Sonia Shah in The New Yorker (2023) on Free-Range Lab Mice

 Sonia Shah, “The Case for Free-Range Lab Mice,” The New Yorker, February 18, 2023.

• The subtitle is "A growing body of research suggests that the unnatural lives of laboratory animals can undermine science." [In an unwise attempt to appear more particular than The New Yorker, let me mention that I usually balk at the phrase "a growing body of research," for multiple reasons that will remain undisclosed for the time being.]

• This excellent piece of journalism opens with a tale of a 2006 false negative, where an experimental drug that was safe at high doses for rodents and monkeys proved life-threatening at much lower doses for humans.

• For new drugs, the FDA requires tests on (two species of) anymals prior to human trials. Most of the drugs that pass the animal tests fail for humans with respect to efficacy, while some prove toxic to humans.

• Most (some 88%), it seems, of the drug tests conducted on anymals cannot be replicated successfully; that is, it is not just psychology and behavioral economics that is facing a replication crisis.

• Lab experiments around the globe are undertaken on some 120 million rats and mice annually.

• More on replicability: the same animal experiment conducted in multiple labs can have different results. The results can differ based on the specific diet of the lab animals, their housing conditions, smells, the gender of researchers, … and just about anything else.

• For decades there have been efforts to produce genetically standardized animals, to ensure research results come with reduced noise from individual animal idiosyncrasies. This effort has not led to the expected research improvements: there is higher variance in drug effects with near-identical mice than with a broader mix. Further, there is lots of variance even among “identical” mice with respect to their basic physiology.

• The standard lab housing of rodents makes them sick, pessimistic, sleepy… "Imagine a study in which subjects are chronically cold, sleep-deprived, inbred, and held captive in cramped conditions. If the subjects were human, the scientific establishment would dismiss such a study as not only unethical but also irrelevant to normal human biology. Yet, if the subjects were non-human, the study could be treated as perfectly valid."

• Since humans are "free-range," it might be that the best animal models also are free-range -- and this thought has led to some researchers now testing lab mice that have been released in the wild, and comparing the results with their unfree brethren.