The Gene: An Intimate History - Siddhartha Mukherjee Page 0,165

recognizably identical—but they shared the first derivative of identity.

Anyone who doubts that genes can specify identity might well have arrived from another planet and failed to notice that the humans come in two fundamental variants: male and female. Cultural critics, queer theorists, fashion photographers, and Lady Gaga have reminded us—accurately—that these categories are not as fundamental as they might seem, and that unsettling ambiguities frequently lurk in their borderlands. But it is hard to dispute three essential facts: that males and females are anatomically and physiologically different; that these anatomical and physiological differences are specified by genes; and that these differences, interposed against cultural and social constructions of the self, have a potent influence on specifying our identities as individuals.

That genes have anything to do with the determination of sex, gender, and gender identity is a relatively new idea in our history. The distinction between the three words is relevant to this discussion. By sex, I mean the anatomic and physiological aspects of male versus female bodies. By gender, I am referring to a more complex idea: the psychic, social, and cultural roles that an individual assumes. By gender identity, I mean an individual’s sense of self (as female versus male, as neither, or as something in between).

For millennia, the basis of the anatomical dissimilarities between men and women—the “anatomical dimorphism” of sex—was poorly understood. In AD 200, Galen, the most influential anatomist in the ancient world, performed elaborate dissections to try to prove that male and female reproductive organs were analogs of each other, with the male organs turned inside out and the female’s turned outside in. The ovaries, Galen argued, were just internalized testicles retained inside the female body because females lacked some “vital heat” that could extrude the organs. “Turn outward the woman’s [organs] and double the man’s, and you will find the same,” he wrote. Galen’s students and followers stretched this analogy, quite literally, to its absurd point, reasoning that the uterus was the scrotum ballooning inward, and that the fallopian tubes were the seminal vesicles blown up and expanded. The theory was memorialized in a medieval verse, an anatomical mnemonic for medical students:

Though they of different sexes be

Yet on the whole, they’re the same as we

For those that have the strictest searchers been

Find women are just men turned outside in.

But what force was responsible for turning men “inside out,” or women “outside in,” like socks? Centuries before Galen, the Greek philosopher Anaxagoras, writing around 400 BC, claimed that gender, like New York real estate, was determined entirely by location. Like Pythagoras, Anaxagoras believed that the essence of heredity was carried by male sperm, while the female only “shaped” male semen in the womb to produce the fetus. The inheritance of gender also followed this pattern. Semen produced in the left testicle gave rise to male children, while semen produced in the right testicle gave rise to females. The specification of gender continued in the womb, extending the left-right spatial code sparked off during ejaculation. A male fetus was deposited, with exquisite specificity, in the right horn of the uterus. A female, conversely, was nurtured in the left horn.

It is easy to laugh Anaxagoras’s theory off as anachronistic and bizarre. Its peculiar insistence on left and right placement—as if gender were determined by some sort of cutlery arrangement—clearly belongs to another era. But the theory was revolutionary for its time, for it made two crucial advances. First, it recognized that the determination of gender was essentially random—and so a random cause (the left or right origin of sperm) would need to be invoked to explain it. And second, it reasoned that once established, the original random act had to be amplified and consolidated to fully engender gender. The developmental plan of the fetus was crucial. Right-sided sperm found its way to the right side of the uterus, where it was further specified into a male fetus. Left-sided sperm was segregated to the left side to make a female child. Gender determination was a chain reaction, set off by a single step but then amplified by the location of the fetus into the full-fledged dimorphism between men and women.

And there, for the most part, sex determination sat, for centuries. Theories abounded, but conceptually they were variants of Anaxagoras’s idea—that sex was determined by an essentially random act, consolidated and amplified by the environment of the egg or fetus. “Sex is not inherited,” one geneticist wrote in 1900. Even Thomas Morgan, perhaps the most prominent proponent of the