The example that I really like is the drug Lyrica. It came from research at Northwestern. Made total sense, take a neurotransmitter (GABA) and modify it so it blocks the GABAase enzyme. Perfect! You get more GABA floating around.

The drug made it all the way to market until some folks realized, it doesn't work via GABA at all. It actually impacts the glutamate neurotransmitter.

So much for rational drug design!

Yeah biology is sophisticomplexicated. But I believe mostly because of wrong approach and tools. Maybe this era will provide finer views and better abstractions to think about cells, organs, etc.