Geneticists call men like this ‘sex-reversed females’. This sort of terminology is blatantly self-contradictory, but so is being chromosomally female yet physically male. Close inspection of the sex chromosomes of sex-reversed females showed, however, that the contradiction was more apparent than real. In each of these men, a piece of the Y had become anomalously shifted onto one of the Xs. Lacking a whole Y, they somehow had the bit that mattered. A bit that, in 1990, was found to contain a gene that encodes a transcription factor – exactly what one would expect in a gene that must directly control at least some of the many other genes that collectively make the difference between the sexes. It was named the Sex-determining Region on Y, or SRY.
The name is curious. Not sex-determining gene, but rather region. It sounds a note of hesitation, of modesty and caution. A desirable caution, since the history of the search for the Y’s power is in large part a history of wasted effort. Before SRY, there was another gene, ZFY; before that, a molecule called the H-Y antigen; they were both false trails. An account of the exploration of these trails would be long and involved. Suffice it to say that the ultimate discounting of these molecules as the determinants of sex is a fine example of how science works. Hundreds of papers were published on these molecules (most especially the H-Y antigen) and many careers were built upon them, but when the evidence against them became damning, all this was set aside, and the search was started anew.
As for SRY, it was certainly a good candidate, but it was quite possible that there was another gene, located nearby but concealed from view, that really mattered. Happily, it was not so. By now, many lines of evidence demonstrate that SRY is the master regulator of gender. Here is one: just as there are apparent sex-reversed females (XX males), so too are there apparent sex-reversed males (XY females). And, just as XX males have a working copy of SRY where they should not, it has recently been found that many XY females do not have a working copy of SRY where they should. One gene, SRY, two normal states (present on Y, absent on X), two abnormal states (absent on Y, present on X), and a complete reversal of everything to do with sex. It is as beautiful a demonstration of the workings of a gene as could possibly be desired.
IF
Perhaps SRY activates a few critical genes needed for masculinity, perhaps it deactivates others needed for femininity, perhaps both; more than ten years after its discovery, we still don’t know how it works. But we do know where it works. Dangling genitalia, hair on the chest and an adult brain excessively preoccupied with sex may all be consequences of having SRY, but they are remote ones. All that SRY does is control the fate of two tiny, foetal organs. We know this from some experiments that were done in Vichy France.
Foetal rabbits are all fragility; to attempt surgery upon one, and have it survive, takes the hand of a master. Such a man was the French biologist Alexandre Jost. In the mid-1940s, he began a series of experiments in which he opened the womb of a pregnant dam, excised the gonads of her unborn pups, and then sewed them all back up again. If mother and foetuses survived surgery – his first experimental subjects often did not – he killed them ten days later and dissected out the foetal genitalia. Jost found that his castrati rabbits failed to develop male sexual organs. Devoid of vas deferens, prostate, scrotum or penis, they had instead oviducts, a uterus and a vagina. It was, perhaps, a brutal experiment (though not much more so than the castration of any pet), but it was also a luminous one: it showed that a male foetus needs its gonads.
Or at least it needs its Leydig cells. These are the cells within the gonad that make the hormones that make a mammal male. Without SRY they and the other cells of male gonad would not exist. One of the hormones is testosterone itself, a steroid that Leydig cells manufacture from that much-maligned molecule, cholesterol. The male foetus begins to make testosterone in large quantities at around day 50, peaking at around day 150. Four enzymes are needed to do the job; each of them represents a signpost, which, if awry, can turn an XY foetus back to the freeway of femininity. Mutations have been found in the genes that encode three of them. These mutations do not cause complete sex reversal but something in between: a hermaphrodite. More precisely, a male pseudohermaphrodite, since the testes are there, albeit dysfunctional.
The biochemistry of masculinity is daunting. If, as Kipling says, failing to keep your head while all about you are losing theirs (etc.) will stymie male development, more surely yet will testosterone synthesis mutations. So too will mutations that cause a failure in the differentation and growth of your Leydig cells. And so too will mutations in the testosterone receptor.
Testosterone enters the cells of the growing male foetus and binds to a protein receptor. Hormone and receptor then enter the cells’ nuclei where they both bind to DNA and switch on the genes that are needed to make a male a male. Dozens of mutations in many families have been identified which cripple this receptor, usually with the effect of making the foetus completely female at birth – at least as far as external appearances go. Were the obstetrician to search carefully for a cervix and uterus, she would fail to find them. But the disorder is usually only picked up at puberty when the apparent girls fail to menstruate.
Such girls are, it is often said, exceptionally feminine – at least externally. Devoid of a testosterone receptor, they have even less exposure to masculinising hormones than do true women who invariably have some. Their one obvious masculine feature is their height: as adults they tend to be rather tall. This suggests that the difference between male and female is due to something other than testosterone (though what, exactly, is still a matter for debate). The combination of feminine looks and male height means that women without testosterone receptors are often strikingly attractive. In the 1950s at least one French woman with defective testosterone receptors made a living as a catwalk model, while a pair of receptorless identical twins from California were air stewardesses.
Many male pseudohermaphrodites are, however, not completely feminised at birth. They have what clinicians call ‘ambiguous’ genitalia: a phallus that is too large to be a clitoris, yet too small to be a penis. Or else a urethral opening that is located somewhere at the base of the penis rather than at the tip, yet that is clearly not a vagina. Whatever the case, nearly all would remain with the genitals they were born with were it not for surgery. But some, very few indeed, transform into their true genetic sex at adolescence.
Which brings us back to Alexina/Abel Barbin, whose growing phallus and ever increasing facial hair were the causes of such pain and confusion. There have always been, and still are, others like her. Ambroise Paré and Montaigne both met Marie Gerard, a peasant from the village of Vitry-le-François who discovered, one day while vigorously chasing swine, that she had a penis. She claimed that it merely fell out from the exertion of leaping a sty, but it is more likely that it was a gradual change, and that her – his – explanation was simply the best that suggested itself. In the event, Marie took a new name: Germain.
Alexina/Abel and Marie/Germain were both isolated cases; we do not know of any relatives or descendants of either man who showed the same symptoms. But the phenomenon of girls-who-become-men is well known in certain remote parts of the world. Until recently, the villagers of Salinas (pop. 4300), located in a remote part of the Dominican Republic, incorrectly assigned one of every ninety boys born as female, only to have them change sex at puberty. The phenomenon was so common that the villagers had a name for it: guevedoche, or ‘penis at twelve’. On the other side of the world, in the Eastern Highlands of Papua New Guinea, something rather similar is found. There a tribe of hunters and horticulturalists called the Sambia refer to such changelings as kwolu-aatmwol (‘changing into male thing’) or, in their brutally direct Pidgin, turnim-men.