How Male Researchers Are Stressing Out Lab Rats
And how it's a huge concern for replicating results.
Image: Maggie Bartlett, NHGRI.
This week, a paper published in Nature Methods found that there is a serious complicating factor in experiments involving lab animals: the gender of the researchers. For years, lab workers have anecdotally suspected that the preferences of their animals might affect their data. But it wasn't until scientists based out of McGill University investigated these suspicions that gender was isolated as the main culprit.
“The rumor was simply that experimenters may be causing analgesia (pain inhibition),” lead author Jeffrey Mogil told me. “People in my lab were saying it to me over the years. People were sort of whispering about that in the halls at meetings. But I had never heard anyone suggest that there was any sex specificity to it, so we were very surprised when we found that the idea that experimenters were causing analgesia was true, but it was only half-true.”
Analgesia is a stress response that temporarily inhibits pain, and the lab mice exhibited it significantly more with men than with women. “There were a lot of experiments,” said Mogil. “Mice were injected with an inflammatory substance and videoed in an empty room, or they were injected and videoed in a room with a male experimenter sitting in a chair, or with a female experimenter sitting in a chair.”
“When a male experimenter was sitting in a chair there was less facial grimacing—that is, less pain behavior. We found later on that this had nothing specifically to do with facial grimacing, and frankly it has nothing really to do with pain. The core finding here is that male olfactory stimuli produce stress, and one of the things that stress does is produce a phenomenon known as stress-induced analgesia. The reason we're seeing effects on pain was simply because there was stress there.”
Mogil's team observed the stress response in both mice and rats. Image via Janet Stephens.
Both male and female mice showed the exact same spike in stress when they sensed a man in the room, and both were unperturbed by women. You might think that the mice were stressed out over fear of a natural predator, but Mogil's team reproduced the experiment with smells from many different male mammals, including non-threatening species. In every case, the mice exhibited more stress-induced analgesia when presented with male smells than with female smells.
“You can get the same effect from a stranger male mouse. That's obviously not a fear of predation, it's a fear of territorial conflict,” said Mogil. “Bedding from stranger mice, guinea pigs, rats, cats, and dogs all produced exactly the same effects. It has nothing to do with people. I's just that human males smell the same ultimately as males of other mammalian species.”
The fact that rodents have a much more extreme reaction to male researchers than females is a huge variable in lab experiments, and could significantly muddy any data collected. But Mogil found that there are various ways to mitigate the problem for male researchers, such as hanging out with the animals for about an hour before conducting experiments.
The stress response is also absent if a male researcher is accompanied by a female, or even just an object with a female's smell, like a piece of clothing. The animals are only wary when they smell a lone male in the room—it is hardwired in the animals' brains to suspect such individuals are up to no good.
Mogil is not optimistic that researchers will take these kind of precautions, however. “I don't expect that people are really going to wait,” he said. “What I really expect and hope will happen is that people start putting this in their methods sections, so if other people try to replicate them at least they can try to replicate [the researchers' genders] too.”
The study has consequences far beyond experiments conducted on mice and rats. “My hope is that other people are going to start showing this in other species, in other circumstances, and in other types of tests,” said Mogil.
He's not just talking about lab animals. “I think it probably extends to humans, and I have a grant to find out,” he said. “That's the next step.”
If even humans behave differently with male researchers, it could complicate a wide variety of medical and psychological studies as well. The upshot? If you're a male lab worker who works with mammals of any kind, be advised that your most powerful piece of scientific equipment might just be your girlfriend's T-shirt.