Comparative Integrative and Comparative Biology Integrative and Comparative Biology , volume 66, pp. 1–11 https://doi.org/10.1093/icb/icag105 Society for Integrative and Comparative Biology SYMPOSIUM ARTICLE Sexed Politics, Histories, and Futures Megan G. Massa 1 Neuroscience and Behavioral Biology Program, Emory College of Arts and Sciences, Emory University, Atlanta, GA 30322, USA From the symposium “Sex Across Origins: Questioning Animal-centric Assumptions and Developing Integrative Frameworks” presented at the annual meeting of the Society for Integrative and Comparative Biology, January 3-7th, 2026. 1 E-mail: mmassa@emory.edu Synopsis The tool of sex is being wielded against both science and society. As certain sex- and diversity-associated words are flagged and used to deny funding or discontinue awarded grants, the language of biology and sex is being used in legisla- tion to roll back legal protections and promote active harm against queer, and specifically trans and intersex communities. The history of sex in Western science and society demonstrates that this is but one more iteration in a long history of sex as a political tool. In order to escape from this curtailment of our work, we scientists must push outside the boundaries of our current sexed frameworks and develop new scientific imaginaries. Introduction “ For the master’s tools will never dismantle the master’s house. They may allow us temporarily to beat him at his own game, but they will never enable us to bring about genuine change ” ( Lorde 1984 ). Scientific research in the United States is being re- made. The autonomy and authority of longstanding funding agencies is being obliterated, the latest of which (as of the acceptance of this paper) was the unceremoni- ous firing of the entire National Science Board ( Mervis 2026 ). Funding cuts have impacted nearly every area of scientific grant funding ( Bhatia et al. 2025 ; Kozlov et al. 2026 ). Programs and grants that mention and target historically and currently minoritized populations are being singled out and defunded for no longer meeting “agency priorities” ( Kozlov and Mallapaty 2025 ). That these moves are overtly politically motivated shatters the oft-held assumption that science is and ever was “value-neutral” ( Whitt 2009 ), that is, independent from and unaffected by social and political context. Concurrently, the United States is experiencing the largest concerted attack on queer rights in recent mem- ory. The number of anti-queer, anti-trans, and anti- intersex bills have skyrocketed. Trackers showing any- where from 600 to over 1000 pieces of legislation in- troduced in 2025 and estimate anywhere from 500 to 800 bills currently active in 2026 ( 2026 Anti-Trans Bills 2026 ; Mapping Attacks on LGBTQ Rights in U.S. State Legislatures in 2025 2026 ; Mapping Attacks on LGBTQ Rights in U.S. State Legislatures in 2026 2026 ). These bills have already restricted people’s movement, access to medical care, safety in public spaces, and pri- vacy. Kansas retroactively cancelled the driver’s licenses of individuals who had changed their gender marker with no grace period ( Irwin and Simon 2026 ; Yurcaba 2026 ), a move which curbs the societal engagement of trans and intersex people whose sex assigned at birth does not match current manifestations. Hospitals across multiple states are limiting access to medical care for trans adults ( Cohen 2026 ; Jackson 2026 ) and minors ( Goldstein 2026a ; 2026b ; Cowan 2025 ) while carving out exceptions for intersex youth to be forced into sur- gical assignment ( Davis et al. 2015 ; Clune-Taylor 2019 ) despite best pediatric practice recommendations from multiple medical and scientific agencies ( Rafferty et al. 2018 ; Endocrine Society 2023 ; Kressly 2025 ). Participa- tion of trans and intersex people in daily life is threat- ened as more states restrict public restroom usage to stringent binary conditions based on arbitrary measures Advance Access publication July 2, 2026 C © The Author(s) 2026. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site-for further information please contact journals.permissions@oup.com 2 M. G. Massa of “sex” which do not align with trans and intersex em- bodied realities ( Adamczeski 2026 ). Tennessee legisla- ture has effectively mandated a public database of trans people receiving medical care in the state ( Kalish 2026 ). The law also has the potential to capture intersex peo- ple in this database given it defines sex as “characteris- tics of the reproductive system that define the individ- ual as male or female, as determined by anatomy and ge- netics existing at the time of birth” ( 114th TN General Assembly 2026 ), which both ignores intersex realities and will ultimately result in increased pressure for med- ical professionals to perform unnecessary surgeries to adhere “unruly” bodies to the sex binary ( Clune-Taylor 2019 ). And most recently, the White House has priori- tized “the rapid identification and neutralization of vio- lent secular political groups whose ideology is radi- cally pro-transgender” in a their counterterrorism strat- egy release ( The White House 2026 ). Providing a seemingly tangential backdrop to these funding cuts and targeted legislation, the definition of “sex” has begun to be publicly contested in the legal and scientific spheres. The law grapples with its definition, often varying across entities as it relates to the catego- rization of individuals ( Currah 2022 ) and the rights of the citizenry as to the designation of “protected class” status ( Lane-Steele 2024 ). Scientists, too, seem divided over whether binary ( Goymann et al. 2023 ; Ponzi and Palanza 2024 ), spectral ( Ainsworth 2015 ), or multifac- torial ( Massa et al. 2023a ; McLaughlin et al. 2023 ) con- ceptualization of sex is more accurate and useful to the scientific study of biological variability. These three phenomena are not unrelated. Their spe- cific manifestations in government, politics, and science are only possible due to their co-occurrence. The social system of the United States and other Western coun- tries is built on “bio-logic”, a cultural logic that relies on biology to form the rationale for the social order ( Oyˇ ewùmí 1997 ). Thus, when the scientific discourse destabilizes a foundational premise of society—here, sex as binary—and legitimizes those which had been pre- viously relegated to the margins of society—women, queer, trans, intersex individuals, and any combination therein—the supposedly given structures which govern our everyday lives and bodies (e.g., bathrooms, mar- riage, social roles) are threatened. In an effort to re- stabilize the social order, the idea of “scientific sex” is being wrested from scientists and reinscribed as binary ( Klibanoff 2025 ; Tucker 2025 ), science that challenges the binary dogma is being defunded (and science in gen- eral, too, for good measure), and people embodying the variation and expanse of humanity are subjected to leg- islative attacks. As scientists in bio-logical society, our way forward is clear: we cannot continue to reinscribe, inadvertently or not, the faulty idea that binary “sex” is a useful framework. And because sex itself is a tool, one forged in a sociohistorical context, all steps to remake “sex” are inadequate. We cannot dismantle the house with the tools that built it. We must make a tool of our own. Multiple, in fact. Because the tools of destruction are not the same as the tools of rebuilding. Sex—not our tool Steps to use the master’s tool—sex—to patch the holes in the master’s house have revealed themselves to be ephemeral. In the political sphere, legal designa- tions of sex have been used as a technology of gov- ernment to control designation, rights, and resource allocation ( Currah 2022 ). Federal course correction for sex-exclusionary laws began with the Nineteenth Amendment to the United States Constitution, stating “(t)he right of citizens of the United States to vote shall not be denied or abridged by the United States or by any State on account of sex” ( Nineteenth Amendment to the United States Constitution 1920 ). Later, Title VII of the Civil Rights Act of 1964 would prohibit employer dis- crimination due to an “individual’s race, color, religion, sex, or national origin” ( 88th US Congress 1964 ). Most recently, queer, trans, and intersex people have used this definition of sex to protect their own rights via the judi- ciary, with the Supreme Court of the United States rul- ing that discrimination on the basis of sexual orientation and gender identity are covered under Title VII ( Bostock v. Clayton County 2020 ). In science, the framework of binary sex has been used to course-correct sex-exclusionary medicine and research practice. The NIH Revitalization Act of 1993 instituted general provisions which required the inclu- sion of women and historically underrepresented pop- ulations in clinical research, not only establishing the Office of Research on Women’s Health and the Office of Research on Minority Health, but also ensuring that trials are “designed and carried out in a manner suffi- cient to provide for a valid analysis of whether the vari- ables being studied in the trial affect women or members of minority groups. .differently than other subjects in the trial” ( National Institutes of Health Revitalization Act of 1993 1993 ). NIH guidelines on this act have been semi- regularly updated to keep implementation current ( NIH 2001 , 2017 ). In a similar fashion, justified outcry over the lack of female animals in basic and preclinical re- search ( Beery and Zucker 2011 ) was combatted with the implementation of sex as a biological variable (SABV) in 2016 ( NIH 2015a , 2015b ). This policy spanned various levels of analysis, from organism to cells, since even “each cell has a sex” 1 ( Clayton 2018 ). Both of these fixes rely on the bio-logic framework of binary 1 For this to be true, one must assume that sex is meaningfully and consistently determined by sex chromosome complement. Sexed politics, histories, and futures 3 sex—women and females are so inherently biologically different that sex difference comparisons will increase rigor and reproducibility in science by revealing foun- dational scientific understandings of importance to sci- ence, medicine, and society ( Maney et al. 2023 ). But exclusion of women from clinical studies and the habitual underfunding of “women’s issues” ( Smith 2023 ) are, at their core, due to patriarchal assumptions about the validity, utility, and universality of these expe- riences. Due to Western bio-logic that posits biology as foundational for social structure ( Oyˇ ewùmí 1997 ), ani- mals and cells deemed female are then “womanized” and thus excluded in basic and preclinical research ( Shansky 2019 ). Indeed, the construction of sex to match gen- dered social structure has been created multiply, defined in direct opposition to and purposefully masking trans, intersex, and nonbinary individuals that challenge this strict binary ( Velocci 2026 ). Thus, the aforementioned attempts to rectify exclusion of women and females are insufficient because they (1) perpetuate the bio-logic crucial to the production of their exclusion, and (2) ne- glect to address the deliberate disregard of not just trans and intersex people but also of the diversity of reproduc- tive strategies across the phylogenetic tree ( Bachtrog et al. 2014 ; Tree of Sex Consortium 2026 ). By relying on the same unsteady foundation that produced the prob- lem in the first place, these legal and scientific policies are vulnerable to repossession. And, indeed, this tool of sex, having been employed to patch the house, is being wrested back. Attempts to legally codify sex as an immutable binary began during the first Trump administration ( Green et al. 2018 ). The effects of this initiative rolled over into the Biden years, with anti-trans bills beginning to rise in earnest in 2020 and jumping significantly in 2023 ( Tracking the rise of anti-trans bills in the US 2026 ). In 2021, now former US Congressperson Marjorie Taylor Greene put up a sign in front of her office that stated “There are TWO genders. MALE & FEMALE. Trust the science!” ( Vallejo 2021 ). Despite some scientists taking issue with this statement ( Stevens 2021 ; Casto and Maney 2024 ), this viewpoint was codified in an executive order in January 2025, which, under the guise of protecting women’s spaces, in- voked the language of science to deny the material reali- ties of trans and intersex people alike ( The White House 2025a ). Because bio-logics were so foundational to this framework, unwieldy scientists, too, had to be brought to heel. Reports began circulating in February 2025 that the Center for Disease Control was instructing its sci- entists to pull yet-to-be-published papers ( Steenhuysen and Lapid 2025 ) containing words and phrases deemed indicative of this new and “inappropriate” application of sex. These included “assigned male at birth”, “biologi- cally female”, “gender”, “transgender”, “LGBT”, among others ( Faust 2025 ). Days later, a bipartisan US House Subcommittee on Cybersecurity, Information Technol- ogy, and Government Innovation held a hearing entitled “Transgender Lab Rats and Poisoned Puppies: Over- sight of Taxpayer Funded Animal Cruelty” which began with attacks on trans research and ended with calls to end all animal-based biomedical research 2 ( Transgender Lab Rats and Poisoned Puppies 2025 ). The Trump ad- ministration doubled down on this anti-trans research rhetoric in a speech to a joint session to Congress on March 4 and in a subsequent blog post which berated the spending of federal research funds on models of hormone replacement therapy in animals as “egregious examples of waste” ( The White House 2025b ). Around the same time, lists of words began circulating which were supposedly unable to be used on government web- sites and would flag grant proposals for automatic re- view. This list included “female” (but not male), “women” (but not men), “trans”, “LGBT”, “LGBTQ”, “biologically female”, “biologically male”, “sexuality”, “gender”, “di- verse”, “diversity”, and “inequity” ( Yourish et al. 2025 ). Guidance for the NIH Revitalization Act of 1993 was updated to remove similar offending language ( NIH 2025 ). And somewhere along the way, SABV’s guidance document was listed as a “Historic document published prior to January 20, 2025”. 3 All of this came to a head in August 2025 with Ex- ecutive Order 14,332, “Improving Oversight of Federal Grantmaking”, which stipulates the following in Section 4, “Considerations for Discretionary Awards:” (b) In reviewing and approving funding opportunity an- nouncements and discretionary awards, as well as in designing the review process ascribed in section 3(a) of this order, senior appointees and their designees shall, as relevant and to the extent consistent with ap- plicable law, apply the following principles, including in any scoring rubrics used to assess grant proposals: (ii) Discretionary awards shall not be used to fund, pro- mote, encourage, subsidize, or facilitate: (B) denial by the grant recipient of the sex binary in hu- mans or the notion that sex is a chosen or mutable characteristic; The White House (2025c) The administration is instructing scientific funding agencies to disregard the scientific evidence, erasing in- tersex individuals and the harm they endure for the 2 One of the leaders of this subcommittee hearing, Rep. Nancy Mace, has also introduced the TRANS MICE Act, which aims to “[ban] the use of any federal funds to conduct, support, or fund research which seeks to alter an animal’s biological sex through drugs, hormones, surgeries, or other interventions, unless the species naturally undergoes sex changes or pos- sesses both male and female reproductive organs” ( Mace 2025 ). 3 The practical implications of this change are unclear, but it seems that the Trump admin- istration is attempting to distance itself from the policy. 4 M. G. Massa sake of maintaining the human sex binary ( Clune-Taylor 2019 ) and further marginalizing trans people seeking treatment ( Spade 2003 ). It is clear that the Trump ad- ministration knows what science and technology stud- ies scholars have been saying for decades (e.g., Latour and Woolgar 1986 ; Longino 1990 ) but that a majority of research scientists have long denied: science is politi- cal. And this is particularly relevant when discussing the science of sex (e.g., Harding 1986 ; Harding and O’Barr 1987 ; Bleier 1988 ). Genuine change, so close to our grasp, was unable to be made with the tools of the master. When science starts to destabilize the logic propping up the house of cards, the control of science becomes a question. By dis- mantling policies, censoring language, and restricting thought, the administration delegitimizes the arc of cor- rective science and reclaims their tools for their own house. Because the master’s tools “may allow us to tem- porarily beat him at his own game, but they will never enable us to bring about genuine change” ( Lorde 1984 ). Sex—not our house The undoing of our perceived progress has to do with the construction of sex ( Clune-Taylor 2021 ) in the Western society and Western science. The defi- nition and applications of sex in science have been molded and remolded throughout time to serve the social functions demanded of it (for another example, see Karkazis 2019 ). In his (in)famous book, Making Sex (1992), Thomas Laqueur presents the idea of a “one-sex” model and a “two-sex” model. According to Laqueur, the one-sex model conceptualizes humans as having a sin- gle sex continuum, males on top, wherein females and males are viewed as containing the same general parts but are inverses (or outverses) of one another. The two- sex model, on the other hand, denotes humans as having two distinct and diametrically opposed sexes—female and male—with males still atop the hierarchy. While Laqueur originally posited that these two frameworks occurred chronologically and transitioned from one- to two-sex around the time of the Age of Enlightenment in Europe ( Laqueur 1992 ), it has since been argued that these models co-existed in antiquity ( King 2016 ). To- day, these seemingly opposing models are both differ- entially (and even simultaneously) employed depending on which better supports the political goals of the ar- gument at hand. For instance, two common refrains for the exclusion of females in science are (1) the universal- ity of male experiences and (2) the increased variabil- ity of “hormonal” females ( Shansky 2019 ) despite evi- dence to the contrary ( Prendergast et al. 2014 ; Becker et al. 2016 ; Rocks et al. 2022 ; Smarr and Kriegsfeld 2022 ). These employ the one-sex and two-sex model, respec- tively: the former posits male universality due to the in- feriority and diminutization of females while the lat- ter requires a logic of two diametrically opposed sexes which can and must be isolated from one another. Our scientific and social obsession with sex dif- ferences is similarly political and can be seen as the confluence between current attempts to produce sex- equalized research, our scientific frameworks which prioritize the finding of differences 4 due to the orien- tation of our statistical analyses, 5 and the political util- ity of sex differences in maintaining the social order. The scientific response to women and females being deemed less important in clinical, preclinical, and basic research has attempted to rectify these biases through scientific affirmation of legitimizing the sex differences ( Oliva et al. 2020 ; Williams et al. 2021 ). This not only reifies bio-logics (as previously discussed), but it also re- inforces societal conceptions of “men are from Mars, women are from Venus” ( Gray 1992 ). It is then unsur- prising that the results of sex differences studies, partic- ularly when significant differences are found, are read- ily and excitedly taken up by media and the public alike ( Maney 2015 ), and the finding of sex differences (but not similarities) are often highlighted in results, discus- sions, and summaries of scientific studies ( Maney 2016 ; Garcia-Sifuentes and Maney 2021 ; Rippon et al. 2021 ; Eliot 2024 ; Sanchis-Segura et al. 2026 ). But our obsession with scientifically backed sex dif- ferences can also be linked to scientific racism, colo- nization, and eugenics. While metaphors of race and sex have been littered throughout scientific study de- sign, interpretation, and dissemination ( Stepan 1993 ), the scientific study of sex differences was explicitly used to justify colonial enterprises in the 1800s. In her piece “Pelvic Politics”, Sally Markowitz demonstrates that sci- entists used the degree of sex difference to place dif- ferent species, and also human cultures and races, on an evolutionary ladder, with one scientist directly stat- ing, “The higher the anthropological development of the race, the stronger [the] contrasts [of secondary sexual characteristics] between man and woman” ( Markowitz 2001 ). Thus, in a stunning application of the two-sex model, sex differences in the colonizing White races were exaggerated, and those in the colonized non-White races were minimized. We can still see this implicitly manifesting in culture today with the incessant mas- culinization of Black women 6 and the feminization of East Asian men ( Takinami 2016 ; Slatton 2018 ; Cheung 4 For more on the politics of difference, see Epstein (2009 ) 5 Statistics is another tool ripe for reimagining. The founders of modern statistics were unabashed eugenicists, and thus the process and logic of statistics are inherently imbued with methods of difference, discernment, and hierarchy ( Clayton 2020 ; Kennedy-Shaffer 2024 , 2025 ). 6 The most recent example of this was in fighter Josh Hokit shouting, “Michelle Obama is a man!” on the White House lawn during the Ultimate Fighting Championship (UFC) event ( Smith 2026 ). Sexed politics, histories, and futures 5 2020 ; Goh and Trofimchuk 2023 ; Armond 2024 ). Thus, sex differences, in particular, are so foundational to our social structures such that the Trump administration’s assessment that “the erasure of sex in language and pol- icy has a corrosive impact not just on women but on the validity of the entire American system ” ( The White House 2025c , emphasis added) is rendered correct. Reclaiming our imaginaries—a case for malicious compliance Critiques of our (over)reliance on the binary sex sys- tems have been present for decades outside of the scien- tific realm, but similar commentary has broken through to journals typically associated with disciplinary science within the past decade and readily picked up steam. These discussions’ adoption by the scientific commu- nity promotes their validity through the “god-trick” of universal objectivity ( Haraway 1988 ; Whitt 2009 ) and conferral of scientific authority ( Stepan and Gilman 1993 ), thus marking the scientific redefinition of sex as politically dangerous. Scientific commentaries within the past two decades have argued that sex as a scientific concept evades con- sensus definition ( Eppley et al. 2026 ) due to the real- ity of organismal diversity ( Bachtrog et al. 2014 ; Tree of Sex Consortium 2026 ) despite attempts to shoehorn their categorization ( Velocci 2026 ). As such, commen- taries reconceptualize sex as multifactorial ( Massa and Correa 2020 ; Eliot et al. 2023 ; McLaughlin et al. 2023 ), eliciting a spectrum ( Ainsworth 2015 ) of overlapping distributions ( Rippon et al. 2014 ) that produces an in- complete picture of between-individual variation upon comparison of group means ( DuBois and Shattuck- Heidorn 2021 ; Sanchis-Segura and Wilcox 2024 ) and an incorrect assumption of within-individual consistency ( Rippon et al. 2014 ). Some therefore argue that the in- herent incoherence of sex as a category makes it diffi- cult or perhaps even inappropriate to continue to use as a heuristic variable ( Massa et al. 2023a ; Rehmann-Sutter et al. 2023 ). Such has led to calls for moving beyond sex as a system of classification ( Pape et al. 2024 ) and push past the binary to move to embrace complexity through a focus on variability ( Joel and Fausto-Sterling 2016 ), “sex contextualism” ( Richardson 2021 ), multivariate de- sign, and/or mechanism-focused design outside of sex differences ( DiMarco et al. 2022 ; Massa et al. 2023a ; Williams et al. 2023 ; Ritz and Greaves 2024 ; Smiley et al. 2024 ). These calls are the tools of house destruction. In recognizing the lack of utility of the binary sex frame- work, these approaches push us to deconstruct our as- sumptions and name our variables outright. Grants and papers will no longer be flagged for language such as “bi- ologically female” if the term is not being used due to lack of clarity and is replaced by variables of interest. By invoking the tool of sex but refusing to use it as such, these strategies use scientific authority and bio-logic to destabilize the foundations of the binary sex framework holding up the house. Simultaneously, new frameworks independent of bio-logics are required to build a scientific study not predicated upon the histories of racism, colonialism, eu- genics, and queerphobia within our current construct of “sex”. These are the tools of rebuilding; they create a radical imaginary ( Naranch 2002 ) which provide a col- lective vision and praxis 7 that remake institutional re- ality. They are inherently maliciously compliant due to their refusal of frameworks and language that are being targeted and reinscribed due to their creation of some- thing wholly new. This new scientific imaginary, like much of scientific inquiry, is a collective project, one that cannot be undertaken alone. It must pay heed to the material realities of biology while also understand- ing that these biologies (as are our research questions, experimental designs ( Shansky 2019 ; Massa et al. 2023a ; Williams et al. 2023 ), and even scientific frameworks of non-animal systems ( Subramaniam and Bartlett 2023 )) are entangled with society’s gendered structures ( van den Wijngaard 1997 ; Milam 2014 ; Rippon et al. 2014 ). New imaginaries of a new “non-sex” derived from the possibilities of plants ( Subramaniam and Bartlett 2023 ), through recognizing the inherent sociality of all organ- isms ( Holmes and Monks 2019 ), via theoretical and sur- vey approaches that allow for coloring outside the lines ( van Anders 2015 ), and in statistical analyses that focus on variability ( Sanchis-Segura et al. 2026 ) provide tangi- ble mechanisms for literally thinking outside the binary and towards a sex eliminative ( Watkins and DiMarco 2025 ) framework ( Velocci 2024 ). This all draws on fem- inist and queer theory frameworks ( van Anders et al. 2025 ) that call for scientists to challenge their own ob- jectivity, question scientific norms, and recognize the category of sex as constructed through the scientific process ( Staller and Koerner 2025 ). And it is this type of thinking that is necessary to create the new language and frameworks that produce tools (and a house) of our own. These tools can come in the form of everyday scien- tific creativity. In my graduate training, I studied the in- terplay and tradeoffs of the reproductive and metabolic axes in mice. My work unearthed a somatostatin- expressing neuronal population in the hypothalamus which promoted feeding during fertile periods in mice with low but not high adiposity. Our team hypothe- sized that fluctuations of ovarian hormones would al- ter the responsivity of these neurons to adipokine cues. 7 Defined as placing theory into action. 6 M. G. Massa Specifically, we predicted that these neurons would show increased responsivity to adipokines when cir- culating estrogen levels were high. To test this, we turned to a collaborator who uses the genotype-tissue expression (GTEx) database. An incredible resource, the GTEx database compiles transcriptomic data from post- mortem human tissue across the body ( Lonsdale et al. 2013 ). Our collaborator has used this dataset to uncover new hormones through examining co-correlations in transcriptomics across various tissues as a proxy for tis- sue crosstalk. Using RNA-seq data from our murine neurons as a hypothalamic input, we endeavored to see what other tissues had transcriptomic elements that correlated (or anticorrelated) with our neurons of interest. Since our hypothesis indicated a key role for estrogen levels, clas- sical paradigms of sex would have prompted us to di- vide our GTEx data along “sex” based on the sex- essentialist assumption of estrogens as predominantly female hormones. However, GTEx is a postmortem database. Around 70% of the included individuals were above the age of 50, capturing people entering or firmly in reproductive senescence and thus declining hormone levels. Even if we had conservatively omitted data from anyone over the age of 45, sex category in this database is defined by Y chromosome presence. Usage of such to classify individuals creates a false binary which not only ignores chromosomal variations and thus miscat- egorizes people with intersex traits, but also fails to ac- curately predict hormonal levels due to changes over the lifespan, medical treatment (including but not limited to hormonal birth control and hormone replacement ther- apy), environmental exposures (e.g., Peng et al. 2023 ), and even major life events and behaviors (e.g., Gettler et al. 2011 ). Instead of using “female” and “male” as a proxy, my colleagues and I leveraged the fact that es- trogens, famously, are transcription factors. We created our own proxy. Our own tool. Using the GSEA Human Gene Set for early estrogen response (HALLMARK_ESTROGEN_RESPONSE_EARLY), we created estrogen signaling Z-scores to normalize expression across tissues before segregating all people, regardless of sex designation and thus karyotype, into “low” and “high” estrogen-signaling groups (for full methodology, see Massa et al. 2023b ). This created a proxy that intentionally focused on our physiology of interest and was not reliant on a potentially misleading category. In its initial introduction, this tool acted as a tool of destruction. We invoked the sex binary to demonstrate the incoherence of estrogen signaling and support the conclusion that a sex heuristic would not only be insufficient but misleading for a study such as this ( Massa et al. 2023b ; Fig. 1 ). However, in its future iterations, no such caveats are necessary. The tool can be one of rebuilding. There is no need to use “forbid- den” language. No “female”, no “diversity”, just estrogen signaling across humans. Conclusion The first Nazi book burning occurred at Berlin’s Institut für Sexualwissenschaft (Institute for Sexual Science) in May 1933. Established by the gay Jewish physician and sexologist Magnus Hirschfeld in July 1919, the Institute had served as a haven for the study of gender and sexual- ity as well as serving as a clinic for treatment of queer in- dividuals. During the two-part raid, the Nazis destroyed a library’s worth of scientific and medical journals and books in an attempt to remove queer history and science from the scientific archive ( Bauer 2014 ; Malatino 2017 ). Science challenging dominant conceptions of sex and sexuality are often the first targets of scientific erasure. Today, this attack looks less like book burning and more like bureaucracy. The tool of a binary, scientific sex is being wielded to simultaneously defund science and the academy and to roll back queer rights. Viewing these oc- currences as unrelated is to treat the symptoms instead of the disease. Definitions of sex have changed to serve political and social needs of the times. The science of sex is and always has been political. Understanding this, internalizing it, and keeping it present while enacting scientific research is the first step to stopping the wheel of history in its un- fortunately repetitious tracks. Only then can we, in the bio-logics of the Western world, assume our responsi- bility to remake and reimagine “sex” for the benefit of both our science and society. We must continue to make tools that reveal the inherent instability of the sex binary and simultaneously create new tools which do not rely on it. We must undo our own binary thinking ( Massa et al. 2023a ) and queer our paradigms to think of biolo- gies currently associated with sex as dynamic processes instead of static, stable, and coherent ( Fausto-Sterling 2014 ; Roy 2018 ). We can maliciously comply, eschewing flagging and censorship by creating our own language and being specific about what we mean ( Miyagi et al. 2021 ; Baker and Hayssen 2024 ). And we must support each other while we do it ( SBN Executive Committee 2023 ; SICB Leadership 2025 ). When we push outside the boundaries that confine us, we not only produce good science, but we free ourselves from that which seeks to destroy our progress. This pro- cess will not be easy. Our developed frameworks and jargon have been built out for understanding and com- munication; creating something new will have grow- ing pains. In this way, our new process of creation will be a work of unbounding imagination, of creating and Sexed politics, histories, and futures 7 Fig. 1 Estrogen-signaling proxy illuminates insufficiency of sex binary. As a mode of example, one estrogen-responsive gene, progesterone receptor (PGR), in one tissue, the hypothalamus, is being extracted to demonstrate the multifactorial model developed in Massa et al. (2023b) (A) Predicted data under a sex binary assumption. If the proxy of binary sex designation and our estrogen signaling proxy aligned, we would expect those designated female and those designated male to exhibit distinct but overlapping distributions. There should also be a large conglomeration of those designated female and male down around the “0” mark due to reproductive senescence. (B ) Actual data does not fit the sex binary assumption. Using hypothalamic PGR as a proxy for estrogen signaling reveals expected reproductive senescence distributions while also showing significant overlap in the rest of the population with no obvious female–male split. enacting a new scientific imaginary. But science has al- ways been about both observing and remaking the world. The question is, “[a]re we brave enough to imagine be- yond the boundaries. .and then do the hard work of sculpting reality. .?” ( brown and Imarisha 2015 ). This past year has shown us that we cannot use the master’s tools to unmake the master’s house. So let’s create some of our own. Acknowledgments Thank you to colleagues Aramati Casper, Jay Falk, and Karen Warkentin for their invitation and tireless organi- zation of the Sex Across Origins Symposium. The valu- able comments and conversations from them, the rest of the Sex Across Origins colleagues and presenters and audiences at SICB 2025 and 2026 greatly contributed to the development of this essay. Additional thank yous to the people who made Fig. 1 B possible: Stephanie M. Correa for the guidance, mentorship, and thoughtful- ness; J Edward van Veen for the generation of the orig- inal single-cell data set; and Marcus M. Seldin for the bioinformatics wizardry and creation of the Fig. panel. 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