With homosexuality moved from the realm of psychiatric pathology into the realm of normal variants on human sexual behavior, research efforts took a new turn. Psychiatry had succeeded in defining what homosexuality is not—not in explaining what it is. Questions of etiology, in this as in other psychiatric matters, thus became by default questions for neurobiology. Are homosexuals and heterosexuals biologically different? In thinking about this question, biologists have been greatly influenced by findings that involve what may be a related question: Just how, neurologically, do men differ from women?
In 1959, at the University of California at Los Angeles, the neuroendocrinologist Charles Barraclough found that if a female rat was injected shortly before or after birth with testosterone, a male sex hormone, the abnormal amount of this hormone would make the rat permanently sterile, unable to ovulate. "Ovulation" as used here is in part a technical term: it refers both to what a lay person would think of as ovulation—the movement of an egg from the ovary into the fallopian tube—and to the series of hormonal interactions that cause that event.
Rats have short estrous cycles. Every four days various glands in the rat's body start pumping estrogens, or female sex hormones, into the bloodstream, setting in motion a series of chemical events. Estrogen levels reach a certain concentration and stimulate part of the hypothalamus, the small portion of the brain that regulates (among other things) body temperature, hunger, thirst, and sexual drive. The hypothalamus in turn stimulates the pituitary gland; the pituitary then releases a burst of something called luteinizing hormone, which causes the ovary to release an egg. Barraclnugh discovered that in female rats even a single perinatal exposure to testosterone will prevent this entire process from ever occurring. If that discovery was intriguing, a subsequent one was even more so: the discovery that male rats can ovulate—at least in the sense of going through the hormonal preliminaries. In 1965 Geoffrey Harris, a neuroendocrinologist at Oxford University, castrated a group of newborn male rats, depriving them of the testosterone from their testes. He found that if estrogen was injected into the bodies of these rats after they reached adulthood, it stimulated the hypothalamus, which initiated the sequence of hormone releases described above. The male rats obviously had no ovaries or wombs, but they went through the biochemical motions of ovulation. If one grafted an ovary onto a male rat, he would ovulate perfectly.
Further tests revealed a strange asymmetry. Whereas newborn male rats deprived of testosterone will, as Harris found, experience female-like ovulation, newborn female rats deprived of estrogen will continue to develop as females. In adulthood they will not seem somehow male. Although the rats' ovaries have been removed, their brains will still produce the stimulus to ovulate. Scientists realized that without testosterone the genetic blueprint for masculinity was essentially worthless. Indeed, they learned, for a male rat's brain to become truly organized as male, the rat must be exposed to testosterone within the first five days of life. After the fifth day the masculinizing window of opportunity is closed, and the genetic male will grow up with a "female" brain. In contrast, the brain of a female needs no estrogen for organization; left alone, it will become female.
Thus it came to be understood that what one might think of as the "default brain" for both sexes of the rat is feminine, and that testosterone is as necessary in the creation of a masculine brain as it is in the creation of masculine genitals. This concept, which is the basis of one approach to the neurobiological search for the origins of sexual orientation, is known as the "sexual differentiation of the brain."
Roger Gorski, a neurobiologist at the University of California at Los Angeles who has long been involved in research on sexual differentiation, looked back recently on the development of his field: "We spent much of our professional careers trying to understand this process of sexual differentiation, and what functions happen within it—male sex behavior, female sex behavior, control of ovulation, control of food intake, body weight, aggressive behavior, some aspects of maternal behavior. You know why male dogs lift their legs when they pee? Because the brain has changed. So this is really a fundamental concept, that the brain is inherently female and to develop as male it must be exposed to masculinizing hormones."
Several years after Harris's experiment other researchers at Oxford University succeeded in confirming anatomically what the principle of the sexual differentiation of the brain had strongly implied: that an observable difference exists between the brains of male rats and those of female rats. In 1971 the anatomists Geoffrey Raisman and Pauline Field published a paper that compared the synapses, or connections between brain cells, in the hypothalamuses of male and female rats. The prevailing view at the time was that all structures of male and female brains were alike. Raisman and Field found that female and male rat brains differed in the number of synaptic connections between brain cells in the hypothalamus: females had more. Rat brains, which varied by sex in terms of function, also varied in terms of structural shape—were "sexually dimorphic." In 1977 a team of neurobiologists led by Roger Gorski located a second sexual dimorphism, again in the rat hypothalamus: a small nucleus, or cluster of cells, five times larger in volume in the male rat than in the female. Gorski found that with the naked eye he could sex rats' brains with almost 100 percent accuracy. Gorski's team named the nucleus, logically, the sexually dimorphic nucleus. Its function is not known.
The groundwork had been laid in rodents. The next step was to see if sexual dimorphism of some kind could be found in the brains of human beings. In 1982 the cell biologist Christine de Lacoste-Utamsine and the physical anthropologist Ralph Holloway published in Science an examination of a structure in the human brain called the corpus callosum. The corpus callosum, which is made up of nerve fibers known as axons, is a long, narrow structure that connects and transmits information between the brain's right and left hemispheres. It is one of the largest and most clearly identifiable portions of the brain, and has for years figured prominently in brain research. De Lacoste-Utamsing and Holloway found that the shape of a portion of the corpus callosum called the splenium differed so dramatically between the sexes, with the splenium being larger in women than in men, that impartial observers were able to sex brains easily by looking at this single feature. The De Lacoste-Utamsing and Holloway study is well known and frequently cited, despite the failure of many of the attempts to replicate it. Whether the dimorphism found by De Lacoste-Utamsing and Holloway truly exists remains a matter of considerable debate.
In 1985, three years after the publication of the De Lacoste-Utamsing and Holloway article, Dick Swaab, a researcher at the Netherlands Institute for Brain Research, in Amsterdam, reported that he, too, had found evidence of sexual dimorphism in human brains—in the form of a human homologue of the sexually dimorphic nucleus that Gorski had found in rats.
Swaab announced an even more remarkable discovery five years later, in 1990. He had found, he wrote in an article in the journal Brain Research, that a cluster of cells in the human brain called the suprachiasmatic nucleus was dimorphic—but dimorphic according to sexual orientation rather than sex. Swaab said that the suprachiasmatic nucleus was nearly twice as large in homosexual men as it was in heterosexual men.
If true, this was something wholly new: an anatomical difference between homosexuals and heterosexuals.
Simon Levay is a young neurobiologist who at the time of Swaab's second discovery was conducting research at the Salk Institute, in La Jolla, California. LeVay would soon become the author of what is surely the most publicized neurobiological article on homosexuality that has appeared to date. I spoke with him one day recently in his West Hollywood apartment. LeVay is a wiry, muscular man, remarkably intense. Perhaps the most striking thing about him is the way he talks. In a crisp British accent he zeroes in on each point and then moves on with an air of impatience.
"You shouldn't draw such a distinction between biological and psychological mechanisms," he chided me at one point during our conversation. "What people are really getting at is the difference between innately determined mechanisms and culturally determined mechanisms, but people screw that up and say that's the difference between biology and psychology. It isn't. It's two different approaches for looking at the same thing: the mind. Biologists look at it from the bottom up, from the level of synapses and molecules, and psychologists are looking at it from the top down, at behavior and such."
LeVay had been intrigued by Swaab's research, but he was troubled by the fact that the portion of the brain examined by Swaab seemed to have nothing to do with the regulation of sexual behavior, at least not in animals. The suprachiasmatic nucleus governs the body's daily rhythms; dimorphism there according to sexual orientation might be provocative, certainly, but it would seem to constitute an effect, not a cause. Why not check out the hypothalamus, a region that is intimately involved with sexual behavior?
Laura Allen, a postdoctoral assistant in Gorski's laboratory, had identified four small groups of neurons in the anterior portion of the hypothalamus, naming them the interstitial nuclei of the anterior hypothalamus (INAH) 1, 2, 3, and 4. Allen's research had shown that INAH 2 and INAH 3 were sexually dimorphic in human beings—significantly larger in men than in women. Was it possible that these nuclei were dimorphic according to sexual orientation as well? That was the focus of LeVay's research, and he presented his conclusions in a short paper titled "A Difference in Hypothalamic Structure Between Heterosexual and Homosexual Men." It was published in Science in August of 1991. In the introduction LeVay defined sexual orientation as "the direction of sexual feelings or behavior toward members of one's own or the opposite sex" and hypothesized that Allen's INAH nuclei were involved in the generation of "male-typical sexual behavior." He went on,
I tested the idea that one or both of these nuclei exhibit a size dimorphism, not with sex, but with sexual orientation. Specifically, I hypothesized that INAH 2 or INAH 3 is large in individuals sexually oriented toward women (heterosexual men and homosexual women) and small in individuals sexually oriented toward men (heterosexual women and homosexual men).
LeVay dissected brain tissue obtained from routine autopsies of forty-one people who had died at hospitals in New York and California. There were nineteen homosexual men, all of whom had died of AIDS; sixteen presumed heterosexual men, six of whom had been intravenous drug abusers and had died of AIDS; and six presumed heterosexual women. No brain tissue from lesbians was available. LeVay's conclusions included the following:
INAH 3 did exhibit dimorphism.... [T]he volume of this nucleus was more than twice as large in the heterosexual men ... as in the homosexual men.... There was a similar difference between the heterosexual men and the women.... These data support the hypothesis that INAH 3 is dimorphic not with sex but with sexual orientation, at least in men.
The results were sufficiently clear to LeVay to allow him to state, "The discovery that a nucleus differs in size between heterosexual and homosexual men illustrates that sexual orientation in humans is amenable to study at the biological level."
The study, as LeVay himself readily admits, has several problems: a small sample group, great variation in individual nucleus size, and possibly skewed results because all the gay men had AIDS (although LeVay found "no significant difference in the volume of INAH 3 between the heterosexual men who died of AIDS and those who died of other causes"). As of this writing, LeVay's findings have yet to be replicated by other researchers. LeVay himself has extended his search for dimorphism according to sexual orientation to the corpus callosum, which he is studying by means of magnetic-resonance imaging. Until his original findings are confirmed, the notion that homosexuals and heterosexuals are in some way anatomically distinct must hold the status of tantalizing supposition.
It needs also to be remembered that, as noted earlier, the issue of dimorphism of any kind in the brain is hotly contested. The idea that the brains of heterosexuals and homosexuals may be different morphologically is derived from the idea that the brains of men and women are different morphologically—recall the corpus callosum study by De Lacoste-Utamsing and Holloway. But that study is itself problematic, efforts to replicate it having turned up inconsistent results. Anne Fausto-Sterling is a developmental geneticist at Brown University. She, along with William Byne, a neurobiologist and psychiatrist at Columbia University, has been among the chief critics of neurobiological investigations of homosexuality. Fausto-Sterling during an interview not long ago itemized some of the results from a long line of attempts to replicate sexual dimorphism: "1985: no sex differences in shape, width, or area. 1988: three independent observers unable to distinguish male from female. 1989: women had smaller callosal areas but larger percent of area in splenium, more-slender CCs, and more-bulbous splenium." A new corpus callosum study by Laura Allen, conducted in 1991, did find sexual dimorphism—and the debate continues. Part of the difficulty is methodological, involving whose brains are being compared, and how. Dead people or living people? Old or young or mixed? Healthy or sick? By means of brain sections or magnetic-resonance imaging? LeVay calls studies of the corpus callosum "the longest-running soap opera in neurobiology." And, of course, he himself is now part of the cast.
Even if LeVay's hypothalamus study stands up to scrutiny, it will not justify drawing extravagant conclusions. Establishing a distinction is not the same thing as finding a cause. Anatomy is not etiology, but it may offer a starting point for a journey backward in search of the ultimate origins of sexual orientation. That journey takes us into the realm of hormones and genetics.