TLDR; While recent efforts to include the study of sex as a biological variable in biomedical research is a well-intentioned effort to correct historic sexism, scientists must recognize that binary sex is itself a social construct – one constructed for the purpose of dominating and controlling human bodies. Recognizing the variability and changeable nature of biology is one way that science can work to counteract the enforcement of sex categories which is the basis of oppression, and uphold the fundamental right of people to self-determine their relationship to their bodies.
In 2015, the National Institutes of Health published a notice that sex must be considered as a biological variable in all biomedical research funded by it. The purpose of this mandate was to correct a historic over-reliance on male animals and cells, a practice rationalized by a sexist idea that female animals were particularly “hormonal”, or else to reduce experimental variability. Of course, excluding female subjects meant that potentially important interactions of sex-related traits and other phenomena were obscured or ignored to the detriment of science and medicine [1, 2]. To counteract this, the NIH urged that “adequate consideration of both sexes in experiments and disaggregation of data by sex allows for sex-based comparisons and may inform clinical interventions” [3, 4].
Those passingly familiar with transgender rights activism may be familiar with the phrase, “gender is a social construct.” Often, gender is described as a matter of psychology and culture, while sex is a matter of biology. However, this obscures an important caveat: namely, that the binary categories of “male” and “female” sex would be uninterpretable and indefensible without the concept of gender. While the NIH’s push to study sex as a biological variable is an important counter to a sexist historical policy, the way that sex is currently used in biomedical research – that is, as an abstract binary category related only to what genitals one has – is not actually a biological variable.
To study the biology of sex, it is necessary to consider how specific aspects of sex – such as hormones, chromosomes, gene expression, for example – interact with a biological subject of interest. What is more, each of these sex-related traits show different prevalence the level of groups, and at the level of individuals. While some traits may be more statistically likely for one sex category than another, every person within a sex category will have a different configuration of hormone levels, hormone effects, secondary sex characteristics, or chromosomes, which may or may not all be “female-typical” or “male-typical” [5-7]. For example, a person categorized to be female may not be “female-typical” for all sex-related traits they possess. This is because sexual difference occurs through multiple different mechanisms that work independently of one another, and which may interact with each other and the environment to create greater or lesser sex differences for any given individual [8]. With all these different interacting spectra, it becomes plain that there is no way to capture all sexual difference within a binary.
Within the brain, the notion of a binary sex becomes even more complicated. It has been repeatedly shown that biological correlates of sex/gender in the brain (such as volume of regions in structural MRI) are hugely variable within an individual, such that even if an individual categorized as male has technically more “male-typical” traits than “female-typical” traits, they may still be more similar to an individual categorized as female with more “female-typical” traits than to another “male” due to how these traits overlap [9, 10]. Even the hypothalamus, a region of the brain that shows a large sex differences in galanin neuron counts, also shows this “mosaicism” of traits, such that an individual with “male-typical” counts for one region may show “female-typical” counts for another [11]. Neuroscience researchers will often measure effects of sex category on neurons, gene expression, proteins, or behavior. However, without examining a particular aspect of sex, the mechanism by which an effect arises – and therefore the clinical usefulness of the research – becomes muddled and unclear.
Treating sex as a binary is a particular danger to people with intersex conditions. Intersex people make up 0.05% to 1.7% percent of the population, and may show a wide variety of “male-typical” and “female-typical” traits in combination [12, 13]. Intersex people are commonly forced to undergo cosmetic surgery or procedures as children to make their bodies conform closer to an imagined normal for a sex, which is often selected by the doctor or parents and may or may not align with their gender identity [13, 14]. In this way, it should be apparent that the sex binary is not only biologically fallacious, but a category which is actively enforced.
The study of sex as a binary reduces the clinical relevance of research on sex effects generally, but particularly excludes people with non-normative sex traits, including intersex people and anyone using medication that alters hormone levels such as hormone replacement therapy and hormonal birth control. Crucially, researchers should be cautious of reinforcing a false sex binary and adding fuel to the fire of sexist and transphobic policy, which exploits biological research to uphold the structures of societal injustice [15, 16].
For the purpose of oppressing people on the basis of their bodies, a sex binary functions identically to a gender binary. By collapsing sex to an abstract, binary variable, researchers actually erase biological variability, produce less accurate science, and legitimize oppression. We must do better science by refusing to collapse real biological variability to fit into colonial structures, and recognizing the fundamental right of people to self-determine their relationship to their bodies.