Earlier this year, the world's largest biomedical research funder announced a radical sex change to its funding decisions. Money would no longer flow as freely to studies that excluded female subjects. Instead, scientists seeking grants from the U.S. National Institutes of Health would have to include plans for studying both female and male cells, mice, monkeys or whatever living things they used in their experiments, according to a commentary published in Nature by two top officials. (Scientific American is part of Nature Publishing Group.) "These policies will be rolled out in phases beginning in October 2014," wrote Janine A. Clayton, director of the NIH’s Office of Research on Women’s Health, and NIH Director Francis S. Collins.

Funding rules, however, have yet to change, with only one week left in the month. Instead, the agency is gathering comments from researchers about which research areas need sex balance the most and the challenges scientists face in including male and female subjects in their studies. Officials have set aside $10.1 million in grants for scientists who want to add animals of the opposite sex to their existing experiments. The NIH is also making videos and online tutorials to teach scientists who are new to studying both sexes how to design such studies. Meanwhile, Clayton "can't say" when new funding rules will take effect. "Details about the policy and implementation plans will roll out during the next year," she says.

Once in place and codified, the requirement would be a major shift for the nation’s biomedical labs, many of which study mostly or exclusively male animals. One estimate found that pharmacology studies include five times as many male animals as female ones, while neuroscience studies are skewed 5.5:1 male-to-female.

Scientists assumed biology findings that held in males would apply just as well to females, but a growing body of research has discovered this is not always true. Female and male mice's bodies make different amounts of many proteins, for example. Men and women have differing risks for many health conditions that are not obviously sex-based, including anxiety, depression, hypertension and strokes. Yet those diseases are still predominantly studied in male animals. Scientists who study sex differences think the mismatch might be the reason women suffer more side effects than men do from drugs approved by the U.S. Food and Drug Administration. Pharmaceuticals that researchers test mainly on male animals may work better for men than for women.

The policy change is meant, in part, to improve how drugs function in girls and women. Yet it may benefit men as well. For instance, another problem the NIH identified arises when researchers average results from pools of lab animals including both females and males. That commonplace practice may obscure sex differences that could help men, if identified. For example, a drug that works well in male mice, but poorly in female mice, might turn out to be useful for men only—and could be developed just for men. An averaging study, however, would make the drug seem mediocre overall and not worth further research.

The article in Nature drew plenty of reactions from scientists. "I think it made a lot of people freak out a little bit," says Rebecca Shansky, a neuroscientist at Northeastern University in Boston who studies sex differences in how brains respond to stress. As October 1 has come and gone, it has become clear that the NIH is proceeding with caution.

NIH officials need time to consider the comments they will receive, Clayton says. Among the rules they will debate is what qualifies a study proposal to not include both male and female cells and animals. (The agency will allow exceptions, the Nature commentary promised.) Officials want to give scientists time to prepare: those who now study animals of just one sex may have to learn new skills to care for animals of another sex and to statistically analyze more complicated data sets. NIH officials want some time for themselves, too. Along with writing guidelines for scientists, officials also will craft corresponding changes in the review process. "NIH is like an aircraft carrier," Clayton says. "We can't turn on a dime."

Before the commentary was even conceived, NIH had made some moves to include female subjects. In 2013 the Office of Research on Women's Health began offering supplemental grants to add animals to existing studies, a harbinger of what was to come.

Abraham Palmer, a geneticist who leads a lab at the University of Chicago, used one such supplement. He already had a grant to look for genes associated with methamphetamine enjoyment, a potential risk factor for addiction to that illegal drug. His study actually included both female and male mice, but he originally planned to average his results from both sexes. It is an understandable choice. If a researcher only has the funding to buy and care for a small number of mice, the results might not be statistically significant if the data have to be split up by sex. Palmer's supplemental grant gave him the money to double the number of mice in his study so he could have statistically strong, sex-specific results.

To Palmer, the grant signals a turnaround at the NIH on how it thinks about sex in experimental designs. About a year and a half ago he applied for an NIH grant for a drug study that proposed to report separate results from male and female animals. He says he was turned down in part because an NIH reviewer thought sex differentiation would undermine the statistical strength of his results. "I think NIH saying explicitly 'We want this' is valuable," he says. "It justifies giving the resources needed to increase sample size."