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Vol. LXVI, No. 23
November 7, 2014

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Females and Males: Same and Different? NIH Workshop Explores Question

How do you incorporate sex as a variable in research with animals and cells?

This question was the focus of an Oct. 20 workshop hosted by NIH’s Office of Research on Women’s Health. Elucidating this topic is a critical first step toward helping NIH-funded scientists consider sex in preclinical research as a result of a new policy announced this past May by NIH director Dr. Francis Collins and NIH associate director for research on women’s health Dr. Janine Clayton. The policy is currently under development at NIH.

The workshop was designed to help scientists understand why sex in preclinical research is important, as well as to provide practical guidance on experimental approaches.

Considering sex as a fundamental biological variable resonates with NIH’s current focus on reproducibility, said NIH principal deputy director Dr. Lawrence Tabak.

He explained that NIH-funded research must be held to the highest standards of rigor and reproducibility and be “free of bias,” adding that while incorporating sex as a basic variable in experimental design is good science, it’s not always simple for scientists to know how to address this issue in their everyday work.

Tabak acknowledged that many in the research community need some pointers on research methods that address sex. “‘How am I supposed to do this in addition to everything else I am doing?’” he quoted researchers as saying. Tabak added that the workshop was intended for this very purpose—to provide a how-to guide for researchers new to thinking about the role of sex and gender in science.

Workshop speakers represented a range of scientific fields, including neuroscience, toxicology, endocrinology and nephrology. All have applied a sex/gender lens to their research for many years and in many different animal models.

One approach introduced was factorial design, which enables a scientist to consider sex in addition to another independent variable without substantial increase in the overall number of animals. This has been a key concern of many scientists not familiar with considering sex in preclinical research.

Keynote speaker Dr. Larry Cahill—a neuroscientist studying memory at the University of California, Irvine—has long recognized the importance of significant differences in female and male biology within the brain. He questioned the historical assumption that fundamental biology is that which is the same in males and females. Rather, he explained, “[what’s] fundamental is same and different.”

Other speakers, including the University of Maryland’s Dr. Margaret McCarthy, described how she was not initially interested in sex differences, but that a separate focus on female and male biology at the outset of her experiments “led to new biological truths,” such as a previously unknown role of microglia in synapse formation in the brain.

Thinking about sex as a variable in research in animals and humans is “not just a women’s health issue,” emphasized Clayton, adding “this is about good science—for women and for men.”

For more information on how to incorporate sex as a biological variable, visit

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