Biomed Researchers Give Subjects a Larger Role in Studies

As tissue and DNA samples are shared more widely than ever, scientists and federal agencies are looking more closely at their responsibilities to the research subjects. Last Thursday, a National Institutes of Health (NIH) advisory committee rejected a request to use 47 lines in federally funded human embryonic stem cell research, saying that the donors had given away too many rights. Separately, researchers for a new DNA project based at Children's Hospital Boston plan to tell families about discoveries relevant to their own DNA. Such information is traditionally not shared because it's easier to anonymize samples and not worry about which discoveries are pertinent to patients.

The NIH decision flows from an ongoing review triggered by new guidelines from the Obama Administration that were announced last spring. Among other things, NIH requires that the embryos that have been coaxed into new cell lines were created by in vitro fertilization and are no longer needed, and that couples gave informed consent for their use in research. So far, 67 new lines have been approved and 101 are under review, with 234 more in the pipeline.

Sorting out which lines NIH-funded investigators can work on and which don't make the cut falls to a committee of ethicists and researchers. It's "a lot of work," says Story Landis, director of the National Institute of Neurological Disorders and Stroke and head of NIH's stem cell task force.

Speaking at a meeting last week of the Advisory Committee to the Director of NIH, Jeffrey Botkin, an ethicist at the University of Utah and the committee chair, said that 47 of 53 lines considered recently were ruled ineligible for federal funding. All were supplied by Reproductive Genetics Institute (RGI) in Chicago, Illinois, which specializes in helping couples who carry genes for rare diseases create healthy embryos that can then be implanted. Indeed, 42 of the lines carried genetic defects, a trait that NIH Director Francis Collins noted would have made them interesting to study.

But Botkin's group blocked all 47 because "donors appear to be asked to relinquish the right to sue" in the informed-consent form they signed. This clause constitutes "exculpatory language" in which subjects have given up important rights, and NIH doesn't allow it in stem cell lines. Botkin said that RGI could go back to the embryo donors and seek new consent. But in an article in USA Today, a scientist at the clinic said that would be impossible for lines that date from as far back as 2003.

The Gene Partnership Project at Children's Hospital Boston takes a different approach. The project, which will look at how genes and environment interact to drive disease in kids, is different from its predecessors, says Kenneth Mandl, a physician, biomedical informaticist, and one of the project's leaders at Children's. "We made the decision not to go with a standard, lightweight consent" form that often comes with DNA sample donation, he says. In those cases, data are stripped of identifiers; if researchers find a gene that raises the risk of schizophrenia by 3%, for example, they don't have to worry about the possible impact on participants.

The Gene Partnership Project will weigh just that kind of question, says Mandl. A committee is now considering which findings might be "pertinent" to patients and, therefore, should be shared. The back-and-forth runs both ways: While researchers working on the samples won't know who they belong to, those running the project will confer with participants regularly to gather more data about their health, ask for additional samples, or seek their participation on surveys. With most biobanks, Mandl says, "if someone comes in with a diagnosis of asthma but 4 years later develops heart disease, ... that person will be tagged with a diagnosis of asthma but not heart disease." In contrast, he says, the dossier of every participant in the Boston effort will keep evolving.

The project so far has collected a few hundred samples. By the end of the year, it hopes to be adding more than 800 samples a month.