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In 1993 came the biggest news: Dean Hamer's discovery of the "gay gene." In fact, Hamer, a Harvard-trained researcher at the National Cancer Institute, hadn't quite put it that boldly or imprecisely. He found that gay brothers shared a specific region of the X chromosome, called Xq28, at a higher rate than gay men shared with their straight brothers. Hamer and others suggested this finding would eventually transform our understanding of sexual orientation.

Researchers at Northwestern University, outside Chicago, are doing this work as a follow-up to their studies of arousal using genital measurement tools. They found that while straight men were aroused by film clips of two women having sex, and gay men were aroused by clips of two men having sex, most of the men who identified themselves as bisexual showed gay arousal patterns. More surprising was just how different the story with women turned out to be. Most women, whether they identified as straight, lesbian, or bisexual, were significantly aroused by straight, gay, and lesbian sex. "I'm not suggesting that most women are bisexual," says Michael Bailey, the psychology professor whose lab conducted the studies. "I'm suggesting that whatever a woman's sexual arousal pattern is, it has little to do with her sexual orientation." That's fundamentally different from men. "In men, arousal is orientation. It's as simple as that. That's how gay men learn they are gay."

researchers need a far deeper understanding of what sexual orientation is before they can determine where it comes from.

Female sexual orientation is particularly foggy, he says, because there's been so little research done. As for male sexual orientation, he argues that there's now enough evidence to suggest it is "entirely in-born," though not nearly enough to establish how that happens.

Bailey's 1991 twin study is still cited by other researchers as one of the pillars in the genetic argument for homosexuality. But his follow-up study using a comprehensive registry of twins in Australia found a much lower rate of similarity in sexual orientation between identical twins, about 20 percent, down from 50 percent.

Males and females have a fundamental genetic difference - females have two X chromosomes, and males have an X and a Y. Still, right after conception, it's hard to tell male and female zygotes apart, except for that tucked-away chromosomal difference. Normally, the changes take shape at a key point of fetal development, when the male brain is masculinized by sex hormones. The female brain is the default. The brain will stay on the female path as long as it is protected from exposure to hormones. The hormonal theory of homosexuality holds that, just as exposure to circulating sex hormones determines whether a fetus will be male or female, such exposure must also influence sexual orientation.

The cases of children born with disorders of "sexual differentiation" offer insight. William Reiner, a psychiatrist and urologist with the University of Oklahoma, has evaluated more than a hundred of these cases. For decades, the standard medical response to boys born with severely inadequate penises (or none at all) was to castrate the boy and have his parents raise him as a girl. But Reiner has found that nurture - even when it involves surgery soon after birth - cannot trump nature. Of the boys with inadequate penises who were raised as girls, he says, "I haven't found one who is sexually attracted to males." The majority of them have transitioned back to being males and report being attracted to females.

During fetal development, sexual identity is set before the sexual organs are formed, Reiner says. Perhaps it's the same for sexual orientation. In his research, of all the babies with X and Y chromosomes who were raised as girls, the only ones he has found who report having female identities and being attracted to males are those who did not have "receptors" to let the male sex hormones do their masculinizing in the womb.

"Exposure to male hormones in utero dramatically raises the chances of being sexually attracted to females," Reiner says. "We can infer that the absence of male hormone exposure may have something to do with attraction to males."

New York University researcher Lynn S. Hall, who has studied traits determined in the womb, speculates that Patrick was somehow prenatally stressed, probably during the first trimester, when the brain is really developing, particularly the structures like the hypothalamus that influence sexual behavior. This stress might have been based on his position in the womb or the blood flow to him or any of a number of other factors not in his mother's control. Yet more evidence that identical twins have womb experiences far from identical can be found in their often differing birth weights. Patrick was born a pound lighter than Thomas.

the research suggests that early on in the womb, as the fetus's brain develops in either the male or female direction, something fundamental to sexual orientation is happening. Nobody's sure what's causing it. But here's where genes may be involved, perhaps by regulating hormone exposure or by dictating the size of that key clump of neurons in the hypothalamus. Before researchers can sort that out, they'll need to return to the question of whether, in fact, there is a "gay gene."

There is, however, a towering question that Sanders's study will probably not be able to answer. That has to do with evolution. If a prime motivation of all species is to pass genes on to future generations, and gay men are estimated to produce 80 percent fewer offspring than straight men, why would a gay gene not have been wiped out by the forces of natural selection? This evolutionary disadvantage is what led former Amherst College biologist Paul Ewald to argue that homosexuality might be caused by a virus - a pathogen most likely working in utero. That argument caused a stir when he and a colleague proposed it six years ago, but with no research done to test it, it remains just another theory. Other scientists have offered fascinating but unpersuasive explanations, most of them focusing on some kind of compensatory benefit, in the same way that the gene responsible for sickle cell anemia also protects against malaria. A study last year by researchers in Italy showed that female relatives of gay men tended to be more fertile, though, as critics point out, not nearly fertile enough to make up for the gay man's lack of offspring.

Those same genes would work one way in heterosexual women and another way in homosexual men. The UCLA lab is examining how these genes might be turned "up" or "down." It's not a question of what genes you have, but rather which ones you use, says Bocklandt. "I have the genes in my body to make a vagina and carry a baby, but I don't use them, because I am a man." In studying the genes of gay sheep, for example, he's found some that are turned "way up" compared with the straight rams.