New article in Cell: Calling for Rigor and Precision in the Study of Sex-Related Variables
By Marion Boulicault, Miriam Miyagi, and Madeleine Pape
Today, the GenderSci Lab has a perspective piece out as part of a landmark special issue in the journal Cell on sex and gender in science. Our piece – titled “Sex contextualism in laboratory research: Enhancing rigor and precision in the study of sex-related variables” – considers how, in the context of policies mandating the consideration of sex (such as the NIH’s Sex as a Biological Variable policy), basic scientists can operationalize, analyze, and interpret sex-related variation in ways that achieve conceptual and statistical rigor, as well as precision in how such knowledge is applied in the clinic and beyond.
“There is thus much at stake…in striving to uphold the highest scientific standards in the study of sex-related variation in basic science.”
Crucially, we emphasize that equity is not separate from the pursuit of rigorous and precise science, but rather is integral to it: the health of all people––regardless of gender or sex––is better served by research that moves beyond a simplistic (and oftentimes inaccurate) account of sex-related variation and towards a richer, contextualist understanding of precisely what “sex” is and how it varies. As we remind readers, such research also has important wider consequences for public attitudes on gender differences (e.g. Saguy 2021).
In our perspective, we respond to three common methodological and statistical pitfalls in basic science analyses of sex-related variation: first, a tendency to treat assigned sex categories as though they are sufficient for understanding the context-specific mechanisms and factors that influence experimental outcomes; second, a lack of rigor in the analysis of group differences; and third, imprecision in how findings are interpreted, particularly where they concern the nature and extent of group differences and the extrapolation of findings from animal models to human populations. As an alternative paradigm, we demonstrate the value of a sex contextualist (see Richardson 2022) approach, which emphasizes the need to operationalize and understand sex-related variables in context- and model-specific ways.
In general, we want to stress that we are not against the study of sex or sex-related variation, but rather pro-sex contextualism. Despite being critical of the implementation of mandates to study sex, we are in no way calling to return to conducting research on male animals (or male humans) only. We recognize that our piece intervenes in a context where researchers have long debated the value of including female models in research, particularly at the basic and preclinical level. For these readers, we hope you will consider our argument that moving from a one-size-fits-all to a two-sizes-fit-all approach is not necessarily a move towards greater precision nor equity, including for cisgender women. Rather, the opportunity is to develop approaches to the study of sex-related variation that expand our understanding of its complexity across species, laboratory environments, and individual humans. We hope that, regardless of background, readers receive in our piece an invitation to reflect critically and openly on how sex-related variation is studied and translated into clinical interventions, such that biomedical research can achieve its overarching commitment to improving health for all.
Radcliffe Institute seminar participants, March 2023.
This piece grew out of a 2023 Radcliffe Institute Seminar on “Sex in Context: Rethinking Sex as a Biological Variable from Research to Policy,” co-organized by Madeleine Pape and Sarah Richardson. The authors of the perspective spent two days critically reflecting on sex and gender research alongside leading interdisciplinary scholars from feminist science studies, biology of sex and gender, and women’s health research and policies. The authors would like to acknowledge these participants: Madina Agénor, Elizabeth Barr, Jill Becker, Cato Clune-Taylor, Marina DiMarco, Kelsey Ichikawa, Rebecca Jordan-Young, Nancy Krieger, Robin Nelson, Tamara Rushovich, and Marcia Stefanick.
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Key Takeaways
Sex difference analyses have rapidly increased in frequency, yet rigorous statistical practice has not kept pace.
By operationalizing ‘sex’ in ways that highlight the specific underlying mechanisms and sex-related variables that are relevant for their work, researchers can realize more precise and reproducible results.
Researchers should consider the ways in which research “occurs in a gendered social world, meaning social gender beliefs, practices, and assumptions are part of the context in which, and could possibly affect, the research being undertaken.”
Sex contextualism provides a framework for integrating the contextual nature of sex into study design and interpretation.
See the following for related GenderSci Lab pieces:
Suggested citation
Boulicault, M., Miyagi, M., and Pape, M. “New article in Cell: Calling for Rigor and Precision in the Study of Sex-Related Variables.” GenderSci Lab Blog. 14 March 2024. genderscilab.org/blog/cell-perspective-rigor-and-precision-explainer
Statement of Intellectual Labor
Marion Boulicault, Miriam Miyagi, and Madeleine Pape wrote the initial text. Additional revision and edits by Kelsey Ichikawa and Sarah Richardson.