Sarah S. Richardson • Sex, Gender, and the Human Genome

um I'm Jim English I'm the director of the Penn Humanities Forum thanks for coming tonight it's rainy um and uh it's great to uh great to see you all here for Sarah Richardson tonight's presentation by Professor Sarah Richardson is a co-sponsorship with our friends in the department of the history and sociology of science so we're grateful to the chair of that department Robert aronowitz and also the um uh it's the the other co-sponsor is the Alice Paul Center for research in gender sexuality and women's studies and um the the director of that Center is Nancy Hershman who's here and uh and we're grateful to Nancy as well for uh for her co-sponsorship the program on sex has been overseen by my brilliant colleague Heather love She's the uh the r Gene Brownlee associate professor of English author of feeling backward loss and the politics of queer history which is a book that shifted the whole field of of queer studies and has become really indispensable for a generation of of Scholars in literary literary studies Heather is going to introduce Professor Richardson and so let's all uh have a round of applause for Heather love the curator of this series [Applause] for coming out on this rainy Wednesday to Rainey um okay I'm very very happy to welcome Sarah Richardson the lobe associate professor of the social sciences at Harvard whose work adds a crucial Dimension to our series on sex Professor Richardson is jointly appointed in the history of science department and in the committee on degrees in the study of women gender and sexuality at Harvard her scholarship addresses questions of gender and race and the life sciences and offers a model of socially engaged interdisciplinary work on the making of scientific knowledge in her influential and critically acclaimed book sex itself the search for male and female in the human genome published by the University of Chicago press in 2013. Professor Richardson considers the history of attempts to stabilize gender through recourse to genetics from the discovery of the X and Y chromosomes at the beginning of the 20th century to the mapping of the human genome human sex chromosomes have become increasingly significant as they have been understood as the hard biological basis for cultural gender norms Richardson draws on the tradition of feminist science studies as well as contemporary work on race and genomics to interrogate the epistemological and methodological grounds of contemporary genetics research for those of us working on the cultural dimensions of sex and gender this account of chromosomes as quote gendered objects of scientific knowledge is crucial since it's so usefully illuminates the biosocial complex that naturalizes gender hierarchy Professor Richardson has also co-edited two books a revising race and a genomic age from 2008 and post-genomics perspectives on biology after the genome which was published earlier this year she's currently working on a book tentatively titled the maternal Mystique which traces the history of research on maternal effects that tradition of research has traced the influence of Mother's Behavior exposures and Physiology on the health and well-being of their offspring this book Promises like sex itself the book not the thing um to clarify what is at stake in a fraught and consequential area of biomedical research by taking on the shifting relationship between nature and nurture in the Modern Life Sciences so today Professor Richardson will be speaking about epigenetics and how to assess the impact of new theories of plasticity and environmental influence please join me in welcoming Professor Sarah Richardson thanks for that wonderful introduction I'm so happy to be part of this series and what I hope to do today is to talk a little bit about how the concept of sex is operationalized and used in the Contemporary Life Sciences as Heather mentioned I'm a historian of science I'm a philosopher of Science and I'm a gender studies scholar and I'm also deeply engaged with the science and so I hope to that you'll learn something about all four of those areas today um here's Charlotte Perkins Gilman the feminist philosopher and activist in 1898 known for her pithy quips saying the brain is not an organ of sex might as well speak of a female liver well here we are in 2015 and uh feminists are talking a very different talk at least some feminists are here is Janine Clayton the head of the NIH office for research on women's health saying just last year every cell has a sex each cell is either male or female and that genetic difference results in different biochemical processes within those cells so this is the expansive space into which I'm entering changing conceptions of where we locate biological sex in the body now sexual science as I call it has changed significantly throughout history the search for sex over time has been conditioned by the Technologies we have available the science of the day and our political conceptions so we've moved from the blood to the pelvis to the skull to the brain to the hormones and now a genomic conception of sex and this and conceptions of sex have also moved back and forth between a more binary and essentialist model that suggests that there is an Essence to males and to females and that they are really two quite different things and an alternative model that emphasizes the overlap between the Sexes the variation within each sex and the context specificity of any differences that we might observe between them Now by way of getting into the current uh tense set of contest stations around sex in biology I'm going to show you a brief video by Leading sex chromosome scientist David page this is just a clip from a TED Talk he did about 18 months ago he's a y chromosome geneticist and here is one perspective of a leading life scientist on sex in the genome it has been said many times that our genomes are all 99.9 identical from one person to the next this idea that we're 99.9 identical has gained great traction and for a number of reasons it's very appealing to say that we're all 99.9 percent identical it's so appealing that this idea was seized upon by President Bill Clinton in his 2000 State of the Union Address when he stated that this fall at the White House we had a distinguished scientist visiting an expert in this work on the human genome and he said that we are all regardless of race genetically 99.9 percent the same well it turns out that this idea is even correct as long as the two individuals being compared are both men it's also correct if the two individuals being compared are both women however if you compare the Genome of a man with the Genome of a woman you'll find that they are actually only 98.5 percent identical in other words the genetic difference between a man and a woman is 15 times the genetic difference between two men or between two women let us consider for example the case of Bill and Hillary so it turns out that bill is as genetically similar to Hillary as he is to a male chimpanzee but Human Genome we have a problem in the human genome era in which we're living this difference this fundamental difference between males and females has been overlooked instead we have been operating with a unisex vision of the human genome and so in fact men and women are not equal in their genomes as I've just explained so here's the one version that binding essentialist conception of sex being recreated in genomic terms and this notion that males and females are very different so different they are like different species has been repeated by many leading geneticists in this research area here's hunt Willard of dunk Duke University suggesting that males and females differ by two percent greater than the hereditary gap between humankind and its closest relative the chimpanzee and this very provocative claim that there is not one human genome the Universalist promise of the Human Genome Project but two male and female so again this is the space that my book sets itself the search for male and female in the human genome was entering in two in this book I look at how the discovery of the sex chromosomes at the turn of the 20th century instigated a historically novel understanding of sex determination rooted in the visually compelling binary of the X and Y and however since then we've been trying to understand how to reconcile our cultural understandings of sex and gender with this materialist biological basis of sex and gender I look at the X and Y as Heather said as gendered objects of scientific knowledge I try to analyze the production of claims of sex differences within this field and model how gender assumptions in The Wider culture played a role in that so if we start to ask questions about this science what do we find if we pick up the corners around these sorts of claims do males and females have different genomes does every cell in fact have a sex I don't give I want to give you some critical tools for thinking about these sorts of claims now let me back up first and talk about chromosomes what are they they are strands of tightly coiled DNA kind of like bundles of genes and humans have 23 chromosomes pairs of chromosomes that is males have 22 and females have 22 that are identical in males and females both males and females have One X and males also have a second a chromosome called the Y and females have a second X chromosome instead of the Y now this notion of the sex chromosome the X and Y as the sex chromosomes as I show in my book led to um a sex chromosome-centric way of thinking about the biology of sex so that researchers assumed that male traits would be found on the Y chromosome and female traits would be found on the X and that the X was the female chromosome and the Y the male that the X would even behave in a feminine Manner and the why in a masculine manner and this has led to all sorts of funny business in the history of genetics one of my favorite case studies that I write about in the book is the history of theories of the X Y Y super male in the 1960s and 1970s researchers suggested that rare males who are born with an extra Y chromosome could explain male crime that they would have in essence an extra dose of maleness this Theory turned out to be terrifically wrong and to lead to the stigmatization of individuals with an extra Y chromosome and it instantiates quite literally the idea that an extra y was like extra maleness this actually xyy research established the Y chromosome in popular and scientific Consciousness as a symbol for maleness even if the final empirical results of research after two decades of research on it undid that Association the popular conception really remained this is a comes out of a thrilly thriller series from the 1970s called The xyy Man a series of kind of crime novels and there was actually a TV series based on this as well okay uh let's start to interrogate this actually the X and Y chromosomes are not female and male um the first way we can go at this is to look at their actual role in sex determination and we can see from this chart that the sex chromosomes are not sufficient to produce uh phenotypic what we call you know typical male and female sex that is you need to be a male you need um not just to be X Y but to have this thing called sry you need to be positive for the sry gene on the Y chromosome to produce testes it's really this one gene on the Y chromosome the testes then produce gonadal hormones androgens and estrogens in a ratio that then produces a typical fertile reproductive male and the same kind of story for females it's not that you need two X chromosomes it's that you need to lack the sry gene um so the X and Y are not sufficient to produce sex but part of a larger pathway of sexual development involving all of these factors coming together in at the right time moreover within the genome as a whole sex factors that is various factors involved in sexual development and differentiation are not localized to the X and Y chromosomes and furthermore the XX and XY Gene complement functionally deliver almost the same identical Gene content why is this well the Y chromosome evolutionarily evolved from an ancestral X chromosome and most of its content content is has a homolog on the X chromosome so that is there are only a few genes on the male on the Y chromosome that are actually specific and exclusive to males so of the genes on the Y chromosome 29 of them are in the region shared with the okay so that means identical with what a female will have 25 of them outside of this region shared with the X um are have copies also on the X chromosome because of that ancestry so we're down to maybe about 15 genes that are male specific on the Y chromosome we're talking out of about 20 000 to 30 000 genes and therefore um and also functional analysis of these 15 or so genes shows that many of them are pseudogenes that means they're they actually do not functionally code for proteins that are functional in the body many of them are duplicates of each other producing exactly the same gene product and these genes are not globally involved in sex differences but are involved exclusively in male specific processes in the testes um furthermore as I mentioned before key genes involved in human sexual development are um not localized to the X and Y chromosome the estrogen receptor genes are on chromosome 6 and 14. the at the Androgen receptor Gene Androgen associated with maleness is located on the X chromosome cah is congenital adrenal hyperplasia and that is um one uh a major syndrome of disorder of sexual development that's located on chromosome six five Alpha reductase is another intersex condition and that's controlled by a gene on chromosome two here are some major genes involved in sex determination that is if you have the wrong an error in any one of these genes you will be a sex reversed XX male or XY female chromosome 1 9 and 17. so sex in the genome doesn't look so much like this but more like like this that is there are genes that are critical and important sex differentiating and sex determining processes all across the genome now um as so as to this question of whether there's a male genome and a female genome um this kind of once we begin to pick up the corners around this this emerges as a highly problematic extrapolation from the X and Y Barrett binary to a global notion of sex differences instead it looks like there are ways in which the genome is used in different ways by differently morphed bodies to produce a range of sexual variation if you're interested in my specific deconstruction of the idea that males and females are like different species like humans and chimpanzees here's an article I published a few years ago on that problematic line of reasoning which actually has a deep history in scientific ways of thinking about sex now um Heather said I'm going to talk about epigenetics how many people know what I might mean by epigenetics okay good number of you yeah so epigenetics now that critique all that critique that I just gave you was based on a very a different notion of the genome than the one that is popular today that notion of the genome was one of the genome as consisting solely of DNA sequence consisting of those 23 pairs of chromosomes and their sequence well we're under we're in a revolutionary moment a major shift underway in the way in which the genome itself is conceptualized away from this genome as just a string of base pairs to one um of a regulatory apparatus a reactive system in which the genome is also composed of the regulatory apparatus that decides when parts of it are turned on and turned off and this is transforming right now over the past five years how we do basic research on sex gender and sexuality this area of research that I wrote about in the book is already transforming to move toward an understanding of how hormones and genes dot interact dynamically and throughout the life course to regulate sex differentiating processes so epigenetics is a growing science across all fields of the life sciences it's a post-genomic science in that it has emerged since the conclusion of the major sequencing projects as a major post a major area of investment for continued work on genomics epigenetic mechanisms include I'll be talking most prominently about things like DNA methylation so here a methyl Mark a methyl group ch3 is appended to the sequence of the to to the structure of the genome itself and when it's appended it represses gene activity so you can have methylation and you can have demethylation as processes turning on and off different parts of the genome and histone modification I had to add DNA acetylation micro rnas and we're adding adding adding different cofactors that could be considered epigenetics practically every day so what does this look like in terms of sex differences we're looking at things like um uh methyl cpg binding proteins working to repress or activate different parts of the genome to then produce different Pathways of differentiation leading to sexually dimorphic epigenomes so this is a radically different way of thinking about sex than what David page was talking about in that video I showed you I want you to pay attention to some of the key phrases here this is by a UCLA sex chromosome geneticist art Arnold who's been one of the main art architects of this new way of thinking about sex a complex interact intersecting causal Pathways G networks pulsating with activity Dynamic net of interactions okay we're looking at a totality of sex bias factors in the network comprising what he calls the sex ohm all right so this is a kind of living breathing Dynamic way of thinking about sex and gender pretty interesting and exciting it it suggests the presence of sex-specific processes and Pathways throughout the genome not restricted to genes or chromosomes conventionally linked to Classic reproductive sexual traits so in this model you've got some epigenetic factors playing a role along with or rather you've got a bunch of cofactors you've got your hormones you have your genes um you have I'm not going to get into all these cofactors and then they're they're mediated through things like methylation to create overtime long-lasting sex-specific modifications all right um I'm going to give you an example of this approach by describing a recent study from a researcher at University of Maryland Margaret McCarthy the study is titled brain feminization requires active repression of masculinization via DNA methylation this study the conclusions of which are summarized in this figure found reduced activity of DNA methyl transferase enzymes in the male rat pre-optic area of the brain suggesting that the masculine phenotype in rats is produced by demethylation or releasing quote-unquote masculinizing genes from epigenetic repression the study further showed that inhabit inhibiting DNA methyl transferase with a drug or knocking out it those genes created a masculinizing effect in adult female rats don't worry if you didn't understand any of that I'm going to unpack what it means by describing some of the key very challenging exciting findings of this study so the study can be read as challenging received understandings of the sexual dimorphism of the brain at several levels first in contrast to a view of male and female brains as organized and hardwired during early development the study conceptualizes um this finding as showing that the quote neuronal DNA methylome is highly modifiable with rapid dimethylation and de novo methylation occurring in response to changes in excitability particularly in genes associated with neural plasticity okay so modifiable second rather than viewing the female condition as the passive default in the absence of masculinizing factors and if you're familiar with Notions of gender across many fields you'll recognize the construct of femaleness as passive and maleness is active so in contrast to that this the authors flip the script okay they interpret the experimental manipulability of male or female phenotype in the rat brain via these epigenetic factors as quote confirming that feminization is the active process of suppressing masculinization via DNA methylation without methylation of masculine phenotype can emerge in female rats that is even in adulthood so hence they conclude that uh quote feminization is the active process of suppressing masculinization via DNA methylation and further that this finding is evidence for the duality of the brain with some arguing for the simultaneous presence of both male and female circuits or phenotypes wow and third the author suggests that methylation is on balance a means of preventing far greater sex differences in the brain so out of um the 381 genes that they looked at only 70 showed sex differences with 34 more highly expressed in females and 36 more highly expressed in males methylation that is this epigenetics assured equal levels of gene expression in those 381 other genes which with the which the authors called convergence genes one of these genes is the much expressed Fox P2 Gene which some have associated with language abilities so this these are Big possibly big findings that the authors show that there is pressure toward the convergent expression of these genes in males and females in reproductively relevant brain regions so of course um from a feminist perspective this is really quite intriguing uh people like me are very interested in models of how gender that is the social norms and expectations associated with masculinity and femininity is corporealized within the biological sex body and this looks like it's going to offer us some mechanisms for thinking about that with its emphasis on the reactivity and responsiveness of the body to Social and environmental influences epigenetics offers a potentially rich and provocative theoretical frame for understanding sex and gender at the level of the body and feminist intellectual Traditions have long conceptualized gendered minds and bodies as deeply conditioned by social and historical context not only Charlotte Perkins Gilman writing in that 1898 Treatise where she famously argued that the social conditions of subjugation had created mentary female creatures weaken body and servile in mind and contended that sexual inequality between the Sexes was produced and maintained not just by social factors by but by social factors working in interaction with the body and biology where she predicted that with greater equality women would grow physically larger and stronger and more agile but actually even in the genomic age in the 1970s here's Joanna Russ in her feminist science fiction classic the female man it follows this pathway of interest in plasticity by constructing an elaborate feminist Parable making very much the same point the book features a meeting between four women with identical genomes but from different time periods with different gender conventions and it brings them together in this this time traveling experiment and shows them having very different ways of being in the world postures modes of interacting how Health statuses and so on so uh and most recently any Orphan Black fans all right uh so most recently the BBC America science fiction series Orphan Black which is praised for its scientific Acumen as well as feminist Vibe features this um thought experiment as well it's a single actress who plays eight different versions of contemporary women with identical genomes the television show is a gender bending phantasmagoria and shows the Clones living wildly Divergent lives my favorite is the timid lesbian scientist kosima but and she contrasts strongly with the uptight Street lace soccer mom Allison there's even a transgender character Tony um so the show's writers actually in the script regularly invoke epigenetics as an explanation for this rainbow of characters so I mentioned all of this because these compelling visions of gender plasticity form an imaginary that it animates history directly and today Intrigue with plus any sort of plasticity affirming biological Theory and attending to the materiality of gender plasticity in the body many people think is a way to ultimately promote greater social tolerance and acceptance of marginalized forms of gender expression and I just invoke the feminist scientist Elizabeth Wilson uh called that for us to those of us who are feminists and gender Scholars to really think about biological substrates and to actually think about them not just as a resistant materiality but as another scene not a met bedrock and to cultivate attitudes toward this biology that are speculative and engaged fascinated surprised enthusiastic amused or astonished um that said even though there is this great affirmation of plasticity and epigenetics we shouldn't lose our critical Edge and I want to encourage some critical and empirical analysis of practices in this field I've been tracing and tracking research on sex and epigenetics over the past five years and it's fair to say that actually taken as a whole this body of research is currently committed far more to providing causal explanations of the programming sort than of the plasticity sort that is in this field epigenetics you know by people in the field is understood as a mechanism that can explain the fixation and maintenance of hormonal effects established in early life creating binary sex differences so now let's return to this paper that I've had so much excitement about this McCarthy paper from University of Maryland so exciting it seems to be a thrilling and intellectually challenging rewriting of long-held paradigms of profound and fixed differences in the biology of the brain right um and it suggests that differences once understood as hardwired are perhaps more accurately understood as tripwired held in place by rather delicate and contingent processes that are open to reversal it opens the possibility of imagining A diversity of sexual phenotypes right not only within a population but even over an individual's life course and of considering environmental and social mediators of sex-related gene expression but let's read what the scientists say about what this study means here's DeVries prominent neuroendocrinologist at University of Massachusetts um and he the public discussion that followed the publication of this study among scientists shows that this the field actually received that study as showing how epigenetics Works to over determine and fix in place sex differences in the brain so here's DeVries saying that this study that our understanding that the female state of the brain is the default still stands what changes now because of the study is our thinking as to how that default state is preserved here's a new scientist article reporting on the study quoting many scientists discussing it and it asserts that taking together these latest findings suggests that there be may be more sex differences in the rodent brain than previously thought and here's the lead author of the study herself Bridget Nugent um saying what she thinks the study shows My Hope Is that these studies meaning new epigenetic approaches to the brain have taken us one step closer to fully understanding how and why males and females are so different in this paper we've shown a mechanism whereby hormones create sex differences in the developing brain by producing sex-specific patterns of DNA methylation maintenance of the DNA methylation patterns established during sexual differentiation of the brain appears to be necessary to sustain the brain's differentiated state right so I want to offer some reflection in three areas looking at ways in which uh epigen their plasticity affirming biology within epigenetics has another side to it there's also a strong discourse of programming and binary and essentialist Notions of sex differences coursing through these new plastic conceptions of the body so first in the emerging post-genomic systems and network-based science of sex with epigenetics at its Center plasticity and complexity is not opposed to programming rather it is positioned as a powerful that is epigenetics as position as a powerful powerful over determining agent in the canalization and programming of sex differences not despite but because of its plasticity so epigenetics is seen as a redundant or over determining mechanism that carries out and maintains the Persistence of classic well published hormonal processes implicated in sex differences second male and female epigenetic plasticity in response to the environment in this literature is itself theorized as sexually dimorphic so when I look at this I actually find that in the literature the inquiry is focused on epigenetics as a source for the elucidation of the biology of sex differences in responses to the environment not on how environmental exposures create variation in sex stereotyped behavior in males and females so um inquiry is presently focused on epigenetics is not focused on epigenetics linking social environment and brain and behavioral phenotype for example instead it is interested in how these key pathways are themselves male and female specific third and here's where I'm going with this for the concluding part of the talk these new plastic spreading Network like network-like systems theories of Sex and the genome established sex as a far more ubiquitous mechanism in the molecular architecture of the body than do previous genomic conceptions of sex so in explanatory models in the biology of sex that invoke epigenetics sex in and gender become ubiquitous processes not localized to gross regions of sex sexual dimorphism so epigenetics does not merely mediate sex-specific processes at the interface of hormones and the genome in early development and throughout the lifespan but epigenetics postulates sex as a much broader part of the substructure of the gene environment interrelation in this model rather than epigenetics or the environment becoming a resource to explain social variation sex differences itself becomes an expanded explanatory resource for explain explaining biological variation itself so in the epigenetics Paradigm in short every Gene Network cell and organ is seen as being within a networked system that itself is sext in the so it within a system that is mediated by sext epigenetic processes so while on the one hand this new sex home approach represents a significant reformulation in the conceptualization of core processes of sexual determination and development it renders The genome a dynamic product of its milieu it problematizes any essential understanding of sex it looks according to this new view like sexual processes can vary mosaic-like over time from cell to cell and body to body in ways that might obviate talking about a male genome and a female genome at the same time in the 20th century linear model of sex that old model sex inherit only in sex-specific elements like the X and the y or the genes involved in reproductive organs such as the testes and ovaries in this new model the epigenetic model the whole body is imbued with networked processes that are sexed so conceptualizing any process that involves genes or hormones is sexed this model greatly multiplies the signs and signifiers of biological sex at the molecular level so now I want to return to this Mantra of every cell having a sex this has emerged as a kind of tagline for Women's Health activists it's a consensus view in certain Elite Women's Health circles um that every cell has a sex and it emerges from a very focused research program to develop a sex-based biology over the last decade or so and you can see how closely tied in this is to the emergence of a genomic and genetic understanding of sex so the society for women's health research uses the slogan what a difference an X makes and because sex double X matters so it's very important to them this new research on the genomics of sex for emphasizing the need for more funding and so on for women's health research this has been a concerted effort to develop a field if you're interested in the sociology of science it's a good model of how you create conferences major research statements you create a whole organization founded in 2007 the organization for the study of sex differences and you produce a new Journal biology of sex differences founded five years ago and um this entire program is focused on finding differences so here I'll just skip ahead to this report a major report that they produced out of this effort an important study 2001 arguing that sex matters here's the sex chromosomes and that every cell has a sex it matters in ways we didn't expect it must matter in ways that we have not even begun to imagine I won't show this video but if you're interested more in this Paradigm take a look at some of the videos what a difference a sex makes by the society for women's health research it's a profound affirmation of very traditional stereotypical Notions of sex differences in this video they go around and interview regular folks about sex differences and that they believe in and then use this to suggest the need for studying genetic differences between males and females the most profound impact of all of this activation has been the achievement of a new policy at the National Institutes of Health it was announced just last year it's going into Implement implementation now requiring all researchers funded by the National Institutes of Health to consider sex as a variable in pre-clinical research now you may know that starting in the 1990s all researchers who study living whole human beings were required to include both women and men in their research that was an important breakthrough for Women's Health this is a different policy that requires all researchers to consider sex when they're looking at cells in a petri dish so this is a major policy shift and so now the question of whether every cell has a sex is not just theoretical but it has policy implications for actual practices all across the Sciences and we have to ask ourselves is this a conception of sex that we're comfortable with is sex in other words omnipresent does every cell have a sex why do we want to think that way as we engage this hypothesis this provocative idea which is not determined by the data of the world but by our ways of thinking and our concepts of sex our pragmatic explanations and platforms that we bring to the life sciences it's worthwhile to revisit Michelle Foucault the sex theorist and his admonition that the signs of sex on the body do not speak for themselves as matters of fact outside of history and discourse that is um there's a way in which the concept of sex is used to create artificial unities that give Force to Notions of sex differences within politically formed moments so he says uh that one way in which these Notions of many biological markers of sex are used is to create a fictitious Unity as a causal principle an omnipresent meaning a secret to be discovered everywhere now there are some good reasons we might want to say every cell has a sex we might want to bring awareness to sex related variables so as to expose androcentrism in science that is maybe it's a bad thing if most of the cells researchers are using in labs are in fact from uh from male donors we might want to capture the full range of biological diversity by studying cells derived from differently sexed and gendered bodies we might want to mobilize and I see this is what's really happening to mobilize gender justice discourses to compel or direct resources that is to create special lines of funding in a competitive research environment and also to address of course Women's Health disparities I actually think three and four are really bad reasons and not true and I'm happy to be able to just point to my new paper coming out next Tuesday in proceedings oh that's cut off down there proceedings at the National Academy of Sciences stating all the many reasons that I actually oppose this new policy that is [Music] um I do think my own view is the claim that every cell has a sex represents an extreme instance of ascribing sex to the factors and parts of the body in a highly binary and essentialist way that it contributes to a notion of sex as a ubiquitous or pervasive signifier or sign and to a conception of bodies as divided in a thorough going way into maleness and femaleness and so I think it's actually unethical but I also think it's empirically underdetermined and it's conceptually unsophisticated and it's likely to use lead to confusion and muddle in the scientific literature so there you go now what I've tried to do today I'm just going to wrap up is to encourage reflection on how we use the concept of sex in biology and especially in these new molecular Sciences when we're thinking about sex at every cell and I've also tried to suggest that we're in a really critical and contested moment as the concept of the genome itself is transforming and that will modify our Sciences of sex and gender and as new discourses of plasticity emerge and new celebrations of plasticity right we need to remain critical and analytic plasticity and programming are not necessarily opposites but two sides of the same coin um I've suggest that our I suggest that our conception of sex that we use every day that we use in biology is not determined by our empirical findings in the laboratory but it's also shaped by our pragmatic and explanatory aims including things like building Platforms in the biological sciences from which we can do other research including things like social justice goals and including things like opening funding Avenues and the Sciences I think we should be aware of the overuse or a really expansive use of the concept of sex itself we should be aware that it's part of our social ontology as well as our biological ontology and we should use it in a critical uh conditional and reflexive way and we should also work to innovate terminology to leave open the possibility of a radically different future thank you [Applause] hi uh where does the existence of an X Y X X chromosome enter into the genetic trees it's something that's common to all primate to all mammals to all animals yes male female plants ah okay so um the um okay great question thank you uh the sex chromosomes that is some sort of system in which you have heterogametic chromosomes in one of the Sexes have evolved six different times independently in the history of evolution that is in different phylogenetic histories it is not necessary to have sex chromosomes in order to get sex so plant some plants some like turtles for example and other organisms sex is determined by temperature and other environmental factors so sex chromosomes are not necessary to get sex in nature and there are multiple conformations of said the sex chromosome binary in nature so in birds for example it's the females who have the X Y and it's males who are XX so there's no essential relationship between an XX chromosome complement and a female for example so when when did it evolve about somewhere between I think I I say it in my book I might need to get a correction on this but it's it's three to six million years ago it's very old I think almost all mammals have sex chromosomes however the sex chromosome systems and how their what their relation is to the actual pathway of determining um a testes versus an ovary is different across many species and there are some species in which the Y chromosome has disappeared within mammals so the famous example of that is voles some species have lost their Y chromosome so the sex determination system is XX in female and X just X in in males so I I probably haven't covered the whole terrain there but just enough to give you a sense it's very old in the mammalian line and fairly I actually have two questions whether you need me to pick um so um I'm a geneticist interested in studying the the genetics of gender one thing that I noticed was your use of the word sex as opposed to or combined with the use of the word gender and a lot of my use of those terms is informed by sort of the social justice concept from trans Community I was wondering if you could speak a little bit to your choice of those words from your study and then I have a second question if I'm allowed later yes I'm using the term sex in a rather conventional sense within the construct of the sex gender distinction and I'm embracing the idea that for the most part um we think of the um biological signs and signifiers of sex on the body such as the X and Y chromosome as sex as opposed to gender but actually if you want me to get really tongue-tied we should always be thinking in terms of gender sex that we assume that these objects are outside of that frame so uh gender that is refers for those who don't know refers to the norms and expectations around masculinity and femininity and sex refers most usually to these signs and signifiers of sex in the body but the problem is they interact intensively and so if You observe a sex difference in levels of gene expression or if you put someone in an MRI you have to then do empirical work to determine what caused that sex differences that sex difference is it from within only or is it through interaction with the way in which we order bodies very very differently in the world I'm really excited that you're interested in doing epigenetic research on sex and gender differences so as you see here I think there's lots of potential for that and it's not there yet and so I'm just waiting for these fabulous researchers to come forward and start asking the questions that this technology gives us the potential to ask so we're in an enormous moment of contestation and there are those who want to use it to look at traditional canalizing binary processes and those who see the possibility of and finally empirically studying how social processes can change biological processes so how do you view these new epigenetic discoveries um such as sex existing in a variety of different ways and factors that contribute in dimorphism and differentiation in the body how do you view that those new discoveries as giving possible support um for uh the notion of gender and sex existing on a spectrum ah well of course um uh I think that they do open up that possibility um I mean uh it's an empirical question right it isn't something we just come to we assert um and I do think though um what you've what these ways of thinking about sex do is they multiply the range of cofactors involved in biological processes and it seems almost inevitably they will produce a greater range of variable phenotypes and underlying mechanisms for that um and so it could be affirming of variation but as you see here ways of thinking in the Life Sciences are very strongly fixed and even such findings can be quickly interpolated into a binary way of thinking about sex so it's going to be a contestation I think in other words the fundamental conceptual debate is still going to be there on the table and different different methods of approaching the research different practices are probably going to determine whether people go one way or another and just what questions they ask from the beginning it's so important to the science we actually create what questions we ask at the beginning right and how we frame them questions okay I feel like that's a perfect lead and then to my my second question which I suppose um you dealing it sounds like with a lot of people of my ilk who will not surprise you maybe you can help me reframe my question so the question really is for those of us who are trying or interested in trying to ask the kinds of questions that you're talking about um I would love and maybe that's the book right there I would love a book an article a checklist something to help me step back and think about you know how much am I framing this particular research question or this this grant specific AIMS in terms of what I've been trained for the last you know 40 years um and how much am I framing it you know and not framing it in Lost ways of thought from past learning if that makes any sense you can see that I'm beaming this is exactly the kind of work we have to do because if you're going to do that then um you know gender is an area of expertise and it's a literature right um and so really strongly engaging with that that expertise and I just I'm so happy to see your openness and excitement about about that um so there is there are a lot of resources for thinking um very it um with great clarity about what it is we would want to measure and what would be politically and socially useful to measure for all sorts of reasons um and so yes I can direct you towards those things now people have been doing sex gender research in other fields so you also might want to look to Social neuroendocrinology and certain areas within the epidemiology of sex differences that have looked at the way gendered lifestyle factors also interact with sex-related biological factors to produce the kinds of stratifications that we see in health outcomes so you there are research is out there it's not new to do sex gender research but there is a growing community of excitement around doing this work so thanks thank you for your wonderful presentation uh so I had a question on I would say on a similar vein uh so when you describe the uh things about each cell having different epigenetic uh uh like epigenous signaling for uh determining what sex is so could you conceptualize uh individuals who are transgender as having basic an issue with the uh basically the signaling epigenetically uh being different in their brains compared to other organs uh like sexual organs or others and that is like the basically this this uh disconnect between uh how the epigenetic signaling is working is having them have the identity there um so I think people are interested in epigenetic research within uh research on transgender individuals I would um uh contest just slightly the way that you framed that which is um the notion that we would expect trans individuals to have an issue with their epigenetic programming I would rather want to suggest that there might be great a great range of normal phenotypic variation and that we're going to be able to see that if we keep an open mind if we look at these many cofactors and processes of mosaicism and change over the life course might lead us away from a notion of transgender that is as pathological since the new requirement that cells be sex balanced has there been any notable findings of significance in terms of that new variable ah so the the policy isn't quite in place yet um I do want to clarify that lots of there are lots of people looking at sex variables in basic pre-clinical research including animal models cell lines and cells what this policy does is require consideration of sex variables and it's only just now going into place so um we haven't seen a kind of shift in research there's all sorts of technical debates about how to put it into place just what what the requirements will be for example not everyone will be required to look at both male and female specimens if they can justify a reason within their research that they would not have to so for example if you're doing prostate cancer research there may not be as much of a reason to look at female variables um so I don't know but there are lots of interesting and significant findings from people who look at xxy and XY cells for example or cell lines however the question is whether those findings can tell us anything about embodied sex differences in humans so if you're the National Institutes of Health your concern and justification for any policy has to be this will advance human health and the the question at the heart of the contestation around this new policy is whether a male an xx and an X Y cell in a Petri dish models male and female bodies in the world um and so they're big questions about that kind of leap of reasoning um I'm not sure I fully answered your question the answer to that question uh well my answer would be no um for a couple of reasons first of all oh the question is about the institution of this new policy about studying um XX or rather male and female derived materials in pre-clinical research so cells tissues cell lines animal models and so on um so the reason I don't think it will be well answered by this is because it requires people who are not specialized in sex difference research to include sex as a variable and often underpowered studies in which sex is not rigorously looked at in terms of intersecting variables so I think it will produce a lot of findings that have uncertain meaning or significance biological significance so it will probably be a muddle but the other reason is that is what I said before that those kinds of models so my contention is that you can't study sex outside of gender um and so you're going to have a set of findings that have little relevance to actual human health so I reject the hypothesis that it's not perfect but we should do it anyway because it will move us closer to sex gender but I understand where you're coming from thank you um is the was it working okay um uh so I guess uh one question was you know I was intrigued by the moment with the rat and the methylation and the demethylation and I I just wondered if you could flesh out a little bit how people are I guess at this point probably speculating about what some of those cofactors might be like in a more social sense right like because they're talking about just giving a drug that would produce these effects so what are people speculating about as this sort of change over the life course um might be like those cofactors um like what what actually produces this plasticity or affects it so that's one question and then the other question is just you know you're saying it's going to be a kind of contestation over the meaning and that seems totally true but I wondered whether to take your caution about the way that plasticity and programming are linked to suggest that some of the what I am familiar with is a kind of more utopian speculation or theorizing about plasticity and epigenetics that's happening whether you want to really add a note of caution to that or you want to say go for it we need a lot more thinking on that that is non-essentialist and non-binary if you see what I'm saying is it a sort of caution that that speculative thinking is always going to be sort of recaptured or is it really a call to to do a lot more um transformative thinking about this research right so on the first question what are some of the environmental factors that could create plasticity such as that observed in that was a study in rats I want to underscore rats and in the pre-optic area of rats which is sexually more sexually dimorphic than in humans um but uh I have heard a lot of speculation a lot of it focuses on the fetal period and on early development and that might include exposures ranging from diet to drugs I've heard some speculation about actually Tylenol as being a major mediator of that so it could be anything like that but it could also be various forms of social interaction right post-natally one thing that the study seemed to suggest is that all adults could flip their sexual phenotype in their brain so that's a rather different model than the fetal programming so I guess the game's wide open for looking at potential variables that could lead to epigenetic changes the question of course is whether those epigenetic changes are fleeting or whether they become fixed under certain conditions um yeah so what is my argument really about plasticity right I am adding a note of caution I do not think we should uncritically celebrate New Sciences of plasticity first we should understand empirically what they can actually do but also we should be aware that plasticity doesn't have the political implications necessarily that we assume it does it can be has this flip side of programming I definitely think that we should however I don't want to suggest that we shouldn't be excited about this new science so I'm working in this complicated space where um there's possible potential there that research hasn't been done so far I do see some people The Orphan Black fans and so on and I am one of them um you know who make over uh who make hyped statements about what epigenetics is what it has shown so far and that's not the space we want to be in um so keeping our critical lenses on while hoping that this provides a new tool for asking the hard hard questions that people working at the intersection of gender sexuality and sex have been asking for a long time thinking about some of the Practical aspects of the research you'd like to see done brings up the question in my mind of cost and I hate to be but but this is this is a real factor and people are doing research if it now takes about a thousand dollars to do a human genome how much does it take to look at at the methylation for one human genome ah that I don't know um hey that's critical yeah I thought I'd look at this kind of work you have to know that stuff well there what are used are um uh alumina microarray chips and other methods that are um now becoming standardized to study uh methylation across the genome you do not need to sequence a genome to do it we have lots of sequenced genomes you can then look at existing samples and existing sequences to look at methylation patterns so I don't think um I I epigenetics is research is going forward it's being used not just in sex gender research but in the pharmaceutical industry and all across the life sciences to flesh out the path biological Pathways so um I think it's it is not like it's a different field than genomics or more expensive than genomics or somehow dispensable it's indispensable you now can't think without epigenetic cofactors um the expense Quest the question of cost is interesting though on the level of the kinds of questions we decide as a society to fund so um you're right that questions that seem to have a lot of relevance for human health in biology might get more funding than questions that seem to get at these theoretical issues of the interaction of socially gendered factors and human sexed behaviors these are theoretically interesting they're interesting within the social sciences but when I talk to scientists in the field they often have trouble getting funding for their research unless they can suggest that that has a health implication and those who work on areas like sexuality that's hot button research that they say that they have a hard time funding because it's not within it usually conceptualizes being within the purview of health problems that are at the top of the list you know for national funding so it's a great question always follow the money hi I was just wondering I'm not entirely clear on how you would suggest we operationalize looking at sex gender variation when working with other cells or animal models in particular I'm just wondering if you had some specific suggestions for how people may look outside of the binary just thinking um if there's a variation not just within yes yes doing this research is very complex and resource intensive um you know if you're uh so so This research is already done with animal models you do different caging scenarios you do different rearing scenarios and then you could study um epigenetic Pathways related to that those kinds of social exposures in cells exactly as you suggested you could look at different ages you could look at different environmental exposures and see how the milieu changes mechanisms within that cell that said as I said in answer to the gentleman in the front I do think that actually just cells are going to be a poor system for studying sex and gender they're good for some things but they're probably not a good way to study sex gender although we might validate some models in which they're useful if you're looking at very particular kinds of of interactions but whole systems whole embodied systems are really what we need to get at to understand how the gendered interactions of everyday life from the moment were born play a role in shaping our biological repertoires so part of my critique is just that cell pre-clinical research is not actually a great realm to be doing this research yes there's a new study out by Sarah van Anders at University of Michigan who's a social neuroendocrinologist you might want to look at her work um where she's looking at so we usually assume that testosterone levels are innate and biologically determined and highly binary between males and females and indeed the Baseline level of testosterone is highly binary however what she showed is that there is um also a contextual basis to Rises and falls in levels of testosterone so that women who are in competitive leadership scenarios whether or not they use male tip stereotypical or female stereotypical patterns of behavior have a much greater spike in testosterone than males do in those scenarios it shows which what she argues and this is just one paper I think it's proof of concept and kind of suggesting an Avenue to go down rather than a final answer to this question it shows that even something is considered as innate in binary as testosterone is actually context dependent and specifically responsive to gender specific signals so um rather exciting lots of research to be done there yeah thank you for bringing that up thank you

Channel: Wolf Humanities Center

Views: 1,394

Keywords:

Id: 6niyGWkNGLQ

Length: 71min 1sec (4261 seconds)

Published: Sun Aug 13 2023