An exhaustive high-level review of unethical syphilis experiments conducted in Guatemala by U.S. researchers in the 1940s has found little to redeem the work or its lead researcher. The Presidential Commission for the Study of Bioethical Issues concluded that the study was shoddy scientifically and did not meet ethical standards at the time.
The 1946-48 experiments, in which U.S. Public Health Service researcher John Cutler deliberately infected hundreds of Guatemalan soldiers, prisoners, and mental health patients with sexually transmitted diseases, were first revealed by a Wellesley College historian last October. They have been compared to the infamous Tuskegee, Alabama, study in which African Americans with syphilis were observed but not treated. Cutler, who died in 2003, was also involved in that study from 1932 to 1972. President Barack Obama asked his bioethics commission to investigate last fall.
The commission's staff members spent 9 months digging through and reviewing more than 125,000 archival documents. The commission conducted "a careful and unvarnished ethical analysis" of what happened, said chair Amy Gutmann, president of the University of Pennsylvania, at a meeting yesterday in Washington, D.C.
The panel found a compelling context for the experiments: Sexually transmitted diseases were rampant among returning World War II veterans. Soldiers at risk were told to apply various prophylactic treatments, and Cutler wanted to find out if penicillin worked better. He and others took blood and other fluid samples, including spinal taps, from more than 5000 patients in Guatemala, without their consent. An overlapping group of more than 1300 patients were exposed to syphilis, gonorrhea, or chancroid by inoculation or contact with prostitutes. Fewer than 700 got some form of treatment.
The Guatemala project violated ethical norms of the day, the panel found, after comparing it with a similar experiment performed by some of the same researchers at a federal prison in Indiana a few years earlier. There, prisoners were also exposed to gonorrhea, but only after they had volunteered and given informed consent. In addition, community standards were emerging: In 1947, The Journal of the American Medical Association published the Nuremberg Code requiring patients' consent—a response to Nazi experiments. "We had enough ethics in the air and in society that would have instructed the Guatemala researchers to do differently than they did," said commission member Anita Allen, a law professor at Penn.
One shocking case cited by the panel was a psychiatric patient who appeared to be dying of syphilis. Cutler put gonorrhea-infected pus in her eyes, urethra, and rectum and reinfected her with syphilis. Days later her eyes were full of pus and her urethra was bleeding. She died after 6 months. "This kind of case cannot be waved away by even the most acute awareness of fluctuation in medical ethics standards of the time," said commission member John Arras, an ethicist at the University of Virginia in Charlottesville.
The commission also found many problems with the study's methodology, including haphazard note-taking and illogical timing of experiments. For example, serological studies, which were meant to determine baseline disease rates in the population, were conducted after the treatment studies had begun. Little was published. "It was bad science," Nelson Michael of the Walter Reed Army Institute of Research in Silver Spring, Maryland, concluded. The commission blames this in part on Cutler's inexperience but also held him and his supervisor, John Maloney, responsible for burying their reports.
Although the Guatemala experiments would not happen under today's rules, "we should be ever vigilant to ensure that such reprehensible exploitation of our fellow human beings is never repeated," Gutmann said. The commission is following up with a second project: reviewing current standards for protecting research subjects in the United States and abroad.
An international subcommittee appointed by the panel reported today that it has found several areas for improvement. They include a need to engage with local communities, ensure ethics training of researchers and ethics reviewers abroad, and setup a U.S. system for compensation for research-related injuries. The subcommittee also urged that all human studies involving some risk, not just drug trials, be registered in public databases. The emphasis is not on creating new rules but on "strengthening the protections that most people agree upon," said commission subcommittee member Christine Grady, a bioethicist at the National Institutes of Health.
The subcommittee's findings will be published in the Federal Register for comment and fed into a final report to the president from the bioethics commission in December.