and public outcry about the Tuskegee Syphilis Study led to the 1979 Belmont Report, the requirement of institutional review boards and the establishment of a federal office that oversees human subjects research. President Bill Clinton publicly apologized in 1997 to the surviving Tuskegee men who were subjects of the study.

The parallels to the Guatemalan study are disturbing: in the Guatemalan study, hundreds of prisoners, soldiers, and people with mental illness were intentionally infected with syphilis between 1946 and 1948. The research goal was to determine if a new antibiotic could prevent infection after exposure to the diseases, but the study ended without answering the question. A Wellesley College historian Susan Reverby discovered archives of the study and brought it to public attention. Secretary of State Hillary Clinton and Secretary of Health and Human Services Kathleen Sebelius both denounced the research in recent public statements.

One of the more troubling aspects of the Guatemalan study is that it took place during the time period in which the world was learning of the war crimes of Karl Brandt, Adolf Hitler's personal physician, who was convicted in 1947 at the Nuremberg trials for medical experimentation crimes. The result of that conviction was the Nuremberg Code, which has 10 principles with the first stating, "The voluntary consent of the human subject is absolutely essential."

While no IRB will want to compare the exploits of Nazi scientists with research conducted by U.S. researchers, the Guatemalan study demonstrates that breaches of research ethics can occur even in a nation that prides itself on respecting human rights.

"To me, the Guatemalan study story is a reminder that the rules and what we think of as standards in these are very far from self-executing," 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.

"Here you have people who were doing the work they were doing in a very brief period after the Nuremberg decision had been handed down and the Nuremberg Code created," he adds.

It's possible Cutler and other investigators involved in the Guatemalan study were unaware of the Nuremberg trial. Another researcher, Chester M. Southam, who in 1962 had injected cancer cells into 22 elderly patients at the Jewish Chronic Disease Hospital in Brooklyn, NY, had confessed to being unaware of the Nuremberg Code when he was up before the Board of Regents in New York for having his license suspended, Capron notes.

"Southam had a lot of prominent witnesses who testified in his defense that the practice of not telling people the truth of what you were doing in research was common practice," Capron says.

"He didn't want to tell patients he was injecting cancer cells into them because of the great fear and phobia about cancer," he adds. "So Southam rationalized that you don't tell people what you are putting in them because they'll be unduly upset, and that's more or less what was going on with Cutler in Guatemala."

The Guatemalan study disclosure brings home the point that this grievously unethical research was not some privately-funded, rogue endeavor, but an investigation sponsored by the U.S. government, Lavery says.

"People do beautiful deflection when they talk about the Tuskegee trials, which takes away from the U.S. government's stain of involvement," he adds. "But like Tuskegee, this study was a program of the U.S. Public Health Service; these were not rogue investigators."

The U.S. government's role in the study makes it even more imperative that IRBs and researchers address this 64-year-old ethical breach and make certain that today's research subjects know that safeguards are in place to prevent anything like this from happening again, experts say.

Be proactive on education

At least one IRB had discussed the Guatemalan study within a week of its announcement.

The IRB at LeHigh Valley Health Network in Allentown, PA, discussed the news at an October IRB meeting, says Scott J. Lipkin, DPM, CIP, an associate vice president of research for LeHigh Valley Health Network.

"It's kind of mind-boggling that this is just being uncovered now," Lipkin says. "I'm assuming that public outcry would have been just as vast and immense as what happened with Tuskegee if people had known about this back then."

IRBs need to think about how to incorporate this latest example of unethical research in their educational and training materials for new members.

"I've already updated my slides," Lipkin says. "I put this in a section after Nuremburg and before Tuskegee — basically bulleting the facts on the slide."

When the Guatemalan study is discussed with new IRB members, it's important to note that this experiment was not known by the general research community and the public until this year, he adds.

"We should explain that the regulations were written as a result of Tuskegee and not Guatemala," he says.

Experts say they are uncertain how much fallout will occur as a result of the Guatemalan study disclosure.

"It underscores the need for regulations," Ruotolo notes. "We assume people will do the right thing, but the right thing is different to different people."

When the public hears even dated comments, such as those reportedly made by Cutler about the Guatemalan experiments, that there are different rules for research, then this can create problems for researchers and IRBs.

"It can feed into the problem of how lay people understand research," Ruotolo says. "At Columbia, we are a major academic research institution that sits in the middle of a densely populated area, and our local population overall has a lack of balanced information about research."

The Columbia University area has populations of Spanish-speaking individuals, including people who are economically disadvantaged, and some of them might be hesitant to enroll in trials out of concern of being used like a guinea pig, she notes.

However, these same populations could find some benefits from being in the proximity of a major research institution, an opportunity that is not widely available to disadvantaged populations, she adds.

"We have an obligation to the community to get out there and provide the other side of it," Ruotolo adds. "People should be informed so they can make a decision, but they shouldn't write off all research participation."