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Researcher Alan Sanders signs up Daniel Velez Rivera on Boston Common for a study using gay brothers to search for the genetic basis for homosexuality. (Illustration / Chris Buzelli; Globe Staff Photo / David Kamerman)

Michael Bailey says Reiner's findings represent a major breakthrough, showing that "whatever causes sexual orientation is strongly influenced by prenatal biology." Bailey and Reiner say the answer is probably not as simple as just exposure to sex hormones. After all, the exposure levels in some of the people Reiner studies are abnormal enough to produce huge differences in sexual organs. Yet, sexual organs in straight and gay people are, on average, the same. More likely, hormones are interacting with other factors.

Canadian researchers have consistently documented a "big-brother effect," finding that the chances of a boy being gay increase with each additional older brother he has. (Birth order does not appear to play a role with lesbians.) So, a male with three older brothers is three times more likely to be gay than one with no older brothers, though there's still a better than 90 percent chance he will be straight. They argue that this results from a complex interaction involving hormones, antigens, and the mother's immune system.

By now, there is substantial evidence showing correlation - though not causation - between sexual orientation and traits that are set when a baby is in the womb. Take finger length. In general, men have shorter index fingers in relation to their ring fingers; in women, the lengths are generally about the same. Researchers have found that lesbians generally have ratios closer to males. Other studies have shown masculinized results for lesbians in inner-ear functions and eye-blink reactions to sudden loud noises, and feminized patterns for gay men on certain cognitive tasks like spatial perception and remembering the placement of objects.

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.

Taken together, 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."

THE CROWD ON BOSTON COMMON IS THICK ON THIS SCORCHER of a Saturday afternoon in June, as the throngs make their way around the 35th annual Boston Pride festival, past booths peddling everything from "Gayopoly" board games to Braveheartian garments called Utilikilts. Sitting quietly in his booth is Alan Sanders, a soft-spoken 41-year-old with a sandy beard and thinning hair. He's placed a mound of rainbow-colored Starbursts on the table in front of him and hung a banner that reads: "WANTED: Gay Men with Gay Brothers for Molecular Genetic Study of Sexual Orientation."

Sanders is a psychiatrist with the Evanston Northwestern Healthcare Research Institute who is leading the NIH-funded search for the genetic basis of male homosexuality (www.gaybros.com). He is spending the summer crisscrossing the country, going to gay pride festivals, hoping to recruit 1,000 pairs of gay brothers to participate. (His wife, who just delivered their third son, wasn't crazy about the timing.) When people in Boston ask him how much genes may contribute to homosexuality, he says the best estimate is about 40 percent.

Homosexuality runs in families - studies show that 8 to 12 percent of brothers of gay men are also gay, compared with the 2 to 4 percent of the general population.

Sanders spends much of the afternoon handing out Starbursts to people who clearly don't qualify for a gay brothers study - preteen girls, adult lesbians wearing T-shirts that read "I Like Girls Who Like Girls," and elderly women in straw hats who speak only Chinese. But many of the gay men who stop by are interested in more than free candy. Among the people signing up is James Daly, a 31-year-old from Salem. "I think it's important for the public - especially the religious right - to know it's not a choice for some people," Daly says. "I feel I was born this way."

(In fairness, there aren't many leaders of groups representing social and religious conservatives who still argue that homosexual orientation - as opposed to behavior - is a matter of choice. Even as he insists that no one is born gay, Peter Sprigg, the point person on homosexuality for the Family Research Council, says, "I don't think that people choose their sexual attraction.")

In the decade since Dean Hamer made headlines, the gay gene theory has taken some hits. A Canadian team was unable to replicate his findings. Earlier this year, a team from Hamer's own lab reported only mixed results after having done the first scan of the entire human genome in the search for genes influencing sexual orientation.

But all of the gene studies so far have been based on small samples and lacked the funding to do things right. Sanders's study should be big enough to provide some real answers on linkage as well as shed light on gender nonconformity and the big-brother effect.

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.

But there will be plenty of time for sorting out the evolutionary paradox once - and if - researchers are able to identify actual genes involved in sexual orientation. Getting to that point will likely require integrating multiple lines of promising research. That is exactly what's happening in Eric Vilain's lab at the University of California, Los Angeles. Vilain, an associate professor of human genetics, and his colleague, Sven Bocklandt, are using gay sheep, transgenic mice, identical twin humans, and novel approaches to human genetics to try to unlock the mystery of sexual orientation.

Instead of looking for a gay gene, they stress that they are looking for several genes that cause either attraction to men or attraction to women. 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.

The lab is also testing an intriguing theory involving imprinted genes. Normally, we have two copies of every gene, one from each parent, and both copies work. They're identical, so it doesn't matter which copy comes from which parent. But with imprinted genes, that does matter. Although both copies are physically there, one copy - either from the mom or the dad - is blocked from working. Think of an airplane with an engine on each wing, except one of the engines is shut down. A recent Duke University study suggests humans have hundreds of imprinted genes, including one on the X chromosome that previous research has tied to sexual orientation.

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