The Gene: An Intimate History - Siddhartha Mukherjee Page 0,174

the genetics of sexual orientation using a twin-study experiment. Bailey’s methodology was classical: if sexual orientation was partly inherited, then a higher proportion of identical twins should both be gay compared to fraternal twins. By placing strategic advertisements in gay magazines and newspapers, Bailey had recruited 110 male twin pairs in which at least one twin was gay. (If this seems difficult today, imagine running this experiment in 1978, when few men were publicly out of the closet, and gay sex in certain states was punishable as a crime.)

When Bailey looked for concordance of gayness among twins, the results were striking. Among the fifty-six pairs of identical twins, both twins were gay in 52 percent.I Of the fifty-four pairs of nonidentical twins, 22 percent were both gay—lower than the fraction for identical twins, but still significantly higher than the estimate of 10 percent gay in the overall population. (Years later, Bailey would hear of striking cases such as this: In 1971, two Canadian twin brothers were separated within weeks of birth. One was adopted by a prosperous American family. The other was raised in Canada by his natural mother under vastly different circumstances. The brothers, who looked virtually identical, knew nothing of each other’s existence until they ran into each other, by accident, in a gay bar in Canada.)

Male homosexuality was not just genes, Bailey found. Influences such as families, friends, schools, religious beliefs, and social structure clearly modified sexual behavior—so much so that one identical twin identified as gay and the other as straight as much as 48 percent of the time. Perhaps external or internal triggers were required to release distinct patterns of sexual behavior. Undoubtedly, the pervasive and repressive cultural beliefs that surrounded homosexuality were potent enough to sway the choice of a “straight” identity in one twin but not the other. But the twin studies provided incontrovertible evidence that genes influenced homosexuality more strongly than, say, genes influenced the propensity for type 1 diabetes (the concordance rate among twins is only 30 percent), and almost as strongly as genes influence height (a concordance of about 55 percent).

Bailey had profoundly changed the conversation around sexual identity away from the 1960s rhetoric of “choice” and “personal preference” toward biology, genetics, and inheritance. If we did not think of variations in height or the development of dyslexia or type 1 diabetes as choices, then we could not think of sexual identity as a choice.

But was it one gene, or many genes? And what was the gene? Where was it located? To identify the “gay gene,” Hamer needed a much larger study—preferably a study involving families in which sexual orientation could be tracked over multiple generations. To fund such a study, Hamer would need a new grant—but where on earth might a federal researcher studying metallothionine regulation find money to hunt for a gene that influences human sexuality?

In early 1991, two developments enabled Hamer’s hunt. The first was the announcement of the Human Genome Project. Even though the precise sequence of the human genome would not be known for another decade, the mapping of pivotal genetic signposts along the human genome made it vastly easier to hunt for any gene. Hamer’s idea—of mapping genes related to homosexuality—would have been methodologically intractable in the 1980s. A decade later, with genetic markers strung like marquee lights along most chromosomes, it was at least conceptually within reach.

The second was AIDS. The illness had decimated the gay community in the late 1980s—and goaded by activists and patients, often through civil disobedience and militant protests, the NIH had eventually committed hundreds of millions of dollars to AIDS-focused research. Hamer’s tactical genius was to piggyback the gay gene hunt on an AIDS-related study. He knew that Kaposi’s sarcoma, a previously rare, indolent tumor, had been found at a strikingly high frequency among gay men with AIDS. Perhaps, Hamer reasoned, the risk factors for the progression of Kaposi’s sarcoma were related to homosexuality—and if so, finding genes for one might lead to identifying genes for the other. The theory was spectacularly wrong: Kaposi’s sarcoma would later be found to be caused by a virus, transmitted sexually and occur mainly in immunocompromised people, thus explaining its co-occurrence with AIDS. But it was tactically brilliant: in 1991, the NIH granted Hamer $75,000 for his new protocol, a study to find homosexuality-related genes.

Protocol #92-C-0078 was launched in the fall of 1991. By 1992, Hamer had attracted 114 gay men to his study. Hamer planned to use the cohort to create