[bkandel]

There's a huge difference between when we know how an organ system behaves in a particular circumstance vs. when we don't. Take, for example, the hepatic function in biogears: https://github.com/BioGearsEngine/core/blob/trunk/projects/b... If you know all the constants and how the liver reacts to a given stimulus, then sure, you don't need to test anything out in vivo. But the reason we do experiments is that we don't know how the liver will react in a given circumstance, so we can't rely on known equations to tell us the answer.

I also think that while there are circumstances where animal models are not helpful, those tend to make the news because they are the exception rather than the rule. There are many, many diseases where animal models were critical for figuring out at least where to look for human disease processes. In addition, a lot of the issues with mouse models are not due to the fact that mice are inherently a poor substitute for humans, but that the models (the specific genes mutated) were a poor mimic of human diseases. For example: "Measurements of gait and grip strength showed that their muscle deficits were in fact mild, and post-mortem examination found that the animals died not of progressive muscle atrophy, but of acute bowel obstruction caused by deterioration of smooth muscles in the gut." [https://www.nature.com/articles/507423a]