Graphic: © Benjamin Fry, MIT
The history of genetic studies offers multiple examples of poor planning, insensitivity to subjects, and illegible consent forms. Many times, it is scientifically necessary to name the populations studied to verify data and provide context. At those times, insensitivity can take on a political tone, and the politics can halt the research. "There's an increasing awareness that sometimes there are unintended political and social outcomes to such studies," says Dennis O'Rourke, a professor of anthropology at the University of Utah, who has participated in many genetic studies. "The more abuse and insensitivity there was in the past makes it that much more difficult to do this kind of work in the future."
Such concerns inform the new initiative to identify common human genetic haplotypes--the International Hap Map Project. The $100 million (US) study will rely on the trust and willingness of dozens of different communities and ethnic groups throughout the world to participate and donate samples. A similar project, the Human Genome Diversity Project, stumbled before its launch date amid bad press and activist attacks. One Native American tribal council issued a press release decrying the project as racist and misleading. A nongovernmental organization in Canada accused it of being "biocolonialist."
TRAINED BY TRIALS Geneticists are now determined to collect samples fairly. The National Institutes of Health recently enacted a nonbinding set of guidelines1 recommending communication with communities before collecting samples. The guidelines suggest that researchers hold community consultations and allow community members to have input into how samples are used and how consent forms are written. Prospective researchers who demonstrate plans to meet the guidelines will no doubt receive high marks in peer review; expenses accrued in communicating with the community will likely not be rejected out of hand. "By far the most important issue is to communicate. It's a matter of anticipating misunderstandings," says memorandum coauthor Judith Greenberg, acting director of the National Institute of General Medical Sciences.
One of the first researchers to follow the new NIH guidelines was Julio Licinio, a University of California, Los Angeles, neuroendocrinologist who studied the genes of Mexican Americans in Los Angeles. He identified 400 community leaders, mass mailed study notices to them, and requested their comments. Then he met with 130 people, just to prepare for a town hall meeting that drew 400. To lure people to that meeting, Licinio paid for a buffet lunch and hired a clown to entertain the children. "I think it's the first time ever that someone had a clown as a line item in an NIH grant," he relates. Three town hall meetings, several community advisory meetings, and dozens of individual lunches later, Licinio completed the $3.8 million study. Of those funds, about $150,000 went to community activities. "In the end, the actual collection of samples was the easiest part of the whole project," Licinio says.
He considers the money and time well spent; to date, no one has filed a complaint. Now Licinio is embarking on another Mexican American gene study, and his upfront communication costs are much lower, thanks to the work done for the previous study.
Compare those efforts to a group of Canadian scientists who landed by helicopter on the island of Tristan Da Cunha in the middle of the Atlantic Ocean a decade ago. Asthma was uncommonly prevalent among the 300 islanders. The researchers, underwritten by Sequanna Pharmaceuticals, drew blood and reboarded their helicopters. Later, Sequanna sold its asthma research, including the cell lines developed from the islanders' samples, to Boehringer Ingelheim, a German pharmaceutical company, for $70 million. Only after complaints and accusations of exploitation did Sequanna try to make amends: It sent workers out to build a youth basketball court. The company has since merged and Celera has acquired the merged concern.
Like the Tristan da Cunha episode, conflicts between geneticists and communities often focus on the potential financial rewards of the research. Scientists can strive to resolve such issues through preparatory community meetings. "If there are commercial gains, some fair share should go back to the community," says Hank Greely, a professor of law at Stanford University who has helped develop ethical study guidelines. "It's a matter of negotiating between the scientists and the community leaders before the study starts, not after it's over."
Not everyone agrees the intellectual property derived from such studies should be shared with the study population. One such exception might be the database that deCODE Genetics is amassing in Iceland. More than 80,000 Icelanders (of a population of 280,000) donated samples, which will be cross-referenced with the nation's medical database and genealogical records. Although it hasn't developed any drug candidates yet, deCode has attracted more than $200 million from foreign drug companies. If it does strike genetic gold, the company will stay true to its for-profit roots and not share earnings with the study group. "The people who have participated in this study did so because they're interested in seeing an end to the diseases we're studying, not to become wealthy," says deCODE chief executive Kari Steffansson. "Iceland as a whole benefits from all the economic activity this company has created."
Some Icelanders debate the study's benefits. Mannvernd, an activist group opposed to deCODE's use of the nation's medical database, says participation rates have declined in the last two years as more than 20,000 Icelanders have opted out of the study. Stefansson disagrees with Mannvernd's numbers, saying participation rates range from 90% to 95%.
TALK SAVES MONEY Often such disputes can be headed off early with concentrated communication. Sometimes, contention focuses on poorly worded individual consents. "Sometimes a consent form will say the purpose is to study a specific disease 'and other research,'" says Morris Foster, an anthropologist at the University of Oklahoma. "Too often, the term 'other research' is interpreted far too flexibly by the scientists." Today, Foster says that inclusion of that term is widely recognized as an unconscionable breach of ethics. "There's no excuse to see that term on any consent form anymore."
Licinio agrees. He says that the community had a big influence on the consent forms. "When the advisory group read it they couldn't understand a word," he relates. "They helped to rewrite it in more practical language (in both Spanish and English)." The key to getting the community to work with you, says Licinio and others, is to communicate, without overstating the potential good that can come from such studies.
Geneticist Mike Bamshad of the University of Utah encourages researchers to improve the community's scientific infrastructure. He helped lead a genetic study of a community in India, where the researchers aided the construction of a molecular biology lab at Andhra University, trained its staff, and sent a graduate student to the United States for a postdoctoral fellowship. "The idea was to provide them with the resources and training so they could work independently of us," he says. In the end, the extra months and dollars were worthwhile. "We're getting better at dealing with our subjects and not making them feel exploited."
Sam Jaffe (firstname.lastname@example.org) is a freelance writer in Philadelphia.