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1 May 2014updated 09 Jun 2021 9:17am

Lab mice are misandrists, and that’s a problem for bioscience

Male scientists evoke stress in lab mice, while female scientists do not – an underappreciated difference that could have consequences for thousands of studies.

By Ian Steadman

A study in Nature Methods has found that lab mice have different hormonal and behavioural responses to male and female human scientists – a discovery that could have wide-ranging impact on how research is conducted and interpreted.

Men, it seems, scare them. Women don’t. Here’s Nature‘s Alla Katsnelson:

This apparent effect is “something that people have been whispering about at meetings for years,” says lead author Jeffrey Mogil, a pain researcher at McGill University in Montreal, Canada. “But no one had bothered to look at this systematically.”

Mogil’s team measured the response of mice and rats to an injection in the ankle, either in the presence of different experimenters or while alone in an empty room (the experimenters gave the injection and then quickly left). To their surprise, the animals seemed to show a decrease in pain response of about 40 percent when a man rather than a woman remained in the room.

40 percent! That’s a huge difference, and one which could be crucial to affecting the results of studies which use mice. And it’s not limited to the presence of male humans, either – a t-shirt previously worn by a man, and samples of armpit secretions from a man, also had the same effect. Male rats, cats, dogs, guinea pigs and rats also caused the same response. The presence of the the male scent gave the mice an elevated level of corticosterone – a stress hormone. The mice were so stressed about being near men that it caused them to temporarily feel less pain.

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The presence of a woman, however, seemed not only to not cause the mice distress, but to actually counter the effect of the presence of a male. It seems that mice hate men.

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(One thing I wasn’t aware until I saw this study is that there is such a thing as the “mice grimace scale”, for measuring their pain – based, in fact, on a similar system used to assess pain in infant humans.)

This study reinforces emerging concerns about the reliance of the scientific establishment on mice and rats for experimentation. An EU study from 2008 found that those two species alone accounted for 80 percent of all vertebrates used in experiments, and indeed it is almost unheard of for new drugs to be approved for human testing without having first passed muster in rodents.

Slate’s Daniel Engber wrote a fascinating three-part series on this issue in late 2011, starting from the point of neuroscientist Mark Mattson – who, in 2007, realised “that his animals were nothing less (and nothing more) than lazy little butterballs”. Lab mice and rats are fat, living sedentary lives that bear as much relation to their “natural” state as humans who live on corn syrup-rich diets without any kind of regular exercise. Applying findings from unhealthy rodents to healthy humans undermines bioscience in a very uncomfortable way.

The reason this happened is, frankly, that scientific study of the body was industrialised. Principles of factory farming were applied to the breeding of rodents, letting them live in cages with near-infinite supplies of food and without space to exercise. They can breed quickly, produce lots of offspring, are cheap, respond well to genetic-engineering, and share more of our genetic makeup than, say, cats or dogs, so it made sense to make rats and mice the standard canvas upon which to first test new drugs and treatments intended for vertebrate humans.

In the process, we undermined that canvas. As Engber writes:

Mattson has seen this problem in his own field of research. Twenty years ago, scientists started to develop some new ways to prevent brain damage after a stroke. A neurotransmitter called glutamate had been identified as a toxin for affected nerve cells, and a number of drug companies started working on ways to block its effects. The new medicines were tested in rats and mice with great success—but what worked in rodents failed in people. After a series of time-consuming and expensive clinical trials, the glutamate-blockers were declared a bust: They offered no benefit to human stroke patients.

Now Mattson has an idea for why the drugs didn’t pan out: All the original test-animals were chubby. If there’s something about the brain of an obese, sedentary rodent that amplifies the effects of a glutamate-blocker, that would explain why the drugs worked for a population of lab animals but not in the more diverse set of human patients. This past June, he published a paper confirming the hunch: When he put his test mice on a diet before administering the glutamate-blockers, the drugs’ magical effects all but disappeared.

What to do about this? It’s not really clear. The usefulness of mice and rats as experimental subjects gives rise to the economic conditions that undermine their usefulness. (Thanks, capitalism!) Scientists working with rodents will need to begin acknowledging and studying these further biases that their implicit assumptions introduce to each experiment, or there may be huge bodies of potential knowledge out there that we just will never know. At the very least, scientists could begin reporting the genders of those taking part in experiments with mice subjects, to address the problem of men ruining things with their presence.