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Somewhere in the middle of the night in a Central African rainforest, a chimpanzee gives birth. Soon after, as the sun rises, mother and newborn sit there, dazed, amid a coffee klatch of friends and relatives. Inevitably, at some point, virtually every member of the group will come over, pull the kid’s legs apart and sniff: Boy or girl?

It’s the most binary question in biology, producing an answer that is set in stone. But in reality the binary nature of gender isn’t all that binary after all. Biologists have long known about exceptions to the boring, staid notion that organisms are, and remain, either female or male. Now our culture is inching toward recognizing that the permanent, cleanly binary nature of gender is incorrect.

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In fact, it’s headline news. Bruce Jenner, a male gold medalist in the 1976 Olympics and a cover boy on a Wheaties box, is now Caitlyn Jenner, a 2015 cover girl on Vanity Fair. Laverne Cox, a transgender actor, is nominated for an Emmy for outstanding actress. America has seen openly transgendered individuals serve as a mayor, state legislator, judge, police officer, a model for a global cosmetics brand, and a high school homecoming queen. Even amid the appallingly high rates of discrimination and violence against the transgendered, there is a growing recognition that gender designation need not be permanent.

Many people are questioning whether there is even such a thing as “gender.” These are individuals whose psychosexual self-image may be of both genders, a third gender, no gender, or whose visceral perception of the social world does not include implicitly seeing people as gendered.

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This new continent was formalized by as august and ancient an institution as Facebook, which offers 58 gender specification options on one’s profile page. These include Agender, Bigender, Intersex, Gender Fluid, Gender Questioning, Non-binary, Pangender, and my two favorites—Two-spirit, with a vaguely Native American grooviness to it, and Other, which basically implies that, Whoa, Nellie, we’ve barely scratched the surface!

In many ways the most radical departures from a binary gender system comes with gamers who spend virtually their entire lives role-playing as their avatars in a virtual world. Be whoever you want—male, female, neither, a hybrid. Be whatever you want—bonobo, parakeet, centaur, Lord Vishnu. Heck, pick the right site and you can spend years online as some paramecium trying to evolve multi-cellularity. And have relationships with other people’s avatars in the process. All easily done, since the physical, phenotypic reality of what kind of body you have is irrelevant online.

Given all this—permanent, binary gender designation becoming increasingly fuzzy—one might expect it won’t be long before it will be non-existent. Unfortunately, society is only going to get so far down that road before it’s stymied by a cognitive feature of our brains. Before we hit that roadblock, though, let’s review just how far our knowledge of gender has come.

COVER GIRL: Caitlyn Jenner, who has put a spotlight on transgender persons like nobody before her, is seen here at the ESPYS, where she received the Arthur Ashe Courage Award.Kevin Winters/Getty Images
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For starters there’s plants, a number of which are “monoecious,” which is to say that any given plant has both female and male organs (those stamens and pistils). Things are stranger with animals. There are parthenogenic species, where females reproduce without males—numerous reptiles fall in this category, including the incomparably cool Komodo dragon. There are synchronous hermaphrodites where, like monoecious plants, an individual has both sexes’ organs simultaneously. This includes worms, sea cucumbers, snails, and sea bass.

Then there’s spotted hyenas, gender-bending pseudo-hermaphrodites. It’s nearly impossible to determine the sex of a hyena by just looking, as females are big and muscular (due to higher levels than males of some androgenic hormones), have fake scrotal sacs, and enlarged clitorises that can become as erect as the male’s penis. None of which was covered in The Lion King.

And then there’s sequential hermaphrodites like the sea wrasse and clownfish, where an individual changes sex opportunistically. There’ll be a single, dominant individual in a group (male among sea wrasse, female among clownfish), while the remaining subordinate members are of the opposite sex. If that dominant individual dies, the highest-ranking of the opposite sex changes sex and assumes the role. There’s even bidirectional hermaphroditic fish, switching back and forth depending on the lay of the land’s reproductive potential.

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OK, aren’t nature’s oddities so charming? But consider this about something as commonplace as lab mice—every mouse’s brain, regardless of its sex, has the circuitry for both male- and female-typical behavior (mounting and pelvic thrusting in the former, arching of the back to expose the rump in the latter). Manipulate things just right experimentally and you can bring either to the behavioral forefront.

Let’s turn now to another humdrum mammal, the solidly dichotomized human. Which turns out not to be so solid.

The sine qua non of human sex designation in humans is chromosomal—all your cells either have two X chromosomes, making you female, or one X and one Y, making you male. End of story. But no: Instead, there’s various chromosomal disorders where individuals can be XYY, XXY, XXX, X, or XXYY. Most result in infertility; some, like Turner syndrome (in which there is solely an X) produce neurological, metabolic, endocrine, and cardiovascular abnormalities.

“Honey, this is called puberty. Sometimes you get acne. Sometimes your clitoris becomes a penis. Whatever.”

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Much more interesting than these rare disorders is the recent finding that adult men typically have some XX (i.e., female) stem cells scattered throughout the body, which have differentiated into mature cells, including neurons. Meanwhile, women who have given birth to a son have a similar scattering of XY stem cells. Remarkably, during pregnancy, some maternal stem cells become incorporated into the fetus, some fetal stem cells into the mother. Thus, many of us are sex-chromosome mosaics (with, at present, unknown consequences).

Once sex chromosomes are determined, everything else about gender designation follows suit: XX versus XY determines whether you wind up with ovaries or testes. That determines whether it’s predominantly estrogen and progesterone, or testosterone in your bloodstream. The hormones you’re marinated in then determines which type of genitals you form as a fetus, as well as secondary sexual characteristics ranging from the chemical composition of your sweat to the workings of your brain. Chromosomal, gonadal, endocrine, genital, and phenotypic sex go hand in hand.

Except they don’t, as it turns out—there are numerous disorders where someone might be male in some of those ways, but female in others.

To begin with, chromosomal sex and gonadal/anatomical sex can disagree. In a syndrome called 46,XY DSD, people have normal male sex chromosomes, testes—genitals that are usually classified as male—plus a womb and Fallopian tubes. In ovotesticular disorder, the person has the sex chromosomes of one sex, but both ovarian and testicular tissue, producing ambiguous genitals.

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Then there’s cases where a disconnect occurs at the level of hormones. One well-studied example concerns the fact that testosterone exerts some of its effects in target cells by being converted to a related hormone, DHT (dihydrotestosterone)—unless you have a mutation that inactivates the enzyme that does that conversion. This occurs in “5-alpha-reductase deficiency”; the individual is XY, has testes and normal levels of testosterone, but the person’s phenotype—their external appearance—can range from male to ambiguous to female. For those with a predominantly female phenotype at birth, there’s typically masculinization at puberty (the long-hidden testes descend, the clitoris enlarges, voice deepens). Clusters of cases of this disorder have been identified in some inbred, isolated populations (for example, in the mountains of the Dominican Republic) where, remarkably, there’s been a fair degree of cultural accommodation—“Honey, this is called puberty. Sometimes you get acne. Sometimes your clitoris becomes a penis. Whatever.”

Hormones affect target cells by interacting with specific receptors (estrogen receptors bind estrogen, insulin receptors bind insulin). Another type of dissociation at the hormone level is seen with “testicular feminization syndrome,” where there is a mutation that inactivates the androgen receptor, which normally binds testosterone and DHT. Normal XY, normal testes, normal levels of the two hormones, but the hormones have no effects, producing a phenotype that ranges from ambiguous to female. In the latter case, the disorder is usually discovered around puberty, when the girl fails to start menstruating. She fails to start because, as it turns out, there’s no ovaries or uterus, the vagina dead ends, and way up in the stomach are testes pouring out androgens.

Thus there’s numerous ways where chromosomal sex and phenotypic sex differ, accounting for 1 percent of births. This is not rare—pick a human at random and the odds are greater that they were born with ambiguous intersex genitals than they have an IQ greater than 140.

Perhaps the most interesting dissociation occurs one step further down the line. This is where the person has the chromosomes, gonads, hormones, genitals, and secondary sexual characteristics—hair, voice, musculature, facial structure, the works—of one sex. But has always felt like the other.

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This is the transgendered world, and some intriguing science hints at its neurobiological bases. There are a number of places in the human brain that are “sexually dimorphic” (where the size, structure, function, and/or chemical makeup of the area differ by sex). The differences aren’t big enough so that you could identify someone’s sex just by knowing the size of one of those regions. However, there are statistical differences between populations of men and women, differences with likely functional consequences.

So you have someone who by every measure discussed, from sex chromosomes to phenotype, is Sex A, but who insists that they have always felt like they are Sex B. What’s up in the sexually dimorphic brain regions? A number of studies report the brain bears a close resemblance to Sex B. And this shouldn’t seem surprising—we are determined by our brains, we are our brains, regardless of our pattern of facial hair, the thickness of our larynx, or what the landscape is like between our legs.

In other words, it’s not that transgendered individuals think they are a different gender than they actually are. It’s that they’ve had the profoundly crappy luck to be stuck with bodies that are a different gender from who they actually are.

Slowly, a word becomes pertinent—“continuum.” Gender in humans is on a continuum, coming in scads of variants, where genes, organs, hormones, external appearance, and psychosexual identification can vary independently, and where many people have categories of gender identification going on in their heads (and brains) that bear no resemblance to yours. All with a frequency that, while rare, are no rarer than various human traits we label as “normal.”

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THE FACEBOOK 58: Our culture’s growing recognition that gender can be fluid was institutionalized by Facebook in 2014, when it allowed users to select from 58 gender choices on their profile page.Facebook

Given current knowledge into the gender continuum, with new scientific insights (and celebrity disclosures) sure to come, we might expect that in the near future people will effortlessly think about gender as fluid and not strictly male or female. To be blunt: No way. That’s because our minds are very resistant to continua. Instead, we tend to break continua into discrete chunks, into categories.

This is the case, for example, in sensory perception. Anthropological linguists have explored this with respect to color perception. The visual spectrum produces a continuum of color; despite this, we perceive color as if it comes in categories, invent words in every language that arbitrarily break the continuum. Such color terms reinforce our categorical perception of color. In English, for example, a language in which there are distinct terms for “blue” and “green,” two shades of blue are viewed as more similar than a shade of blue and one of green, even if all are equidistant on the visual spectrum.

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Our propensity to break continua into categories on a neurobiological level was shown in a beautiful study in which monkeys looked at pictures of a dog or a cat, while the electrical activity of neurons in their frontal cortexes were recorded. There would be neurons that solely responded to dog, others to cat. Then, the scientists morphed the dog and cat together, producing pictures of an 80 percent dog/20 percent cat, a 60 percent dog/40 percent cat, 40/60 and 20/80. Remarkably, neurons responded categorically. For example, a “dog” neuron would respond equally robustly to 100 percent dog and 60 percent dog, and hardly at all to 40 percent dog. In other words, the drive toward categorizing is so strong that in this circumstance, these neurons consider 60 to be closer to 100 than to 40.

So we think categorically. And dichotomized gender is one of the strongest natural categories the brain has. The categorization is crazy fast—neuroimaging studies show the brain processes faces according to gender, within 150 milliseconds—that’s 150 thousandths of a second—before there’s conscious awareness of gender.

For a hunter-gatherer, a beneficial automatic categorization would probably have been “animals that I do/don’t have to run away from ASAP.”

Automatic categorization by gender is deeply ingrained. This was shown subtly in a study. In the first part of the study, subjects are shown a series of photos of guys in basketball jerseys, each paired with a sentence, such as “You were the ones that started the fight.” Half of the players are white and half are black; all are dressed the same. Afterward, subjects are asked to match the player with his particular remark. When subjects pick the wrong player, there’s a greater than 50 percent chance the misidentified player will be of the same race as the person who uttered the sentence. That tells us our minds make automatic categorizations by race. As subjects search to remember who made a particular remark, they’re not thinking, “Hmm, I’m not sure, it was definitely one of the guys with square shoulders, but which one?” They’re thinking, “Not sure, but it was definitely one of the [whichever race] guys.”

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In the second part, photos show half the players of each race wearing yellow jerseys and half gray ones. Once again, subjects are asked to match the player with his sentence. Now misattribution is more likely to be by jersey color than by race, revealing race may not be as deeply engrained as expected, given it can be trumped by something as seemingly trivial as a jersey’s color. Finally, the study repeats the same experiment, but this time the players, rather than differing by race, differ by gender. When all the players are wearing the same colored jerseys, subjects misidentify by gender. And when players are wearing different colored jerseys, subjects still misidentify by gender. What does that tell us? That gender is a stronger, deeper automatic category in our minds than race and visual cues.

There are many advantages to thinking categorically. It’s easier to remember things that have been categorically labeled, and easier to manipulate, organize, and make executive decisions about information that is categorically digital rather than on an analog continuum. For a traditional hunter-gatherer, a beneficial automatic categorization would probably have been “animals that I do/don’t have to run away from ASAP.” An example from our Westernized lives is so ingrained it’s hard to appreciate: “Red means stop and green means go.” If we were in a foreign country whose red lights were a different shade than our own, that sure wouldn’t make us hesitate about stopping at a busy intersection.

There are disadvantages, of course: We underestimate the differences between points arbitrarily chunked in the same category, overestimate the difference when they are in separate ones. This is the heart of parochialism and xenophobia, of stereotyping and prejudice. But nonetheless the advantages of categorical thinking have seemingly been sufficient to make it the strong cognitive tendency that it is.

Why have our brains evolved to think in such a powerfully categorical way when it comes to gender, despite the biological reality of it not being all that categorical? The simple answer is we are not monoecious plants, sea bass, or hyenas. The human exceptions to cleanly dichotomized gender are still uncommon, and many are not easily detected, phenotypically. After all, before some scientific advances in the mid 20th century—that is to say, 99.9 percent of hominid history—a male with testicular feminization syndrome was just a female who couldn’t get pregnant.

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Culture and its artifacts can affect the distribution of biological traits, as well as our attitudes about those traits. It is commonplace now to have a trait that everyone back in our hunter-gatherer past would have correctly viewed as eventually fatal—being near-sighted and therefore not-so-hot at spotting predators. Thanks to eyeglasses, there has been relaxed selective pressure against myopia. Unlike the distant past, people with lousy eyesight pass on as many copies of their genes as do the sharp-eyed, and the genes related to myopia are no longer being winnowed away by natural selection.

It’s difficult to imagine, though, any strong selective pressure against our brain’s automatic binary categorization by gender—it can be handy when it comes to that evolutionarily relevant goal of finding a mate. Accepting the fragility of that categorization requires some heavy lifting by the neocortex, the recently evolved, egg-heady part of the brain that is tasked with assimilating the information in an article like this. In 35 years, most of us will still be sniffing at crotches, asking, Boy or girl? Maybe things will be different in 350 years, or 3,500 years. It’s possible. Of course, by then, maybe all anyone will be asking is which operating system you had your consciousness uploaded to.

Robert Sapolsky is a professor of biology, neurology, and neurosurgery at Stanford University.

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Additional Reading

Ainsworth, C. Sex redefined. Nature 518, 288-291 (2015).

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Freedman, D.J., Riesenhuber, M., Poggio, T., & Miller, E.K. Categorical representation of visual stimuli in the primate prefrontal cortex. Science 291, 312-316 (2001).

Garcia-Falgueras, A. & Swaab, D.F. A sex difference in the hypothalamic uncinate nucleus: Relationship to gender identity. Brain 131, 3132-3146 (2008).

Hahn, A., et al. Structural connectivity networks of transgender people. Cerebral Cortex (2014). Retrieved from doi:10.1093/cercor/bhu194

Kimchi, T., Xu, J., & Dulac, C. A functional circuit underlying male sexual behavior in the female mouse brain. Nature 448, 1009-1014 (2007).

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Kurzban, R., Tooby, J., & Cosmides, L. Can race be erased? Coalitional computation and social categorization. Proceedings of the National Academy of Sciences 98, 15387-15392 (2001).

Nawata, H., et al. Regional cerebral blood flow changes in female to male gender identity disorder. Psychiatry and Clinical Neurosciences 64, 157-161 (2010).

Rametti G., et al. Effects of androgenization on the white matter microstructure of female-to-male transsexuals. A diffusion tensor imaging study. Psychoneuroendocrinology 37, 1261-1269 (2012).

Rametti G., et al. White matter microstructure in female to male transsexuals before cross-sex hormonal treatment. A diffusion tensor imaging study. Journal of Psychiatric Research 45, 199-204 (2011).

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Schöning, S., et al. Neuroimaging differences in spatial cognition between men and male-to-female transsexuals before and during hormone therapy. Journal of Sexual Medicine 7, 1858-1867 (2010).

Zhou, J.N., Hofman, M.A., Gooren, L.J.G., & Swaab, D.F. A sex difference in the human brain and its relation to transsexuality. Nature 378, 68-70 (1995).

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