Harvard Gene Study in China Is Questioned
Federal officials on Friday issued a stinging rebuke of research practices at Harvard University and raised questions about the ethics of working with one of the world’s most coveted caches of genetic information: the rural population of China.
Thanks to their isolation, the people of rural China have a genetic uniformity that makes it easier to track disease genes. Researchers from a variety of American institutions are working there to find the genetic basis for obesity, hypertension, asthma and other ailments.
But in letters Friday to two Harvard units, the federal Office for Human Research Protections underscored the ethical pitfalls of working with impoverished people in developing countries. Particularly in authoritarian countries, these people might be easily coerced into volunteering for research and yet unable to afford the new treatments that result, the office said.
The letters said that Harvard research supervisors failed in a variety of ways to make sure that the rights of research participants were protected.
Consent forms often included complex language that rural Chinese subjects would probably not understand, federal officials said. Researchers in one study recruited thousands more volunteers than were authorized. And supervisors failed to show that volunteers would benefit in any way from the research they had participated in--a prime consideration in deciding whether a research project is ethical.
Federal officials had particular concerns about how researchers navigated China’s much-criticized law that limits most couples to having a single child.
In one asthma study, supervised by the Harvard-affiliated Brigham and Women’s Hospital, researchers sought out families that on average had more than four children. Federal officials said they were “concerned” that identifying these families “could have placed them at risk” with the Chinese government for violating the one-child law.
And in a study of lead levels in the blood, supervised by Harvard’s School of Public Health, researchers apparently asked women to participate just as they were registering with the government to marry. Federal officials said this might “possibly coerce the women into enrolling [in the study] with the thought that it might improve their chances for marriage or conception permission.”
In a statement, the Harvard School of Public Health said that “we fully agree” with the thrust of the federal letter. But the school noted that federal officials “found no instances of harm to any participants in our studies.”
The school also said that the federal study of its practices prompted it to make a variety of changes in the way it handled research supervision. Among other things, it has added staff and begun shadowing researchers to monitor how people are recruited for research studies.
Brigham and Women’s, in a statement, said that it also “understands that no study participants were harmed and that the confidentiality of the patients involved was maintained.”
“The pace and scope of international collaborative research is increasing, so we will see more and more cases like this,” said Eric Meslin, director of the Indiana University Center for Bioethics. “When the U.S. exports its research rules, the interpretation and application get murkier the farther you get away from” the U.S.
Research institutions that take federal money are obliged to follow federal rules aimed at protecting the people who volunteer for medical experiments. An ethics board at each institution is supposed to review all research to make sure volunteers are protected.
But as research becomes more complex and international, the job of these ethics boards has become more complex.
Federal officials, for example, found that the Brigham and Women’s ethics board “lacked the background and expertise to review the above-referenced research because of its apparent failure to consider the cultural conditions, including the social, economic and political status of the subject population.”
Violations of the federal rules can prompt federal officials to shut down a research project. Harvard officials said that all the research in question had been completed or suspended until all federal and university questions were answered.
In their letters, federal officials ordered the School of Public Health and Brigham and Women’s Hospital to provide an array of information about their research in China, including how its supervision of research had been improved. The letters said that both units had already made a number of improvements that satisfied some of the government’s concerns.
A third and similar letter went to the Massachusetts Mental Health Center, requiring it to provide more information about two studies in China.
Twelve of the 14 Harvard studies drawing federal attention were conducted by Dr. Xiping Xu, associate professor of occupational epidemiology. Ten were conducted through the public health school and two through the hospital.
Xu’s work in China was the focus of an extensive report two years ago in the Washington Post.
The Harvard School of Public Health said that Xu was now required to submit to a review of his research involving human subjects every three to six months, instead of the usual 12. All of Xu’s research involving human subjects was suspended last August and will not resume until the federal government and the school are satisfied that new oversight procedures are in place, a school official said.
Brigham and Women’s said that Xu had told hospital reviewers that he had taken measures “intended to ensure that participants were aware of the risks and benefits of participation. The hospital has been and continues to be engaged in addressing each of the issues cited by” federal officials.
