The Interpretation of Genes

Among scientists, there is a tendency to get excited when a genetic association appears in two or three studies of a thousand people. However, that does not make the association robust enough to be clinically actionable. For some diseases, like Huntington’s, there is a definitive single-gene link—if you have the gene, you will develop the disease at some point in your life. Then there are ailments like diabetes, for which the genetic links are “murky,” as Dr. Francis Collins, Director of the Human Genome Research, admitted at a World Science Festival event entitled “Your Biological Biography: Genes and Identity” last weekend in New York City. “For diabetes, we know 10 percent of the heritability,” he said.

At the event, Collins sparred with co-panelist, Dr. Jim Evans from UNC-Chapel Hill, about how the medical science community can best use the emerging body of genetic knowledge to make clinical decisions.

Evans emphasized the murkiness of the diabetes-genes link, saying, “It’s relevant, but I’m not sure it will ever be robust.” In contrast, Collins was more optimistic, noting that with a disease like diabetes, there has not been enough clinical research to tell us whether a genetic disorder responds better to a particular type of diet or a to particular type of exercise.

Collins also reminded the audience that even though, “we can’t manipulate genes, we can manipulate environment.” Evans, who explained that he has enough difficulty getting his patients to stop smoking, felt that most people would not be motivated enough to change their diets or exercise habits based on a few percentage points of increased risk. As far as he was concerned, the kind of treatments that patients are waiting for are drugs.

Evans also stressed that the development of effective treatments depends on how many “large effect” genes we find. Collins thinks we will find a lot, and Evans does not. Citing Alzheimer’s disease as an example, Evans noted that the average American has a 12 percent chance of developing the disease, and then posed the question, “But what would 20 percent tell me?”—implying that a mere genetic probability might not be clinically actionable. This led Collins to retort, “Actionable is in the eye of the beholder.”

Citing the Risk Evaluation and Education for Alzheimer’s Disease Study (REVEAL) conducted by the NHGRI and the National Institute on Aging (NIA), Collins explained that after a year, most people in the study who found out they had a high risk of getting Alzheimer’s Disease handled it pretty well. Unfortunately, for most of the general public, misconceptions remain about genes being the primary determinants of one’s fate.

Because of this, Nikolas Rose, a sociologist from the London School of Economics, disagreed with Collins’s use of an “instruction book” as a metaphor for the genome, contending, that “genes don’t tell us who we are,” and that protein formation, environment, and society also comprise a person’s identity. Misha Angrist, a science writer, assistant professor at Duke University, and a subject in the Personal Genome Project (a Harvard University effort to sequence and make public the genomes of 100,000 volunteers), also pointed out the fallacy of genetic determinism by noting that there are over fifty genes which influence height by only one or two inches. But he nevertheless insisted that regardless of what one thinks of genetic tests, “People want this information.”

The group did agree that the recent passage of the Genetic Information Non-discrimination Act was a good thing. Still, Evans expressed concern that the even though GINA applies to heath insurers and employers, it does not apply to long-term care insurance, disability insurance, and life insurance, which are arguably the types of insurance where the lifetime probabilities provided by genetic tests might be most relevant. This sentiment was echoed by Collins, who added that GINA also takes family history into account and that health insurance companies are okay with that as long as it’s off limits to all companies.

Delving into the practical implications of genetic discrimination, the panel moderator, Nobel Prize-Winner and President of Rockefeller University Paul Nurse, posed a question about whether an airline might be justified in denying a job to a pilot who has a genetic predisposal to having a heart attack. This prompted Evans to burst the gene-centric bubble of the conversation by reminding the panel and audience that physiology is the most important diagnostic tool because, “it tells me what’s going on with your heart right now.” Collins quipped that the probability of death for all of us is one, and that half the population has a genomic characteristic that makes them 16 times more likely to commit a crime—it’s called a Y chromosome.

Rose continued to debunk determinism and concluded by noting, “Nothing that we find will transform philosophically or practically whether we have free will.” He even admitted that he agrees with Leon Kass, former chair of the President’s Council on Bioethics for the Bush aministration, on the point that we need to stop thinking, “if only this, if only that, we will relieve all suffering.”

Tags: genetics

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