The Barbed Noose with the Mice. Paul Klee. The Berggruen Klee Collection, 1987. Image courtesy of The Metropolitan Museum of Art.
The Barbed Noose with the Mice. Paul Klee. The Berggruen Klee Collection, 1987. Image courtesy of The Metropolitan Museum of Art.

When the initial report was first published, and the story circulated, news agencies and scientific magazines alike jumped on the simple and relatable study. Headlines ranged from the accurate if slightly simplified, “Men Trigger Mouse Stress” in The Scientist to the absurd and sensationalist, “Male Scientists’ Threat to the Integrity of Research” in The Atlantic. All this coverage, which I’m sure you’ve witnessed, was reporting on a recent study published in April 2014 in Nature Methods titled “Olfactory exposure to males, including men, causes stress and related analgesia in rodents” – an appropriately precise, if not eye-catching title. But before you panic and start second guessing your own work, consider that the study was primarily a behavioral one and really has no bearing on our immunological work.

The study by Sorge et al. is a well-controlled and thorough examination of how mice, in the context of pain responses, react to the presence of males or more specifically male hormones. The experimenters used several methods to show that male androgens, across species, can elicit a stress or in this case analgesic response in mice under pain responses. The effect was validated with clear biological evidence of increased corticosteroid levels. After reading the primary literature, I am convinced of its validity. My only quip is with the exaggeration of its implication by the authors of the paper, their colleagues, and the media that had reported on its findings.

In a Nature News report of the work, a well-known researcher in the field, Joseph Garner, is quoted as saying, “The work indirectly demonstrates potential effects on nearly any kind of medical research”. For a more realistic interpretation of the work, the corresponding author of the study, Jeffrey Mogil, says “that the findings should at least prompt researchers to report the gender of experimenters in their publications, and if the experimenters change mid-stream, to include their gender as a variable in the analysis”. I think that these suggestions might apply to behavioral studies on pain in rodents but are entirely unnecessary for the type of work that cellular and basic immunologists may perform with rodents.

[pullquote]The normal handling of mice through scruffing, injection, or any other technique will already cause excessive stress, regardless of the experimenter’s sex.[/pullquote]The findings of these studies do not apply to immunological mouse studies because the handling methods of the mice are so different from normal procedures. The majority of this study was conducted on mice placed in in Plexiglass containers and left in open rooms. The mice were injected with compounds to induce stress and then monitored hours later in the presence or absence of an experimenter. This situation is unique to behavioral work as mice are handled, injected, and then monitored hours later. This interlude provides a refractory period to any stress induced by the act of handling or injecting the mice. The authors of the paper themselves noted that changing the sex of the technician providing animal husbandry or changing the sex of the person administrating the pain-inducing compound did not alter the results. That’s because the mice in their experiments are rested for hours and then placed in open rooms.

This is in clear contrast to the handling of animals in normal immunological studies, which takes place in restricted biosafety cabinets and uses vented cages. Researchers entering an animal facility typically must wear a gown, mask, gloves, hairnet, and shoe covers to minimize exposure to any contaminating compounds. The root of my issue with the broad implication of the study’s work is that the normal handling of mice through scruffing, injection, or any other technique will already cause excessive stress, regardless of the experimenter’s sex.

Although the findings of this study and their implications on behavioral pain research has merit, extending the conclusions to other biological sciences is unwarranted. If you’re doing animal work, variation caused by differential stress stimuli is unavoidable. The sex of the experimenter will have little effect on stress responses when compared to the actual stress of handling and treatment.

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Yuriy Baglaenko

Founding Editor
Yuriy is a 4th year PhD student studying the suppression of autoimmunity at the University of Toronto. He is an avid musician with an at-home amateur recording studio and a mediocre intramural volleyball player.
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