Mice: A lousy Model for Drug Development?

February 12, 2013

A recent article in PNAS (Genomic responses in mouse models poorly mimic human inflammatory diseases; Seok et al, February 11, 2013, doi: 10.1073/pnas.1222878110 PNAS),  presents evidence from gene profiling investigations that mice and humans respond very differently to sepsis, activating completely different gene families as a defense mechanism. The authors conclude that investigators have wasted millions, maybe billions of dollars pursuing candidate compounds that had no chance of performing adequately in human populations.

This should come as no surprise, that mice are a long ways from humans. If confirmed, these findings bode ill for the development of new anti-sepsis therapies. These observations come a time when animal models are on the decline, a result of astronomical increases in costs and severe ethical constraints. As data accumulates on animal behavior and intelligence, it is becoming more and more evident that animals experience pain and suffering in a fashion that is quite comparable to humans. And the closer their evolutionary relationship to ourselves, the more precise is the parallel between their responses and our own.

These considerations, combined with the costs of dealing with housing and care issues mean that non-human primates are being totally phased out from laboratory investigation. We can expect movement in a similar direction concerning the use of rodents, for the same reasons.

Mice, engineered with human genes to mimic metabolic pathways under evaluation, may turn out to be the best alternative. Advances in computer modeling and tissue culture model systems may offer some support. Nonetheless, the road to truly original and effective therapies  for cancer, cardiovascular disease, Alzheimer’s, diabetes and other complex chronic conditions  promises to be long and frustrating.

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