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The history of sex research: Is “sex” a useful category?

2024; Cell Press; Volume: 187; Issue: 6 Linguagem: Inglês

10.1016/j.cell.2024.02.001

1097-4172

Beans Velocci,

Sex and Gender in Healthcare

The history of sex research demonstrates an ongoing coexistence of multiple, conflicting meanings of sex. This history raises questions for scientists about the deployment of a research variable that lacks precision. Cross-disciplinary collaboration between scientists and science and technology studies (STS) scholars offers a way to find solutions to this problem. The history of sex research demonstrates an ongoing coexistence of multiple, conflicting meanings of sex. This history raises questions for scientists about the deployment of a research variable that lacks precision. Cross-disciplinary collaboration between scientists and science and technology studies (STS) scholars offers a way to find solutions to this problem. When I teach my undergraduate seminar "Studying Sex," we begin with what students assume will be a straightforward exercise. I ask, "What is sex?" and write students' responses on the board as they shout out ideas. Chromosomes! Genitals! "Yes, what else?" Gonads. A biology major chimes in with "gamete size." This goes on for a while, until we turn to how people identify sex. The list grows longer: presence or absence of breasts, amount of body hair, bone structure, choice of sexual partners, reproductive capacity. In the end, we come up with something that looks like Figure 1. The answer to the question "What is sex?" is, in both theory and practice, just about everything, and therefore also nearly nothing. This exercise demonstrates that sex is an incoherent category, one that has perhaps outlived its use. The multiplicity that my students articulate is the inheritance of a long history of sex research. Over the course of centuries, the meaning of sex has not only changed over time but accumulated increasing numbers of conflicting yet coexistent meanings. In the present, this means that sex—a key research variable in the life sciences, not to mention its role in structuring our everyday lives—is not a singular and stable entity. This has real, practical ramifications. On one hand, it introduces a tremendous lack of specificity and rampant imprecision to scientific research; on the other, it fuels ongoing arguments about the purportedly biological reasons that transgender (and especially nonbinary) people are not deserving of rights or do not even exist. Understanding this history raises an important question for scientists: how does the incoherence of sex shape contemporary research? Sex has been a topic of inquiry since at least antiquity when thinkers like Aristotle and Galen theorized maleness and femaleness as the outcome of the heat of a person's body. Ever since, scientists have relied on a vast range of characteristics and processes to define what makes an organism male or female, how a given body ends up a particular sex, and if there are more (or fewer!) than two sexes. It may be tempting to view those shifts as more accurate models replacing inadequate ones over time, but the history of sex research is not a matter of better explanations falsifying older. Rather, multiple models and meanings of sex have, for millennia, coexisted. Some models, like the classical heat approach to sex determination, have fallen out of favor, and others, as I'll discuss below, have accrued to the mélange, but there has not been a steady march of progress. On the contrary, the more scientists have studied sex, the more contradictions the category has come to contain. A brief journey through some of the major additions illustrates the increasing convolutions of the category. Scholars in the history of science and science and technology studies (STS) have identified many models of sex. Perhaps the most long-standing and familiar is an anatomical model, in which sex is identified through the visual inspection of external genitalia and marked by the presence of a vulva or penis—indeed, this remains the way that most infants are assigned a sex at birth. Beginning in the latter decades of the nineteenth century, however, as science professionalized and the science of sex specifically became a field of study, sex rapidly expanded (this does not mean that there was total agreement before this period—scholars of the medieval and early modern periods, too, have shown a range of scientific and medical conceptualizations of sex).1DeVun L. The Shape of Sex: Nonbinary Gender from Genesis to the Renaissance. Columbia University Press, 2020https://doi.org/10.7312/devu19550Crossref Google Scholar Around the 1870s, a gonadal model of sex rose to prominence.2Mak G. Doubting Sex: Inscriptions, Bodies and Selves in Nineteenth-Century Hermaphrodite Case Histories. Manchester University Press, 2012Google Scholar Anatomy, it turned out, was not foolproof, and an ongoing scientific fascination with hermaphroditism—what we would now call intersex—increasingly turned to the pathologization of ambiguous genitalia and what would soon be described as secondary sex characteristics. Descriptions of humans of "doubtful sex" rapidly entered the pages of medical journals.2Mak G. Doubting Sex: Inscriptions, Bodies and Selves in Nineteenth-Century Hermaphrodite Case Histories. Manchester University Press, 2012Google Scholar Scientists latched onto the gonadal model to aid in determining the sex of nonhuman animals, which often had wildly different sexual morphologies depending on species—hyenas, for example, had long captured the interest of scientists who found it nearly impossible to distinguish between phallus and clitoris due to the idiosyncrasies of the hyena body.1DeVun L. The Shape of Sex: Nonbinary Gender from Genesis to the Renaissance. Columbia University Press, 2020https://doi.org/10.7312/devu19550Crossref Google Scholar Sex, then, could perhaps not be identified at a glance after all. Dissection came to the rescue: scientists and medical practitioners argued that they could identify an animal's "true" sex by determining if it had testes or ovaries. Internal organs came to define "true" sex even as external genitalia continued to serve as the baseline means of identifying sex. The turn of the century brought additional ideas about the root of sex difference and how to make sense of it, now within a widespread conception of sex as universally bisexual ("bisexual" here refers to the presence of both male and female traits, the word's primary usage before the contemporary sense of sexual orientation).3Ha N.Q. The Riddle of Sex: Biological Theories of Sexual Difference in the Early Twentieth-Century.J. Hist. Biol. 2011; 44: 505-546https://doi.org/10.1007/s10739-010-9257-1Crossref Scopus (18) Google Scholar In this period, endocrinological theories of sex differentiation emerged from a combination of the gonadal model and the new science of embryology. This was thanks in large part to Frank Lillie's work on free-martins (intersex co-twins of bulls) that culminated in the 1910s and demonstrated that the exposure to "male" hormones in utero resulted in ambiguous sexual characteristics in the bull's co-twin. Much debate ensued over whether these co-twins were modified females or underdeveloped males. Meanwhile, a coeval metabolic theory of sex contended that tendencies toward catabolism resulted in maleness, while anabolism produced femaleness—notably reminiscent of the classical model. Patrick Geddes and J. Arthur Thomson first proposed this metabolic theory of sex in 1889, and Oscar Riddle expanded upon it in the 1910s.3Ha N.Q. The Riddle of Sex: Biological Theories of Sexual Difference in the Early Twentieth-Century.J. Hist. Biol. 2011; 44: 505-546https://doi.org/10.1007/s10739-010-9257-1Crossref Scopus (18) Google Scholar Hormones and metabolism joined anatomy and gonads as defining features of sex. In contrast to the imagined stability of external anatomy and internal organs, the endocrinological and metabolic models both emphasized the malleability of the body: changes to hormone levels and metabolism produced changes in sex characteristics, and scientists latched onto these possibilities in their research.4Meyerowitz J. How Sex Changed: A History of Transsexuality in the United States. Harvard University Press, 2004Crossref Google Scholar This focus on malleability drew on and, in many respects, gave credence to the long-held idea that degrees of sexual dimorphism increased with a species' travels up the evolutionary hierarchy. Throughout the nineteenth century, scientists (Geddes and Thompson included) frequently argued that Africans exhibited less sexual dimorphism than Europeans, characterized by a variety of traits including genital appearance, pelvic structure, and body hair, among others, and were therefore less evolved on a racial level. Scientists thought they could identify the "true" binary sex of animals by looking at gonads during the same period that race science required human and nonhuman sex to exist on a spectrum, with full sexual dimorphism reserved for only the most evolutionarily advanced (from Binary Logic: The Power of Incoherence in American Sex Science, forthcoming from Duke University Press). With the advent of a new mode of scientific inquiry, cytologists and geneticists offered yet another way of thinking about sex through a chromosomal model that reemphasized stability. As Riddle, for example, was changing the feather patterns of birds in the lab in his "sex reversal" experiments using his metabolic malleability model, scientists investigating the X and Y chromosomes reencoded the notion of binary and stable sex in genes. Scientists first described the X and Y chromosomes in 1890 and 1905, respectively, though they wouldn't be referred to consistently as "sex chromosomes" until the 1910s. Chromosomes thus became another marker of "true" sex. In this genetic approach to sex, sex determination could be found in every cell, and it was decidedly either/or.5Richardson S. Sex Itself: The Search for Male and Female in the Human Genome. University of Chicago Press, 2012Google Scholar These are only a small handful of the definitions and ways of identifying sex that coexisted in the mid-nineteenth through mid-twentieth century in the United States and western Europe. Countless other versions of sex proliferated across research practices: scientists working on fungi turned to disembodied chemical reactions, sexual object choice spoke volumes about a person's sex at a time when a heteronormative sexual inversion model (i.e., a woman attracted to other women must necessarily be somehow physically and psychically masculine for that attraction to make sense) reigned supreme, and psychological gender relocated sex from the body to the mind. Still, with these debates raging around them, researchers deployed sex as a static research variable when statistical methods transformed the norms of scientific research; organisms could still be sorted into self-evident categories of "male" and "female" to track differences across populations. Binary sex, too, continued to structure day-to-day life throughout the United States and Europe, with science serving as justification for a whole array of patriarchal and white-supremacist social arrangements.6Karkazis K. The Misuses of "Biological Sex.".Lancet. 2019; 394: 1898-1899https://doi.org/10.1016/S0140-6736(19)32764-3Abstract Full Text Full Text PDF PubMed Scopus (33) Google Scholar The point is this: even as scientific inquiry produced endless evidence that sex was neither straightforward to identify nor binary, sex continued to function as a foundational classification system for science and everyday life. It is that very incoherence that gives sex the flexibility to stand up to such an onslaught of evidence. "The only thing we can say for sure about what sex means," Paisley Currah noted in his recent book on government sex classification, "is what a particular state actor says it means."7Currah P. Sex Is as Sex Does: Governing Transgender Identity. New York University Press, 2022https://doi.org/10.18574/nyu/9781479812011.001.0001Crossref Google Scholar So, too, for scientific approaches to sex—because it is so many things at once, all we can say for sure about what sex is is what a given scientist does with it. This is not merely a historical quirk but a use of sex that persists into the present. The term "sex" has collapsed entire constellations of traits and processes into one point. As a result, it functions as a nearly universally accepted research variable with little consistency in its conceptual definition, and less in its usage. This does not make for accurate or reproducible science. As several scientists have pointed out, these contemporary uses of sex—simultaneously attached to an oversimplified binary, yet in practice depending on a vast, rarely analyzed multiplicity—actually make it harder to understand biological variation.8McLaughlin J.F. Brock K.M. Gates I. Pethkar A. Piattoni M. Rossi A. Lipshutz S.E. Multivariate Models of Animal Sex: Breaking Binaries Leads to a Better Understanding of Ecology and Evolution.Integr. Comp. Biol. 2023; 63: 891-906https://doi.org/10.1093/icb/icad027Crossref Scopus (3) Google Scholar There are also human costs: a broader cultural idea of "biological sex" as binary, imagined to be backed by science, is routinely deployed to exclude trans and intersex people and indeed anyone with bodily characteristics that do not fit neatly into male and female norms.6Karkazis K. The Misuses of "Biological Sex.".Lancet. 2019; 394: 1898-1899https://doi.org/10.1016/S0140-6736(19)32764-3Abstract Full Text Full Text PDF PubMed Scopus (33) Google Scholar The status quo, built on the history sketched above, therefore generates unsound research results that falsely uphold cis- and heteronormative assumptions. Some scientists8McLaughlin J.F. Brock K.M. Gates I. Pethkar A. Piattoni M. Rossi A. Lipshutz S.E. Multivariate Models of Animal Sex: Breaking Binaries Leads to a Better Understanding of Ecology and Evolution.Integr. Comp. Biol. 2023; 63: 891-906https://doi.org/10.1093/icb/icad027Crossref Scopus (3) Google Scholar,9Packer M. Lambert M.R. What's Gender Got to Do with It? Dismantling the Human Hierarchies in Evolutionary Biology and Environmental Toxicology for Scientific and Social Progress.Am. Nat. 2022; 200: 114-128https://doi.org/10.1086/720131Crossref Scopus (2) Google Scholar,10Prum R.O. Performance All the Way Down: Genes, Development, and Sexual Difference. University of Chicago Press, 2023Crossref Google Scholar are already contending with this problem. Cell itself has taken steps in that direction: the author guidelines for submission include a note addressing the multiplicity of sex. "[T]here is no single, universally agreed-upon set of guidelines for defining sex," the guidelines point out. "'[S]ex' carries multiple definitions" including genetic, endocrinological, and anatomical features.11Kuhn T.S. Hacking I. The Structure of Scientific Revolutions.Fourth Edition. The University of Chicago Press, 2012Crossref Google Scholar Contributors should therefore reduce ambiguity by specifying their methods for collecting and recording sex-related data to "enhance the research's precision, rigor, and reproducibility." The Cell guidelines are aligned with a broader conversation that names increased precision when talking about sex as a solution to these problems.8McLaughlin J.F. Brock K.M. Gates I. Pethkar A. Piattoni M. Rossi A. Lipshutz S.E. Multivariate Models of Animal Sex: Breaking Binaries Leads to a Better Understanding of Ecology and Evolution.Integr. Comp. Biol. 2023; 63: 891-906https://doi.org/10.1093/icb/icad027Crossref Scopus (3) Google Scholar Calls for specificity are an important step, and acknowledging and accounting for the fact that sex is neither static nor unitary in its meaning are crucial for scientific precision and rigor. But as a historian with the long view of efforts to better know sex, I wonder what makes this time any different than before. When researchers split "sex determination" from "sex differentiation," for example, that certainly increased precision; so did cleaving chromosomal factors from hormonal ones. Yet little changed. Organisms are still referred to simply as "female" and "male," and "sex" deployed as a largely unspecified category. Regardless of the coexistence of multiple models, everyone is supposed to know what sex is. Similarly, while reports of nonbinary sex in various organisms have filled the pages of scientific texts with evidence that sex is not binary for centuries, that evidence has had little effect on conceptions of sex writ large. Recall the hyenas—twentieth-century scientists also contended with whether Hymenoptera have two sexes or three, how hermaphroditic oysters reproduce, and what sex gynandromorph butterflies "really" are. In contemporary research, sex is rarely defined. In other words, scientists have used multiple meanings of sex for a long time, and here we still are. STS scholars provide insight into this conundrum. Over fifty years ago, Thomas Kuhn, a physicist who later turned to history and philosophy of science, argued that scientific paradigms shift when an accumulation of anomalies within a given paradigm cause a crisis. Anomalies, though, have to be made meaningful, otherwise they are written off as calibration errors and similar flukes.11Kuhn T.S. Hacking I. The Structure of Scientific Revolutions.Fourth Edition. The University of Chicago Press, 2012Crossref Google Scholar Kuhn never addressed the social dynamics that influence which anomalies are considered mere exceptions and which are taken seriously, but decades of scholarship in feminist STS have clued us in: assumptions about and investments in maintaining the status quo of gender and sex play a major role in how scientists ask questions and develop research methodologies. Engaging with these social factors illuminates how scientists know what they know and why they don't know what they don't know.12Proctor R. Schiebinger L.L. Agnotology: the Making and Unmaking of Ignorance. Stanford University Press, 2008Google Scholar We live in a social world that is fundamentally structured around the idea that sex is a binary, biological truth. Scientists are therefore constantly conditioned to ignore anomalies that do not fit into that scheme. Precision and rigor are incredibly important. They're also not enough to counter hegemonic social forces. When considering the historical record, broader questions emerge. They are questions that are difficult to answer. What if sex as a category isn't reparable? What if the anomalies, contradictions, and multiplicities of meaning are not something that can be solved by doubling down on "sex" and doing it better, and instead suggest that "sex" itself needs rethinking? What if "sex" persists as a category because of social pressure to maintain binary sex as a scientific reality, not because evidence from actual bodies supports it? What possibilities might arise if we let go of the idea of a singular category that has perhaps outlived its utility? The good news is that scholars in several fields have been thinking about this problem for decades. Many of the scientists currently pushing for critical thinking about sex are engaged with STS scholars—many of us humanists and social scientists coming from disciplines like history, anthropology, and sociology, and fields like Indigenous studies, Black studies, and queer studies. We in STS are poised to offer life scientists additional conceptual and practical ways forward. Knowing the history of science is, of course, part of this equation: it shows us that knowledge production of all kinds (including the history of science!) is an iterative process, where what we know is always changing. Scientists, then, don't have to reinvent the wheel, nor become experts in STS, before tackling the problems I've outlined here. There are massive bodies of work and a wealth of expertise that already exist and scholars whose STS work is born of a desire for more ethical and accurate science. Collaboration between life scientists and STS scholars can be incredibly fruitful and take many forms. One approach involves embedding an STS scholar in a lab setting.13Wesner A. Messing up Mating: Queer Feminist Engagements with Animal Behavior Science.Wom. Stud. Interdiscipl. J. 2019; 48: 309-345https://doi.org/10.1080/00497878.2019.1603987Crossref Scopus (5) Google Scholar Another is mutual critique of existing scientific work and generating ideas for improvements.10Prum R.O. Performance All the Way Down: Genes, Development, and Sexual Difference. University of Chicago Press, 2023Crossref Google Scholar Cross-disciplinary publishing initiatives like The American Naturalist's special section on nature and power14Kamath A. Velocci B. Wesner A. Chen N. Formica V. Subramaniam B. Rebolleda-Gómez M. Nature, Data, and Power: How Hegemonies Shaped This Special Section.Am. Nat. 2022; 200: 81-88https://doi.org/10.1086/720001Crossref Scopus (6) Google Scholar and this issue of Cell are making space for collaboration within the existing structures of the field. There's significant room for experimentation, too: I'm working on an article with quantitative psychology researcher Shana Stites about the collection of sexual orientation and gender identity (SOGI) data in studies of dementia, what that information stands in as a proxy for, and how it may often reflect social norms and policy rather than biology. I'm also a faculty affiliate with the University of Pennsylvania's new Eidos LGBT+ Health Initiative, which brings together researchers from across the university to improve healthcare for queer and trans people. This kind of cross-disciplinary work is hard. Our disciplines are not set up for it, from funding opportunities to tenure processes. Ideas of what counts as rigorous scholarship differ—collaborating across disciplines means having to accept there are different ways of knowing that may not align with the evidentiary standard one has spent a career developing. For this reason, among others, humanists and scientists often struggle to take each other seriously. Yet it is our ability to ask different questions and use different methods that strengthens cross-disciplinary collaboration. In the case of sex, we know equally important but separate things about it: I have not been trained in the intricacies of the SRY gene, just as my scientist colleagues have not been trained in the critical close reading of the texts that got us to where we are now. Collectively, however, we know quite a lot. Questioning fundamental truths is, in its most aspirational form, the point of any knowledge-producing enterprise. Imagine what we might find out if we were to let go of a category that hundreds of years of history demonstrates to be more useful for maintaining social hierarchies than for generating scientific knowledge. Thank you to Ambika Kamath and Caz Batten for feedback on an early draft of this article. The author declares no competing interests.