Emiliano Ponzi

Science of the Sexes (continued)

Klein saw firsthand, time and again, that sex was remarkably relevant to her research on animals’ susceptibility to infection and their response to pathogens. Indeed, sex often was the only difference between those that recovered and those that succumbed to disease. With influenza, for example, when she gave male and female mice a standard dose of virus, none of the females would survive past two weeks, while more than half of the males would recover, surviving the infection. For many infectious disease mouse models, if fewer than half of the mice of a particular strain survive an infection, then that strain is defined as “susceptible” and if more than half of the mice live, that defines the strain as “resistant.” But while working with two sexes of the same strain, Klein noted stark differences.

There are other people—not so many in infectious disease but more studying the heart and brain—who are as convinced as Klein that males and females differ in their basic physiology and, therefore, in the susceptibility to and progression of diseases. Arthur P. Arnold, a professor and chair of physiological science at UCLA who assumed editorship of the just-launched journal Biology of Sex Differences, has been doing sex-based biology since the mid-1970s when he was a neurophysiology postdoc at The Rockefeller University. He realized early on that gonadal hormones explained only part of the reason a brain structure in male songbirds was six times larger than in nonsinging females. Some sex differences, he has since discovered, are the result of direct action of genes encoded on the sex chromosomes: XX and XY cells differ functionally because of the action of X and Y genes intrinsic to the cells.

“Sabra was the prepared mind in the right place at the right time. H1N1 threw her—and sex-based biology—into the limelight.”   —Florence Haseltine

The fact that there are sex differences in disease implies that one sex has something protective about it, Arnold says. If that something could be enhanced or modified, it might affect the disease. That something might make an attractive drug target, for instance, and only a lack of understanding of the biological basis of sex differences in disease keeps us from hitting that target with new therapies.

Researchers like Arnold and Klein quietly celebrated a milestone 10 years ago when the Institute of Medicine issued a report (“Exploring the Biological Contributions to Human Health: Does Sex Matter?”) concluding that every cell has a sex, and therefore sex matters in health “from womb to tomb.”

Heartening as that was, it more or less preached to the choir, Klein says. That choir subsequently formed a new academic society—the Organization for the Study of Sex Differences—to promote the interests of this emerging field, not least of which was to address the fact that only a pittance of NIH grants supported the study of sex differences.

Klein, with a small cadre of colleagues across various disciplines, proposed in 2008 to establish a center for the study of sex-based biology at Hopkins. Helping lead that effort was Pam Ouyang, a cardiologist based at Bayview Medical Center, who says, “Men and women are different in lots of ways that we don’t necessarily understand yet because we don’t study them. I thought it would be really nice to have a place where general conversations about sex differences could be discussed with people from various spheres of knowledge who would approach questions—such as why are men’s and women’s risks of heart disease different—from all angles.”

Ouyang no doubt would have been intrigued by DeLisa Fairweather’s perspective on autoimmune heart disease in men. A staunch advocate of sex-based biology who is based in the Bloomberg School, Fairweather is teasing out how inflammation induces chronic conditions in males and females.

Despite their common interests, Ouyang and Fairweather were not yet destined to meet. The proposal for a center was denied. The upstart field of sex-based biology limped along on its uphill trek.

Then the flu hit.