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.

That laboratory tradition has had enormous consequences for women. Name a new drug or treatment, and odds are researchers know far more about its effect on men than on women. From sleeping pills to statins, women have been blindsided by side effects and dosage miscalculations that were not discovered until after the product hit the market.

Now the National Institutes of Health says that this routine gender bias in basic research must end.

In a commentary published on Wednesday in the journal Nature, Dr. Francis Collins, director of the N.I.H., and Dr. Janine A. Clayton, director of the institutes’ Office of Research on Women’s Health, warned scientists that they must begin testing their theories in female lab animals and in female tissues and cells.

The N.I.H. has already taken researchers to task for their failure to include adequate numbers of women in clinical trials. The new announcement is an acknowledgment that this gender disparity begins much earlier in the research process.

“Most scientists want to do the most powerful experiment to get the most durable, powerful answers,” Dr. Collins said in an interview. “For most, this has not been on the radar screen as an important issue. What we’re trying to do here is raise consciousness.”

Women now make up more than half the participants in clinical research funded by the institutes, but it has taken years to get to this point, and women still are often underrepresented in clinical trials carried out by drug companies and medical device manufacturers.

Partly as a result, women experience more severe side effects from new treatments, studies have shown. The Food and Drug Administration last year told women to cut in half their doses of the sleeping pill Ambien, for example, because new studies showed they metabolize the active ingredient more slowly than men do.

Although statins are the most widely prescribed drugs in America, they were tested mostly in men, and evidence of their benefit to women is limited. Indeed, women respond differently from men to a broad array of treatments, and often do not derive the same benefits from them as men.

The ideas for new treatments are often generated in the laboratory, where gender bias in basic biomedical research and neuroscience is ingrained.

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.

Jill Becker, a senior research scientist at the University of Michigan who studies gender differences in addiction, has found that women increase their drug use much more rapidly than men and that the hormone estradiol plays a critical role in the escalation, especially during ovulation.


Read the full article "Labs Are Told to Start Including a Neglected Variable: Female" at The New York Times.