02 Sept 2012
Dr Arul Chinnaiyan stared at a printout of gene sequences from a man with cancer, a subject in one of his studies. There, along with the man’s cancer genes, was something unexpected –genes of the virus that causes AIDS.
It could have been a sign that the man was infected with HIV; the only way to tell was further testing. But Chinnaiyan, who leads the Center for Translational Pathology at the University of Michigan, was not able to suggest that to the patient, who had donated his cells on the condition that he remain anonymous.
In laboratories around the world, genetic researchers using tools that are ever more sophisticated to peer into the DNA are increasingly finding things they were not looking for, including information that could make a big difference to a donor.
The question of how, when and whether to return genetic results to study subjects or their families "is one of the thorniest current challenges in clinical research," said Dr Francis Collins, the director of the National Institutes of Health. "We are living in an awkward interval where our ability to capture the information often exceeds our ability to know what to do with it."
The quandaries arise from the conditions that medical research studies typically set out. Volunteers usually sign forms saying that they agree only to provide tissue samples, and that they will not be contacted. Only now have some studies started asking the participants whether they want to be contacted, but that leads to more questions: What sort of information should they get?
The complications are procedural as well as ethical. Often, the labs that make the surprise discoveries are not certified to provide clinical information to patients. The consent forms were approved by ethics boards, which would have to approve any changes to the agreements –if the patients could even be found.
Sometimes the findings indicate that unexpected treatments might help. In a newly published federal study of 224 gene sequences of colon cancers, for example, researchers found genetic changes in 5% that were the same as changes in breast cancer patients whose prognosis is drastically improved with a drug, Herceptin. About 15% had a particular gene mutation that is common in melanoma. Once again, there is a drug, approved for melanoma, that might help. But under the rules of the study, none of the research subjects could ever know.
Other times the findings indicate that the study subjects or their relatives who might have the same genes are at risk for diseases they had not considered. For example, researchers at the Mayo Clinic in Rochester, Minn, found genes predisposing patients to melanoma in cells of people in a pancreatic cancer study – but most of those patients had died.
Such ethical quandaries grow more immediate year by year as genome sequencing gets cheaper and easier. More studies include gene sequencing and look at the entire genome. Yet while some findings are clear-cut, more often the significance of a genetic change is not so clear. Or, even if it is, there is nothing to be done.
Researchers are divided on what counts as an important finding. Some say it has to suggest prevention or treatment. Others say it can suggest a clinical trial or an experimental drug.
"If you are a PhD in a lab in Oklahoma and think you made a discovery using a sample from 15 years ago from a subject in California, what exactly are you supposed to do with that?" asked Dr Robert C Green, an associate professor of medicine at Harvard. "Are you supposed to somehow track the sample back?"
Then there are the consent forms saying that no one would ever contact the subjects. "If you go back to them and ask them to re–consent, you are telling them something is there," Green said. "There is a certain kind of participant who doesn't want to know," he added, and if a researcher contacts study subjects, "you are kind of invalidating the contract." NYT NEWS SERVICE