Greetings -

This article* is an oldie and a goodie: The Mouse Trap by Daniel Engber. The author provides the historical context for how and why we arrived at what amounts to a monoculture in medical research. “The great majority of how we understand disease, and attempt to cure it,” writes Engber, “derives from a couple of rodents.” About 4/5ths of all animal studies reported in biomedical research papers from 1950-2010 were done in rodents (59% in mice, 18% in rats).

* This is a three-part series and the link above provides all three parts in one in a text-only version. Here’s Part I, Part II, and Part III with all of the accompanying images and videos.

It seems most of us are numb to the caveat that’s included (or should be included) in rodent research: ‘this finding may not translate to humans.’ But we shouldn’t be. For example, one study found that fewer than 10% of highly promising basic science discoveries enter routine clinical use within 20 years, “supporting the notion that basic science research rarely translates into clinical research and clinical practice, even when they seem highly promising,” writes John Ioannidis and his colleagues in 2003.

Perhaps a related story from 2012: the New York Times reported on a study in mice showing autophagy is accelerated by exercise, and this may be a crucial benefit of physical activity. Autophagy reportedly increased in cardiac and skeletal muscle after 30 minutes of treadmill running and reached a plateau at 80 minutes.

This sounds great...for mice. Remember the caveat? The basal metabolic rate (per gram of bodyweight) of a mouse is roughly seven times faster than a human’s. Studies have also shown that if you fast a mouse for two days it loses 20% of its body weight. (To put this in perspective, this is the equivalent of starting a fast on Sunday night weighing 180 lbs. and dropping 36 lbs. by Tuesday.) Humans live roughly 40 times longer than mice. Think about how this might impact translation from mouse to human.

Mice fasted for 18 hours lose about 15% of their body weight. Keep this in mind if someone is telling you that intermittent fasting and exercise boosts autophagy. It might. (And boy are “intermittent fasting” and “exercise” umbrella terms.) They may be unknowingly relying on research in rodents. If autophagy is upregulated in response to nutrient deprivation — and the extent and duration of the deprivation matters — it doesn’t seem unreasonable to think that we’re talking about two entirely different situations when comparing mice to humans, whether comparing the effects of a 30 minute run on the treadmill or skipping breakfast.

Unfortunately, it’s very difficult to study autophagy in humans (and mice are not furry little humans). Have I mentioned how nice it would be if we could?

- Peter

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