Biological sex is strictly binary: male or female, determined by XX or XY chromosomes.

In most secondary school biology curricula, the lesson was brief and tidy: females have two X chromosomes, males have one X and one Y. The chromosomes determine sex. Sex is determined at fertilization. The categories are two, and every human being belongs to one or the other. The simplicity was pedagogically appealing and seemed, on casual inspection, to match observable reality well enough.

The biology, examined carefully, was always more complicated. The history of genetics knew as much. The existence of XXY individuals, described systematically by Harry Klinefelter in 1942, was documented long before molecular mechanisms were understood. Turner syndrome (XO), Klinefelter syndrome (XXY), and XYY karyotypes were catalogued in the medical literature across the 1940s and 1950s, and their existence was not secret; it was simply quarantined to clinical medicine and not incorporated into the general biology classroom.

The chromosome story became still more nuanced in 1990, when Andrew Sinclair and colleagues at the Imperial Cancer Research Fund in London published a paper in Nature identifying SRY, the sex-determining region Y gene, as the primary switch for testicular development. The paper, titled "A gene from the human sex-determining region encodes a protein with homology to a conserved DNA-binding motif," showed that SRY presence drives the embryonic gonad toward testicular differentiation. But exceptions documented in subsequent years made clear that the switch was not absolute: XX individuals with a translocated SRY fragment develop as males; XY individuals with SRY mutations develop as females. The gene matters; the chromosome is a delivery vehicle.

Beyond chromosomes and the SRY gene, the developmental pathway from genotype to anatomy involves hormonal signaling at multiple stages, receptor sensitivity, and the interaction of dozens of other genes. Congenital adrenal hyperplasia, complete androgen insensitivity syndrome, 5-alpha reductase deficiency, and Mullerian agenesis each produce anatomical configurations that do not fit the binary template, and each arises through a distinct mechanism. Anne Fausto-Sterling's 2000 book Sexing the Body drew on medical literature to estimate that approximately 1.7 percent of births involve some degree of difference in sex characteristics from the standard male or female pattern, a figure that has been debated, with estimates ranging considerably depending on how "intersex" is defined, but which confirmed that biological variation in this domain is neither negligible nor exotic.

What the genetics and embryology revealed, collectively, was not that sex is a social construction but that it is a biological system with multiple interacting components, chromosomes, gonadal tissue, hormonal environment, receptor function, and anatomy, none of which invariably aligns with all the others. The binary model described the most common developmental outcome. It did not describe the full range of human biology. For generations, the medical response to that range had been surgical and hormonal intervention on intersex infants to enforce conformity with the binary, a practice that the human rights community, beginning in the 1990s, and an increasing number of medical ethicists began to characterize as ethically problematic. The reckoning began, as it often does, with the science finally being read.