Most non-human test subjects are male. Aarthi Gobinath wants to change that.
Photo of Aarthi Gobinath courtesy of the author
When we talk about female representation in science, we’re rarely talking about test subjects. We tend to want more women behind the microscope, not under it.
Neuroscience is one of the most skewed fields when it comes to testing on female physiology. One review found single-sex brain studies using male animals outnumbered those using females 6.7 to one.
Aarthi Gobinath, a neuroscientist at the University of British Columbia, calls this a “hidden gap” in her field. She says there’s reason to question the assumption that the brains of males and females are identical, particularly in unique states like pregnancy.
This is particularly true for early animal testing, where new drugs for depression and anxiety are first developed. “This leads to the ultimate outcome of our research not even benefiting males and females equally,” Gobinath told VICE.
Gobinath wanted to tackle the issue of sex bias by trying to understand what depression looks like in female rat brains, specifically looking at postpartum depression. Her research suggests our standard depression treatments don’t apply to new moms.
VICE caught up with Gobinath to ask about her new study, which could have wide-ranging implications for humans of all sexes and genders.
VICE: What do you mean when you say there’s “sex bias” in brain research?
Aarthi Gobinath: So when I say sex, what I mean is genetic sex meaning XX or XY chromosomes. (Sex bias) is a bias towards using male subjects in research and then concluding from that research that what was true in that experiment will be true for both sexes without necessarily addressing that maybe it won’t be true for the female physiology.
When did you first come across this issue?
I first became aware during my transition between undergraduate and graduate research. I was working on a project that was looking at stress on the hippocampus of mothers. And we realized that there were quite a few differences in the way stress affects moms versus the brains of non-moms. That was really interesting and so I wanted to pursue that for my graduate education.
Why do researchers generally use male subjects in the first place?
(Cis) women have a menstrual cycle in humans, or the estrous cycle in rats, so some researchers see that as a complication or as an inconsistency that makes it difficult to study female subjects. Because male subjects don't have that some would argue that it's easier to work with male subjects. I've worked with male rats and I've worked with female rats. I don't find it to be problematic or more work. I think I've gotten more answers that way. I find it more rewarding to know that I've addressed both sexes in my work.
Have you found instances in your research where things we thought were true for males weren’t true for females?
Absolutely. We were looking at the drug fluoxetine, commonly known as Prozac, this drug is a well validated antidepressant. But a lot of that work was confirmed in males. When I applied it to female rats with postpartum depression we actually found that fluoxetine was unable to prevent depressive-like behaviour in the mother.
And you thought the best way to address this problem was to specifically study female subjects?
Yeah, and to specifically study things that were unique to female physiology and female biology. I actually take part of the problem—something that was different about female physiology, pregnancy and postpartum—and explicitly study it.
What relation does your work have with how we understand sex bias?
My work is laying the foundation that will hopefully inform the clinical world. Hopefully, laying out where we see sex differences will be clues to clinical researchers to say "OK, maybe we do need to start thinking about drugs affecting men and women differently,” and "maybe we do need to think of postpartum depression being a distinct disorder from major depression.”
Do you have a solution for the sex bias that's in neuroscience?
I think that transparency and appreciation for sex differences will be key here. It's OK for researchers to just study male subjects, that's fine. But then they have to include in their titles and in their abstracts that their research it was done in male subjects only and acknowledge that what they have found to be true is true for one sex specifically.
There are mandates put in place that state that human trials must include both male and female test subjects. So is there a sex bias even in studies that look at humans?
Yes. Both sexes will be represented in the human data, but they’ll just collapse the data into one category without acknowledging the sex differences. If a clinical trial found that there was no significant effect of a drug, but they didn't analyze by sex, maybe that drug was actually beneficial for one sex, but not the other. But because the dataset was collapsed we've lost information that way.
Do you know any cases where a sex bias has had a negative impact on humans?
This has happened with the drug Ambien. Work that was done on Ambien was primarily optimized in male subjects. When doctors started prescribing Ambien for men and for women, women were suffering from more adverse effects and were at higher risks for overdosing. This is because the way the drug is working throughout the body is actually different for (cis) men and women. Researchers we weren't aware of that until serious errors and problems had come up in the clinical population. And so now we can look back on that and say "OK, research supports that (cis) men and women should be given different doses of Ambien," but it took errors being made and actual human lives being affected before we thought to reconsider.
How can we improve the current model of research only focusing on males?
There are two sides to that. First of all I think that funding agencies need to appreciate that we need to study both males and females. The other side is that researchers need to see this as more of an opportunity and less of as an inconvenience. If it's true that some treatments act different between males and females, then there's an opportunity there for discovery and for innovation for what we know about treating diseases. We should be getting excited instead of becoming frustrated by it.
Were you worried that the results of your study could be misinterpreted?
There are some people who misconstrue any study about a sex difference as some sort of biological basis for misogyny. Which is unfortunate. There’s also a lot of pushback. I find it exciting when we find a sex difference because it means that we can better understand how to help male subjects as well as female subjects. But there are those who argue that they don't see sex differences so they don't believe there is a point to studying it. That's frustrating for researchers.
What would you tell a person that was completely unaware about this gap in the research?
If you're wondering "why don't we have the cure for Alzheimer's disease, why don't we have the cure for depression, why don't we have the perfect cure for any disease currently out there?" It is partly because we have been biased towards using male subjects. Depression affects twice as many women than it does men. Alzheimer’s is also characterized by a sex difference in that it affects more women than men. And yet, a large amount of knowledge on drug treatments for these diseases has been from research on male subjects only. This is part of the reason why we don’t have the best treatments out there.
So if you're wondering why as scientists we're not "done yet" with a disease, it may be because we didn't actually think about male subjects versus female subjects.
This interview has been edited for length and clarity.
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