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Why don’t drugs work as well for women? They’re tested on male mice.

Rebecca Shansky, associate professor of psychology, works in her lab in Nightingale Hall. Photo by Ruby Wallau/Northeastern University

After decades of research, scientists have developed countless therapeutics to improve human health. But they’ve also created a problem. Many of these drugs don’t work as well for half of the population—that is, the female half. Women are also more often misdiagnosed for a variety of ailments, including stroke and ADHD.

Rebecca Shansky, associate professor of psychology. Photo by Ruby Wallau/Northeastern University

The root of this widespread public health inequity lies in mice and other animal research models. Up until very recently, the vast majority of basic science researchers used only male animals and cells in their studies. This has led to an incomplete understanding of how certain drugs work in both genders, and in some cases, dangerous health consequences for women. A recent study found that women experience adverse drug reactions nearly twice as often as men.

“The health outcomes are known, and they are very troubling and problematic,” says Rebecca M. Shansky, associate professor of psychology at Northeastern University. Shansky is a neuroscience researcher who studies sex differences in the brain. She has been an outspoken advocate for the importance of using both genders in scientific studies, and has helped debunk the myth behind the use of male subjects in animal studies: that hormone variations in female mice complicate research more than hormone variations in males.

In 2016, the National Institutes of Health (NIH) took action to address the exclusive use of male mice in research by implementing a policy known as Considering Sex as a Biological Variable. The policy requires scientists applying for grants to design studies that include both male and female animals or cells. However, beyond the initial grant application, scientists are not held accountable to follow through on this promise.

In a paper published recently in Nature Neuroscience, Shansky and her colleague Anne Z. Murphy of Georgia State University argue that without more enforcement, researchers will continue conducting male-only studies, leading to less rigorous science and more harmful health outcomes for women.

Shansky sat down with the News@Northeastern to talk about the issue of gender equity in scientific research.

The scientific consensus is that hormones are not a valid excuse to exclude female mice from studies. So why are researchers still resistant to studying females?

The resistance is coming from the culture of science where the only thing that matters is getting high-profile papers—that’s the currency of being an academic scientist. It’s getting harder and more expensive to get a paper in Nature and other high-impact journals. Reviewers are looking for more experiments, more techniques, and more figures, not necessarily that the research applies to both sexes. Given the current way you allocate money for a research project, some scientists are saying, “I’d rather dive deeper into the scientific mechanism in males than study it in both sexes.”

What do you say to scientists that still aren’t including females in their research?

In the paper, we present a body of evidence that there are a lot of super interesting sex differences at all levels of neuroscience, from behavior down to synaptic signaling. People don’t necessarily recognize that as being interesting and important. They see it as a nuisance. I just think it couldn’t be further from the truth. These things are worth studying, and they are just as interesting and important as doing that next experiment in males. My main goal is to help people do good science.

If the NIH’s Considering Sex as a Biological Variable policy isn’t enough to get scientists to change the structure of their research studies, what needs to occur to affect real change?

We have to start holding researchers accountable at the level of peer review, not just at the level of grant funding. The high-profile journals—Nature, Science, Cell, Neuron—they’re supposed to be publishing high-profile science. It’s got to include females. If one of those journals came out and said, “We will not publish any NIH-funded research that is only one sex,” then I think people would do it. It’s about the incentives and making those align with using males and females in research.

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