“The obvious issue is, if you’re only studying males, you don’t know if that therapy is going to work in females,” says lead researcher and Northwestern surgery professor Melina Kibbe, who has since been named editor-in-chief of JAMA Surgery. “The problem is not studying males per se—the problem is studying only one sex. Research really needs to be conducted in both sexes.”
Human biology backs up her argument. Past research has suggested that the health benefits of aspirin, for example, may differ by sex, helping to prevent heart attacks in men and strokes in women. Last year, the Food and Drug Administration issued its first (and, to date, only) set of sex-specific dosage guidelines, halving the recommended dose for women of the prescription sleep aid Ambien. And as a 60 Minutes report on the issue noted in February, “Drugs are just the beginning. Sex differences have been found in pain receptors, liver enzymes, even the wiring of the brain.”
So why do such stark differences still persist in basic science research?
Partly because of ignorance within the scientific community, Kibbe explains, adding, “I think I’m a perfect example of that.” Her own interest in sex disparities in research subjects arose only after Teresa Woodruff, who heads Northwestern’s Women’s Health Research Institute (WHRI), asked if Kibbe had used rats of both sexes in her vascular therapy research. She hadn’t: “I really wasn’t thinking about the issue. It wasn’t something that was on my radar.”
When Kibbe accepted WHRI funding to support additional research on female rats, “There was a dramatic difference in how female animals responded to my therapy compared to male animals. And that’s how I became a convert and very, very aware of the issue.”
But the reason Kibbe originally used only males—and the reason why male animals are vastly more common as test subjects in general—is one that presents a hurdle for those looking to level the scientific playing field. The more dramatic hormone fluctuations of female animals mean that they’re generally considered more difficult, Kibbe explains: “It’s a variable that is not held constant throughout the experiment.”
Money, too, is a deterrent for many researchers; including animals or cells of both sexes means more subjects and more work to be funded.
“I think some people, if they actually did think about it, would say, ‘Oh, I’m duplicating costs, I’m just making it more expensive,’” says Woodruff, a professor of gynecology and molecular biosciences at Northwestern and a co-author on the Surgery study. But, she adds, “I actually think that’s the wrong economics.”
“In the end, it serves the public better that we understand about sex at the cheaper end of the equation, before it gets so much more expensive as you go closer to clinical trials,” she explains. “It is going to be better in the long run, less costly, for us to have inclusion of both sexes in basic science.”