More Trouble in Mouse Animal-Model Land

Mice — inbred to reduce genetic variation — are used as laboratory models of humans in hundreds of situations. Researchers assume there are big similarities between humans and one particular genetically-narrow species of mouse. A new study, however, found that the correlation between human genomic changes after various sorts of damage (“trauma”, burn, endotoxins in the blood, and so on) and mouse genomic changes was close to zero.

According to a New York Times article about the study, the lack of correlation “helps explain why every one of nearly 150 drugs tested at huge expense in patients with sepsis [severe blood-borne infection] has failed. The drug tests all were based on studies in mice.”

This supports what I’ve said about the conflict between job and science. If your only goal is to find a better treatment for sepsis, after ten straight failures you’d start to question what you are doing. Is there a better way? you’d wonder. After twenty straight failures, you’d give up on mouse research and starting looking for a better way. However, if your goal is to do fundable research with mice — to keep your job — failures to generalize to humans are not a problem, at least in the short run. Failure to generalize actually helps you: It means more mouse research is needed.

If I’m right about this, it explains why researchers in this area have racked up an astonishing record of about 150 failures in a row. (The worst college football team of all time only lost 80 consecutive games.) Terrible for anyone with sepsis, but good for the careers of researchers who study sepsis in mice. “Back to the drawing board,” they tell funding agencies. Who are likewise poorly motivated to react to a long string of failures. They know how to fund mouse experiments. Funding other sorts of research would be harder.

In the comments on the Times article, some readers had trouble understanding that 10 failures in a role should have suggested something was wrong. One reader said, “If one had definitive, repeatable, proof that the [mouse model] approach wouldn’t work…..well, that’s one thing.” Not grasping that 150 failures in a row is repeatable in spades..

When this ground-breaking paper was submitted to Science and Nature, the two most prestigious journals, it was rejected. According to one of the authors, the reviewers usually said, “It has to be wrong. I don’t know why it is wrong, but it has to be wrong.” 150 consecutive failed drug studies suggest it is right.

As I said four years ago about similar problems,

When an animal model fails, self-experimentation looks better. With self-experimentation you hope to generalize from one human to other humans, rather from one genetically-narrow group of mice to humans.

Thanks to Rajiv Mehta.

2 Replies to “More Trouble in Mouse Animal-Model Land”

  1. Reminds me of a Mulla Nasrudin (after Idres Shaw. Seems the Mulla was on his hands and knees under a lamp post. When asked why he was, the Mulla said, “I’m looking for my keys.” Several people started to help him, and after a while someone asked him where he lost his keys. He said, “Over there in that dark area.” “Then why are you looking here!? “The light is better here, I’d never find them in the dark.”

    Perhaps we could use raccoons, they have similar diets and have hands.

    Oh, yes and the problem of using genetically identical animals makes statistical analysis easier, but misses the point, some things may be quite toxic to a small fraction of the population and harmless to the vast majority or vice versa. For example, some people are very salt sensitive and get high blood pressure, but the majority has trivial effects from salt. So there is a movement to cut down salt from everybody.

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