Revolutionizing Research on Male and Female Brains

Margaret M. “Peg” McCarthy

Margaret M. “Peg” McCarthy, PhD | University of Maryland School of Medicine

Margaret M. McCarthy, PhD, thinks a lot about sex — or rather, sex differences in the brain.

For 20-some years, McCarthy has been exploring how the brain develops differently in males versus females to understand why males are at higher risk for developmental disorders, ranging from autism to stuttering and dyslexia, than females.

She is also chair of the Department of Pharmacology — and as the only female of 26 chairs at the University of Maryland School of Medicine, she is passionate about promoting the professional careers of women. Since becoming chair, she’s hired three female faculty and doesn’t plan to stop there. And as a leading neuroscientist at the University of Maryland, Baltimore (UMB), McCarthy has made significant discoveries on sex differences in the brain.

McCarthy’s interest in sex differences extends to how those differences affect a person’s response to treatment. She was instrumental in a national policy change that now requires researchers to account for sex as a biological variable in any research funded by the National Institutes of Health (NIH). Researchers must now include at least some animals of both sexes in their preclinical studies and must analyze their data for the influence of sex on the effects they observe. Previously, this was not a NIH requirement, and the majority of brain studies only used male animals. 

“The hope is that incorporating sex as a variable in biomedical research will prevent the mistakes that were made in the past in which women received treatments that had never been assessed in female animals, which in some cases led to severe adverse outcomes,” says McCarthy, UMB’s Researcher of the Year in 2015. “An additional hope is that much more will be learned about basic biological processes by contrasting males and females.”

Now in the second phase of that policy change, the NIH is monitoring the policy’s impact, creating metrics for measurement, and developing new tools to help understand, organize, and share data so researchers have the necessary information for maximum impact.

It’s too soon to tell, but qualitative data suggest they’re on the right track. Already, a number of colleagues have reached out to McCarthy saying they’ve seen significant differences in females versus males in their research. “We’re just at the tip of the iceberg,” she says. “I anticipate we’re going to see some major shifts in our understanding of the brain, as well as other organ systems, once we incorporate sex as a biological variable.”

McCarthy’s lab has discovered a number of novel ways in which the brain is shaped during development, including a central role for the immune system, as well as “the brain’s own marijuana,” the endocannabinoids. She has found that common over-the-counter drugs like aspirin can impact normal processes that shape the brain, highlighting how little we still know about the most fundamental aspects of neural development. 

Clearly, McCarthy is not your average researcher. But this isn’t just because she’s world-renowned for her pioneering work on sex differences in the brain. She also finds joy in the more tedious aspects of science work.

“For instance, I particularly like writing grants,” says McCarthy, whose five current studies have attracted more than $4 million in support. “You have to be part scientist, part lawyer, and part poet. I think it's the most creative thing we do and being awarded taxpayer dollars to pursue your idea of what you think is important, generating new knowledge, and contributing to the larger scientific discourse, there is nothing more fun than that.”

McCarthy’s peers have high praise and respect for her work. “In many scientific interactions with Peg, I find her to be a deep thinker, highly creative, and fearless in her entry into new fields and use of new technologies,” says Arthur P. Arnold, PhD, director of the Laboratory of Neuroendocrinology at UCLA’s Brain Research Institute. “This is a formidable combination of traits, and accounts for her emergence as a top leader in her field.”

Geert de Vries, PhD, director of the Neuroscience Institute at Georgia State University, waxes poetic on McCarthy’s “major impact” as a mentor and role model. “Five of her former graduate students and nine of her postdoctoral trainees have faculty positions at major research institutions. Many of these are doing very visible work themselves. Precious few of my colleagues can make similar claims.”

McCarthy is known as a powerhouse of productivity who has delivered countless speeches and authored close to 200 journal publications and at least 60 reviews and book chapters. Her ability to work, produce, and be an involved parent has been an inspiration to many in the field. Says de Vries, “When one of my students asked her what her secret is, Dr. McCarthy answered that she takes it one day at a time. Clearly, most of those days must be very rich.”