Medicine Needs More Research On Female Animals, NIH Says

By Richard Harris

Published May 15, 2014 at 2:05 PM EDT

Sex can matter, whether you're looking at drug side effects, the response to treatment, or the progression of a disease.

Many potential new drugs look like they could be big winners — at least when judged by how well they work in mice or other lab animals. Over the years, there have been a number of promising cancer "cures," possible Alzheimer's treatments, and candidate drugs for holding back the ravages of various degenerative diseases.

But, time after time, these great promises fade away once the potential treatments are tried in people. There are lots of reasons for that. Humans aren't rodents, for starters.

But now the National Institutes of Health is targeting a more subtle problem in animal studies: Labs often don't consider that the sex of the animal could also influence research findings.

There are obvious sex differences in people when it comes to disease. Low-dose aspirin affects men and women differently. It appears that some of the gene variants that increase the risk of Alzheimer's are more potent in women than in men. And women are more likely than men to have bad reactions to drugs.

It should be no surprise, then, that mice and other lab animals also have sex differences in their response to drugs and diseases. Yet scientists often don't take that into account when planning their laboratory studies. In fact, sometimes they deliberately choose male mice, because scientists worry that the cycling reproductive hormones in female animals might make it harder to interpret the results. It also appears that males are sometimes favored because that's simply the conventional thing to do.

Enough! says Janine Clayton, director of the Office of Research on Women's Health at NIH, and NIH Director Francis Collins. They're starting to roll out new guidelines to make sure that research on animals — as well as on tissue samples taken from animals — takes into account potential differences between the sexes. Clayton and Collins laid out their plans this week in a Nature commentary.

These days, following an abysmal history of ignoring women in clinical trials in the late 20th century, a bit more than half of all participants in NIH-funded studies are women.

But "there has not been a corresponding revolution in experimental design and analyses in cell and animal research — despite multiple calls to action," Clayton and Collins write.

Scientists who do the research often ignore the issue; so do colleagues who review the studies. And scientific journals also don't demand that scientists state the gender of animals used in the studies they publish.

NIH is now developing policies to make sure that scientists who use NIH funding for research take animal gender into account. Clayton and Collins say the policies will be rolled out in phases, beginning in October 2014.

It won't be a cure-all. Researchers have documented other serious shortcomings with animal studies. Many are done with so little rigor that they can't be reproduced by other scientists. It also turns out that the gender of the researcher handling the animal can sometimes affect results. But getting rid of gender bias in the animals — and their cells — is one way to nibble away at this problem.