Female mice experience pain differently than male mice, according to a study published last week in the scientific journal Nature Neuroscience. That means pain medication that works on a male mouse might not work for a human woman, researchers say.
Those findings might seem trivial to people who don’t spend their days wearing white lab coats, but the study highlights a larger, oft-overlooked issue in scientific research: Males—both animal and human—are regularly used as proxies for females, furthering the assumption that the female experience of biological phenomena is always the same as the male’s. Yet from heart attacks to multiple sclerosis (MS), this assumption has proven untrue. And it has potentially dire consequences.
“In many disciplines, the animals used to study diseases and drugs are overwhelmingly male,” wrote The New York Times editorial board in an op-ed published Saturday, “which may significantly reduce the reliability of research and lead to drugs that won’t work in half the population.”
The NIH Revitalization Act of 1993 stipulates that all clinical research funded by the National Institutes of Health (NIH) must include both women and minority groups. Yet while that goal has been achieved—women now make up about half of all participants in NIH-funded clinical research—research on animals has yet to catch up.
Since experiments on animals are often foundational to developing research on diseases and the drugs that treat them, the lack of female subjects could have serious implications for women.
Eight out of 10 biological disciplines have a bias towards using male animals, a 2010 study found. For example, neuroscience used 5.5 male animals to every one female, while pharmacology’s 5 to 1 animal ratio was not much better. (This bias may be especially dangerous, NIH executives pointed out in a Nature editorial, because women tend to experience more adverse drug reactions than men.) Moreover, the same study discovered that 75 percent of studies in three highly regarded immunology journals did not disclose their animal subjects’ sex at all.
Scientists frequently explain the dearth of female animals in basic and preclinical research by insisting that females are more complex and variable than male animals, since they undergo an “estrous cycle” (similar to a menstrual cycle in humans). They claim that female test subjects’ hormonal variability can disrupt experiments and hinder scientists’ ability to make conclusions. However, a 2014 meta-analysis of academic articles on neuroscience and biomedical research found that females are no more variable than males.
“Convention is another probable reason for reliance on the male-only models that have been typical in many research areas for decades,” admitted NIH Director Francis S. Collins in Nature, adding that many researchers probably don’t grasp how influential sex may be in determining an experiment’s outcome.
Under Collins’ guidance, the NIH announced in June that it now expects researchers applying for NIH grants to factor sex into preclinical research on animals. Animals’ sex must be recorded, while research that focuses only on one sex must “provide strong justification” for doing so.
Proclaimed The New York Times, “This new policy for grants sends a good message to scientists and drug makers on the importance of considering sex in designing research projects.”
Photo courtesy of Flickr user Jean-Etienne Minh Duy Poirrier, licensed under Creative Commons 2.0.