Are Cold Mice Skewing Cancer Study Results?

Designing experiments is a tricky task. In order to prove or disprove a hypothesis, scientists first have to eliminate or account for the influence of as many variables as possible. But in order to do that, first they must realize that these variables exist. A review article published today in the journal Trends in Cancer shows that standard laboratory temperatures—which are comfortable for humans but chilly for mice—are likely affecting biomedical study results. 

As oversights go, this is a pretty big one. Lab mice and rats are the subjects of more than 100,000 journal articles every year … and those are just the experiments that are published. But unlike dogs, cats, rabbits, or chimpanzees, mice and rats are not protected under the 1966 Animal Welfare Act, which regulates how research animals are treated. This lack of protection means that there has been relatively little research, and less regulation, regarding their treatment. 

This is a bad situation for rats and mice, and it’s not great for us, either. The mouse model, as it’s known, is generally seen as a pretty good indicator of how a given drug or medical occurrence may affect humans. So if tests on a cold mouse yield different results from those done on a mouse at a comfortable temperature, as two immunologists now argue, then millions of studies on drugs and disease have been affected.

Today, rodent research labs are kept between 68°F and 78.8°F. Researchers wear layers of protective gear, including gowns, gloves, and masks, so a higher temperature might cause them to overheat. Keeping the thermostat down also helps keep down the smell.

Image Credit:Guanxi (Christina) Qiao

But a mouse’s ideal temperature averages between 86°F and 89.6°F. A 70°F room will cause mice to shiver, which uses up their energy and affects their metabolism, blood flow, and heart rate. Realizing this, immunologists Bonnie Hylander and Elizabeth Repasky decided to take a look at the relationship between mouse temperature and study results. In 2013, they found that a cold mouse is less able to fend off tumors than one that’s toasty warm—a finding that had big implications for cancer drug research.

But these findings were just the start. Hylander and Repasky conducted a sweep of scientific literature, looking for studies like theirs. They found that researchers of obesity, inflammation, atherosclerosis, and a number of other diseases all concluded that keeping mice cold led to “significant differences in experimental outcomes.”

"Most people only look at results from experiments at standard lab temperatures," Hylander said in a press statement. "They're not necessarily aware that if you repeat the experiments with mice at a different temperature, you might get a different outcome." 

Unfortunately, there’s no quick fix to be had here. “The mice want different temperatures for different parts of the day,” animal welfare scientist Brianna Gaskill told Dan Engber at Slate. “There is no way that humans can pick a single, perfect temperature for mice.” And, as mentioned earlier, what’s good for mice is not so good for researchers. 

Hylander and Repasky aren’t suggesting that labs simply turn up the heat. One approach might be for researchers to experiment with keeping the mice warm in incubators, or offering them more nesting material. They also recommend that researchers consider the effects of temperature in both their experimental design and their analysis of their results in the future.