Science Has a Huge Diversity Problem … in Lab Mice

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THE HISTORY OF science is a history of men excluding women. This goes way beyond Rosalind Franklin: Look around any lab, anywhere in the world, and you’re likely to see it crowded with males. A boy’s club, hopped up on the sweetest preclinical pharmaceuticals.

Mice, people. I’m talking about mice. Also rats. Most rodents used in biomedical studies—the ones that suss out the effects of treatments before they make it to humans—have boy parts and boy biological functions. And that particular kind of gender imbalance has cascading effects. A growing body of evidence indicates that females process pain differently than males. But many lab scientists who study ways of treating pain still use all-male cohorts of lab mice.

They say it’s because male mice and rats aren’t as hormonal as females—because isn’t that what they always say—and are therefore more reliable in terms of getting data. And that means the scientific community is ignoring research that might help women manage pain better.

Most patients who visit the doctor are female. Most patients who report being in pain are female. “The epidemiology is clear, women are up to 70 percent of all pain patients” says Jeffrey Mogil, a neuroscientist at McGill University and author of a new commentary in Nature arguing for greater diversity in lab animals.

A growing body of evidence—including a 2012 analysis of 11,000 patient records—indicates that women are more sensitive to pain. In fact, they may be hardwired to feel pain differently. Last year, Magil and a plethora of co-authors published a study showing that female lab mice actually used different cells to transmit pain signals through their spinal cord. And while no one has confirmed that this is also the case in human females (paging the ethics committee…), Magil says evidence in animals is both compelling and growing stronger.

Down with the ratriarchy
“This is not news for those of us who have worked in this field for a long time,” says William Schmidt, president of NorthStar Consulting, a pain research company. “It’s still a struggle to get some very traditional investigators to understand the importance of gender in preclinical and clinical pain research.” In 2015, just 4 percent of all the rodent-based papers published in the journal Pain used both males and females, says Mogil. That’s roughly the same as it has been for a decade.

Mogil says this inertia comes partly from scientists who believe female rodents aren’t reliable model organisms. And true, there is research that indicates their hormonal fluctuations (female rodents have oestrous cycle that is roughly analogous to the human menstrual cycle) do affect the data. “The problem is if you look at those studies, their results are going in different directions,” says Mogil. In some studies rats are more sensitive, in others less. Overall, it averages out, he says.
If anything, male rodents are the ones throwing the hormonal curveballs. Unlike females, male mice and rats fight each other for dominance. And where there’s a fight, there’s also stress. “Anything that causes stress can cause pain, and these fights cause all kinds of variability in pain data,” says Mogil. Boys, boys, boys.

Like all diversity problems, this rodent issue is not just about males and females. “We do things that are convenient for us and will lead to better and more papers for us, and forget that the use of work is to people in pain,” says Mogil. Mice are the dominant model organism in biomedical experimentation, and almost all of that work is done in a single strain of inbred mice. “It’s like doing studies on humans but only using data from identical twins,” says Mogil. The justification is the same as with the all-male mice: Homogenous data is more reliable. It lets scientists easily compare past results with the present.



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