[salt-licker]

Well-written post, but the suggested solution of HTS on mice is nonsensical. First of all, we’ve cured cancer in mice many times but it’s obviously still unsolved in humans. Secondly, you’re constraining yourself to synthesized chemical space, which as others have mentioned is a grain of sand (charitably 10^10 in human history) compared to a planet’s worth (10^60 by some estimates) of possible druglike molecules.

Target ID is hard, but we also have known biologically valid targets that are simply undruggable so far (KRAS is the most obvious example). Solving computational chemistry problems is a much more tractable, high-leverage endeavor. And we can in fact use that progress to accelerate biological research itself — for example, quickly developing bioavailable tool compounds via virtual screen to test biological hypotheses in mice, a rational “pharmacological knockout” approach.

We can reduce the biological space in a smart way, we don’t have to brute force this.