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I don't think it is just about mice though- it is also about "pure bred" anything. Imagine there was a single human that we could do all kinds of knockout exper

I don't think it is just about mice though- it is also about "pure bred" anything. Imagine there was a single human that we could do all kinds of knockout experiments with, but we would always be starting with that base human (and on top of that it would be inbred and always live in the same kind of environment). Some of the conclusions we would draw would certainly not extend to all humans, probably not to most even. If the entire field became centered around this human, we would be missing huge amounts of information in space we are not exploring at all. Controls are great, and it makes perfect sense to have studies that produce these extremely well controlled results. But controlling does have its own tradeoffs in practice, as results may very well not be robust/not generalize to things we care about. My problem is that the entire system operates under essentially the same paradigm, so we have very little work trying to address these downsides.

ethbro 6y ago
The solution to population variability is not to use variable models. That just trashes your result set. There are enough confounding, uncontrollable variables in biology already.
- throwaway4666 6y ago
  Seeing how identical individuals from literally the same cell line in an exactly identical and controlled environment sometimes give different results I don't think you can ever achieve 'perfect controls' anyway. The solution is to delve deep into what things actually do (in the case of people I know, that involves a lot of live single-cell imaging and suchlike) but that's expensive.
- mennis16 6y ago
  I didn't propose any specific solution, all I said is that the field doesn't do enough to account for population variability. It is hardly acknowledged! You will find PhD students at top programs who say "huh hadn't thought about that being a problem before". Because the training and grants and whatnot largely revolve around this same experimental setup. And IMO it is not a good approach to have everyone working on these problems think in largely the same way. Btw, in these cases where they find a result seems to only apply to a particular mouse strain, that feels like a pretty trash result to me too. What are we supposed to do with that knowledge? Currently what we often do is build on it, cite it completely out of context, and happily walk away with a publication.

ethbro 6y ago

The solution to population variability is not to use variable models. That just trashes your result set. There are enough confounding, uncontrollable variables in biology already.

throwaway4666 6y ago
Seeing how identical individuals from literally the same cell line in an exactly identical and controlled environment sometimes give different results I don't think you can ever achieve 'perfect controls' anyway. The solution is to delve deep into what things actually do (in the case of people I know, that involves a lot of live single-cell imaging and suchlike) but that's expensive.
mennis16 6y ago
I didn't propose any specific solution, all I said is that the field doesn't do enough to account for population variability. It is hardly acknowledged! You will find PhD students at top programs who say "huh hadn't thought about that being a problem before". Because the training and grants and whatnot largely revolve around this same experimental setup. And IMO it is not a good approach to have everyone working on these problems think in largely the same way. Btw, in these cases where they find a result seems to only apply to a particular mouse strain, that feels like a pretty trash result to me too. What are we supposed to do with that knowledge? Currently what we often do is build on it, cite it completely out of context, and happily walk away with a publication.