EA - Cause area: Short-sleeper genes by JohnBoyle

Link to original articleWelcome to The Nonlinear Library, where we use Text-to-Speech software to convert the best writing from the Rationalist and EA communities into audio. This is: Cause area: Short-sleeper genes, published by JohnBoyle on August 10, 2022 on The Effective Altruism Forum. The claim There is decent evidence that there are "short sleeper genes": individual genetic mutations that cause a human to naturally get only 4-6.5 hours of sleep per night (instead of ~8) while remaining healthy, happy, and productive. There don't seem to be any negative side effects, although there might be positive ones. So far, 5 short-sleeper mutations across 4 genes have been identified. Probably at least one of these is a good candidate for developing a drug to mimic the effects of the gene. Such a drug would be enormously valuable. If it worked, presumably it would give people at least one extra waking hour per day, and maybe the "higher resilience and productivity" side effects would be real too. If you care about overall utility, then consider the value of 1 extra waking hour per day, times 365 days per year, and imagine that 100 million people ended up taking the drug; if we say each hour is worth at least $1 (a lowball), then that's $36 billion per year. Just to illustrate the point, if an investment yielding 3% returns were that profitable, the investment would be $1 trillion. Even if you assume the probability of success were as low as 1%, that'd be worth $10 billion. Such an opportunity is clearly worth looking into. The evidence I've skimmed several of the papers on the subject of familial natural short sleepers (FNSS), most of which were written by UCSF professor Ying-Hui Fu and colleagues. (Disclosure: I've emailed Ying-Hui, video chatted with her, and consider her something of a friend.) As I understand it, what they've done is collect people who might be natural short sleepers, validate that they are, look among family members, find candidate short-sleeper genes, and test those genes in mice or similar organisms, and publish papers if an effect is demonstrated in the mice. The DEC2 mutation reduced sleep in mice by about an hour. The ADRB1 mutation reduced by 55 minutes. NPSR1 by 71 minutes, and the two GRM1 mutations (roughly equivalent to each other) by 25 minutes. Ying-Hui says it's expected that the effects in mice are smaller than in humans. All the genes in question are known to affect wakefulness. For example, the DEC2 protein suppresses expression of a neuropeptide called orexin, and mutant DEC2 suppresses it less; orexin is known to promote wakefulness (e.g. people who can't produce orexin are narcoleptic). This part of the mechanism seems reasonably clear. What's less clear is how these genes accelerate the repairs/maintenance the body performs during sleep. (If they did not do any such acceleration, then you'd expect these people to be miserable, unhealthy insomniacs.) But there is at least one experiment that seems to show that they do accelerate some type of repair: They took mice that were engineered to generate amyloid plaques and tau protein tangles—pathologies that seem associated with Alzheimer's disease (though the causality seems unclear and you should take such research with a grain of salt). Anyway, they gave some of them the DEC2 and others the NPSR1 mutations, and found that both genes significantly reduced those Alzheimer-correlated pathologies. Side effects? I'll just directly quote this summary article: [Short sleepers] report greater flexibility around sleep timing and less subjective deficit after sleep deprivation. They often deny experiencing jetlag (unpublished data). However, it is not just sleep duration that characterizes this group of individuals. There is a high behavioral drive among those with FNSS, and individuals report a need to always be mentally active resulting commonly in high profile, high pressure jobs or holding multiple jobs. FNSS individuals also appear to have high pain thresholds and rela...