The Gene: An Intimate History - Siddhartha Mukherjee Page 0,170

acted within the range of cultural and social norms to pass as female for forty-eight years. Yet despite her guilt about her sexuality, crucial aspects of her identity—kinship, fantasy, desire, and erotic drive—remained fastened to maleness. C had been able to learn many of the essential features of her acquired gender through social performance and mimesis, but she couldn’t unlearn the psychosexual drives of her genetic self.

In 2005, a team of researchers at Columbia University validated these case reports in a longitudinal study of “genetic males”—i.e., children born with XY chromosomes—who had been assigned to female gender at birth, typically because of the inadequate anatomical development of their genitals. Some of the cases were not as anguished as David Reimer’s or C’s—but an overwhelming number of males assigned to female gender roles reported experiencing moderate to severe gender dysphoria during childhood. Many had suffered anxiety, depression, and confusion. Many had voluntarily changed genders back to male upon adolescence and adulthood. Most notably, when “genetic males” born with ambiguous genitals were brought up as boys, not girls, not a single case of gender dysphoria or gender change in adulthood was reported.

These case reports finally put to rest the assumption, still unshakably prevalent in some circles, that gender identity can be created or programmed entirely, or even substantially, by training, suggestion, behavioral enforcement, social performance, or cultural interventions. It is now clear that genes are vastly more influential than virtually any other force in shaping sex identity and gender identity—although in limited circumstances a few attributes of gender can be learned through cultural, social, and hormonal reprogramming. Since even hormones are ultimately “genetic”—i.e., the direct or indirect products of genes—then the capacity to reprogram gender using purely behavioral therapy and cultural reinforcement begins to tip into the realm of impossibility. Indeed, the growing consensus in medicine is that, aside from exceedingly rare exceptions, children should be assigned to their chromosomal (i.e., genetic) sex regardless of anatomical variations and differences—with the option of switching, if desired, later in life. As of this writing, none of these children have opted to switch from their gene-assigned sexes.

How can we reconcile this idea—of a single genetic switch that dominates one of the most profound dichotomies in human identity—with the fact that human gender identity in the real world appears in a continuous spectrum? Virtually every culture has recognized that gender does not exist in discrete half-moons of black and white, but in a thousand shades of gray. Even Otto Weininger, the Austrian philosopher famous for his misogyny, conceded, “Is it really the case that all women and men are marked off sharply from each other . . . ? There are transitional forms between the metals and nonmetals; between chemical combinations and simple mixtures, between animals and plants, between phanerogams and cryptogams, and between mammals and birds. . . . The improbability may henceforth be taken for granted of finding in Nature a sharp cleavage between all that is masculine on the one side and all that is feminine on the other.”

In genetic terms, though, there is no contradiction: master switches and hierarchical organizations of genes are perfectly compatible with continuous curves of behavior, identity, and physiology. The SRY gene indubitably controls sex determination in an on/off manner. Turn SRY on, and an animal becomes anatomically and physiologically male. Turn it off, and the animal becomes anatomically and physiologically female.

But to enable more profound aspects of gender determination and gender identity, SRY must act on dozens of targets—turning them on and off, activating some genes and repressing others, like a relay race that moves a baton from hand to hand. These genes, in turn, integrate inputs from the self and the environment—from hormones, behaviors, exposures, social performance, cultural role-playing, and memory—to engender gender. What we call gender, then, is an elaborate genetic and developmental cascade, with SRY at the tip of the hierarchy, and modifiers, integrators, instigators, and interpreters below. This geno-developmental cascade specifies gender identity. To return to an earlier analogy, genes are single lines in a recipe that specifies gender. The SRY gene is the first line in the recipe: “Start with four cups of flour.” If you fail to start with the flour, you will certainly not bake anything close to a cake. But infinite variations fan out of that first line—from the crusty baguette of a French bakery to the eggy mooncakes of Chinatown.

The existence of a transgender identity provides powerful evidence for this geno-developmental cascade. In an anatomical and physiological sense,