Daniel Cressey reports on research that points out the problem of laboratory rodent analogs for human health conditions: the mice and rats start out unhealthy:
Mattson and his colleagues note that the standard lab practice of allowing rats and mice continuous access to food without much opportunity to exercise can cause some to balloon in weight to up to 1 kilogram. Beneficial effects of a potential drug or behaviour could simply result from its effect on the consequences of an animal's unhealthy lifestyle, they say, and studies showing that caloric restriction can extend lifespan may have to be reinterpreted. "A major reason the lifespan of rats and mice is extended by caloric restriction is they started from an unhealthy baseline," argues Mattson. He and his co-workers identify areas as diverse as immune function, cancer and neurological disorders that could be affected by the problem (emphasis added).
I can add the little-noted fact that lab rodents have been selected for fecundity. Faster reproduction and larger litters are enabled by larger body size, rapid maturation, more milk production.
Some of this may help make rodents a better analog for humans, at least fat American humans. But for many studies, it may be useful to replicate results on multiple species of laboratory animals, including some kept deliberately in different environments than the usual lab.
UPDATE (2010-03-02): I've read the paper by Bronwen Martin and colleagues ("Control" laboratory rodents are metabolically morbid: Why it matters."). It's a nice piece of work, and includes a well-written introduction followed by a list of possible biases and problems for specific disease conditions including diabetes, cancer and neurological disorders.
It occurs to me that understanding the problem isn't enough to get research labs to maintain healthier controls. Labs have a positive payoff from keeping their control animals fat and unhealthy, if that means the experimental treatment is more likely to show a difference.
Especially at the level of "pilot" results, which go into grant applications and determine the chance of further funding to study a new intervention. The difference between a significant and insignificant result in a small pilot study isn't very much.
