6/12/95 SCIENCE: Search for a gay gene

A DNA transplant made these male fruit flies turn away from females. What does that say about the origins of homosexuality?

BY LARRY THOMPSON/BETHESDA

Fruit flies are among the most sexually proficient creatures on earth. Their ability to produce a new generation in two weeks has made them the darlings of genetics researchers for nearly a century. Put a male fruit fly into a bottle with a female, and he doesn't waste any time before getting down to business.

So it's a bit bewildering to watch the behavior of certain fruit flies at the National Institutes of Health in Bethesda, Maryland. There, in the laboratories of biologists Ward Odenwald and Shang-Ding Zhang, strange things are happening inside the gallon-size culture jars. In some experiments, the female flies are cowering in groups at the top and bottom of the jars. The males, meanwhile, are having a party--no, an orgy -- among themselves.

With a frenzy usually reserved for chasing females, the males link up end-to-end in big circles or in long, winding rows that look like winged conga lines. As the buzz of the characteristic fruit fly "love song" fills the air, the males repeatedly lurch forward and rub genitals with the next ones in line.

What's going on?

Without a wink or a chuckle, Odenwald claims that these male fruit flies are gay -- and that he and Zhang made them that way. The scientists say they transplanted a single gene into the flies that caused them to display homosexual behavior. And that's very interesting, they assert, because a related gene exists in human beings, although there is no evidence yet that the human gene has an effect on sexual preference.

A report of Odenwald and Zhang's findings, to be published this week in Proceedings of the National Academy of Sciences, adds to the mounting evidence that homosexuality has genetic origins, and is sure to produce new fireworks in the contentious debate over what it means to be gay. The two scientists are not foolhardy enough to claim that a single gene can make a person homosexual. But they think their studies may yield important new insights into how genetic makeup, through a complex series of biochemical reactions, influences sexual orientation.

Such work stirs mixed emotions in the gay community. To some extent, gays and lesbians welcome the research because it supports what most of them have long felt: that homosexuality is an innate characteristic, like skin color, rather than a perverse life-style choice, as conservative moralists contend. And if that is true, then gays deserve legal protection similar to the laws that prohibit racial discrimination. "On a political level, genetic research does seem to move the debate along a certain path," says Denny Lee of the Lambda Legal Defense and Education Fund, a gay advocacy group in New York City. "When people understand that being gay or lesbian is an integral characteristic, they are more open-minded about equality for gay Americans."

On the other hand, many gays are wary of the genetic hypothesis. It could, they fear, help promote the notion that gayness is a "defect" in need of "fixing." "Any finding will be used and twisted for homophobic purposes," says Martin Duberman, head of the Center for Lesbian and Gay Studies at the City University of New York. "If it does turn out that for some people, there is a genetic or hormonal component, the cry will then arise to take care of that." Indeed, the cry is already rising.

The Rev. Louis P. Sheldon, president of the Traditional Values Coalition in Anaheim, California, says that if a biological cause of homosexuality is found, then "we would have to come up with some reparative therapy to correct that genetic defect."

No matter how people feel about the issue, it is increasingly hard to argue that genes play no role in homosexuality. The evidence began to pile up in 1991, when studies showed that identical twins were more likely to have the same sexual orientation than other pairs of siblings. That same year, a California scientist reported slight brain differences between gay and straight men, although the conclusion is disputed. And in 1993, an NIH researcher found a stretch of DNA on the X chromosome that seemed to harbor one or more genes affecting sexual orientation. But no one has proved that a particular gene promotes gayness or has offered any convincing theory of how genes could influence a person's choice of sleeping partners.

Odenwald and Zhang do not pretend to have any easy answers. In fact the type of gene they've been studying in fruit flies could not begin to account for the complex variations in human homosexual behavior. For one thing, the gene does not cause flies to renounce heterosexuality altogether. If a "gay" fly is surrounded by females instead of males, he'll fertilize the lady flies. So strictly speaking, the NIH flies are not homosexual but bisexual. And the gene produces no unusual behavior when transplanted into females: the scientists have produced no lesbian fruit flies.

Yet the way the gene works is intriguing, and may offer some clues to the biochemical roots of gayness. Surprisingly, the swatch of DNA in question was discovered long ago, and is one of the most thoroughly studied of all fruit-fly genes. It is called the "white" gene because, among many effects, it influences eye color, and a particular mutation in the gene causes a fly's normally red eyes to be white.

The gene's specific job is to produce a protein that enables cells to utilize an essential amino acid called tryptophan. If fruit flies are unable to process tryptophan properly, then they cannot manufacture red eye pigment.

Under normal circumstances, the white gene is active only in certain cells, including brain cells, and does nothing to disrupt standard sexual behavior. In the NIH experiments, Odenwald and Zhang inserted a normal version of the gene into embryonic flies, but transplanted the gene in such a way that it was activated in every cell. That's what apparently played havoc with the flies' sex lives. With every cell sucking in tryptophan from the blood, a shortage of tryptophan developed in the brain, where it has important uses. Since tryptophan levels were altered, the researchers hypothesize, the brain was unable to make enough serotonin, one of the neurotransmitters that carry messages between nerve cells. Serotonin is a multi-purpose chemical, and abnormal levels of it in humans have been linked to everything from depression to violent behavior. In the case of the gay fruit flies, the scientists speculate, a shortfall of serotonin produced those all-male conga lines.

Though the idea seems far-fetched, it jibes with two decades of research suggesting that serotonin plays a role in regulating sexual behavior. One piece of evidence is the action of the drug Prozac, which relieves depression by lifting serotonin levels in the brain. At the same time, though, the serotonin boost tends to dampen sexual desire. In contrast, low serotonin levels can produce heightened sexual activity, at least in lab animals. In experiments done in the U.S. and Italy, scientists used drugs and special diets to suppress serotonin in rats, mice, cats and rabbits. The result was increased sex drive and, sometimes, homosexual couplings.

As intriguing as it sounds, the serotonin theory is still full of holes. Even if shortages of the chemical increase sexual activity, why would it often be homosexual rather than heterosexual? And if sexual orientation is genetically determined, then why do some identical twins differ in sexual preferences?

Getting the answers, if possible at all, will require much more research. Even harder will be knowing how to use any knowledge that emerges. Will children be given genetic tests to determine the odds of their becoming homosexual? Will prenatal tests lead to abortions of fetuses that might grow up to be gay?

Scientists caution against jumping to conclusions about the meaning of the NIH studies. To complicate the picture, some of the work shows that environment, along with genetics, influences sexual behavior. In one experiment, a small group of "straight" flies was mixed with a larger group of genetically altered "gay" flies.

While the gays formed their conga lines, the straights stayed to the side -- but only temporarily. After a few hours, the straights joined in and, for the time being, acted gay.

In fruit flies, and certainly in humans, sexual orientation is just not a simple matter. And no amount of scientific research is going to change that fact of life.

Copyright 1995 Time Inc. All rights reserved.

CANCER FACTS
National Cancer Institute
National Institutes of Health

A new study has found a correlation between a specific region of the X chromosome and male homosexuality. The finding represents new evidence that sexual orientation may be influenced by heredity.

The study is reported in the July 16 issue of Science by scientists from the National Institutes of Health in Bethesda, Maryland.

By analyzing the inheritance of genetic markers in pairs of homosexual brothers, the scientists localized the region related to sexual orientation to a minute segment of the human genome. However, a specific gene has not yet been isolated.

Dean Hamer, Ph.D., chief author of the study, said, "The region that we've discovered represents a significant variation in the human genetic repertoire. If the gene itself can be isolated, then it will be important to understand how it interacts with other genes, the brain, and the environment to influence a trait as complex and variable as human sexuality."

Hamer is with the National Cancer Institute and conducted the study as part of the Institute's effort to identify genetic factors involved in cancers that are frequently found in gay men infected with the AIDS virus.

Hamer and colleagues studied the family histories of 114 gay men and found that their brothers, maternal uncles, and maternal male cousins were more likely to be homosexual than would be expected among the general male population. In some families, gay relatives could be traced back for three generations. Because the homosexual uncles and male cousins of the gay subjects were raised in different households, the scientists hypothesized that a genetic factor was involved. Furthermore, the maternal link suggested that homosexuality might be associated with the X chromosome, which is the sex-linked chromosome that men inherit only from their mothers.

Explicit evidence for a genetic link was obtained by studying the X chromosome DNA of 40 pairs of gay brothers. The scientists used a technique called linkage mapping to search for patterns of similarity in the genetic information of related individuals. Thirty-three of the gay sibling pairs had coinherited genetic markers in the same chromosome region called Xq28, suggesting that 65 percent of the families studied were transmitting a gene for homosexual orientation.

"The statistical significance of the results was better than 99 percent, which means that the possibility of obtaining our findings by chance is extremely unlikely," said Hamer. However, he noted that replication on an independent population of families will be necessary to confirm the results.

The scientists do not know why 7 of the 40 pairs of gay brothers did not coinherit the Xq28 genetic marker. Hamer postulated that these gay men may have inherited other genes that are associated with homosexuality, or they might have been influenced by environmental factors or life experiences.

"Given the intricacies of human behavior, it is not surprising that a single genetic locus [region] fails to account for all of the variation seen in the study group," said Hamer. "What is remarkable is that we can account for at least some of the inherited variability with a fair degree of statistical confidence."

The scientists are also studying the families of lesbians. Preliminary results suggest that female sexual orientation is genetically influenced, but DNA markers have not been detected yet.

Hamer emphasized that the study was not designed to test for sexual orientation. The findings do not permit determination of an individual's sexual orientation, he pointed out, because the complexities of sexuality cannot be fully explained by a gene or genes.

As efforts to map the human genome progress, there will be increasing concern about how the information is used. Scientists, educators, policymakers, and the public should work together to ensure that behavioral genetics research is used to benefit all members of society and not to discriminate," said Hamer.

The study is titled "A Linkage Between DNA Markers on the X Chromosome and Male Sexual Orientation." The authors are Dean H. Hamer, Ph.D., Stella Hu, M.A., Victoria L. Magnuson, Ph.D., Nan Hu, M.D., and Angela M. L. Pattatucci, Ph.D.

Date Last Modified: 07/93

Angier, Natalie. "Research on Sex Orientation Doesn't Neatly Fit the Mold." New York Times, 18 July 1993.

Describes Dr. Dean Hamer's research into a genetic basis for sexual orientation. Hamer's study, reported in the journal Science, found that 33 of 40 pairs of gay brothers had identical regions on a tip of the X chromosome, suggesting that one or more genes at that location may be partially responsible for their sexual preference. Dr. Hamer, with the National Cancer Institute (Bethesda, MD), claims that other genes, as well as environmental factors, almost certainly help determine a person's sexual orientation.

Leaders of gay groups, policy makers and others are grappling with the social implications of the research. While some gays embrace the idea that sexual orientation is innate and unchangeable, others worry that the emphasis on the biology of homosexuality is motivated by a desire to "fix" it with some kind of medical intervention. There's also a concern that Hamer's research could lead to prenatal testing for a gay-linked gene and then the aborting of fetuses with the gene. In any case, many doubt that biology alone can explain something believed to have social, environmental and even political roots.

Will the new discoveries aid efforts to block anti-gay rights ordinances, promote anti-discrimination laws, or counter homophobia? Richard Green at UCLA said if homosexuality were discovered to be as unchangeable as race, then laws discriminating against gays and lesbians may fall. Gregory King, spokesman for the Human Rights Campaign Fund (Washington, DC): "We know from polls that when people understand that sexual orientation is not chosen, they are more inclined to support basic civil rights for lesbian and gay people." Kevin Cathcart, executive director, Lambda Legal Defense and Education Fund (NY): "Bigotry does not respond well to facts. Race and gender are clearly biologically determined, and yet that hasn't eliminated racism and misogyny."

Lon Mabon, chairman of the anti-gay Oregon Citizens Alliance (Wilsonville, OR), believes that homosexuality should not be condoned even if it has a biological basis: "Some people have said there's a genetic link to alcoholism, but that does not excuse the drunk."

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[ Of course, the last idiot seems to have ignored the fact that drunks kill people due to thier, uh, happy state... and gays don't... - Joe Seatter ]