Ushering the politically explosive study of the origins of sexual orientation into a new and perhaps more scientifically rigorous phase, researchers report that they have linked male homosexuality to a small region of one human chromosome.
The results have yet to be confirmed by other laboratories, and the chromosomal region implicated, if it holds up under further scrutiny, is almost surely just a single chapter in the intricate story of sexual orientation and behavior. Nevertheless, scientists said the work suggests that one or several genes located on the bottom half of the sausage-shaped X chromosome may play a role in predisposing some men toward homosexuality. (The researchers have begun a similar study looking at the chromosomes of lesbians.)
The findings, which appear today in the journal Science, indicate that sexual orientation often is at least partly inborn, rather than being solely a matter of choice. But researchers warn against overinterpreting the work, or in taking it to mean anything as simplistic as that the "gay gene" has been found.
The researchers emphasized that they do not yet have a gene isolated, but merely know the rough location of where the gene or genes may sit amid the vast welter of human DNA, Until they have the gene proper, scientists said they had no way of knowing how it contributes to sexual orientation, how many people carry it, or how often carriers are likely to become gay as a result of bearing the gene.
And even when they do have this gene on the X chromosome pinpointed, scientists said they will continue to search for other genes on other chromosomes that may be involved in sexual orientation. "Sexual orientation is too complex to be determined by a single gene," said Dr. Dean H. Hamer of the National Cancer Institute in Bethesda, Md., the lead author of the new report. "The main value of this work is that it opens a window into understanding how genes, the brain and the environment interact to mold human behavior."
In the new work, the scientists studied the genetic material from 40 pairs of gay brothers and found that in 33 of the pairs, the brothers had identical pieces of the end tip of the X chromosome. Under ordinary circumstances ruled by chance alone, only half of the pairs should have shared that chromosomal neighborhood in common, a region designated Xq28. The odds of Dr. Hamer's results turning up randomly are less than half a percent, indicating that the chromosomal tip likely harbors a genetic sequence linked to the onset of the brothers' homosexuality.
The gene could work by directly influencing sexual proclivity, perhaps by shaping parts of the brain that orchestrate sexual behavior. Or it might affect temperament in a way that predisposes a boy toward homosexuality. At the moment, researchers said, all scenarios are mere speculation. Despite the cautionary notes, the latest study is likely to add fuel to the debate over gay rights in the military and civilian realms.
If homosexuality is shown to be largely inborn, a number of legal experts say, then policies that in any way discriminate against homosexuals are likely to be shot down in the courts.
"We think this study is very important," said Gregory J. King, a spokesman for the Human Rights Campaign Fund in Washington, the largest national lesbian and gay lobbying group, "Fundamentally it increases our understanding of the origins of sexual orientation, and at the same time we believe it will help increase public support for lesbian and gay rights."
Not all gay rights leaders have sanguine view of the work. some denounce it as yet another attempt to draw a reductionist and implacable line between homosexuality and heterosexuality, while others see in in the dangers of attempts to "fix" homosexuality, perhaps through gene therapy.
"I don't think it's an interesting study," said Darrell Yates Rist, co- founded of the Gay and Lesbian Alliance Against Defamation. "Intellectually, what do we gain by finding out there's a homosexual gene? Nothing, except an attempt to identify those people who have it and then open them up to all sorts of experimentation to change them."
The study appears in the same journal that two years ago unleashed a furious debate when it published a report asserting to have found an anatomical difference between the brains of gay and straight men. Other recent reports have also weighed in on the possible biological basis of homosexuality in both men and women, and all have been subject to volleys of scientific and political attack.
Other attempts to make a genetic link to behavior, like alcoholism, manic depression and schizophrenia, have thus far all been disappointing. By contrast, today's study is considered to be impressive science even by many who denounced the previous studies.
Dr. Eric Lander of the Whitehead Institute for Biomedical Research in Cambridge, Mass., said, "From a geneticist's point of view, if you strip away the nonscientific considerations, it's an interesting finding that merits being followed up in a larger sample."
Dr. Simon LeVay, chairman of the Institute of Gay and Lesbian Studies in West Hollywood, Calif., who did the 1991 study comparing gay and hetero- sexual brains, was considerably more ecstatic in his appraisal of the latest report.
In the latest experiments, the researchers began by taking the family histories of 114 men who identified themselves as homosexual. Much to their surprise, the researchers discovered a higher than expected number of gay men among the men's maternal uncles and male cousins who were the sons of their mothers' sisters. The ratio was far higher than for men in the general population, suggesting a gene or genes that is passed through the maternal line and thus through the X chromosome.
The scientists then focused on gay brothers, on the assumption that if two boys in a family are homosexual, they were more likely to be so for genetic reasons than were those homosexual men without gay brothers. Using a well-known genetic technique called linkage mapping, they scrutinized the X chromosome in the brothers and other relatives by the application of DNA markers, tiny bits of genetic material that can distinguish between chromosomes from different people. The researchers found that more than three-quarters of the brothers had inherited identical DNA markers on the Xq28 region of the chromosome.
"I was surprised at how easy this was to detect," Dr. Hamer said. "Part of that ease was because we were working with the X chromosome, the most extensively studied chromosome in the human genetic blueprint. So far the study has been limited to men who said they were gay, eliminating the ambiguity that would come from considering the genes of men who called themselves heterosexual.
Nonetheless, the region is about four million bases, of DNA building blocks long, and hence holds hundreds of genes, meaning the scientists have much work ahead of them to sort out which gene or genes is relevant. The researchers are also trying to perform a similar linkage study on lesbian sisters, but so far they have not managed to find a chromosomal region that is consistently passed along in families.