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James_Miller comments on What is the future of nootropic drugs? Why can't there be ones more effective than ones that have existed for 15+ years? - Less Wrong
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Comments (20)
If it was easy to make a human brain work better by tweaking a few chemicals, evolution probably would have done it.
Then why are some people so much smarter than others?
Probably because of different genes, which are thousands, and different early development wiring and education. It can't be replaced by a few drugs.
Miller's point being that those thousands of genes can easily be driven to fixation by evolution within a fairly short time, yet have not, and it's not clear from the GWASes yet if they're even under directional selection.
Right now, between the GCTAs and the failure to find lots of important rare variants affecting intelligence such as mutation load (eg no Swedish paternal age effect, unlike many disorders), the consensus seems to be swinging towards some sort of frequency-dependent or stabilizing selection: greater intelligence comes with some sort of fitness penalty (greater energetic consumption?) or maybe greater vulnerability to developmental disruption through poor environment and so a net disadvantage which favors poorer but more robust variants (and eventually, canalization). Given the accumulation of archaic & ancient genomes and further intelligence GWASes, we may be able to get a definitive answer to the old puzzle of why intelligence is heritable at all in the next few years.
Hence my old point about nootropics: for the effective ones, the reason the evolutionary argument fails may simply be that they require more metabolic resources which would be a fitness disadvantage but that no longer applies in the modern calorie-overload environment.
I believe CronoDAS is referring to Algernon's Law. Gwern describes the issues pretty well here, including several classes on "loopholes" we might employ to escape the general rule.
The classifications of different types of loopholes is still pretty high level, and I'd love to see some more concrete and actionable proposals. So, don't take this as saying "this is old hat", but only as a jumping off point for further discussion.
We know that the variation in any single locus is responsible for < 1/100 of the variance of IQ. If genes corresponded to drugs, then that gives an upper bound on the efficacy of drugs. I think that we can agree that 100 does not counts as "a few."