droger does n Evidence for a Biological Gors especi have a in the 1 Influence in Male Homosexuality INAH nucleu in the I Two pieces of evidence, a structure pothal in men w-thin the human brain and a genetic link, er, sizt one se: point to a biological component for male homosexuality by Simon LeVay and Dean H. Hamer ost men are sexually attract- play a significant role. How, we do not than in female rats. Although this cell ed to women, most women to yet know. It may be that genes influence group is very small, less than a millime- M men. To many people, this the sexual differentiation of the brain ter across even in males, the difference seems only the natural order of things- and its interaction with the outside between the sexes is quite visible in ap- the appropriate manifestation of bio- world, thus diversifying its already vast propriately stained slices of tissue, even logical instinct, reinforced by education, range of responses to sexual stimuli. without the aid of a microscope. religion and the law. Yet a significant The search for biological roots of sex- Gorski’s finding was especially inter- minority of men and women-estimates ual orientation has run along two broad esting because the general region of the range from 1 to 5 percent-are attract- lines. The first draws on observations hypothalamus in which this cell group ed exclusively to members of their own made in yet another him-that for phys- occurs, known as the medial preoptic sex. Many others are drawn, in varying ical differences between men’s and wom- area, has been implicated in the gener- degrees, to both men and women. en’s brains. As we shall see, “gay” and ation of sexual behavior-in particular, How are we to understand such diver- “straight” brains may be differentiated behaviors typically displayed by males. sity in sexual orientation? Does it derive in curiously analogous fashion. The se- For example, male monkeys with dam- from variations in our genes or our phys- cond approach is to scout out genes by aged medial preoptic areas are appar- iology, from the intricacies of our per- studying the patterns in which homo- ently indifferent to sex with female mon- sonal history or from some confluence sexuality occurs in families and by di- keys, and electrical stimulation of this of these? Is it for that matter a choice rectly examining the hereditary materi- region can make an inactive male mon- rather than a compulsion? al, DNA. key approach and mount a female. It Probably no one factor alone can elu- should be said, however, that we have cidate so complex and variable a trait esearchers have long sought with- yet to find in monkeys a cell group anal- as sexual orientation. But recent labo- in the human brain some mani- ogous to the sexually dimorphic one ratory studies, including our own, indi- R festation of the most obvious occurring in rats. cate that genes and brain development classes into which we are divided-male Nor is the exact function of the rat’s and female. Such sex differentiation of sexually dimorphic cell group known. the brain’s structure, called sexual di- What is known, from a study by Gorski morphism, proved hard to establish. On and his co-workers, is thatandrogens- SlMON LrVAY and DEAN H. HAMER in- average, a man’s brain has a slightly lar- typical male hormones-play a key role vestigate the biological roots of homo- sexuality. LeVay earned a doctorate in ger size that goes along with his larger in bringing about the dimorphism dur- neuroanatomy at the University of Got- body; other than that, casual inspection ing development. Neurons within the tingen in Germany. In 1971 he went to does not reveal any obvious dissimilar- cell group are rich in receptors for sex Harvard University to work with David ity between the sexes. Even under a mi- hormones, both for androgens-testos- Hubel and Torsten Wiesel on the brains croscope, the architecture of men’s and terone is the main representative-and visual system. He moved to the Salk In- women’s brains is very similar. Not sur for female hormones known as estro- stitute for Biological Studies in San Diego prisingly, the first significant observa- gens. Although male and female rats in 1984 to head the vision laboratory. In tions of sexual dimorphism were made initially have about the same numbers 1992 he left Salk to found the Institute of Gay and Lesbian Education. Hamer re- in laboratory animals. of neurons in the medial preoptic area, ceived his Ph.D. in biological chemistry Of particular importance is a study a surge of testosterone secreted by the from Harvard in 1977. For the past 17 of rats conducted by Roger A. Go&i of testes of male fetuses around the time years, he has been at the National Insti- the University of California at Los Ange- of birth acts to stabilize their neuronal tutes of Health, where he is now chief of les. In 1978 Gorski was inspecting the population. In females the lack of such the section on gene structure and regu- rat’s hypothalamus, a region at the base a surge allows many neurons in this lation at the National Cancer Institute. He of its brain that is involved in instinc- cell group to die, leading to the typical- studies the role of genes both in sexual orientation and in complex medical con- tive behaviors and the regulation of ly smaller structure. Interestingly, it is ditions, including progression of HIV and metabolism. He found that one group only for a few days before and after Kaposi’s sarcoma. of cells near the front of the hypothal- birth that the medial preoptic neurons amus is several times larger in male are sensitive to androgen; removing an- 44 SCIENTIFIC AMERICAN Muy I994 drogens in an adult rat ny castration In 1990 one of us (LeVay) decided to LeVay examined the hypothalamus in does not cause the neurons to die. check whether INAH or some other autopsy specimens from 19 homosexu- Gorski and his colleagues at U.C.L.A., cell group in the medial preoptic area al men, all of whom had died of com- especially his student Laura S. Allen, varies in size with sexual orientation as plications of AIDS, and 16 heterosexual have also found dimorphic structures well as with sex. This hypothesis was men, six of whom had also died of AIDS. in the human brain. A cell group named something of a long shot, given the pre- (The sexual orientation of those who EWH3 (derived from “third interstitial vailing notion that sexual orientation is had died of non-AIDS causes was not nucleus of the anterior hypothalamus”) a “high-level” aspect of personahty mold- determined. But assuming a distribution in the medial preoptic region of the hy- ed by enviromnent and culture. Infor- similar to that of the general populace, pothalamus is about three times larger mation from such elevated sources is no more than one or two of them were in men than in women. (Notably, howev- thought to be processed primarily by likely to have been gay.) LeVay also er, size varies considerably even within the cerebral cortex and not by “lower” included specimens from six women one sex.) centers such as the hypothalamus. whose sexual orientation was unknown. [Zeus] cut the members of the human race in hali like fruit that is to be dried and preserved, or like eggs that are cut with a hair. -Plato, Symposium SCIENTIFIC AMERICAN May 1994 45 HYPOTHAL4MUS of the human brain i HETEFIOSE was examined for differences related to sexual orientation. The hypothalamus of each of the 41 subjects was stained to mark neuronal cell groups. The cell group termed INAH in the medial pre- optic area was more than twice as large in the men as it was in the women. INAH also turned out to be two to three times larger in straight men than it was in gay men (micrographs at far right). This finding suggests a differ- ence related to male sexual orientation about as great as that related to sex. After encoding the specimens to elim- the AIDS victims. If the disease were ences were present early in life-per- , deed inate subjective bias, LeVay cut each having a nonspecific destructive effect, haps even before birth-and helped to such i hypothalamus into serial slices, stained one would have suspected otherwise. establish the men’s sexual orientation. at thi! these to mark the neuronal cell groups Finally, after completing the main Tbe second is that the differences arose Ass and measured their cross-sectional ar- study, LeVay obtained the hypothala- in adult life as a result of the men’s sex- differ eas under a microscope. Armed with mus of one gay man who had died of ual feelings or behavior. Thethird pos- tion v information about the areas, plus the non-AIDS causes. This specimen, pro- sibility is that there is no causal connec- I divide thickness of the slices, he could readily cessed “blind” along with several spec- tion, but both sexual orientation and didatc calculate the volumes of each cell group. imens from heterosexual men of simi- the brain structures in question are al ste In addition to Allen and Go&i’s sexu- lar age, confirmed the main study: the linked to some third variable, such as a this ir ally dimorphic nucleus INAH3, LeVay volume of INAH in the gay man was developmental event during uterine or ences examined three other nearby groups- less than half that of INAH in the het- early posmatal life.