That dirty open secret in biomedical research: bias gets built into the study design.

For decades, scientists have embarked on the long journey toward a medical breakthrough by first experimenting on laboratory animals. Mice or rats, pigs or dogs, they were usually male: Researchers avoided using female animals for fear that their reproductive cycles and hormone fluctuations would confound the results of delicately calibrated experiments.

“Delicately calibrated” seems to be used as a synonym for “not robust”. If your results are so finicky that they don’t hold true in translation from male to female rats, why would you expect them to hold up in translation from rats to people? There are detectable differences in male and female physiology that turn out to matter, so this business of ‘simplifying’ by focusing entirely on one sex means women’s medicine suffers.

There is good news. Now the NIH is cracking down and telling researchers that they must test mixed sexes, or no money for you. That’s an effective incentive.

It also turns out that the decision to ‘simplify’ by studying only male experimental animals is a bad one, borne of a bias that women are hypervariable because of their menstrual cycle — other studies find that male animals tend to be more variable.

Bias in mammalian test subjects was evident in eight of 10 scientific disciplines in an analysis of published research conducted by Irving Zucker, a professor of psychology and integrative biology at the University of California, Berkeley. The most lopsided was neuroscience, where single-sex studies of male animals outnumbered those of females by 5.5 to 1. Contrary to the conventional wisdom in laboratories, there is far more variability among males than among females on a number of traits and behaviors, Dr. Zucker has found. Yet even when researchers study diseases that are more prevalent in women — anxiety, depression, thyroid disease and multiple sclerosis among them — they often rely on male animals, according to another analysis led by Dr. Zucker, who has written extensively on gender bias in scientific research.

At least I can say I’m safely innocent of this bias: all my work is on zebrafish embryos between fertilization and about 48 hours, and they don’t have sexes yet. I couldn’t sort out male and female embryos if I wanted to.