The debate over sexual identity has polarized America.
On one side, progressives believe that “sex” and “gender” are distinct concepts. They argue that sex, which results from an elaborate cocktail of biological processes, forms a spectrum with “male” and “female” inhabiting opposite poles. A simple graph from Scientific American illustrates this idea:
Blogger Cade Hildreth offers the following chart for those seeking a more nuanced take:
Progressives also claim that each person determines her own gender, and this identity can evolve as the individual’s feelings change.
As Planned Parenthood elaborates:
Sex is a label — male or female — that you’re assigned by a doctor at birth based on the genitals you’re born with and the chromosomes you have. It goes on your birth certificate.
Gender is much more complex: It’s a social and legal status, and set of expectations from society, about behaviors, characteristics, and thoughts. Each culture has standards about the way that people should behave based on their gender. This is also generally male or female. But instead of being about body parts, it’s more about how you’re expected to act, because of your sex.
Most importantly, an individual’s interpretation of her sexual identity overrules any biological markers:
Some people call the sex we’re assigned at birth “biological sex.” But this term doesn’t fully capture the complex biological, anatomical, and chromosomal variations that can occur. Having only two options (biological male or biological female) might not describe what’s going on inside a person’s body.
Instead of saying “biological sex,” some people use the phrase “assigned male at birth” or “assigned female at birth.” This acknowledges that someone (often a doctor) is making a decision for someone else. The assignment of a biological sex may or may not align with what’s going on with a person’s body, how they feel, or how they identify.
Unsurprisingly, traditionalists reject the above formulation, arguing that not only is “gender” interchangeable with “sex”, but also that sexual identity results from chromosomes instead of feelings. They also define sex as binary, which means that — except in rare cases — a person is either male or female.
This debate has energized activists on both sides. In fact, it seems that a quarter of Substack accounts rail against the emerging view of sex as a social accessory that can be chosen like an ascot for the upcoming rehearsal dinner. Since the new definition of sex clashes with textbook orthodoxy, its growing acceptance by doctors, researchers, and politicians would seem to condemn progressive epistemological norms.
Some traditionalists, such as the evolutionary biologist Dr. Colin Wright from Reality's Last Stand, have scientific credentials. Others, such as Chaya Raichik from Libs of TikTok, have built a mighty subscriber base by rooting out gender activists within the educational establishment.
Perhaps the most famous lightning rod in the cultural storm, however, is Matt Walsh’s “What is a Woman?”, which gained notoriety when Elon Musk, in a blow against free speech and participatory democracy, refused to de-platform the documentary, maliciously allowing it to accumulate 177 million views.
With all the ink spilled on this issue, it would seem that any further essays would be like reheating leftover turkey. However, to quote Ann Pratchet, “Sometimes if there’s a book you really want to read, you have to write it yourself.” And I believe that there’s an overlooked perspective in this debate: Is viewing human sexual identity as a spectrum scientifically useful?
See, critics usually argue that viewing human sex as a continuum clashes with basic biology. But does it? In order to evaluate this claim, we have to review the basics.
The Basics
Most people have 23 pairs of chromosomes; 22 are autosomal while the 23rd consists of sex chromosomes. Males have an XY chromosome pair while females have XX. Although both sexes inherit one copy from each parent, men can only get their Y chromosome from their father. Mitochondria have their own DNA that is inherited almost exclusively from the mother for still mysterious reasons. So far, so good.
Alas, the issue is — ain’t it always? — more complex. As the above Scientific American chart indicates, the body undergoes many steps to convert chromosomal information to bodily function, any of which can go awry. To gain a broader perspective, let’s first review how the body turns a DNA code into a functioning protein.
Chromosomes1 are essential to protein production because they house the DNA that stores the cell’s information. Recall that DNA is a two-stranded molecule located in the cell’s nucleus that carries its code in nitrogenous molecules known as nucleotides. Nucleotides are the building blocks of genes, which are stretches of DNA that specify particular proteins. However, even the best-laid blueprints are useless unless they can be converted into an actual building. This requires careful coordination with a single-stranded molecule known as RNA. RNA is similar to DNA in its overall structure, and different types of RNA play specific roles in transcribing a gene and then translating it into a protein. This process requires careful coordination.
When the body needs a protein, a cell usually sends a message to another cell’s membrane. The recipient cell then transmits the signal — amplifying it along the way — until the message moves to the cell’s nucleus, where a helicase enzyme unzips the two-stranded DNA in order to allow the single-stranded “pre-mRNA” molecule to transcribe the gene that codes the relevant protein. With the help of a polymerase enzyme, the pre-mRNA reproduces the DNA code nucleotide by nucleotide as it binds to the gene’s complementary strand.
After the raw transcription is complete, the pre-mRNA waits in the cell’s nucleus while a spliceosome snips out the parts of its transcript — known as “introns” — that don’t code for the protein. The sliceosome then stitches together the remaining protein-specifying “exons”. The freshly processed messenger RNA (“mRNA”) then moves outside the nucleus to the jelly-like part of the cell known as the cytosol.
As it travels through the cytosol, the mRNA encounters a Frankenstein patchwork of proteins and nucleic acids known as the “ribosome”. The messenger RNA slides through the ribosome like punched computer tape ratcheting through an old teleprinter. The mRNA’s stored code provides a template for the arriving transfer RNA (“tRNA”) molecules, each of which bears an amino acid. As a tRNA clamps onto the mRNA conveyer belt, it passes its amino acid to an adjacent tRNA entering the next codon stall. Little by little, the amino acids link together to form a primitive protein. After subsequent folding and other processing, the protein is ready to be transported to its destination.
But how does this process determine a person’s sex? Time to fasten your seatbelt.
It turns out that embryonic gonad cells are bipotential, which means they can develop into either ovaries or testes. Primordial gonads start as a genital ridge that nestles adjacent to Müllerian and Wolffian ducts; the former becomes the female oviduct while the latter matures into the male vas deferens. To determine the gonad’s fate, an embryonic XX chromosome cell sends chemical messengers such as the Wnt4 and R-spondin-1 proteins to bind to the whimsically-named Frizzled receptor on a nearby XX cell’s surface receptor.2 The receptor then unleashes a network of the equally eccentrically-named “disheveled” proteins to initiate the process of gene transcription.
To pinpoint the correct gene, the cell relies on a cluster of transcription factors that sit a bit upstream of a gene’s promoter (the gene’s “on” switch). To differentiate the gonad, transcription factors such as the β-catenin and forkhead box L2 (FOXL2) proteins tell the mRNA where to start copying the ovary-forming genes. Since FOXL2 interacts with many different types of body tissues, it works in harmony with other transcription factors in a process called combinatorial regulation to ensure that the right balance of proteins are produced in, say, skin tissue as opposed to gonad tissue.
Interestingly, the FOXL2 transcription factor not only promotes ovary and follicle formation, it also suppresses SOX9 gene transcription so that male gonads won’t form. FOXL2 thereby plays an antagonistic role in sexual differentiation: should this factor malfunction, the SOX9 transcription complex will convert the gonad tissue into Sertoli and Leydig-like cells (for more on these cells, see below).3 For an adult woman, a mutation in the FOXL2 transcription factor can cause tumors in her granulosa cells. Nasty business, that.
Like men of all ages, prenatal males insist on following their own path. Instead of relying on the WNT4 signaling pathway, an embryo with XY chromosomes uses a cascade of mitogen-activated kinase proteins to start the process of sexual differentiation (mitogen oversees cell division and differentiation, critical for embryonic development). The kinase proteins relay the “start gene transcription!” command to a specific transcription factor known as GATA4. Along with other transcription factors, GATA4 binds to a specific region of the DNA to underscore which gene needs copying. In this case, the relevant gene, the Sex-determining Region Y (SRY) gene, codes for the corresponding SRY protein4 that activates SOX9, which in turn activates the DMRT1 transcription factor that induces the formation of Sertoli cells. The versatile SRY gene also interacts with a signaling molecule called Desert Hedgehog to promote Leydig cell formation.
Why are Sertoli and Leydig cells important? In male embryos, Sertoli cells suppress the development of the internal female reproductive organs by secreting an anti-Müllerian hormone that, you guessed it, causes the “female” Müllerian ducts (remember them?) to whither away. After all, what use has a male for an oviduct? Sertoli cells also help produce sperm, which men do need. Meanwhile, Leydig cells secrete the androgens that generate the male urogenital structures that deliver the sperm. Analogously to the FOXL2 factor, DMRT1 shows its antagonistic side by suppressing the formation of granulosa cells responsible for regulating female ovulation.
The following chart outlines the diverging developmental pathways between male and female embryos:
from Arboleda, Sandberg, and Vilain (2014)
For those seeking a more detailed take, this article provides a blow-by-blow description of embryonic sex determination.
Let’s Test The Claims
If you didn’t fully grasp the above, don’t feel bad — nobody else really does.
However, after one understands the multilayered nature of sexual differentiation, it becomes easier to dispel the ink cloud squirted by the Scientific American graph that opened this essay. Because, make no mistake, such “illustrations” are intended to dull the critical faculty instead of engaging it. The graphic is meant to be accepted, not questioned.
Even more importantly, understanding of the process behind sexual determination reveals why the conservative response “Don’t those gender activists remember their 9th grade biology? yuk yuk” is a rhetorical face plant. Instead of offering the critic an intellectual high ground, this gambit only provides the opportunity for a progressive to declaim how science has moved beyond Grandpa’s textbooks and how this modern, nuanced perspective better serves marginalized communities. For example, Claire Ainsworth concludes a discussion of sex differentiation with the following call to action:
Yet if biologists continue to show that sex is a spectrum, then society and state will have to grapple with the consequences, and work out where and how to draw the line. Many transgender and intersex activists dream of a world where a person's sex or gender is irrelevant. Although some governments are moving in this direction, Greenberg is pessimistic about the prospects of realizing this dream—in the United States, at least. “I think to get rid of gender markers altogether or to allow a third, indeterminate marker, is going to be difficult.”
So if the law requires that a person is male or female, should that sex be assigned by anatomy, hormones, cells or chromosomes, and what should be done if they clash? “My feeling is that since there is not one biological parameter that takes over every other parameter, at the end of the day, gender identity seems to be the most reasonable parameter,” says Vilain. In other words, if you want to know whether someone is male or female, it may be best just to ask.
Hi, Dr. Vilain, hope you don’t mind me using your diagram!
Other activists advance bolder takes, such as Simón(e) D Sun’s claim that the cutting-edge science has already settled matters:
While this is a small overview, the science is clear and conclusive: sex is not binary, transgender people are real. It is time that we acknowledge this. Defining a person’s sex identity using decontextualized “facts” is unscientific and dehumanizing. The trans experience provides essential insights into the science of sex and scientifically demonstrates that uncommon and atypical phenomena are vital for a successful living system. Even the scientific endeavor itself is quantifiably better when it is more inclusive and diverse. So, no matter what a pundit, politician or internet troll may say, trans people are an indispensable part of our living reality.
Transgender humans represent the complexity and diversity that are fundamental features of life, evolution and nature itself. That is a fact.
So, is the sex binary obsolete?
I think we’d all agree that for a scientific claim to be conclusive, it must first be useful, which brings us back to my original question: Is viewing sex as a spectrum scientifically useful?
I don’t think it is.
First, a scientifically useful concept solves puzzles. Continental drift offers a classic example of a fruitful scientific model.
Even though it was initially a fringe idea, drift was attractive to a scientific minority because it explained why the South American and West African coastlines fit together so snugly, why the Appalachian mountain’s terrain matches the Scottish Highland’s; how glaciers could once thrive in South Africa, Arabia, and India; and why similar fossils are dispersed on widely separated continents. The coup de grace arrived, however, when paleomagnetic maps of the seafloor revealed magnetic “stripes” of reversed polarity that were symmetrically bracketed across the Mid-Atlantic Ridge. These pieces of evidence jointly support the model of a primordial mass that broke apart through the process of continental drift, creating the current landscape. Once scientists understood how convection within the Earth’s mantle could move tectonic plates, the remaining skeptics fell silent and drift became scientific consensus.
Alas, instead of resolving questions, the sexual spectrum model only raises a host of them: If sex is a spectrum, then why do almost all animal species come packaged in only two sexes? Why are intersex conditions so rare? Why are intersex people so frequently infertile? Why do intersex people who are fertile (almost invariably) produce a single gamete?56 Why do intersex people experience so many health problems? There are puzzles galore, but solving them points us towards the binary model. The spectrum model is forced to build an apologetic sandcastle to mimic the binary model’s explanatory scope.
To see the true power behind the sexual binary, we have to understand why so many biologists reduce sex to eggs and sperm. After all, isn’t sex a multi-layered network of chromosomes, hormones, and behavior? Recall Ainsworth’s concern over reductive definitions:
[Should] sex be assigned by anatomy, hormones, cells or chromosomes, and what should be done if they clash? “My feeling is that since there is not one biological parameter that takes over every other parameter, at the end of the day, gender identity seems to be the most reasonable parameter,” says Vilain. In other words, if you want to know whether someone is male or female, it may be best just to ask.
However, the cocktail of chemical signals, genes, and proteins have a central goal: reproduction. Without reproducing, a species can’t survive. Any process that interferes with the mechanics of generating and delivering complementary sex cells to form a viable organism won’t be selected by evolution.
In a 2022 BioEssay “Biological sex is binary, even though there is a rainbow of sex roles”, Goymann, Brumm, and Kappeler provide the evolutionary-based definition of sex:
Biological sex reflects two distinct evolutionary strategies to produce offspring: the female strategy is to produce few large gametes and the male strategy is to produce many small (and often motile) gametes. This fundamental definition is valid for all sexually reproducing organisms. Sex-associated genotypes or phenotypes (including sex chromosomes, primary and secondary sexual characteristics and sex hormones), sex roles and sexual differentiation are consequences of the biological sex.
The authors elaborate:
As explained above, basically every sexually reproducing species produces two distinct types of gametes which are either large (eggs in animals, ovules in plants) or small (sperm in animals, pollen in plants). Neither are there “speggs” or “pollules” (gametes of intermediate size) or five different biological sexes as postulated by Fausto-Sterling,[34] nor are the male and female sex “context-dependent categories with flexible associations to multiple variables”.[6]All there is are two reproductive strategies based on two distinct categories of gametes that fuse to make offspring.[9, 17, 35] As Joan Roughgarden, a biologist who identifies as a transgender person, put it: “[…]‘male’ means making small gametes, and ‘female’ means making large gametes. Period!”.[36] Moreover, it is important to note that the fundamental definition of the biological sexes (based on gamete size) must be distinguished from any operational usage of the term, for example that based on chromosomes or genes, etc., because fundamental and operational definitions are not equivalent.
[my emphasis]
Even though chromosomes, genes, and proteins manufacture the sex cells and the genitals deliver them, the sex cells themselves are primary. Any sexual mechanism lacking eggs or sperm is an evolutionary dead end. This explains why intersex conditions occur in at most 1 out of 2000 births, while milder conditions such as Klinefelter syndrome occur in approximately 1 out 500 male births.
But how did the sex cells evolve, and why are they different sizes? Geoff Parker, Robin Baker and Vic Smith published an intriguing hypothesis in 1972. According to Parker, Baker, and Smith’s evolutionary model, gamete selection favors anisogamy, or the different size between sperm and eggs. Furthermore, anisogamy leads to two, and only two, sexes:
The reason that [this model] generates anisogamy is that ‘proto-females’ (parents producing large gametes) have zygotes that survive well, while ‘proto-males’ (producing many small gametes) ‘capture’ most of these valuable large gametes, effectively parasitizing their investment. Because of gamete competition, the small gametes become ever smaller and more numerous, so that eventually all of the resources for the zygote are provided by the large gametes. Intermediate ‘proto-sexes’ are lost from the population by disruptive selection. Without the assumption of pre-existing mating types, many of the ‘proto-males’ waste their gametes fusing with other tiny gametes by producing inviable zygotes, which helps to explain the evolution of microgametes that selectively fuse with macrogametes (reasons why macrogametes should not favour fusions with other macrogametes are more complex; see Parker, 1978).
The equations behind this model are robust to changes in their parameters, and numerical simulations and computer models offer additional support.
No model is perfect. The binary doesn’t fully explain why some parts of the regulatory cascade vary among animals7. Evidence for the evolutionary transitions has probably been irretrievably lost. Nevertheless, this model has passed its evidentiary tests so far.
Evolutionary pressures also explain why sexual differentiation is so antagonistic. Although gender activists may disdain the “cis hetero-patriarchy”, nature wants you to choose a side, already. Hence the dueling FOXL2 and DMRT1 transcription factors. Hence the SRY gene’s ability to produce maleness even when it’s translocated to the X-chromosome. Let’s let the MedlinePlus website explain:
In most individuals with 46,XX testicular difference of sex development, the condition results from an abnormal exchange of genetic material (translocation) between the Y chromosome and another chromosome, most often the X chromosome. This exchange occurs as a random event during the formation of sperm cells in the affected person's father. In this condition, the SRY gene (which is on the Y chromosome) is misplaced, almost always onto an X chromosome. A fetus with an X chromosome that carries the SRY gene will develop male sex characteristics despite not having a Y chromosome.
Although sex chromosomes are useful markers for biological sex, they can be misleading. Even if the biological actors change, though, the need to produce the next generation remains.
The binary model also helps doctors treat medical conditions. Let’s review the scientific chart that began the essay. See the reddish area of the spectrum where “Klinefelter syndrome” resides? Even though the chart concedes that people with Klinefelter syndrome (KS) possess male sex organs, you’d probably conclude that “assigning” these individuals as “male” without their consent violates the tenets of Settled Science™ (PBUH). Why not dunk some witches while you’re at it?
But did you know that treating these individuals as men with fertility problems is the only way to help them? From the Mayo Clinic:
Fertility treatment. Most men with Klinefelter syndrome are typically unable to father children because few or no sperm are produced in the testicles. For some men with minimal sperm production, a procedure called intracytoplasmic sperm injection (ICSI) may help. During ICSI, sperm is removed from the testicle with a biopsy needle and injected directly into the egg.
In contrast, my admittedly cis hetero-patriarchical mind fails to see the clinical use in proclaiming, “Dude, you’re partly a chick!” Seems pretty heartless, to boot.
Of course, the advocates of the spectrum model would say all of the above is bullsh*t. Well, at least the binary stuff anyway. And point to a shiny new paper that shows why, mostly by misunderstanding its own sources and playing with definitions. For now, I will leave you with a three responses from Colin Wright. However, my next post will have plenty to say about these counterclaims.
Until then, Happy New Year!
Technically, it would be better to call them “chromatin” as they’re the default DNA storage unit. The cell condenses chromatin into chromosomes before dividing.
The β-catenin protein can also override the male developmental pathway in embryos, leading to male-to-female sex reversal. Consequently, XY individuals will be phenotypically female. Although sex-reversed individuals are normally infertile, there’s at least one case of an XY-female giving birth. Overexposure to the Wnt4 cellular signaling protein can also cause sex reversal.
Please keep this humble protein in mind; I will mention it later.
For example, people with ovotesticular disorders generally produce eggs instead of sperm. As Acién and Acién (2020) note, “From the point of view of fertility, it should be taken into account that the ovarian component of the gonad tends to have a relatively normal histology, whereas the testicular component is more frequently dysgenetic, with limited germ cells and rarely sperm [62]. Gomes et al. [41] pointed out that while spontaneous pregnancies have been reported in 11 women with TH [79], successful paternity has only been described in an infertile male with TH and a 46,XX/46,XY karyotype after extraction of testicular sperm and intracytoplasmic sperm injection (ICSI) [80]”
However, there is one case study of a self-fertilizing intersex rabbit — an astonishing process in mammals. Additionally, there is a case study of an intersex individual who fathered a child with testicular sperm while also bearing an egg-producing ovary. Of course, the human subject couldn’t get pregnant. In general, although many plants and fungi self-fertilize, among vertebrates, only a handful of fish species have this ability.
You’d think that such an important process would be sensitive to mutations.