Gene advances bring ethical quandaries

A revolution in genetics is leading to almost weekly discoveries about genes linked with diseases such as diabetes, but also creating a dilemma for medical scientists: Should they tell the patients whose DNA was used in the research that they may be at risk for a serious illness? At present, that's almost taboo because of privacy policies governing most medical research.

"Researchers are coming up with more and more information, but we're using 'privacy' and our own ingrained paternalism as excuses for not sharing information that could be important to [individual research] subjects," said Dr. Isaac S. Kohane, associate professor of pediatrics at Harvard Medical School and a researcher at Children's Hospital in Boston.

Now, in a break with research tradition, Children's is creating a pilot program that will enable families whose children provide DNA for broad medical research to receive individually tailored information on the findings. The Harvard-affiliated hospital plans to use computer technology and counselors to allow families access to research while still guarding their privacy, as required by law and research ethics.

The Children's concept may prove controversial -- especially if it gives families medically useless information that sows needless alarm. For instance, research might show individuals with a certain genetic make up may have a statistically elevated risk of heart disease. But that's a scientific finding, not a clinical diagnosis, and in many cases, there will be no treatment or cure available.

"What I'm really worried about is clinically meaningless tests being deployed without adequate testing to establish their ability" to provide therapy or a cure, said Dr. David Altshuler of the Broad Institute of Harvard and MIT, a genetics research center.

But the program aborning at the Developmental Medicine Center at Children's may also become a model for research hospitals across the nation, all struggling with thorny moral and medical questions raised by powerful new genetic tests able to scan vast regions of DNA and extraordinary quantities of data.

"This offers an innovative and intriguing approach to some of the complex issues that are being raised as we accumulate more and more information about genetic risks of disease," said Dr. Jordan W. Smoller of the Center for Human Genetic Research at Massachusetts General Hospital.

Like other researchers, he warned that findings in genetic studies are often fuzzy. "The effects of a single gene or even groups of genes may be very small, and we don't yet know how to translate them into personalized medicine," he said.

Researchers and clinicians at Children's are keenly aware of the challenges.

"This could be a breakthrough, one that gives families more information without compromising their privacy," said Dr. Leonard Rappaport, director of the Developmental Medicine Center. "But we've got to go carefully -- much good could come of this, but also bad."

Kohane and five co-authors, however, argue in today's issue of the journal Science that damage is already being done when privacy laws and medical paternalism are used as the excuse for not giving research subjects access to pertinent information that might be revealed by their tissue samples.

"The research community has, albeit with the best intentions, broken the historical doctor-patient compact," they wrote, "distorting an ideal of information exchange that might inform subjects of health risks or benefits."

In accordance with federal law, tough procedures are in place at all major medical research institutions to protect the privacy of people who provide blood and other tissue for research. In part, keeping test subjects anonymous to researchers is meant to ensure the objectivity of research. Another primary aim is to prevent individuals' medical records from falling into the wrong hands, such as purveyors of medical products or insurance companies.

Yet another idea underscoring privacy policies is that test subjects don't understand that science that is scrutinizing them, and that receiving information about research would only cause alarm. Under policies in place at most hospitals, research results can only be released to the subject group, not to an individual subject.

In other words, if genetic research on depression showed, incidentally, that a few of the subjects possessed genetic traits that put them at substantially higher risk -- even danger -- of cancer, that information could only be released to the entire subject group, or "cohort" in research parlance, not to the individuals affected.

"This is inefficient, inelegant, and in my view, unethical," Kohane said in an interview. "We can't risk scaring an individual. But we can scare the entire cohort."

With extraordinary amounts of genetic information now stored on tiny chips, and researchers able to complete "genome-wide" studies across wide swaths of DNA -- instead of seeking out specific mutant genes -- disease hunters are increasingly likely to chance upon genetic indicators of one disease while looking for clues to an entirely different ailment.

"The ethical questions are just getting more and more complicated as researchers find whole regions of the chromosome that suggest risk, not just a single mutation," said Dr. Michael Grodin, director of medical ethics at Boston University's School of Public Health. "Results are going to be harder to interpret, and decisions on what to release, and to whom, are going to get more and more difficult."

Colin Nickerson can be reached at nickerson@globe.com.