Mutants

IN FEBRUARY 1868, a Parisian concierge entered one of the rooms under his care. The room, a mere garret, dark and squalid, on the rue de l’École-de-Médecine, contained only a bed, a small table, a coal-gas stove, and a corpse. Cyan-blue skin and a dried froth of blood upon still lips showed that the stove had caused the death; the corpse itself was what remained of a twenty-nine-year-old man named Abel Barbin.

The coroner would call the death a suicide, and without a doubt, so it was. But, as the autopsy report makes clear in the matter-of-fact prose of the morgue, the death of Abel Barbin was not a tragedy compounded merely from the usual ingredients of poverty and solitude, but also from an error that had occurred thirty years before. It was the long-delayed dénouement of a mutation that caused a single enzyme within Abel Barbin’s body to fail, and fail critically, somewhere around April 1838, seven months before he was born. We know this, for we know that when the future Abel Barbin was first lifted to his mother’s breast, it was not a son that she thought she held, but rather an infant girl.

This chapter is about the devices that divide the sexes and what happens when they fail; the errors that occur at that fragile moment in the life of a foetus when the events, molecule binding to molecule, take place that will decide its fate as a girl or a boy. It is about genetic mistakes that start as disorders of anatomy and end as disorders of desire. ‘A man shall leave his father and his mother and cleave unto his wife and they shall be as one flesh.’ Yes, but only if he is able: the biblical injunction, so blithely given, assumes so much. Not least that we know whether we should be man or wife, but that flesh will permit us to be one with another. But some of us do not know, and for some of us flesh does not permit. When it comes to sex, we are unforgiving of mistakes.

The child who would become Abel Barbin was born in Saint-Jean-d’Angély, a quiet and rather dull town on the coastal plain of the Charente, four hundred kilometres south-west of Paris. She was baptised Herculine Adélaïde Barbin, though she would call herself Alexina. She had, by her own account, a happy childhood. At least, so she would recall, years later, when writing her memoirs. She was twelve and in love:

The object of her passion was an older friend, the daughter of an aristocratic family, fair and possessed of the delicate beauty and languor of the consumptive. Alexina, on the other hand, was dark, swarthy and graceless – or so she describes herself. What is more, she was from a poor family; was, indeed, a charity case in a convent school that catered to the local haute bourgeoisie and nobility. If the words with which she recalled her love seem to have a tinge of melodrama about them, we must remember that the language of Romanticism would have come naturally to a French schoolgirl of the 1850s; a language in which to love, to truly love, was to exalt the beloved, to abase oneself, to love without hope of return (one thinks of Stendhal’s De l’amour); and passionate friendships were nothing strange.

Alexina was a model student, a favourite of the Ursulines who taught her. True, she would sneak to her blonde friend’s cubicle at night (and, when caught, was nearly refused First Communion by her much adored and adoring Mother Superior). But such peccadilloes aside, she prospered, and at seventeen was sent to the nearby town of Le Château to train as a teacher. There, another friendship was formed, a more overtly sexual one. This was more troubling to the nuns.

Troubling, too, was Alexina’s failure to menstruate. Her journal is allusive and shamefaced on the fact, but her meaning is clear. Cures and diets were tried to no avail. Her looks failed to cooperate as well. As classmates blossomed into rounded womanhood, she remained thin and angular. She became increasingly hairy and took to shaving her upper lip, cheeks and arms to avoid girlish taunts. Life in the convent had other torments as well. A trip to the seashore: the girls strip to their petticoats and frolic in the waves; Alexina alone watches, afraid to disrobe, rent by ‘tumultuous feelings’. She has disturbing dreams.

The following year, 1857, Alexina Barbin obtained a post as assistant teacher in a girls’ school and began the love affair that was to prove her undoing. The beloved was one Sara, a young schoolmistress like herself, with a cot in an adjacent dormitory. Instantly close, their friendship became one of tender attentions. Soon Sara was forbidden to dress herself; Alexina alone would lace her up – but not without planting a kiss upon a naked breast. More kisses in the oak-wood, the intensity of which Sara found puzzling but not, apparently, repugnant. Passionate outbursts followed: ‘I sometimes envy the man who will be your husband!’ And then, one night, Alexina won all and became her friend’s lover. ‘Ah well! I appeal here to the judgement of my readers in time to come. I appeal to that feeling that is lodged in the heart of every son of Adam. Was I guilty, a criminal, because a gross mistake had assigned me a place in the world that should not have been mine?’

But even as Alexina tasted the joys of requited love, rumours of the schoolmistresses’ fondness for each other began to circulate. Her health was deteriorating too: ‘nameless, unfathomable’ pains pierced her in – we are left to infer – the groin. A doctor was summoned, and left shocked by what he found (‘My God! Is it possible?’). He suggested to the school principal that Alexina be sent away, but did so in terms far too oblique for any effect. And so, happy in love, Alexina stayed. But, tormented by guilt, she confessed to Monsignor J.-F. Landriot, Bishop of La Rochelle. This elderly and worldly priest listened with compassion, and asked if he might break the seal of the confessional to consult his doctor, a ‘true man of science’. And it is here that Alexina’s story no longer depends entirely upon her opaquely allusive memoirs, for Dr Chesnet published:

Chesnet knew well what he had uncovered: Alexina was a hermaphrodite. Medicine may have recognised hermaphrodites, but not so the law or society. A choice had to be made, and those ovoid bodies decided it. Since the seventeeth century, medical convention had held that, when gender is in doubt, gonadal sex is what matters; and Alexina had testicles. It is still so: a modern clinician would call Alexina a ‘male pseudohermaphrodite’, for she had only testes (‘female pseudohermaphrodites’ having only ovaries and ‘true hermaphrodites’ having both). Leaving her employment and her lover, Herculine Adélaïde Barbin shortly became, by legal statute, Abel. He appeared in public to general scandal, suffered a brief flare of notoriety in the press, and fled to the anonymity of the capital where he attempted to start life anew. And it is in Paris, just a few years later, that the memoir ends. It was found beside the bed on which he died.

GENITALS

To understand Abel Barbin and the many others whose lives have fallen, and fall, between the two sexes, would be to know all that makes us male or female. And yet his story can be simplified, reduced to its essentials. It is not merely that he fell in love with one gender rather than another, nor even that he found himself in a body whose gender was poorly suited to his desires, nor even yet that he lived in times that were unforgiving – such stories are familiar enough. No, his story is more remarkable than any of these. It is about having a body that failed to negotiate either of the two paths to gender in an altogether convincing fashion. It is, fundamentally, a story about genitals.

When we consider the male and female body we see in each, without pausing to think about it, an identity, a homology, to the other. A heart is a heart no matter which gender it sustains. Genitals are not so obvious. Their fleshy intricacies seem less versions of each other than organs of radically divergent construction which, somehow, miraculously enough, work together. Below the navel, we are mostly interested in the differences.

Anatomists, however, have other tastes. Confronted with diversity, their instinct is to simplify and unify, to search for schemes that will yoke together the most unlikely structures. This theme – the finding of homologies – runs throughout this book. But here we’re concerned with something a little different: not homology among species that have long evolved apart, but rather between the two sexes. The first reasonable account of the correspondence between male and female genitals was given in 1543 by Andreas Vesalius, the founder of a great school of Renaissance anatomists at the University of Padua. Ovaries, he argued, were equivalent to testicles. And each female fallopian tube was equivalent to a male vas deferens, as was the uterus to the scrotum, the vulva to the foreskin, while the vagina, a hollow tube, was the female version of the penis itself. For Vesalius, then, female sexual organs were the same as those of males, but merely located internally. This theory seemed to explain everything. To give it maximum effect he illustrated it with a depiction of the vagina, cervix and uterus as male genitals in a state of perpetual semi-erection.

Sex-education manuals invariably depict the male and female reproductive systems in some detail, often as two-toned tangles of labelled tubes. Unappetising though such diagrams may be, they are reasonably accurate. The reader who recalls one of the female reproductive tract will immediately observe that it bears little resemblance to Vesalius’. A close look at his diagram, figure twenty-seven from the fifth book of De fabrica, shows that it is wrong in a host of details. Vesalius showed the vagina as a long, stiff, rod-like structure, but it is not; nor does it have a swelling at its tip where the glans would be. And though the scrotum may be divided into two halves (by the raphe – the point of fusion between the two foetal genital folds), the uterus is not. Some of Vesalius’ errors were surely simply made in haste. His diagram was based on the remains of a Paduan priest’s mistress that had been illegally exhumed by his students, and suggests a swift and brutal dissection. Even so, the errors are puzzling; Vesalius is usually so meticulous. One cannot help but think that the vagina he drew is as much a product of what he saw on his dissecting table as it is of his theory of the unities between male and female.

That such unities – homologies – exist is certain; it’s just that they’re quite different from what Vesalius thought they were. But Vesalius’ errors were not merely a matter of a bump more or a groove less. Allowing that it is difficult for us to see the world as a sixteenth-century anatomist did – to truly know what he did and did not know – as one looks at Vesalius’ diagram, one senses that something is awry with the whole thing; that something is simply missing. Indeed, that is so. Intimate though his knowledge of the female reproductive tract was, Vesalius failed to put his finger on the most important bit of all.

It was another Paduan anatomist, Renaldus Columbus – the same Columbus who got into trouble over an extra rib – who, in 1559, discovered what Vesalius missed: the clitoris. He called it ‘the Sweetness of Venus’, and his description is evocative, ecstatic, and imprecise: ‘Touch it even with a little finger, semen swifter than air flows this way and that on account of the pleasure even with them unwilling… When women are eager for a man’, he continues, it becomes ‘a little harder and oblong to such a degree that it shows itself a sort of male member.’ But then he places this delightful organ in the uterus. And it is by no means clear that Columbus was really that original. Rival anatomists accused him of naming a structure that was already known to the Greeks.

Even Columbus failed to find all there was to the clitoris. In 1998, to the delight of all who have ever perceived that there is more to sex than the titillation of what is, after all, a tiny piece of flesh, the clitoris more than doubled in size. A team of Australian anatomists (headed, perhaps unsurprisingly, by a woman) working on fresh, young cadavers rather than the preserved, elderly ones that are the usual fare of medical students, revealed that the clitoris is not merely the smallish stalk of anatomy textbook and sexological dogma, but a large fork-shaped structure that surrounds the urethra and penetrates the vaginal wall.

It seemed a remarkable discovery; perhaps even the incarnation of Sigmund Freud’s much derided vaginal orgasm. In Britain, newspapers hailed the discovery and wondered how so marvellous a thing could have been missed for so long. Of course, it hadn’t been. The new, improved, clitoris is merely an old and well-described landmark that has been repositioned and reassessed. It is a structure long known as the vestibular bulbs, two obscure lumps of spongy tissue deeply riven with blood vessels. The seventeenth-century Dutch anatomist Jan Swammerdam thought they were part of the clitoris, but the greatest of all students of the genitals, Georg Ludwig Kobelt (author of Die Männlichen und Weiblichen Wollusts-Organe des Menschen und Einiger Saugetiere, 1844), considered them with care and decided, on balance, that they were not. The issue turns on whether these bulbs have the kind of rich innervation that the glans clitoris and the glans penis both have. If so, then perhaps it is reasonable to label them as part of the clitoris. Nerves there are, indeed, but it is still not clear what, if any, sort of sensations they transmit. And that is surely the critical point: an expanded clitoris that is devoid of feeling is probably unworthy of the name.

Large or small, Columbus’s identification of the clitoris as ‘a sort of male member’ was accurate, if rather phallocentric. It solved part of the homology problem (clitoris = penis), but left the rest still obscure. What, then, was the female equivalent of the scrotum? And where was the male vagina? It was only in the nineteenth century that embryologists, tracing the development of the embryo’s organs, truly clarified what was homologous between male and female genitals and what was unique to each.

By day 28 after conception the embryo is about half a centimetre long, has four small limb-buds, and a tail. This is when the first external signs of sex appear: nothing remarkable, just a small bump between the lower limb-buds and above the tail. The bump is the genital tubercle and it is soon surrounded by two small sets of folds, one inside the other.

The genital tubercle and its two folds together make the whole of the external genitalia. (The internal genitalia – all those tubes – have other origins.) The genital tubercle rather resembles a pale, dwarfish asparagus elongating in a flesh-coloured furrow. As it grows its fate becomes obvious: a phallus – though whether a penis or a clitoris still hangs in the balance. The innermost set of folds elongate in synchrony with the tubercle to form a kind of groove beneath it, and both – tubercle and fleshy groove – nestle within the outermost folds that are, themselves, expanding to form shallow ramparts.

This is the ground-plan of gender: the developmental events common to both males and females. The differences appear only at day 63 when the embryo is a few centimetres long and its tail is a mere docked terrier’s stump. If the embryo is male, the tubercle elongates even more and the groove that runs beneath it fuses to form a tube – the ‘genitourinary meatus’ – the viaduct of urine and semen. Below that, the larger external folds fuse to make a sack, the scrotum – but a sack that is still empty. The testes are buried deep in the abdominal wall, and will stay there until day 160 when they migrate down to the scrotum. If the embryo is female, the genital tubercle remains much as it is, but the walls of the groove that run beneath it expand and deepen and become the labia minora. The external folds swell, but do not fuse as they do in males, and become the labia majora. The labia majora continue growing until the rather minute female genital tubercle, now more properly called the clitoris, can hardly be seen.

But what of the vagina? It has no male equivalent. Part of the vagina comes from the same folds that make the labia minora, but the innermost reaches originate from a set of ducts that also make the rest of the female sex organs, but not the male’s. The homologies are now clear: penis and clitoris; scrotum and labia major; urethra and labia minora; and a vagina unique to females. Homologies that also tell us something about what happened at Saint-Jean-d’Angély around April 1838. They tell us how Abel née Alexina Barbin could have both a penis, albeit a small one, and a vagina, albeit a shallow one. It is as if, as a foetus, he travelled part of the route to maleness, but stopped before completing the journey. Or else that he missed the molecular signposts pointing the way.

FIFTY-FIFTY

To develop as a female is to travel a highway that is straight and wide. It is the male embryo that takes the exits; should he lose the way, he will find himself back on the route to femininity. The first signpost is the most famous of all: the Y chromosome. The Y was discovered in 1956; three years later it was identified as the master control of human gender. Within the human body, all chromosomes come in pairs matched for size and the number and kind of genes they carry. So do the sex chromosomes, but the pairing is more complex: in females, an X is paired with another X; in males an X is paired with a Y. (Normal males and females are, then, said to have XX and XY chromosomal complements respectively.) The X and the Y are physically ill-matched: the first is large, the second small. They remind one of those apparently odd couples – a large matronly woman and a small dapper man – that one sometimes finds among professionals of the Argentinean tango. The metaphor is an apt one, for no matter how implausible the pairing may seem, the two partners work smoothly together.

In sex determination, as in the tango, the Y commands and the X yields. Indeed, the proof that the Y chromosome determines sex rests upon the fact that its action is dominant over that of the X. That proof came from men who possess a Y but who also, abnormally, possess more than one X (that is, who are XXY, XXXY or even XXXXY). Such people are unambiguously male (and have perfectly normal genitalia), proving that any number of Xs are apparently powerless to curb the action of the male-making Y. True, this power does wane slightly by adolescence, when such males frequently develop breasts and an uncertain sexual orientation. But in the womb it is clear: the presence of a Y chromosome sets a foetus decisively on the route to masculinity.

The dominant behaviour of the Y is not an arrangement that should give male chauvinists any cause for delight (or ardent feminists cause for chagrin). ‘Dominance’ refers only to the molecular rules that are used to make sex, and not to relative male and female abilities of any sort. The dominance of the Y is also probably just an accident of history. Birds also have sex chromosomes, but they have evolved quite independently of the mammalian ones and are called W and Z rather than X and Y. These avian W and Z sex chromosomes seem to work rather like those of mammals, except that it is the female of the species that has the mismatched pair of chromosomes (WZ), while males have the matched pair (ZZ). In birds, then, the chromosome that is unique to females (W) is dominant over that also found in males (Z). It might have been so in mammals, but it seems that by chance it is not.

The search for the source of the Y’s power to control gender took thirty-four years. The Y may be a dwarf among chromosomes, but it is still forty-odd million base-pairs long. Whittling this vast length of DNA down to manageable proportions took the aid of a small and unusual group of people who seemed to defy the imperious directions of the sex chromosomes. These were men who, bizarrely, seemed to lack Y chromosomes. Identified when seeking treatment for azoospermia (infertility due to immobile sperm), they were not hermaphrodites since they had testes, perfectly good male genitalia and those alone.

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.

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.

THE OBJECT OF DESIRE

In The symposium, Plato gives Aristophanes a speech to account for the origin of sexual desire. There once were, Aristophanes says – he is speaking of some mythical past epoch – three human genders: male, female and hermaphrodite. These humans were not as humans are now, but rather fused together in pairs: male to male, female to female and, the hemaphrodite majority, male to female. His description suggests that these Ür-humans looked something like cephalothoracoileopagus conjoined twins. Able to cartwheel on their eight limbs, they were troublesome, vigorous and proud, and Zeus was puzzled what to do about them. His solution was to cut them in half. Since then, every human has sought to be reunited with his or her other half. This explains why some of us are drawn to our own sex, but most of us are drawn to the other.

The causes of our various sexual orientations are so obscure that Aristophanes’ explanation is about as good as many others current today. Perhaps this is why many people resist the search for a biological explanation of sexual orientation. But unless we are Cartesian dualists (and no biologist is), the distinction between body and mind is merely a matter of the degree of our ignorance – bodies being things we understand, minds being all that we do not. And there is no doubt that the complex chain of molecular events that controls the devices of desire, our genitals, also influences its object – whom we choose when we give away our hearts.

What makes the case of Alexina/Abel so fascinating is that, raised as a girl, she fell in love with girls – that is, her loves were those appropriate to her sex, but her true, hidden, sex rather than her apparent one. This may seem reasonable enough, but many physicians and anthropologists think otherwise. For them, sexual orientation is made by social influences, by how a child is raised, especially early in life. In their view, Alexina/Abel having been raised as a girl among girls should have grown up to love men. Physicians take this idea from 1950s sexology; anthropologists from the writings of Franz Boas and Margaret Mead. Whatever the source, such social constructivist notions of gender are swiftly losing ground to the molecular genetic study of sexual behaviour.

Even in 1979, a study of the sexuality of the Dominican Republic guevedoche made a convincing case that hormones must count for something. Like Alexina/Abel, the guevedoche have traditionally been raised as girls and yet, almost invariably, take on a male identity as adults. They may not have had enough DHT to make good male genitals, but it seems that they received enough testosterone, either in the womb or at puberty, to make them feel like men and to make them desire and marry women. Yet they do not have it easy. As youths, they are often diffident lovers, fearing that women will ridicule them for the shape of their genitals. The label ‘guevedoche‘ is, for the villagers of Salinas, a term used in unkindness rather than anything else.

The kwolu-aatmwol of Papua New Guinea have it no easier. There, only a minority of male pseudohermaphrodites are mistaken for girls; the rest are seen as boys, albeit somehow incomplete. To become men, Sambian boys must pass through an elaborate and secret set of initiation ceremonies, six in all. As in so many New Guinea cultures, these ceremonies are overtly homoerotic: young initiates must fellate older ones so that they may acquire, as the Sambia believe, a source of future semen. To the Western mind, the Sambia seem to heap cultural sexual confusion upon biological, but the boys who go through these homoerotic ceremonies mostly end up as heterosexual married men. Not the kwolu-aatmwol, however. They, it seems, are admitted to the lowest rungs of this ladder of initiation but not the higher ones; they may fellate, but not be fellated – indeed, their genitals would hardly permit it. And so though they may mature in body and mind, they come to be socially stranded in late adolescence, a twilight world in which they can be neither boys nor men.