It was the guevedoche who shed light on the matter; they all lack an enzyme called 5-?-reductase. In most parts of the body, testosterone is transported directly into cells to switch on genes for masculinity. But in the foetal male genitalia, much of it is first transformed into a more potent form, dihydroxytestosterone or DHT. This is what 5-?-reductase does; any mutation that cripples this enzyme will cause a lack of DHT and a failure of genital growth. DHT may be needed by the foetus, but at adolescence it is testosterone itself that does the work, and of that the guevedoche have plenty, so they masculinise. They can all trace their ancestry to a single woman by the name of Altagracia Carrasco; the defective enzyme is most likely her legacy. The same enzyme is, remarkably, defective in the Sambian kwolu-aatmwol. And although we cannot be sure, in all likelihood this was also the enzyme that Alexina/Abel lacked and which set in train the events of which I have told.
HYENAS
When I said that the route to femininity was a highway straight and wide, I meant that in humans, at least, there are few mutations that will result in a female pseudohermaphrodite, that will cause an infant with ovaries – a girl – to have masculinised genitalia. But there are some mutations that do so, and of these perhaps none has spoken more eloquently of the delicate balance of gender in the womb than a mutation that, just a few years ago, disturbed a young Japanese woman expecting her first child.
The pregnancy was without complications, or at least it was at first. But the third trimester brought the first hint that not all was well, as the young woman started growing a beard. Endocrinologists were consulted, and the cause was easily identified: instead of the estrogens common in pregnancy, her blood contained absurdly high levels of testosterone. Inevitably the child was affected as well. Though obviously female (and genetically proven to be so) the infant had, at birth, an abnormally large clitoris – about two centimetres long – and partially fused labia, sure signs of masculinisation.
It was the placenta’s fault. During any pregnancy, placentas make testosterone in abundance. Normally this does not affect the foetus, for the testosterone is promptly converted into estradiol and estrone by an enzyme called aromatase in which placentas are notably rich; it was this enzyme that was defective. The mutation was a recessive one: each parent must have carried a single defective copy of the gene with no ill-effects, and each had transmitted that defective copy to their child – and to the placenta, part of which is an extension of the foetus and has its genotype. The result was a child who, in all innocence, became a kind of hormonal Trojan Horse, inflicting havoc upon her mother before she was even born.
Next to SRY itself, aromatase is arguably the single most important regulator of human gender. It sits at the crossroad of testosterone and estrogen production and directs the traffic. Girls who lack aromatase are not only born with masculinised genitalia, but as they grow up tend to be very hairy – sometimes bearded – and have enlarged ovaries. Boys who lack the enzyme, on the other hand, scarcely feel its effects – although, as discussed in the previous chapter, for want of estrogen they keep growing long after they should have stopped.
Boys, however, do not escape that easily. Not all aromatase mutations cripple the gene. There are also gain-of-function mutations that cause the enzyme to be hyperactive – and that cause an excess of estrogen and a lack of testosterone. Girls with such mutations grow up (prematurely) into short women with large breasts. Boys with such mutations are also short and, more disconcertingly, also have breasts. Aromatase mutations are not the only cause of breasts in boys and men: up to 60 per cent of adolescent boys have detectable breasts which, however, almost always disappear – at least until old age when estrogen produced by fat tissue brings them back.
People who express sex-identity mutations are often sterile. Superficial damage (ambiguous genitalia) can sometimes be repaired by surgery – though who should undergo such surgery and at what age they should do so is increasingly controversial. But all of the sex-identity mutations that I have written about have their equivalents in other mammals. Animals that find themselves between the two sexes must rarely reproduce. Such mutations, one would think, are always evolutionary dead-ends.
Always? It is difficult to generalise, for so capricious is natural selection, and so readily does it avail itself of whatever genetic variation is to hand, that the most unlikely things can happen in evolution. Spotted hyenas are unsympathetic creatures. They have ungainly bodies, cackling calls and disgusting habits. Never mind that they delight to eat carrion; they will also urinate in the water they drink and happily roll in their own vomit. More curious than this, their society is one of powerful females and milksop males. Both males and females have their own strict dominance hierarchies, but the lowliest female outranks even the most powerful male, When a clan of hyenas are having their messy way with the carcass of a wildebeest, the males have to eat quickly, for the females – which are larger – invariably drive them away. Their bulk and penchant for unprovoked aggression make female hyenas seem, one hesitates to say it, almost male. One hesitates, but then one considers their genitals.
Female spotted hyenas have genitals like no other mammal. Their most prominent feature is a clitoris as large as a male’s penis, complete with a genitourinary tract, an orifice at its tip and the ability to jaunt erect during dominance displays. Beneath that, where the vagina should be, is a structure that looks remarkably like a scrotum but which contains a pad of fat rather than testicles. Lacking a vagina, the female spotted hyena copulates and gives birth through her clitoris.
And a painful business it is. The first time spotted hyenas give birth their clitoral tracts are so narrow that labour takes hours, during which time more than 60 per cent of the cubs suffocate and about 9 per cent of the mothers die. Though Aristotle denied it, the idea that spotted hyenas are true hermaphrodites persisted until the nineteenth century. They are not, for internally female and male hyenas are quite distinct – one has ovaries, the other testes and that’s all. Since the females of the striped and brown hyenas (the spotted’s closest living relations) have typical mammalian genitalia, spotted hyenas are, in a real sense, female pseudohermaphrodites, albeit ones in which the pathological has become normal.
The placentas of spotted hyenas have been examined; they too produce large amounts of testosterone and have – one might have guessed it – a natural deficiency of aromatase. The hyena aromatase gene has not yet been cloned, so we do not know quite how it differs from those of the brown and striped hyenas. But it is likely that the spotted hyena acquired, somewhere in its history, an aromatase gene with a mutation rather like that which our Japanese girl had. This need not be the case – it could be that the mutation occurred in another gene which regulates aromatase – but whatever the truth may be, aromatase levels almost certainly explain, at least in part, why female spotted hyena cubs are born with masculinised genitalia. What effect this testosterone has on expectant hyena mothers is difficult to say; they are hairy at the best of times.