Born That Way

by William Wright

  A clue to the search’s difficulty is suggested by a statement of Richard Dawkins, who was speaking about the genes that construct the body: “The manufacture of a body is a cooperative venture of such intricacy that it is almost impossible to disentangle the contribution of one gene from that of another. A given gene will have many different effects on quite different parts of the body. A given part of the body will be influenced by many genes and the effect of any one gene depends on the interaction with many others.” The complexity he describes may well be greater with behavioral genes. The concept of one-gene-one-behavior is the reductionism the critics quite rightly deplore.

  Robert Plomin is among many who hold to the multigene view of behavioral traits and is quite sure this complexity explains the lack of success in implicating specific genes for specific behaviors. In an April 1994 article in Science, Plomin argued that all the evidence suggested that behavioral traits were not influenced by single major genes but by an array of genes, each with small effects. He views the single-gene approach as doomed to failure. While stressing the complexity, Plomin sees hope for progress in a different direction. “I’m interested in merging molecular genetics and quantitative genetics,” he says. “That’s what many of us are trying to do, not saying we think there’s a single gene and we hope to stumble on it. But rather let’s bring the light of molecular genetics into this dark alley and look for genes here. And that means we need approaches that will allow us to find genes that account for very small effects—not 20 percent of a trait’s cause, not 10 percent, but less than 1 percent. There are ways to do that. Association approaches. The Human Genome Project will speed up this sort of research.”

  Plomin is aware this is a controversial area. “Some would say there’s nothing to this. But they don’t like it because it’s so against the idea that if something is genetic, there must be a simple gene there. You can find it if you just measure correctly. They say the reason we’re not finding single genes is that the psychiatrists and psychologists are not measuring them right. I just don’t buy that. You can measure neuro-transmitter levels and I don’t think they are single-gene phenomena. They are incredibly complex physiologically, and I’m sure that a lot of genetic variance contributes to it.”

  MANY BEHAVIORAL GENETICISTS have long been aware of the complexity of not only the gene-environment interaction but also the gene-gene interaction—the entire human motherboard making New York Telephone’s mainframe seem simple and straightforward. Even before awareness of complicating factors, behavioral geneticists have known that human DNA is a sprawling and quirky vastness. But they take heart by reminding themselves that forty years ago we didn’t know what DNA was. It is just beginning to be explored and understood. Few in the field see the failures as evidence they are not on the right track. In contrast, the critics’ precipitous claims of vindication over the few failed efforts are seen by many geneticists as nothing more than strong evidence of the opposition’s dread of hard scientific proof of the genes-behavior dynamic.

  For the faithful, however, even the failures suggest the distance behavioral research has traveled in the past ten years. The picture lingers of scientists drawing blood from the fingertips of Amish and Israeli patients in search of the cause of their emotional problems and mental illnesses. The tableau stands in vivid contrast to another that served as the twentieth-century paradigm for mental therapy: a patient stretched out on a couch with an analyst seated to the rear taking notes. Together, the opposing vignettes provide eloquent testimony to the revolution behavioral genetics has brought about, not only in psychiatry but also in our entire concept of human behavior, sick or well.

  ELEVEN

  MOVING RIGHT ALONG THE DOUBLE HELIX

  IN 1991 EXCITEMENT again ran high that a physiological link to a behavior had at last been found, one strongly suggestive of a genetic basis to the trait—this time homosexuality. Science magazine published a paper by Simon LeVay (then conducting neurological research at the Salk Institute in La Jolla, California) that reported the discovery of a structural difference within the brains of a group of gay men.

  LeVay had been intrigued by Dutch research that had found an anatomical difference between gay and straight males; a cluster of cells in the brain known as the superchiasmatic nucleus was nearly twice as large in homosexual men as it was in heterosexual men. LeVay, however, knew that this region of the brain had not been associated with sexuality and the variation might be an effect of homosexuality rather than a cause. He undertook to investigate an area that had been linked to sexual behavior, the hypothalamus—in particular, four regions of the hypothalamus. These regions, because they were known to be larger in men than in women, appeared to be sex-connected, so were seen as likely candidates for an anomaly linked to sexual orientation.

  LeVay examined the brains of nineteen deceased homosexual men, sixteen heterosexual men, and six heterosexual women. He found that one of the four hypothalamic regions, INAH-3, was twice as large in the heterosexual men as in the homosexual men. Remarkable as this finding was, the study came under strong criticism, as all of the homosexual men and six of the heterosexual men had died of AIDS. To most observers’ satisfaction, LeVay disposed of this criticism by pointing out that no significant difference could be found in the size of INAH-3 in the heterosexual men who had died of AIDS from the ten who had died of other causes. It seemed clear to LeVay that AIDS had no effect on the size of this portion of the hypothalamus, while homosexuality appeared to have a big effect.

  Stunning as was LeVay’s discovery, it was still vulnerable to the same fallacy that left the Dutch discovery inconclusive; that anomalous brain size might be a result of homosexuality rather than a cause. Until the exact origins of this brain irregularity could be determined, its significance was uncertain. There were two additional confounding possibilities: LeVay’s sample was small and his finding had not been replicated. Aware of his discovery’s tentativeness, LeVay was highly cautious in his conclusions, saying only that the anatomical difference he found between gay and straight men “illustrates that sexual orientation in humans is amenable to study at the biological level.” It certainly shifted the entire subject of sexual orientation still further from the psychoanalyst’s couch, ink-blot tests, and smothering mothers. Many hoped LeVay’s surprising finding might also move homosexuality away from the guilt and shame that had long accompanied it.

  With the concept in the air of an innate basis of homosexuality, strong corroboration arrived two years later. In July 1993, the New York Times, now understandably skittish about claims of specific genes-behavior connections, again heralded on its front page a major finding linking homosexuality to DNA. A research team at the National Institutes of Health led by molecular biologist Dean Hamer published in Science the results of a study in which they had established a genetic anomaly on the X chromosome of thirty-three out of forty pairs of brothers, both of whom were homosexual.

  For years behavioral geneticists had been closing in on homosexuality. Earlier twin and adoption studies, including Minnesota’s, had turned up persuasive evidence of heritability of this trait, and the issue appeared to be resolved in 1991 with the publication in the Archives of General Psychiatry of a twin study by Michael Bailey, of Northwestern University’s Psychology Department, and Richard Pillard, a psychiatrist at Boston University’s School of Medicine. Recruiting no male twin pairs (56 MZs and 54 DZs) in which at least one was homosexual, they found that 52 percent of the identical twins were also gay as opposed to 22 percent of the fraternal twins. When these men had adopted brothers as well, only 11 percent of the nonbiological brothers were gay. While this suggested that the environment still played a large role in the development of homosexuality, the far higher concordance between the identicals than the fraternals was powerful evidence that genes were involved.

  As with most observational studies of complex behaviors, the Bailey-Pillard study was vulnerable to numerous criticisms on recruitment, assessing gray areas of dubious s
exuality and so on. The study was also damaged by an odd statistic: a 9.2 percent rate of homosexuality in the subjects’ nontwin brothers. Inexplicably, this was a lower figure than that for adopted brothers who had no genetic connections; to fit tidily into the model it should have been higher, and roughly the same as the percentage for fraternal twins. Still the 52 percent for MZs as opposed to 22 percent for DZs was taken by most people as telling evidence of a genetic influence on homosexuality. Then with LeVay’s riveting finding in the hypothalamus, homosexuality was ripe for hard DNA evidence, and the Hamer study appeared to have delivered it.

  While designing his experiment, Hamer worked on the belief that if a genetic component to male homosexuality were to be found, it would be on the X chromosome because of a pattern of transmission he had observed through the maternal side. Analyzing the family histories of 114 male homosexuals, Hamer was surprised to discover a much higher than expected number of homosexuals among the subjects’ uncles and male cousins, but always on the mothers’ side of the family, never the fathers’ side. This observation greatly strengthened Hamer’s hunch that if the condition were genetically caused, the gene would be on the X chromosome that comes from the mother.

  I was struck by the scientific community’s years of obliviousness to this strong evidence of maternal transmission, which had long been apparent to people with homosexuality in their families. To me, it spoke volumes about environmentalism’s stranglehold on thinking about behavior. If a gay man’s maternal uncle and grandfather were gay, it would be written off as conditioning by some hidden rearing factors—a family passion for Judy Garland, perhaps, or season tickets to the Metropolitan Opera—if not simply a family tradition. (As in the old joke about the French duke: Fed up with an Englishman’s boast about his ancient family, the duke said, “My dear fellow, when your ancestors were living in caves and painting themselves blue, my family was already homosexual.”) For many years, such readily at-hand information as gayness on the maternal side, no matter how evocative of a genetic pattern, if inconsistent with environmental theories about a “psychological” condition like homosexuality, was rendered, if not invisible, at best anecdotal, meaningless, coincidental. To suggest a pattern of genetic inheritance was to brand oneself as scientifically ignorant.

  Hamer and his research team, proceeding on his X chromosome hunch, examined the DNA of their sample and quickly found that the majority of the gay brothers, 83 percent, shared a region at the tip of the X chromosome that was unusual in an identical way. If the distinctive tip had occurred by chance alone—that is, if it were unrelated to homosexuality—it would have been shared by roughly 50 percent of the brothers since it must have come from one parent or the other. Surprisingly, the Hamer group made no effort to determine whether or not nonhomosexual brothers or other relatives of the gay pairs also possessed the same chromosomal tip. Still, the 83 percent concordance between the gay brothers was seen as proof of the DNA region’s involvement in their homosexuality. It would be related to the homosexuality, Hamer stressed, but not necessarily the cause. He also stressed that his findings might relate to only one type of homosexuality; other types might exist that had altogether different causes, either genetic or environmental.

  In the resulting paper, the Hamer group pointed out that the region on the long arm of the X chromosome where they had located the shared variation, while representing less than .2 percent of the human genome, was still some four million base pairs in length. This was a lot of base pairs to rummage through in search of the actual gene or genes involved. Hamer felt that locating them would require either a study with many more pairs of gay brothers or the complete DNA sequence of the region. Although he knew either strategy would require considerable time, perhaps years, zeroing in on the specific gene was a highly desirable goal in that it was a crucial step toward the big prize: to learn how the gene produced homosexuality.

  Hamer showed his awareness of his data’s ramifications by a cautionary note at the end of his paper: “We believe it would be fundamentally unethical to use such information to assess or alter a person’s current or future sexual orientation, either heterosexual or homosexual, or other normal attributes of human behavior. Rather, scientists, educators, policy-makers, and the public should work together to ensure that such research is used to benefit all members of society.” While such declarations of humanitarian concern were becoming commonplace in behavioral genetics papers, Hamer further demonstrated his concern by taking out a patent on the genetic region he had located, a move aimed at giving him a degree of control over future use of the information.

  Most gay organizations heralded the finding, as they had Simon LeVay’s discovery two years earlier, deeming both studies as substantiating what they had long believed, that homosexuality was not a choice but innate. A few gay groups protested the data, claiming it would be used to screen for gayness, to wrongly stigmatize people who might not be affected, and to attempt curing those who were. I watched astounded as Simon LeVay was attacked on a TV talk show by a gay man incensed at the suggestion his homosexuality was not pure choice. I suspect most homosexuals were as surprised as I was at this position.

  Interesting as the arguments were, they demonstrated the speed with which discussion of behavioral genetics developments shifted from whether or not a finding was valid to whether or not it was desirable. For many, the latter controversy is irrelevant to any scientific insight—but especially to Hamer’s, which most people saw as an important leap ahead in unraveling a complex and puzzling condition.

  WHILE DEPRESSION AND HOMOSEXUALITY were two of the most interesting conditions to the behavioral geneticists, other traits were also being investigated by molecular biologists. Traditionally, I.Q. headed the list of traits about which curiosity ran high, but that dicey subject had all but been driven underground in 1969 by the outcry caused by Arthur Jensen’s painful conclusions about racial differences. It was not to stay underground, however, and reerupted with full fury in late 1994 with the publication of Charles Murray and Richard Herrnstein’s book The Bell Curve.

  Up until this revival there seemed to have been a tacit compact among those who knew the score, so to speak: Educators could continue using I.Q. measures for appraising their students provided that psychologists would shut up about group I.Q. differences. (The Bell Curve and the revival of the I.Q. wars will be discussed at the end of the chapter 12.) Once the Jensen explosion had subsided into a period of peace, the lull permitted molecular biologists, without loss of political virtue, to join in the quest for the behavioral genes to which twin and adoption studies had pointed.

  The next important advance occurred in Holland in 1993. Han Brunner, a geneticist at the University of Nijmegen, published a paper in Science about a Dutch family with a history among its male members of bizarrely aggressive, often violent behavior. A large number of males in the family reacted to minor frustrations and stress with wild outbursts—shouting, swearing, and sometimes assaulting the person they saw as their problem. The aggressive spasms included exhibitionism, arson, and attempted rape. Other males in the family were similarly afflicted, but to lesser degrees, perhaps only shouting and using obscene language. Still other males in the family showed no unusual behavior of any sort.

  In the afflicted males, Brunner claimed to have found a small defect in a gene that produces an enzyme, monoamine oxyidase-a, essential in the breakdown of the chemicals that enable communication between brain cells. While some of the mechanisms are still a mystery, the Dutch researchers believed that because of the absence of the critical enzyme, those with the faulty gene accumulated excessive deposits of powerful neurotransmitters like serotonin, noradrenaline, and dopamine. These buildups led to the explosions of violence.

  If Brunner’s claim held up, it would be the first time a specific gene had been found that was responsible for a specific form of behavior. But even more exciting to some was that Brunner also believed he had a good idea of the way the gene functioned to produce the v
iolence. If his explanation proved valid, it would be a major step forward in unlocking the mysteries of the “black box.”

  While many saw the study as a milestone in behavioral genetics, the authors demonstrated the now obligatory caution in presenting their results. Their finding, they wrote, said nothing about violence in general but concerned only one form of violence, probably an extremely rare form. The wariness was picked up by the scientific media reporting the study. While most publications played up the study in prominent stories, they watered down the implications until the public was left with the ludicrous picture of scientists having established a genetic link for the violent aggression of just one Dutch family, while all the other people in the world who threw plates at loved ones, made scenes in public, exposed themselves, and attempted rape remained as free of genetic influence as they had been in Skinner and Wilson’s behaviorist cosmos. None of the writing about the study gave any reason to believe that other violent people had anything wrong with their genes but were violent merely as a logical reaction to their infuriating environments.

  One rowdy Dutch family does not a scientific revolution make. But one Dutch family might explain the hyperviolence of countless people, alive and dead, who were never studied in this way. Even more important, one Dutch family can show the way in which genes control neurotransmitters, which control behavior. For all the modesty and caution of Brunner and his group, most observers knew their discovery was very important.

  There was another reason for this caution. The possibility of a link between genes and violence is almost as politically charged as claims of a link between genes and I.Q. Some see any discussion of the topic as a sneak attack on America’s black population, which, at the present time, is responsible for a disproportionate amount of the nation’s violence. Although not broken down along racial lines, evidence exists of a genetic basis for at least some forms of violence. This information and its potential usefulness for society will be discussed in chapter 17.