Study highlights male bias in animal studies

Photo: Emily Jacobs, a postdoctoral researcher at UC San Francisco, recently published a study on the effects estrogen has on working memory in women that explored the issue of gender bias in animal research.
Kevin Foote/Staff
Emily Jacobs, a postdoctoral researcher at UC San Francisco, recently published a study on the effects estrogen has on working memory in women that explored the issue of gender bias in animal research.

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Gender Bias in Research

Claire Perlman talks about the issue of male bias in animal-based research.

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Research is often only conducted on male animals, even while the results are applied to men and women alike, a problem University of California researchers explored in a study published April 6 in the Journal of Neuroscience.

According to the study, research conducted on animals, which informs human models of neurological function and disorders, does not take into account the hormonal differences between the sexes. Researchers often only use males because they are less costly and they do not have to worry about a female's menstrual cycle interfering in the study.

The study looks in particular at the effects estrogen has on a cognitive process called working memory that drives problem-solving and reading comprehension. Working memory depends on exact levels of dopamine, which is enhanced by the presence of estrogen.

"Human research is richly informed by work in animals," said co-author of the study Emily Jacobs, a postdoctoral researcher at UC San Francisco and graduate of UC Berkeley, in an email. "But when data from males are being used to draw conclusions about everyone's health, we risk ignoring important differences that can limit progress in public health. This seems especially pertinent for neuroscience and pharmacology and, ironically, these fields show the largest bias."

Because estrogen fuels dopamine and because working memory is a dopamine-dependent process, Jacobs and her co-researcher Mark D'Esposito, a UC Berkeley professor of psychology, examined whether estradiol, the main estrogen found in mammals, affected women's ability to perform basic working memory tasks.

Female subjects were tracked over a period of five months. The researchers monitored their menstrual cycles and measured brain activity when estrogen levels were naturally high and low.

"When estrogen levels were elevated, women with low dopamine showed a cognitive boost, while women with naturally high dopamine were impaired," Jacobs said in the e-mail. "It's a Goldilocks scenario in which you need just enough for optimal performance. Since estrogen increases dopamine, women with naturally low levels of the neurochemical may receive a cognitive boost when estrogen levels rise. But for women who already have optimal dopamine, the same rise in estrogen can lead to over-optimal dopamine levels. As such, they perform better when estrogen levels are low."

The study produced a result that would have been overlooked had working memory been studied in only male subjects, Jacobs said.

"It's a tradition in the biological sciences to study male animals," she said in the email. "There are reasons to take pause when interpreting the logic of this research practice and when considering the implications."

A study published last year by Annaliese Beery, a UC Berkeley graduate and current assistant professor of psychology at Smith College, found a male bias in eight out of 10 of the disciplines they looked at, including neuroscience, pharmacology and physiology. The bias in neuroscience was the most evident, with 5.5 males used as subjects to every female. According to Jacobs, such a bias can lead to incorrect conclusions for females, whose physiology is often not represented in animal research.

Jacobs said there is bias present even in research on conditions that occur predominantly in women, such as anxiety and multiple sclerosis, which is "alarming."

"I suspect changes are on the horizon (that) will require applicants of federally funded research grants to justify the use a single sex, with the assumption that both sexes should now be used by default," Jacobs said in the email. "And, although it was offered in jest, one committee member suggested that if a study uses only male animals journals should require authors to tack on two little words to the end of every paper - (in males)."


Claire Perlman is the lead research and ideas reporter. Contact her at [email protected]

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