By Anthony Hickey, PhD
How scents from human males (and other animals) induce stress responses in laboratory mice, which can impact experimental results.
During my early years as a graduate student, I worked with a very meticulous scientist who paid extraordinary attention to detail. On more than one occasion, he would lecture me on the virtues of careful note taking and had even once stated (half) kiddingly that the cycle of the moon during an experiment should be noted in one’s experimental journal. While it is common scientific practice to document every possible detail and variable of an experiment, a recent article published last April in Nature Methods by Sorge et al. discusses an experimental variable that is almost always overlooked: the experimenter.
According to the study conducted at McGill University and led by Dr. Jeffrey Mogil, experimental mice respond differently to painful stimuli depending on the gender of the observing experimenter. The researchers report that rodent pain responses to the injection of proinflammatory molecules, as measured by facial grimacing and wound licking, are significantly blunted in the presence of male experimental observers (or clothing worn by male observers), but not female observers. The authors of this study concluded that this phenomenon is due to a stress/fear response that is triggered in mice upon olfactory stimulation by male axillary secretions (as documented by increases in murine corticosterone levels), which results in a protective response known as stress-induced analgesia. The team further demonstrates that the gender of an experimenter influences baseline measurements in behavioral testing and suggests that experimenter gender be accounted for in standard laboratory protocols regarding studies involving animal stress.
“The results of these experiments are surprising, but important,” said Dr. Thangavel Karuppudurai, a postdoctoral fellow studying synaptic transmission in Drosophila visual neurons and visual-based behavior in the laboratory of Dr. Chi-Hon Lee. Dr. Karuppudurai was quick to point out that Drosophila have an olfactory system as well, and although different from its mammalian counterpart, much behavioral testing of this animal model is conducted using this system.
For Dr. Julia Rodiger, a postdoctoral fellow working in the laboratory of Dr. Yun-Bo Shi, the findings of this study go beyond just the gender of the experimenter. The authors of this work have also demonstrated that exposure of laboratory mice to other unfamiliar male mice (and their bedding), or to other male animals of different species, produces similar effects as does exposure to human males, which may have ramifications for animal husbandry practices. “Many other factors may also cause stress for the animals,” said Dr. Rodiger, who studies intestinal epithelial stem cell development in mice, “including the noise level in the animal facility, the number of people in the room when animals receive treatment, or even the presence of other male animals. The findings of this article could provide an explanation why different laboratories can have trouble reproducing the results of other groups.”
This study is the first to show that different experimenters can influence both the behavior and physiology of a laboratory animal in a non-technical manner. It also reminds us that even the most meticulously designed experiments can still have non-obvious variables that are unaccounted for. Although this may be alarming to some, it is important to remember that scientific progress is about moving forward by learning from observations made in the past. This new knowledge has not only already improved our understanding of experimental systems, but will also provide insight on how to design tighter and better controlled experiments in the future. At the very least, these findings validate the sentiments of my former mentor in that no experimental detail is too small to record.
- Sorge, R. E. et al. (2014) Nature Methods 11, 629–32.