[Suckling K. Animal research: too much faith in models clouds judgement. Nature. 2008 Sep 25;455(7212):460.]
Your News Feature ‘Standard model’ (Nature 454, 682–685; 2008) raises issues about the use of mouse models of disease that go well beyond the field of neurodegenerative disorders. As a former head of atherosclerosis research at GlaxoSmithKline laboratories, I can attest that the situation is similar for models of atherosclerosis and dyslipidaemia.
Informed users of mouse models are well aware of their limitations in relation to human pathology, so their expectations from drug studies and the relevance of these to humans are tailored accordingly. But it seems to me that, beyond this relatively small group of practitioners, wider concerns arise.
These might be viewed as a criticism of the rigour of much of the dialogue between preclinical and clinical research. One is about overuse of the glib term “animal model of disease X”, which raises expectations and clouds proper interrogation of experiments. As you suggest, it is better to consider a mouse model as primarily one of mechanism and to make a reasoned extrapolation to humans from there.
This approach links in more closely with the current critical preoccupation with translational research. Another concern is one that permeates all science, namely the tendency to regard the model (in whatever form it is expressed) as being identical to its prototype, often coupled with the idea of a ‘complete explanation’, which is, of course, illusory.