Were subjects guinea pigs or nuclear pioneers?

THE BALTIMORE SUN

The historian specializing in human experiments sees an opportunity to restore confidence in government science. The law professor cautions that radiation experiments of 40 years ago be reviewed in the context of their time. The radiologist wonders if it's possible to determine just how much the patients of yesteryear knew about the medical procedures they underwent.

Over the next year, these and other bioethicists, historians, law professors and nuclear medicine specialists on a presidential committee will serve as the nation's conscience on a subject that has brought into question ethical standards of research a half-century ago.

What began as an Albuquerque, N.M., reporter's search for the identities of 18 patients injected with plutonium in 1948 has mushroomed into a massive hunt for government files on federally funded radiation research that occurred over three decades.

The task facing the Advisory Committee on Radiation Experiments is no less daunting than the documents search under way in the basements, archives and warehouses used by six federal agencies.

As many as 800 people may have been involved in the experiments between 1944 and 1974. And it will be the job of the 15-member panel to determine if the experiments on America's so-called "nuclear guinea pigs" had a "clear medical or scientific purpose" and met the ethical standards of the time.

The committee members -- among the leaders in their fields -- will have to decide such things as whether the researchers associated with the experiments informed patients of the medical procedures and risks involved, consistent with the standards of the time. Was there medical follow-up? Were patients harmed? Should they or their families be compensated for any injury?

"I think it's a remarkable undertaking," said one panel member, Susan E. Lederer, a historian of human experiments who teaches at the Milton S. Hershey Medical Center of Pennsylvania State University. "It is a history that has been largely unwritten -- a subject that has had the least attention of all. . . . It [the review] would be a tremendous service to the families of people who have been used, if only as a means of restoring confidence in government science."

A tremendous service, perhaps, but a time-consuming and potentially expensive review of experiments as diverse as these: the irradiation of the testes of 64 inmates at a Washington state prison between 1963 and 1971, the 1949 release of radioactive gases in the air over Richland, Wash., the injection of plutonium into 18 hospital patients between 1945 and 1947.

"We have a responsibility to all the people who served as subjects in the studies in question. We have an obligation to do right by them," said Dr. Ruth R. Faden, the panel chairwoman and a professor at the Johns Hopkins School of Hygiene and Public Health.

"We have an obligation to be fair to the [research] investigators. And we also have the overriding obligation to the American public to assure that this is a serious, independent investigation that will be conducted with the utmost integrity."

The work will require of its investigators knowledge of ionizing radiation, the relationship between doctor and patient, the evolution of informed consent, research ethics, the theory of liability.

The personal side

Dr. Faden, a bioethicist credited with writing the book on informed consent, is the daughter of Holocaust survivors. Dr. Jay Katz, a psychiatrist and Yale University law professor, was on the panel that reviewed the Tuskegee syphilis study of the 1930s. Retired bank vice president Lois L. Norris has served for 10 years on an institutional review board at the University of Nebraska.

The parameters of the inquiry have already been defined as experiments involving "intentional exposure" to radiation, excluding common and routine clinical practices and "incidental exposures" to radiation; and "intentional releases of radiation" designed to test the health effects of radiation on humans and the extent of exposure, according to the Jan. 15 executive order establishing the advisory committee.

"Anybody today is going to find it very difficult to put themselves in the shoes of people who made those decisions to do the studies many years ago," said Dr. Jerome P. Kassirer, editor in chief of the New England Journal of Medicine.

Of the key issues facing the committee, the concept of informed consent -- how much information patients were given about research projects and experiments -- may be the most troublesome. The ethical standards that govern research today were not in place in the late 1940s when the government first made radioactive isotopes generally available.

"The idea of informed consent is much older than the 1950s," said Ms. Lederer, the Penn State historian. "It began at the turn of the century. Walter Reed used written contracts. So certainly, it would not have been a novel idea in science at the time."

Nuremberg ruling

In 1947, the Nuremberg Code required, among other things, that research subjects give voluntary consent without coercion. Government regulations first spelled out how experiments should be explained to patients in the 1960s. But a comprehensive, government-wide set of rules didn't hit the books until the the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research issued its recommendations in the mid-1970s.

"Patients have to have an understanding of what they are getting into," said another panel member, Dr. Eli Glatstein, chairman of the department of radiation oncology at the Simmons Cancer Center at the University of Texas. "No one has a right to give something to a patient just because we believe it is safe. Patients have a right to refuse treatment."

"It's not clear whether the ethical requirements were so different then or not. Even still we have to investigate this area of historical relativism: If it's wrong today, why isn't it wrong yesterday?" said Dr. Faden, the panel chairperson. "This is an area that people must debate. Surely it's relevant to look at what the practice was at the time."

Dr. Faden hopes the committee will meet in March.

"I would hope one of the issues the panel would look at was that if the informed consent regarding [radiation] patients was any different from the informed consent in other types of experiments," added a third panel member, Dr. Henry D. Royal, associate director of the division of nuclear medicine at the Mallinckrodt Institute of Radiology at Washington University School of Medicine in St. Louis.

Harm to subjects

Another issue before the panel will be whether the subjects in the radiation experiments were harmed. "There is confusion going on about not distinguishing between harm to research subjects and obtaining their informed consent," said Dr. Katz of Yale Law School. "It is one thing if the experiments were harmful or not and it is another matter whether the subject had been invited to participate in the research."

And not all radiation exposure is harmful.

"If you give someone a dose of radiation, it does not necessarily follow that everything that happens after that is related to the radiation," said Dr. Glatstein of the Simmons Cancer Center at the University of Texas. "It is customary for radiation to wear a black hat, but that is not necessarily accurate."

If the panel determines that patients were harmed or not properly informed of the risks they faced, the committee may then decide whether subjects should be compensated as a result.

"This will not be easy work," added Dr. Glatstein. "We will have to assess this very carefully. It is not obvious what has taken place."

But, he said, if anyone has been injured or harmed in an unethical research project, "As a taxpayer, I would be in favor of seeing a patient compensated."

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