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From drug trials to brain research, mice are critical to scientific studies. Some labs
are just lousy with mice. You know what science needs though? More mice.
Hi everyone, Julian here for DNews. The power of science derives from testing an idea over
and over. Obviously that raises ethical problems when something needs to be tested on humans.
You can’t just create a new drug and then immediately start trying it on people, who
knows what the side effects might be? That’s why between test tube experiments and human
trials, a new drug has to pass the gatekeeper that is Mus musculus, the humble lab mouse.
Mice have been crucial to advancing science. They’ve contributed so much to so many fields
that there’s even a statue dedicated to them outside the Institute of Cytology and
Genetics in Novosibirsk, Russia. Animal rights groups may not like it, but the mice’s sacrifices
have saved many a human life.
Still, there’s a bit of a problem. For years, decades even, studies have mostly been using
male mice. When studies report what sex mice they used, males outnumber females five fold.
And in a survey of 1,200 papers, only 42% of them bothered reporting what sex their
lab animals were at all, meaning that gap could be much greater. According to a Scientific
American article by Brook Borel, the thinking was that male mice didn’t have that pesky
hormone cycle female mice have, so their results would be more consistent. Once the male mice
gave you a result, you could just extrapolate to females and start testing with humans.
Well not to sound like a hackneyed comedian, but have you ever noticed that men and women
are different? Our brains and bodies do not function identically so if a drug is going
to be used for both sexes, it’s probably a good idea to know how that drug will affect
each sex. The drug example Borel gives is Ambien. As it turns out, many women metabolize
the sleep aid much slower than men, to the point that they’re still too impaired to
drive the next day. It took 21 years for the FDA to half the recommended dose for women.
Oh incidentally the U.S. National Institute of Health (NIH) mandated the inclusion of
women and minorities in clinical trials receiving their grant money in 1993, a year after Ambien
was approved by the FDA,
So for over two decades women have been represented in human trials, but female mice have been
getting snubbed. The problem with excluding female mice is researchers might miss something
important. Women have adverse reactions to prescription drugs more often than men do,
even with a drug as innocuous as aspirin. A low-dose has long been recommended to help
prevent heart attacks. But according to a study published in the journal Heart in 2014,
healthy women under 65 are more likely to suffer from intestinal bleeding from regular
use. Since women are 1.5 to 1.7 times more likely to have an adverse drug reaction, it
makes sense to have analogues that might catch that early. And they may benefit from certain
drugs more too. One experiment looking into using oxytocin as an autism treatment used
males and females of a strain that had problems socializing. The female mice started socializing
more quickly than the males, suggesting oxytocin might be a more effective treatment for women
than for men.
Sex differences can also help point researchers in a new direction. For example, women are
more susceptible to multiple-sclerosis (MS), but the disease is usually less severe. By
studying male and female mice that suffer from a similar condition called rodent experimental
autoimmune encephalomyelitis, it’s been discovered that some genes on the Y chromosome
may have a protective effect, while some genes on the X chromosome may cause the disease.
With the benefits in mind, a year ago the NIH mandated that all research grant proposals
submitted would either have to use both sexes or justify why they used only one. It’s
a pretty big deal considering the NIH funds over 300,000 researchers. But are those initial
worries that a hormone cycle and behavioral differences would corrupt data justified?
Jill Silverman of University of California, Davis, has been using male and female mice
in her autism research for years. When comparing how mice from six different strains performed
on various behavioral tests, there was no significant difference between the sexes.
That’s not to say they don’t exist, but it’s more dependent on how the test is designed
and what the researchers are looking for.
Really the biggest issue is cost. The number of mice used would need to double in some
experiments, and they would have to be separated to make sure they don’t breed. Silverman
says she needs to use at least 20 mice in each test group to make her findings statistically
significant, which usually means at least 60 mice per experiment. If that number doubles
for other studies, taking care of twice as many mice over the course of months can inflate
costs dramatically. Still, the benefits of finding out how something affects both sexes,
or discovering a new path for research to go down is probably going to be worth it in
the long run.
During this whole thing you were probably wondering, why do we even use mice??? Well
Trace has that covered right here.
I’m all for more females in STEM, even if they’re fuzzy and tiny and white. Are you
a woman in the STEM fields? What do you do, and what’s your take on mandatory female
mice? And even if you’re not, we want to hear your opinion anyway. Let us know in the
comments. Subscribe for more, and I’ll see you next time on DNews