Holes in Those Genes

MAYBE WHAT WE HAVE HERE ARE the death throes of a paradigm, the last spasms of a way of thinking that has no more intention of going gently into the good night than the dinosaurs did. The paradigm is genetics. Ever since Gregor Mendel crossbred pea plants in his garden at the Austrian abbey, scientists have known that snippets of inherited chemicals dictate the body plan and appearance of all living things. But in this era of genetic triumphalism, the paradigm has gone far beyond that. Genes are no longer invoked only to explain diseases, such as Huntington's, that are unambiguously the result of DNA gone awry. Hardly a month goes by without news of a gene "for" a complex trait like aggression, shyness or alcoholism. Last week it was temperament's turn. Two research teams announced that they had independently discovered a gene that makes people fickle, excitable and exploratory--in short, "novelty seekers." Can it really be so simple? Or, as some researchers believe, does Emperor Genes have no jeans? "Finding a gene involved in a behavior is a crucial first step," says biologist Michael Meaney of University, "but it is only a first step."

The novelty-seeking gene, not surprisingly, acts in the brain. Two groups--one led by Dean Hamer of the National Cancer Institute and the other by Richard Ebstein of Sarah Herzog Memorial Hospital in Jerusalem--report that people with a long form of a certain gene score higher on a scale of novelty-seeking than do people with a short form. (Novelty-seeking was assessed by asking 124 volunteers in Israel, and 315 in America, whether, for instance, they "have sometimes done things just for kicks or thrills.") The gene, the teams explain in the journal Nature Genetics, holds instructions for building receptors in the brain. The receptors stud the surface of neurons like docking ports stud "Deep Space Nine," and attract a brain chemical called dopamine, long known to trigger an urge to seek new experiences. The theory, then, is that a longer gene makes a longer receptor; a longer receptor somehow affects dopamine's influence on the brain, making the owner of the brain want to, well, bungee-jump. But this receptor accounts for only 10 percent of the genetic difference in people's yen for roller coasters, admits Hamer. And genes of any sort,estimates psychiatrist C. Robert Cloninger of Washington University, account for less than half the difference in people's desire for novelty.

If that wasn't clear from last week's claims, scholars aren't surprised. Dorothy Nelkin, a sociologist of science at New York University, argues that the notion of an all-powerful genetics--able to cure disease and explain personality at a single bound--is so appealing because "it lets you blame everything on individuals' biology. If nothing is the result of social forces, it grants society a certain absolution." The other power behind DNA's throne is the Human Genome Project. This $3 billion attempt to discover all 3 billion chemical units in a person's DNA promises medical utopia: gene therapy for inherited disease, identifying who would get lung cancer from smoking, treatments for mental and physical ills. All this is predicated, of course, on the primacy of genes. "The people in the genome project gain greatly from the misperception that if you [identify] a gene you have explained something," says McGill's Meaney.

Recent experiments threaten to dethrone DNA as surely-- and as stealthily and unexpectedly--as little mammals replaced dinosaurs. In one study, Meaney separated newborn rats from their mothers for an easy 15 minutes or for a stressful six hours a day. "We found that receptors [for certain brain chemicals], and the gene for the receptors, are both altered," Meaney says. As adults, the rats that were stressed as pups had fewer of certain receptors and so tended to over-produce stress hormones; normal rats had more receptors and were less likely to be flooded with hormones during stress. Might certain childhood experiences--being menaced by a new dog, falling from a new Jungle-Gym--determine whether one develops more or fewer brain receptors for novelty-seeking? All it would take is a mechanism like the one Meaney found. But his results go further. Early life experiences were so influential in the rats, he found, that they literally determined which receptor genes turned on, and thus how many receptors the brain built.

If genes can be altered by experience, where does that leave the question of whether nature or nurture contributes more to who we become? Meaney likes to quote a former teacher who compared that question to asking which contributes more to the area of a rectangle, its length or its width? DNA has not been knocked off its throne yet. But with more re search showing that experience can reach into our very genes, its days may be numbered.

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