By AMY HARMON
Published: April 23, 2010
The cultural gap between the impoverished Havasupai Indians who view their blood as sacred and the Arizona State University researchers who helicoptered in to their Grand Canyon home to collect it was at the heart of a lawsuit over the scope of a genetic study that ended last week with a settlement for the tribe.
But the case, scientists and bioethicists said, serves as a cautionary tale about the equally significant gap between scientists and all research subjects, who often seem to hail from different cultures even when the surface differences are less apparent.
As troubling questions, some involving other lawsuits, have surfaced recently among a range of research subjects who have learned that their genetic material is being used in ways they weren’t consulted about, scientists are debating how to better apply the principle of “informed consent” to large-scale genetic research. At stake, they say, is the success of such research, which relies on voluntary participation by increasingly large numbers of human subjects.
Some have proposed an international tribunal akin to the Helsinki human rights agreement, which would lay out the ethical obligations to research participants. Others suggest staying in touch with subjects so they can be consulted on new projects — and because under current practices they tend to learn of breakthroughs based on their own DNA only if they become close readers of scientific journals.
Courts have ruled that individuals do not have a property right to their cells once they are taken in the course of medical care, but they do, under federal guidelines, have a right to know how they will be used. Complicating matters is the increasing impossibility of ensuring that DNA data can remain anonymous. Do participants need to be told that their privacy cannot be guaranteed? Can “blanket” consent up front do the trick, or is even that misleading because researchers can’t adequately describe the scope of studies they have yet to design? Is it O.K. to use DNA collected for heart research to look for genetic associations with intelligence, mental illness, racial differences?
For one thing, “we have to communicate a hell of a lot better to the public what is going on when we put their specimens in our biobanks,” said Stephen J. O’Brien, a geneticist who runs the Laboratory of Genomic Diversity at the National Institutes of Health.
At issue in the Havasupai case was whether an Arizona State geneticist had obtained permission from tribal members to use their DNA for anything other than finding clues to Type 2 diabetes. More than 200 of the 650-member tribe signed a consent form stating that their blood could be used to “study the causes of behavioral/medical disorders,” but many said they had believed they were donating it only for the study of diabetes, which tribal members suffer from at extraordinarily high rates.
When they learned years later that the DNA samples had been used to investigate things they found objectionable, they felt betrayed. Researchers had investigated genes thought to be associated with schizophrenia, a condition the tribe considered stigmatizing, and traced the tribe’s ancestral origins to Asia, contradicting traditional stories holding that the Havasupai had originated in the Grand Canyon.
Dr. O’Brien said he sympathized with the position of Dr. Therese Markow, the geneticist who had overseen the research at Arizona State and who insisted she had received consent from her subjects. But it was her responsibility, Dr. O’Brien added, to make sure her subjects actually understood.
He noted that a similar question arose much more recently about what should be done with some 200,000 DNA samples that government-funded scientists had collected for studies of specific diseases. His own laboratory, for instance, has gathered DNA from thousands of AIDS patients who gave permission for it to be used in studying the genetics of H.I.V.
Should the samples be made available in a public database, so other federally funded researchers can use them for additional studies? After all, they were collected at considerable taxpayer expense. On the other hand, what if patients disliked the purposes it was used for?
“What if someone decides to use them to look for a gene for homosexuality?” Dr. O’Brien said. “They might be pretty surprised to learn that.”
Most likely they would never find out. (The Havasupai learned of the research Dr. Markow had done only because another professor at the university made a tribe member aware of it.) But what if they did find out?
That happened in Texas, when a newspaper report tipped parents off to the fact that the drops of blood taken from newborns in the hospital for screening in state laboratories — a legally mandated practice that can stave off disease and save lives — were being stored and made available to scientists for other research.
“The irony is if you had asked me, I probably would have consented,” said Andrea Beleno, a legal aid attorney in Austin, Tex., who was among those who sued the state health agency. “I would love for there to be a cure for breast cancer, which runs in my family. I would love for there to be a cure for diabetes. The way the state went about it just made me distrustful.”
It didn’t help to learn from another newspaper report, after the state settled the case, that some of the samples had been provided to a database used by the military to improve the interpretation of forensic DNA evidence.
“I’m not much of a conspiracy theorist,” said Ms. Beleno. “I would have laughed if someone said the state has a multimillion-person DNA database and they’re sending samples to the U.S. military.”
The state’s resulting decision to destroy the samples, legal advocates said, was a loss for science that could have been prevented.
Some marginalized groups have shied away from genetic research for historical reasons like the infamous Tuskegee syphilis study on African-Americans. As a result, said Marcus Feldman, a Stanford geneticist, those who may have the least access to medical care are also those whose genetics scientists know the least about.
Studies have estimated that most individuals — perhaps more than 90 percent — are willing to allow their data to be used for a range of biomedical research. It is when they are not asked that problems arise.
Rebecca Skloot, author of a book that recounts how cells taken by doctors from a black woman with cervical cancer in the 1950s became a vital tool for medicine, said people ask at every stop on her book tour how they can find out what is being done with the blood or biopsy they may have left at a hospital.
“There is this sense of, ‘it’s a piece of my body, and I want to know what’s happening to it,’ ” said Ms. Skloot, whose book, “The Immortal Life of Henrietta Lacks,” has become a best seller.
Some advocates for patients have criticized a paternalism among scientists who may tend to believe they are working to benefit humanity and prefer not to slow down, or spend grant money, to explain their work. But part of the problem may also be that communicating with the public is not what scientists are trained to do.
“If you go to a hospital and you don’t speak English, you’re going to get a translator,” said Ms. Skloot. “If you go to the hospital and you don’t speak science, you’re not, and in a way, that’s what people need.”
For pragmatic reasons and ethical ones, some researchers are trying out new models. In pursuit of the huge volume of research participants that appear to be necessary to find the many gene variants that contribute to common diseases like diabetes, the Children’s Hospital Boston, for instance, is pioneering a project that lets researchers report whatever they find directly to the subjects, a practice that has been considered impractical in the past, and fraught with ethical issues of its own.
With that as incentive, they hope to enroll nearly every family that walks through the door in a study that makes their medical records, as well as their DNA, available to researchers.
Over the first six months of the project, genetic counselors have spent as much as an hour with each family.
“We talked a lot about how this kind of information can be shocking and nerve-racking, and the things people can find out,” said Chellamal Keshavan, 21, a senior at Wheelock College in Boston. Then, readily, she gave her consent.
