Lab rats are overwhelmingly male, and that's a problem

(CNN)The data didn't make sense.

Five years ago, University of Maryland researcher Alisa Morss Clyne was studying pulmonary hypertension -- a type of high blood pressure that affects the arteries in the lungs -- in human cells she had cultured in her lab. But the results she was seeing just didn't stack up.
"We had these huge error bars. It didn't make any sense," she said. "And we said, OK, let's just graph it by male versus female, and what we found was really interesting."
    The blood vessels in the lungs of people with pulmonary hypertension take up more glucose, and she found the female cells metabolized the glucose in way that changed a protein that was critical to blood vessel function.
      In other words, the sex of the cells became an important variable that affected the outcome of the research.
      "Because we were grouping our sexes together, we were missing the difference. We were getting the average with a big deviation," said Clyne, an associate professor at the University of Maryland's Fischell Department of Bioengineering and the director of the Vascular Kinetics Laboratory.
      "I was shocked when we saw the cells themselves were different based on sex."
        Concern has been growing in recent years that ignoring or downplaying differences in sex as a biological variable -- whether in cells under a microscope or in lab animals -- is undermining biomedical research at the earliest stages.
        This matters because many diseases -- including Covid-19 -- affect men and women differently, and missing sex-based differences can make misdiagnosis and mistreatment more likely.
        "When researchers don't consider sex as a biological variable, that means we have incomplete data. And if we have incomplete data, we run the risk of making judgments that are incorrect. And incomplete data and erroneous conclusions in preclinical research, ultimately, can have an impact on the health of all of us, the health of women and men," said Chyren Hunter, associate director for basic and translational research at the National Institutes of Health Office of Research on Women's Health, which is holding a conference on sex as a biological variable this week.

        The default lab rat is male

        While it's often unclear what sex the cells used in lab research are, and to what degree female cells are underrepresented, the default lab rat has long been male.
        One study from 2011 found that in neuroscience research, male animals were used six times more often than females, and figures from a more recent analysis in 2017 suggest they have only improved marginally.
        Women have been routinely included in clinical trials since the 1990s, but "integrating female animals into basic and preclinical research -- which is the key building block for studies in humans -- has been much slower," said Hunter.
        Women are more likely to be misdiagnosed than men when it comes to a wide range of conditions, including heart attacks and ADHD. And women typically experience more -- and more intense -- side effects from pharmacological drugs.
        Some drugs are more effective in men than women, including common over the counter ones such as ibuprofen and naproxen -- both forms of nonsteroidal anti-inflammatory drugs (NSAID).
        And it goes both ways: Alosetron, a drug approved to treat severe irritable bowel syndrome, is only approved for treatment in women as it is largely ineffective in men.
        "We're saying here that not all researchers need to study sex differences. But all researchers really should consider how biological sex can impact the questions that they're studying," Hunter sa