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Science of the SexesEmiliano Ponzi

Science of the Sexes

Why hasn't infectious disease research reflected fundamental differences in women and men?

Sabra Klein forgoes a handshake, coughs by way of greeting.

“Would you like one?” she rasps, sharing a bag of mentholated lozenges. “It’s not the flu. I don’t think.”

Flushed and weary, Klein plans to retreat early from her office and lab in the Bloomberg School, quarantine herself at home, rest and drink lots of fluids. But not before she infects you, via this article, with the germ of an idea she has long championed: Sex matters. In ways we never fathomed.

It matters, for instance, with the flu that Klein hopes she doesn’t have. Her ongoing studies show that females have a bigger and badder inflammatory response. They don’t just feel worse. They don’t just visit doctors more or complain more. They literally experience worse disease than males. Klein’s talking sex-based biology, not gender issues. (Although “sex” and “gender” often are used interchangeably, sex is biology while gender refers to the social constructs related to one’s sex.) Molecularly speaking, females respond differently to flu than males. They mount a more robust immune response—which sounds like a good thing, until you delve into Klein’s data and see that this heightened immunity contributes to tissue damage and even death. Females respond so differently to immunizations, she concluded, that a woman needs about half the flu vaccine dose of a similarly sized male.

Klein coughs, pops another lozenge and launches into why she loves the flu.

For a dozen years, the assistant professor in the W. Harry Feinstone Department of Molecular Microbiology and Immunology has investigated infectious diseases, first focusing on hantaviruses, then malaria, now flu. The constant throughout Klein’s career has been her dogged insistence that sex matters.

That concept, neither new nor original, holds that every cell in us—indeed, every cell in the H1N1-infected mice languishing in Klein’s lab—has a sex. Advocates of sex-based biology contend that maleness or femaleness in humans as well as rodents needs to be considered, compared and contrasted in order to uncover basic biological truths about everything from heart disease and depression to lupus and liver cancer.

Klein’s data always have spoken louder to her than naysayers. As an infectious disease expert working in nonreproductive tissues and cells, Klein sensed for years that her grant submissions or research papers focusing on sex differences didn’t so much pique reviewers’ interest as annoy them. Fellow researchers who ignore sex differences have distinguished careers and mountains of data invested in their way of doing things. Some told her flat out: Sex did not matter.

Still, she stayed the course, giving sex differences center stage instead of sloughing them off. She used both male and female animal models in her hormone-centric studies. She manipulated estrogen and testosterone, surgically removing the bird-seed-size ovaries and testes of mice, and then put hormones back, always looking for cause-and-effect relationships between sex and disease. She analyzed her results by separating the sexes in the statistics instead of lumping males and females together in one big androgynous data set, as was—and still remains—conventional practice. (In top-tier journals, it’s common for authors of clinical studies to demonstrate demographic correctness in Table 1, showing 50 percent of their subjects were male and 50 percent female. However, after that obligatory nod, the breakdown by sex simply goes away, never to appear again in Tables 2, 3 or 4, Klein says: “There’s no more mention of sex. No statistical comparison. It’s sooooo frustrating!”)


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  • Keith Berry

    Sterling Va 10/31/2011 01:06:34 PM

    Very nice article, I wish Ms Klein great success, my wife was recently tested for lyme disease, and it came out negative, but now has swelling in the knee. I am thinking there might be some correlation here. I hope not but can't help but wonder. Maybe we need to make a trip up to Baltimore?

  • Denise Dalton

    Baltimore 11/08/2011 05:51:24 PM

    Keith, Swelling in the knee is a very typical presentation of Lyme disease. Tests can be negative in the early stages. I'm not sure of her exposure risk, or the timing between her test and knee swelling, but to further educate, I highly recommend the Columbia University Research Center for Tick-Borne Disease Website to get accurate information on testing, symptoms, etc. First, read through all the patient links on the left, then scour the rest of the site for additional information regarding the current state of research, etc. I wish your wife the best.Untreated lyme disease can create a host of challenging health issues beyond the typical presentations; especially if there is a co-infection that can complicate accurate diagnosis & treatment. ~Denise

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