Emiliano Ponzi

Science of the Sexes (continued)

Sex differences complicate the story. No doubt about it. Marc Lipsitch, director of the Center for Communicable Disease Dynamics at the Harvard School of Public Health, will attest to that.

His lab was looking for evidence that early exposure to certain strains of influenza proved protective against infection in the 2009 pandemic. Lipsitch’s group noticed, as others had, that older people seemed at lower risk of being a confirmed flu case in 2009. Why would that be? Did they have antibodies from immune responses earlier in life? Did they have fewer children at home and therefore were less exposed to school kids, known transmitters of flu?

“We thought it would be important to know differences between men and women in the context of this drop-off in risk,” Lipsitch says, “because you might expect a bigger drop-off in women than men if it was due to exposure.” When his team separated out the data by sex, they realized that although the drop-off in risk is much stronger in women, it does not appear to be due to any lack of contact with flu-infected people.

Sabra Klein came to mind: Lipsitch recalled seeing a poster at a conference by one of her students, showing how the immune system behaved differently according to sex.

“We thought she’d be interested in our unpublished data,” he says, admitting that he originally intended to ignore sex. “We actually had hoped to reject the idea that what we were seeing had something to do with sex differences in the immune experience.”

“But it was really helpful that Sabra pushed us to look at both age and sex at the same time and make sense out of data of this sort, even though now it’s a more complicated story.”

OraLee Branch, an assistant professor of medical parasitology at New York University, studies the immune response to malaria infection. When her students, who accompanied her to Peru for a field investigation, noticed sex-based trends in their data, she scrambled to find anything even remotely related in the malaria literature, finally unearthing a paper Klein published in 2006.

“I right away picked up the phone and explained to her what we were finding,” Branch recalls. “I wondered if she had followed up, if there was more information. Her work had since veered toward viral pathogens. But still, she offered to help.”

One of the things Branch had spent time investigating was differences in malarial symptoms based on differences in exposure.

Now she wants—no, she needs, she says—to go back into her data to reanalyze it, taking sex differences into account. “It’s really opened up a can of worms, it has,” Branch says. “We might find immunity is developing better in males than females, or maybe the other way around. But pretending sex differences don’t exist is just going to obscure the real mechanisms we’re all trying to find. Pretending differences don’t exist is not the answer.”

All was unusually quiet throughout the Bloomberg School of Public Health on the snowy holiday commemorating Dr. Martin Luther King.

Michael Coronado—winner of the Florence P. Haseltine Award for young investigators at the 2010 annual meeting of the Organization for the Study of Sex Differences—was hard at work in DeLisa Fairweather’s lab, however.

First, he was extracting blood from male and female mice that were infected with the same virus but producing different levels of cytokines—the signaling molecules that cells generate to communicate with each other.  Then, he was removing their hearts to study the diseased tissue. Later, on other live mice, there were gonadectomies to perform.

By de-sexing the males and females, he was attempting to make them biological equals, at least in terms of the type of heart disease he’s studying. It’s apparent that testosterone drives the disease. But it also could be that estrogen protects from it. Or both could be true.

One thing’s for sure: Male and female mice are anything but equals in terms of their hearts, as the males’ floppy, scarred organs clearly show.

Some investigators would justify using only male mice to study disease that affects mainly males. They’d argue that it’s expensive and inconvenient to deal with female rodents because it means having to account for hormonal cycles.

For that matter, lots of researchers who study equal opportunity diseases such as cancer don’t use both sexes of mice either, no matter that half the population whom the research is ultimately meant to serve happens to cycle, too.

The converse is also true. Lots of researchers studying so-called women’s diseases such as lupus and multiple sclerosis use only female mice and therefore risk missing half the picture.