The Personality Genes

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Molecular biologist Dean Hamer has blue eyes, light brown hair and the goofy sense of humor of a stand-up comic. He smokes cigarettes, spends long hours in a cluttered laboratory at the National Institutes of Health, and in his free time clambers up cliffs and points his skis down steep, avalanche-prone slopes. He also happens to be openly, matter-of-factly gay.

What is it that makes Hamer who he is? What, for that matter, accounts for the quirks and foibles, talents and traits that make up anyone's personality? Hamer is not content merely to ask such questions; he is trying to answer them as well. A pioneer in the field of molecular psychology, Hamer is exploring the role genes play in governing the very core of our individuality. To a remarkable extent, his work on what might be called the gay, thrill-seeking and quit-smoking genes reflects his own genetic predispositions.

That work, which has appeared mostly in scientific journals, has been gathered into an accessible and quite readable form in Hamer's provocative new book, Living with Our Genes (Doubleday; $24.95). "You have about as much choice in some aspects of your personality," Hamer and co-author Peter Copeland write in the introductory chapter, "as you do in the shape of your nose or the size of your feet."

Until recently, research into behavioral genetics was dominated by psychiatrists and psychologists, who based their most compelling conclusions about the importance of genes on studies of identical twins. For example, psychologist Michael Bailey of Northwestern University famously demonstrated that if one identical twin is gay, there is about a 50% likelihood that the other will be too. Seven years ago, Hamer picked up where the twin studies left off, homing in on specific strips of DNA that appear to influence everything from mood to sexual orientation.

Hamer switched to behavioral genetics from basic research; after receiving his Ph.D. from Harvard, he spent more than a decade studying the biochemistry of metallothionein, a protein that cells use to metabolize heavy metals like copper and zinc. As he was about to turn 40, however, Hamer suddenly realized he had learned as much about metallothionein as he cared to. "Frankly, I was bored," he remembers, "and ready for something new."

Instrumental in Hamer's decision to switch fields was Charles Darwin's The Descent of Man, and Selection in Relation to Sex. "I was fascinated to learn that Darwin seemed so convinced that behavior was partially inherited," he remembers, "even though when he was writing, genes had not been discovered, let alone DNA." Homosexual behavior, in particular, seemed ripe for exploration because few scientists had dared tackle such an emotionally and politically charged subject. "I'm gay," Hamer says with a shrug, "but that was not a major motivation. It was more of a question of intellectual curiosity--and the fact that no one else was doing this sort of research."

The results of Hamer's first foray into behavioral genetics, published by the journal Science in 1993, ignited a furor that has yet to die down. According to Hamer and his colleagues, male homosexuality appeared to be linked to a stretch of DNA at the very tip of the X chromosome, the chromosome men inherit from their mothers. Three years later, in 1996, Hamer and his collaborators at NIH seconded an Israeli group's finding that linked a gene on chromosome 11 to the personality trait psychologists call novelty seeking. That same year Hamer's lab helped pinpoint another gene, this time on chromosome 17, that appears to play a role in regulating anxiety.

Unlike the genes that are responsible for physical traits, Hamer emphasizes, these genes do not cause people to become homosexuals, thrill-seeking rock climbers or anxiety-ridden worrywarts. The biology of personality is much more complicated than that. Rather, what genes appear to do, says Hamer, is subtly bias the psyche so that different individuals react to similar experiences in surprisingly different ways.

Intriguing as these findings are, other experts caution that none has been unequivocally replicated by other research teams. Why? One possibility is that, despite all of Hamer's work, the links between these genes and these particular personality traits do not, in fact, exist. There is, however, another, more tantalizing possibility. Consider the genes that give tomatoes their flavor, suggests Hamer's colleague Dr. Dennis Murphy of the National Institute of Mental Health. Even a simple trait like acidity is controlled not by a single gene but by as many as 30 that operate in concert. In the same way, he speculates, many genes are involved in setting up temperamental traits and psychological vulnerabilities; each gene contributes just a little bit to the overall effect.

Hunting down the genes that influence personality remains a dauntingly difficult business. Although DNA is constructed out of a mere four chemicals--adenine, guanine, cytosine, thymine--it can take as many as a million combinations to spell out a single human gene. Most of these genes vary from individual to individual by only one chemical letter in a thousand, and it is precisely these minute differences that Hamer and his colleagues are trying to identify. Of particular interest are variations that may affect the operation of such brain chemicals as dopamine and serotonin, which are well-known modulators of mood. The so-called novelty-seeking gene, for example, is thought to affect how efficiently nerve cells absorb dopamine. The so-called anxiety gene is postulated to affect serotonin's action.

How can this be? After all, as Hamer and Copeland observe in their book, "...genes are not switches that say 'shy' or 'outgoing' or 'happy' or 'sad.' Genes are simply chemicals that direct the combination of more chemicals." What genes do is order up the production of proteins in organs like the kidney, the skin and also the brain. Thus, Hamer speculates, one version of the novelty-seeking gene may make a protein that is less efficient at absorbing dopamine. Since dopamine is the chemical that creates sensations of pleasure in response to intense experiences, people who inherit this gene might seek to stimulate its production by seeking out thrills.

Still, as critics emphasize and Hamer himself acknowledges, genes alone do not control the chemistry of the brain. Ultimately, it is the environment that determines how these genes will express themselves. In another setting, for example, it is easy to imagine that Hamer might have become a high school dropout rather than a scientist. For while he grew up in an affluent household in Montclair, N.J., he was hardly a model child. "Today," he chuckles, "I probably would have been diagnosed with attention-deficit disorder and put on Ritalin." In his senior year in high school, though, Hamer discovered organic chemistry and went from being an unruly adolescent to a first-rate student. What people are born with, Hamer says, are temperamental traits. What they can acquire through experience is the ability to control these traits by exercising that intangible part of personality called character.

Over the coming decade, Hamer predicts, scientists will identify thousands of genes that directly and indirectly influence behavior. A peek inside the locked freezer in the hallway outside his own lab reveals a rapidly expanding stash of plastic tubes that contain DNA samples from more than 1,760 volunteers. Among them: gay men and their heterosexual brothers, a random assortment of novelty seekers and novelty avoiders, shy children and now a growing collection of cigarette smokers.

Indeed, while Hamer has maintained a professional distance from his studies, it is impossible to believe he is not also driven by a desire for self-discovery. Soon, in fact, his lab will publish a paper about a gene that makes it harder or easier for people to stop smoking. Judging by the pack of cigarettes poking out of his shirt pocket, Hamer would seem to have drawn the wrong end of that genetic stick. He has tried to stop smoking and failed, he confesses, dozens of times. "If I quit," he says, "it will be an exercise of character."And not, it goes without saying, of his genes.