As her teenage years approached, she looked forward to experiencing the same sexual development she saw in older girls. By the age of 14 she was really worried: What she did have was a pain in her left groin that eventually subsided, only to be replaced by the appearance of a mass in the left side of her labia.
With growing shock, she felt her voice dropping, her facial hair growing, and her clitoris enlarging to become more and more like a penis. By now she had become convinced that she was really a boy and that the mysteriously shifting mass within her was in actuality a testis.
But Barbara still struggled with the problem of how to present herself to her parents and friends, before whom she avoided being caught naked. She knew they had to suspect something. When they found out, would they ridicule her--or him--as a freak? Gender constitutes the most fundamental distinction we make among ourselves, the first question we ask when a baby is born.
It establishes two radically contrasting possibilities and determines how we view ourselves and how other people view us. In almost all cultures it also establishes a division between contrasting economic and social roles.
The vast majority of us are born unmistakably male or female and remain that way throughout life. We have all the sexual parts appropriate to a single gender, with no discordant pieces. It is very rare indeed that you find among humans true hermaphrodites--individuals possessing both male and female gonads.
However, there are some unfortunate individuals called pseudohermaphrodites, whose sex presents an ambiguous appearance. Like Barbara, some appear to be born as girls but develop as boys at puberty. Some have a vagina and female external organs but lack such internal organs as ovaries and fallopian tubes; instead, they have certain male internal organs, like seminal vesicles, as well as testes hidden up in the body.
Most of these walking mosaics of sex manage to survive this adversity: But their stories are also instructive, for they shed light on a number of basic questions that concern all of us.
Foremost among them are the questions: What actually determines our gender? How could the mechanisms that determine something so fundamental go so wrong? Ultimately, of course, our gender is laid down by our genes, which are bundled together in each cell in 23 pairs of microscopic packages called chromosomes. The 23 human chromosome pairs can be numbered and distinguished from one another by consistent differences in appearance.
For chromosomes 1 through 22, the two members of the pair appear identical. Only in the case of chromosome 23, the sex chromosome, do the two representatives differ, and even then only in men, whose twenty-third chromosomes are of unequal sizes: Women have two paired X chromosomes instead. What do the sex chromosomes do?
Many X chromosome genes specify traits unrelated to sex, such as the ability to distinguish red and green. However, the Y chromosome contains genes specifying the development of testes. Between the fifth and seventh week after fertilization, human embryos of either sex develop an all-purpose gonad that can later become either a testis or an ovary.
If a Y chromosome is present, that all-purpose gonad will begin to commit itself by the eighth week to becoming a testis. Thus the natural tendency of our primordial gonad is to develop as an ovary if nothing intervenes; something special--a Y chromosome--is required to change it into a testis. As developmental biologist Alfred Jost put it, Becoming a male is a prolonged, uneasy, and risky venture; it is a kind of struggle against inherent trends toward femaleness.
Chauvinists might hail becoming a man as heroic, and becoming a woman as the easy fallback position. Conversely, one might regard womanhood as the natural state of humanity, with men just a pathological aberration that regrettably must be tolerated as the price for making more women.
I prefer merely to acknowledge that a Y chromosome switches gonad development from the ovarian path to the testicular path, and to draw no metaphysical conclusions. A penis is among the many other obvious necessities, just as women need more than ovaries--for example, it helps to have a vagina. To form the penis, vagina, and other sex organs, the embryo is endowed with other all-purpose sexual structures besides the primordial gonad. However, unlike the case of the testes, the development of these structures is not directly specified by the Y chromosome.
Instead, these structures are channeled toward male organs by secretions of the testes themselves, while a lack of testicular secretions channels them toward female organs. For example, in the eighth week of gestation the testes begin producing the hormone testosterone, some of which gets converted into the closely related substance dihydrotestosterone, or DHT.
Such hormones are called androgens. DHT goes on to convert some all-purpose embryonic structures into the glans penis, penis shaft, and scrotum. Those same structures would otherwise develop into their female equivalents: Barbara grew up as an apparently normal girl enjoying a happy childhood. With testes present, the opposite happens: Instead, you might think, a Y chromosome should guarantee percent male organs, whereas the lack of a Y chromosome should guarantee percent female organs.
In fact, a long series of further biochemical steps, programmed by chromosomes other than the sex chromosomes, is required to produce all the structures other than ovaries or testes. Every step involves the synthesis of one enzyme, specified by one gene. Thus, an enzyme defect may result in a male pseudohermaphrodite, defined as someone with one X and one Y chromosome, and hence intrinsically male, but with a mixture of both male and female structures.
In the pseudohermaphrodite, some male structures continue to develop normally because they depend on enzymes and hormones that remain normal. However, male structures dependent on the defective enzyme are either completely missing or replaced by their female equivalents.
This can be illustrated by a discussion of two types of male pseudohermaphrodite-- one resulting from a defective androgen receptor, the other from a defect in the enzyme that converts testosterone to DHT.
The former type looks like a normal woman. Indeed, she often conforms to the male ideal of feminine beauty even more than the average woman does because her breasts tend to be well developed and her legs long and graceful. Her complexion is usually flawless and she tends to have the added height of a man. Hence, cases have turned up repeatedly among female fashion models. At that point the doctor discovers a simple reason for that failure: Instead, the vagina ends blindly without connecting to a uterus although it is generally adequate for intercourse.
Further examination reveals testes that are normal except for being buried in the groin or labia; they secrete normal testosterone and are programmed by a normal Y chromosome. In other words, the beautiful model is a male who happens to have a genetically determined biochemical block in the ability to respond to testosterone.
That block turns out to be in the cell receptor that would normally bind testosterone and dihydrotestosterone and thereby enable those androgens to trigger further steps in the development of male genitals. Take away that androgen receptor and all you normal male readers might look like beautiful models, too.
However, the process by which the usual male machinery is activated by testosterone is interrupted. As a result, development of the remaining all-purpose embryonic sex organs follows the female channel by default: Despite having a Y chromosome, hidden testes, and normal male testosterone levels, almost all such people unquestionably view themselves, and are viewed by others, as women.
Most find husbands and marry. Most are well adjusted to their role as women and show no signs of unusual emotional stress. In these cases, not only do testes fail to make a man, but they fail to interfere with much of the happiness available to women as wives and mothers. The second type of pseudohermaphrodite is exemplified by the case of Barbara, with which I began this article.
Barbara and dozens of other similar people suffer from an enzyme defect called 5-alpha-reductase 5AR deficiency. Their external genitals appear largely female at birth, though they may be somewhat ambiguous and have some male features; this ambiguity sometimes allows babies with 5AR deficiency to be recognized at birth. At puberty, however, many of these children become much more malelike.
A mutation in the gene specifying 5AR yields a more confusing picture than does androgen receptor deficiency. In the first type of pseudohermaphrodite that we discussed, the effects of the androgens were blocked completely. But in this second type the influence of only one androgen, DHT, is affected, while the influence of the other, testosterone, is exerted normally. Because the two androgens function somewhat separately, the result is that in 5AR-deficient pseudohermaphrodites, reproductive organs specified by testosterone are normal and only those dependent on DHT are abnormal.
Ironically, the resulting blend of male and female traits has helped researchers distinguish the precise physiological roles played by testosterone and DHT in male development. Which male traits are normal in 5AR-deficient males and hence influenced by testosterone? Because these babies are born with testes albeit concealed in the groin or labia and normal male internal organs seminal vesicles, vas deferens, and epididymis , we can conclude that the growth of these structures must be triggered by testosterone secretion while the fetus is still in the womb.
Hallmarks of adolescent male development that remain normal include muscle development, growth of the penis and scrotum, capacity for erections and ejaculation, and lack of breast development.
These may be influenced by testosterone secretion at puberty. At birth, though, these genetic males show numerous female traits. Their external genitals look much more like a clitoris and labia than a penis or scrotum. There is a vagina, although it ends as a blind tube. Inside, the prostate gland is small or absent. These features make it reasonable to assume that the normal molding of the prostate and male external genitals probably depends on DHT--which is deficient in these pseudohermaphrodites--rather than on testosterone.
At puberty these pseudohermaphrodites experience less-than-normal growth of the beard and body hair, while later on the baldness that gradually comes to characterize most older men fails to develop.
These traits of normal men, then, are likely to depend on postnatal effects of DHT. Because the 5AR gene is not on the sex chromosomes, both males and females donate a copy of it to their offspring.
A single normal copy of the gene, inherited from either parent, suffices to generate enough 5AR enzyme for normal male development. Only if a male fetus inherits a defective gene from both his mother and his father will he develop as a pseudohermaphrodite with 5AR deficiency. Therefore, most known examples are clusters of related cases in remote, isolated Third World villages, where marriages between close relatives are common and children can inherit many of the same genes from both parents.
For example, one such cluster was discovered in a rural, inbred village that until had no paved road to the outside world. In Xanadu, physicians have identified a total of 38 pseudohermaphrodites, all descended on at least one side from the same now-deceased woman and many of them traceable to that woman through both their mother and father. Evidently, that lady had a single copy of the mutant gene, which she passed on to many of her numerous descendants.
Eventually there were enough such descendants so that some marriages within the village began to involve partners who both carried the mutant gene, thus making it increasingly likely that their children would develop as pseudohermaphrodites. How do such 5AR-deficient pseudohermaphrodites cope with the Kafkaesque metamorphosis that their genes force upon them?