Chapter One
THE SEARCH FOR A âGAY GENEâ
Every single day, in laboratories and universities, scientists make discoveries, some great and some small, but few of them are reported on the front pages of the worldâs major newspapers, featured on talk shows, included in Time magazineâs list of âThe Best Scienceâ of the year, heralded in the National Enquirer, and turned into catchy slogans for T-shirts.
Once in a while, though, a study will hit the right buttons at the right time and will cause a wave of scientific and popular reaction that, for the scientists involved, can be both encouraging and frightening. Thatâs what happened to me in the summer of 1993, when a scientific journal reported the results of a two-year study performed in my normally quiet U.S. government laboratory. The topic was a genetic link to homosexuality, and the study appeared when gay issues were at the top of the political agenda because of the rancorous debate over homosexuals in the military.
The day the study appeared, the front-page Washington Post story bore the straightforward headline: STUDY LINKS GENES TO HOMOSEXUALITY. USA Todayâs headline asked, IS THERE A GAY GENE? That evening I was invited to appear on âNightlineâ for the first of many television interviews.
The follow-up stories began to raise the implications of our study. GAYS AND THE DNA LINK: STUDY SHOWING THAT HOMOSEXUALITY MAY RUN IN THE FAMILY SETS OFF ALARM BELLS, warned Canadaâs Edmonton Journal. Another Canadian paper, the Ottawa Citizen, wrote, GENE FIND OPENS PANDORAâS BOX OF ETHICAL AND LEGAL ISSUES.
Some headlines were alarmist, like the Daily Telegraph of Londonâs darkly foreboding CLAIM THAT HOMOSEXUALITY IS INHERITED PROMPTS FEARS THAT SCIENCE COULD BE USED TO ERADICATE IT. Others apparently were meant to be reassuring: STUDY LINKING GENES TO HOMOSEXUALITY DOESNâT ALTER RELIGIOUS LEADERSâ STANCE (Louisville, Kentucky, Courier-Journal). Many papers welcomed the study. As North Carolinaâs Greensboro News & Record editorialized, âResearch might lead to more tolerance of gays.â
Then skeptics appeared in the form of guest columnists, such as the medical doctor writing in the San Francisco Examiner who advised that reports of a genetic link to homosexuality smelled like a âfish story.â The National Enquirer sounded a more âpositiveâ note with the promise: SIMPLE INJECTION WILL LET GAY MEN TURN STRAIGHT, DOCTORS REPORT.
Many of the reactions were more personal, and my mailbox filled with letters from people thanking me for doing the study. Other letters promised I would burn in hell. One woman wrote to express her âamazement and disgust,â while a âgay man and a molecular geneticistâ writing from England castigated me for results that he felt would increase hatred of gays. âI fear that your work will make our lives more unbearable,â he wrote. âMaybe this is your aim?â A man from the Virgin Islands, who accused me of âattempting to gain publicity and legitimize a purely moral question through science,â ended his angry missive with âTake that, you scientist.â
More common, and often very moving, were letters from people writing about their own families. One man explained that he was the father of two young men who recently had announced, to the surprise and dismay of the rest of the family, that they were gay. Badly shaken by the news, the father sought help from his church. He was told that homosexuality was wrong but that it could be cured through prayer. Most damning of all, he was told that it was caused by parents who lacked faith or didnât properly raise their children. The burden of guilt was tremendous, he wrote, and his first reaction was to hate himself, reject his sons, and deny what they had told him.
Then he saw an article about my work that said homosexuality might be genetic. His sense of relief was overwhelming because he wasnât the problem, after all. This was something out of his control; it was nature, not his nurture. He could forgive himself, and more importantly, forgive his sons and welcome them back into the loving embrace of the family, now made stronger by this test of faith.
Perhaps I should have been gratified by testimony like this. Every scientist wants to think his or her work matters, that long hours of tedious research wonât just be filler for some little specialized journal but will improve lives and make the world a better place.
Instead, I was saddened. This man had changed the course of his life, and the lives of everyone in his family, because of a few paragraphs in a magazine. He decided to forgive his sons because we found a genetic link to homosexuality. But what if the experiment had failed? Or what if we gave his family a blood test and found they didnât have the âgay gene,â that the sons were gay for some other reason? Then would this father go back to blaming himself for raising two gay sons, and would they be less worthy of his love?
These kinds of questions, and all the attention, were new to me, an obscure molecular geneticist who had spent the previous sixteen years bustling about in a small federal laboratory, jumbled floor to ceiling with beakers, vials, and other paraphernalia. It is the kind of place that has âemergency showersâ in case something spills, but on most days not much happens that is very exciting. No one outside of my immediate scientific circle ever had paid much attention to my work before, but now strangers were sending me letters, reporters wanted interviews, lawyers subpoenaed me to testify in court, and members of Congress wanted to know just what in the world was going on.
All because I wondered what makes people gay.
The origins of human sexuality, and of homosexuality in particular, have puzzled philosophers, theologians, and ordinary people for thousands of years. In a few scattered cultures, homosexuality has been regarded as a normal part of life or even as a special talent or gift from the gods. In most societies we know, however, same-sex attractions or homosexual behavior have been treated as an unforgivable sin or a terrible crime. Beginning in the late 1800s, psychiatrists and psychologists turned their attention to homosexuality and concluded that it was a mental disorder caused by a misguided upbringing. This disease model remained the primary way of thinking about homosexuality during most of the twentieth century.
More recently, however, some scientists have begun to view both heterosexuality and homosexuality as natural variations of the human condition that are at least as deeply rooted in nature as in nurture. During the past several years, researchers have detected minute but significant differences between the brains of heterosexual and homosexual men. Others have shown that genetically identical twins are more likely to both be gay than are brothers who arenât twins. These results suggest that homosexuality is at least partly inheritedâa finding of no great surprise to gay men, most of whom feel they were âborn that way.â
No one had ever been able to prove that homosexuality was swayed by genes, however, until our study offered the most convincing evidence to date that sexual orientation was genetically influenced. Thatâs why we were in magazines and on TV, and why I was receiving kindness from strangers. We didnât invent a new idea, we just showed it was true.
The first part of our study was something that could have been done years ago, only nobody bothered. We simply traced back the lineages of gay men, looking for signs of homosexuality in all the twigs and branches of their family trees. We drew orchards of these trees, going back as far as anyone could remember and stretching as wide as possible to include second cousins and great uncles. We found far more gays on the motherâs side of the families than on the fatherâs side, a pattern consistent with a special type of inheritance called sex linkage. The expression comes from the fact that the relevant gene is on one of the two sex chromosomes, in this case the X chromosome.
The second part of the study was something that never had or could have been done before because the scientific tools and techniques were brand-new. We looked directly at gay menâs genetic informationâtheir DNA, the long threadlike molecule that contains both the blueprints of life and the instructions for carrying them out. Using an approach called DNA linkage analysis, we found that a small region of the X chromosome, Xq28, appeared to be the same in an unexpectedly high proportion of gay brothers. This finding provided the first concrete evidence that âgay genesâ really do exist and narrowed the location of one of them to a few million out of the several billion bits of information that make us human. What we found was a marker, a strip of DNA usually transmitted whole, rather than the smaller bit of DNA regarded as a single gene.
Our results were published on 16 July 1993, in Science, the technical journal of the American Association for the Advancement of Science. The title of our six-page article was not likely to win any awards for headline writing: âA Linkage Between DNA Markers on the X Chromosome and Male Sexual Orientation.â* A pithier summation of the study appeared a few days later on T-shirts sold at gay and lesbian bookstores: âXq28âThanks for the genes, Mom!â
WHY ALL THE FUSS?
Most of the time, proving something that people already suspected doesnât cause such a stir, but sexual orientation is no ordinary topic. Itâs at the center of a fierce debate involving politics, the law, religion, ethics, and the origins and meaning of human behavior. Remember how etiquette books used to advise that certain topics were not appropriate for dinner-table conversation? Put a bunch of those topics together and you have the âgay geneâ story.
Our results were published during the midst of the great debate over gays in the military. In fact, the date set by President Clinton for the Pentagon to have a new policy on homosexuality was 15 July 1993, just one day before our paper appeared. When the study was published, my phone rang off the hook with questions about how the results might affect the new Pentagon policy. Some people said our study proved that keeping gay men and lesbians out of the military was the same as the earlier discrimination against African-Americans. Others, however, including a guest who appeared with me on the program âNightline,â thought it now would be necessary to treat gay and lesbian service members as a âthird sexâ and segregate them in separate barracks.
Our research also had legal implications outside the military. The Supreme Court has made subtle but important distinctions between characteristics that are âimmutable,â or deeply ingrained and not easily changed, and those that are freely chosen. Many legal experts felt the evidence for a genetic link to homosexuality would strengthen the evidence for immutability and therefore cause tighter scrutiny of laws that permitted discrimination against gays and lesbians in housing, employment, or participation in the political process. Others, though, argued that immutability was a red herring and that the real issue was equal protection, not biology.
There were ethical, medical, and economic issues as well. Although our research did not provide any sort of test for the still hypothetical âgay gene,â there were legitimate concerns that we were headed in that direction. If such a test were developed, might parents decide to screen the fetus for homosexuality, just as they do now for Down syndrome and other genetic defects? Would some doctors regard homosexuality as a genetic defect that should be âcuredâ or weeded out of the population? Would insurance companies charge men with the âgay geneâ more for coverage or refuse to serve them, knowing the high risk of AIDS faced by gay men? These were possibilities that deeply worried many people, including myself. Making sure the results of our study were used ethically and responsibly would be at least as difficult as conducting the research itself.
Last but not least, there were implications for the hoary question of ânature versus nurture.â Most scientists now agree that the very wording of this question represents a false dichotomy and that both biology and the environment play some role in virtually all human behaviors. The relative contributions and precise nature of these factors, however, remain a matter of considerable speculation and debate, largely because of the lack of tools to dissect them. Our finding of a molecular linkage for an obviously complex and diverse aspect of behavior, sexual orientation, suggests the same approach could be used to identify genes for many different facets of human existence.
The goal of scientists around the world is to know, sometime during the next five to fifteen years, the precise structure of every single one of the 100,000 or so genes that make up our inherited information. If we were able to find a gene for such a complex behavior as homosexuality knowing only a fraction of this information, wonât others soon find genetic links for anger, impatience, or joy? Could there be genes that predispose some people to become great musicians and others to become criminals? And if such genes were found, wouldnât parents be tempted to manipulate or select the ones for characteristics they consider desirable? Everyone accepts the idea that genes give some people blue eyes and others brown eyes or make some people tall and others short. No one before our study, however, had proved a genetic linkage to a complex behaviorâany kind of behavior, not just sexual behavior. Finding and proving more of these genetic links will change the way we understand ourselves and perhaps change the very future of the human race.
AT LAST, NOT YEAST
As a molecular geneticist at the National Institutes of Health (NIH), the worldâs largest biomedical research facility, I was in a perfect place to look for genes involved in sexuality and other aspects of human behavior. The NIH has more than 16,000 employees, including 3,700 doctoral-level researchers, 1,800 clinicians, and 7,800 professional and technical staffers spread out over a âcampusâ in Bethesda, Maryland, just outside Washington, D.C. There are 370 beds dedicated to research, and the most modern laboratories anywhere. The complex has specialized institutes dealing with a growing range of health issues from cancer to alcoholism to child development and mental health. A new genetic research institute, the Human Genome Center, opened during 1993.
The ideal place to do research on homosexuality would be the National Institute of Sexuality. If only we had one. Despite the importance of sexuality to healthâafter all, sex is the very source of continued lifeâthere is no federally funded research center for sexuality. In fact, when I started our research in 1991 there was not even a single research group or laboratory at the NIH devoted to sexuality.
The Cancer Institute, where I work, certainly is not noted for its research into human sexuality. My own work there was not about sex, either. In fact, my work didnât even involve human beings. My usual subjects were yeast cells and mice, which are far less complicated than people, and I was studying things about them that are far less mystifying than sexuality. For ten years my entire laboratory had worked on one problem: the regulation of metallothionein (MT) gene transcription by heavy metal ions. Our goal was to understand how genes are turned on and off, or regulated.
Briefly, metallothionein is a protein that binds to heavy metal ions, such as copper, cadmium, mercury, and zinc, to protect cells against poisoning. When there are no metals around, the cell doesnât make MT, but when metals are present, the cell does. No one knew how this worked until 1988 when we discovered the secret of MT gene regulation, at least in yeast cells. We found that metals bind to a regulatory protein that changes shape. The altered protein binds to DNA sequences close to the beginning of the MT gene, which activates it. Other proteins bind to the regulatory protein, forming a complex that turns the MT gene DNA into messenger RNA and finally into the protein. This is a neat example of a molecular switch and provides a simple model of the type of switch that might be involved in more fundamental life processes, such as cellular determination and differentiation.
This was pure, basic science with few obvious applications. Fortunately, the NIH recognizes the importance of basic science, and not every project that is funded has to have an immediate application to medicine. Though my own lab is part of the Cancer Institute, during ten years the only possible connection to cancer we had come up with involved the use of a cancer drug called cis-platinum. One problem with this drug is that after extended therapy, patients build up a resistance, partly because the cancer cells start making more MT, which inactivates the platinum in the drug. If we could understand how this process worked, we might be able to improve the treatment.
People often ask why I switched from a field as obscure as metallothionein research to one as controversial as homosexuality. The answer is the same that most scientists give for why they do what they do: a combination of curiosity, altruism, and ambition (especially curiosity, both personal and scientific), combined with one more factorâboredom. After twenty years of doing science, I had learned quite a bit about how genes work in individual cells, but I knew little about what makes people tick.
The turning point in my career occurred in 1991, during a pair of conferences I attended in Oxford, England. Our work on MT was recognized internationally, and I was invited to be a guest speaker at both meetings. I was honored, but when I opened the floor to discussion, I had an extreme case of dĂ©jĂ vu: the questions people asked were exactly the same ones that had been asked the very first time I had talked about MT ten years earlier. Another speaker talked about work at his lab that was farther along than ours, but instead of being inspirational, that news only depressed me more. I realized that even if I stuck with this research for another ten years, the best I could hope for was to build a detailed three-dimensional replica of our little regulatory model. It didnât seem like much of a lifetime goal.
So even though the meetings focused on our work and I was an invited speaker, my mind was elsewhere. The evidence for this comes from a simple test that applies to all scientists. To determine what scientists really are interested in, donât focus on what they are doing. That just shows what they have been funded for and what experiments they think will work and produce another publication. Focus instead on what they are reading. By this time I had almost stopped looking at my longtime favorite journals, Molecular and Cellular Biology and Cell, which have terrific reads like âProtein Translocation into Proteoliposomes Reconstituted from Purified Components of the Endoplasmic Reticulum Membrane.â Instead, I carried in my traveling bag Nature Genetics, the American Journal of Human Genetics, and the Journal of AIDS Research.
What finally made up my mind to switch fields were two books that I picked up at a bookstore in Oxford during a lull between the conferences. The first was Descent of Man, and Selection in Relation to Sex, by Charles Darwin, published in 1871. I confess that even though Darwin is considered the father of modern biology, I never actually had read any of his work, except for the usual summaries in textbooks. I was surprised to find that fully three quarters of this 872-page book are devoted to âsexual selection,â the process whereby natural selection favors certain traits that make either males or females more successful in mating and therefore passing on their genes. The result is a sexual dimorphism, which refers to the differences between the two genders in nearly every species, from peacocks to human beings. Darwin also paid a great deal of attention to behavior, not just physical characteristics, and seemed quite certain that variations in behavior between individuals and between species must be at least partly inherited. The implication is that even sexuality most likely has a significant genetic component.
The second book was Not in Our Genes, by Richard Lewontin and colleagues. I knew Lewontin, a professor at Harvard University, was a very respected scient...