Transgendered people—people who appear to be one sex but report the experience of being the other—have been in the news lately. The conservative reaction to this phenomenon is, in some respects, puzzling. Conservatives do not take these introspective reports seriously; they believe that people seeking sex-change operations (now more often referred to as sex-reassignment surgeries or gender-affirming surgeries) are almost uniformly confused. Their approach to transgendered people is often polite, even compassionate, but always firm in the conviction that transgendered people are mistaken.
Now, subjective experience is often, but not always, reliable. In this case, there are good scientific reasons for supposing that subjective experience of gender can legitimately diverge from the sex of one’s reproductive organs, so conservatives should be cautious in accusing transgendered people of confusion. To show why this is true, I will show that developmental biology demonstrates that there are multiple pathways of sexual development, that one of those pathways is in the brain, and that the pathways of sexual development can diverge from one another.
I will follow the convention of using the word “sex” to refer to the sexual characteristics of the body exclusive of the brain, and “gender” to refer to the subjective, internal experience of being a male or female. Sexual characteristics are either primary or secondary. Primary sexual characteristics develop prenatally and directly relate to reproduction (for example, having testes vs. ovaries). Secondary sexual characteristics develop at puberty, and may or may not relate to reproduction. For example, breast tissue in females may eventually provide food for an infant, whereas facial hair in males does not contribute to reproduction. The biological categories of female vs male sexual characteristics are defined empirically. That is, most babies with male primary sexual characteristics go on to develop a particular set of secondary sexual characteristics.
Sex can be male, female, or in rare cases, somewhere in between, and can be analyzed scientifically. As I will explain, gender appears to depend strongly, but not exclusively, on the brain. Analysis of the brain can allow an outside observer to make a reasonable, albeit imperfect, guess about a person’s gender.
Mismatched Pathways of Sexual Development
Except in cases of monozygotic twinning, humans reproduce sexually. This requires some individuals to be male and others female. The biological triggers for an individual to be either male or female vary from species to species. For most mammals, including humans, females usually have two X chromosomes; males usually have an X and a Y chromosome. But for birds, this situation is reversed, and for many species of reptile, sex is determined by egg incubation temperature. Therefore differential sexual development in the animal kingdom is not reducible to a common physical trigger. Furthermore, some species, such as the clownfish, can change their sex over the course of their lifespan. Thus it is a mistake to think of the sex of an individual organism as fixed in every case for every species.
Humans, of course, are not fish, and we don’t observe our fellow humans undergoing a natural change from one sex to the other. But individual humans do go through a stage of development in which we have both male and female physical parts at the same time. At about six or seven weeks of development, a human embryo clearly has a human body. It has a head with eyes and a torso with limbs. Fingers and toes are beginning to develop but have not yet separated. Internal organs like the heart, brain, and liver are present, if incompletely developed. Not surprisingly, given that these other organs are well into their development, the reproductive organs are developing, too. But instead of an incompletely developed version of either male or female reproductive structures, the embryo has both. It has one set of tubules that can develop into the uterus, fallopian tubes, and the upper third of the vagina, and another that can develop into a series of tubules that transport sperm. The gonads are also present, and can develop into either ovaries or testes.
As the human embryo moves forward from this bipotential state, the default developmental pathway is female. The Y chromosome normally initiates a number of different pathways that inhibit the development of female structures, instead masculinizing the gonads, genitals, and brain. It is possible to have a mismatch between chromosomal sex and bodily sex. For example, in cases of the intersex condition called complete androgen insensitivity syndrome (CAIS), a human with XY chromosomes develops into a girl due to the lack of androgen receptors; the androgens (testosterone and others) that are present cannot affect their development. At puberty, these girls develop physically as women and have a female gender identity. They typically look even more feminine than XX women, who, at least, are sensitive to the small amounts of testosterone that they have.
Their condition may not be discovered until they fail to menstruate as teenagers. They have no uterus and have testes rather than ovaries. In this case, the pathways of sexual development were mismatched. The male pathway was activated for the gonads and the embryonic structures that give rise to the uterus, but the female pathway was activated for the brain and external genitalia.
Women with CAIS are easily diagnosed as intersex in early adulthood, but more subtle types of intersex conditions might go unnoticed. In one case, the XY karyotype of a fetus was determined during a check for chromosomal abnormalities. But at birth the baby turned out to be a girl with normal uterus and ovaries. It appears that in her case, all of the pathways of her sexual development were female, due to a mutation that affects them all. If she had not had her chromosomes tested, she might not ever have known that she is intersex.
Sexual Development of the Brain
So what do intersex conditions have to do with being transgender? One of the pathways of prenatal sexual development is in the brain. There is good evidence that babies are born with predispositions to consider themselves male or female, that is, to have a gender. Some male infants who lose their genitalia in accidents have been reconstructed as girls, with little success. That is, they often grow up to experience the same thing that transgendered people experience—their perception of their own gender does not match their apparent sex.
Further evidence that infants are born with a predisposition towards a gender is seen in cases of an intersex condition called 5-alpha reductase deficiency (5-ARD). In 5-ARD, chromosomal males lack the hormone that masculinizes the genitals, so they appear to be girls. But in most cases, the child will identify as a male, despite being born with female genitals and, for that reason, being raised as a girl. It appears that testosterone masculinizes the brain, but not the genitals, during male embryological development. Individuals with such a mutation end up with some parts of the body (testes, brain) masculinized but others (genitals) following the default female pathway.
Other data support the conclusion that transgenderism has a genetic basis; there is a strong concordance of occurrence among identical twins, but not among fraternal twins. That is, if one identical twin is transgender, then, in more than a third of cases, the other will be, too. Although we might expect concordance to be higher, there is precedence for identical twins with intersex conditions in which one twin is more severely affected than the other. Because identical twins live in similar environments, we might think that some of the concordance is due to shared environment. But fraternal twins also share environment, and the study that found strong concordance for identical twins found no concordance at all for fraternal twins. Human neurology is complicated.
Thus gender appears to be influenced by genes but not absolutely determined by them. Specific mutations leading to transgenderism have not been discovered, but that is what we’d expect considering its rarity; one report from Sweden, where transitioning from one sex to the other is relatively well-accepted, shows that over 30 years (1972-2002), only 0.006% of the population over age fifteen requested sex reassignment.
Possibly Reliable Introspection
If we put the pieces together, we know that there are multiple pathways of sexual development and that they are not all regulated together. One pathway is the development of the gonads into either ovaries or testes; another is the development of external genitalia, and another is the development of the brain to be predisposed toward one gender. We know that the gonads and external genitals can differ from each other, and that both can differ from chromosomal sex. So we ought to expect to find individuals whose brain pathway differs from the other pathways. Given the mutation rate, the size of the genome, and the number of humans in the world, if a molecular pathway can be mutated without killing the individual, the mutation will most likely show up in someone. And I would predict that people with such a mutation would look just like cases of transgendered people.
Consider a case study of a genetic male with normal male genitalia who, since childhood, has had the first-person perception of a female identity. It’s possible that this is a case of confusion about identity rooted in psychological trauma. But it’s also possible that this person has some mutation that prevented the masculinization of the brain. The biology leads us to expect that there will be some people in the latter category, even if we don’t currently have a genetic test to identify these people. On the other hand, psychologists do have some ability to identify trauma-induced identity disorders, so in the meantime it’s possible to eliminate people from the former category. We might first look for signs of dissociative disorders or schizophrenia, for instance.
But unless such disorders seem to be the problem, isn’t it most likely that this individual has some intersex condition, one in which the brain does not match genetic sex, in a way that is—currently—only discernible through introspection? Given how little is known about these rare cases, a high degree of certainty is not possible, but inference to the best explanation seems to warrant this conclusion.
To be sure, our subject would still be a genetic male with Y chromosomes in the brain cells. But absolute reduction of sex to the sex chromosomes is not supported by the biology, for as we have seen above, with the right mutation, one could have a Y chromosome but an otherwise unambiguously female body, including ovaries and uterus. For that reason, chromosomal reductionism is an unacceptable account of sex.
Now, it is worth considering a more principled objection from the conservative front. Some might contend that, if we accept first-person accounts with respect to gender identity, we will have no principled reason to reject them in other cases. For instance, the first-person report is unreliable in the case of anorexia.
An anorexic person is convinced that she is overweight, even when she is already underweight. This, it might be claimed, is analogous to the case of a transgender person. A transgender person might sincerely believe that he is female, but that does not mean that he is not mistaken. Indeed, the objector might press that brain chemistry cannot solve this problem. For suppose that an anorexic person does have the brain chemistry of an overweight person, and this similarity is accountable in terms of genetic factors; in such a case, we would not say that the girl really is overweight, despite appearances. We’d say that she is really underweight, personal conviction notwithstanding. Anorexia just is a condition characterized in terms of a desire to be thin in spite of already being thin; her brain chemistry and emphatic beliefs don’t defeat this. Moreover, the anorexic person is not correct merely because her reports match her brain and indeed her brain (if not the rest of her body) developed along pathways characteristic of overweight people. Why, our objector continues, can’t a transgender person be similarly mistaken? The fact that a transgender person is making reports in line with her neurological development does not establish that she cannot be incorrect.
But the analogy between people who are anorexic and those who are transgendered breaks down when we consider the respective goals of the two relevant parts of the brain. The part of the brain that regulates body weight exists so that a healthy weight can be maintained. There is a range for healthy body weight that is the norm; someone with anorexia wants to achieve a body weight that will lead to electrolyte imbalances that can be fatal. Thus in anorexia, subjective perception is clearly at odds with proper function of the human body. On the other hand, the part of the brain that contributes to the perception of gender doesn’t regulate anything, but exists just for psychological identity. One can survive, and even reproduce, without having any gender identity at all.
I am not arguing that introspective reports of sex are infallible. But according to some studies, a majority of people who undergo sex reassignment surgery are happy with the decision. There is a real danger of misdiagnosing someone as transgender and doing surgery that does them harm, and conservatives have been correct to raise this concern in the face of those who are prepared to affirm every request. In giving the impression that this is a decisive reason against every desired sex-reassignment surgery, though, some conservatives have overstepped. Trying to change a legitimate self-perception of gender also does harm.
Jennifer Gruenke is professor of biology and director of the Hammons Center for Scientific Studies at Union University.