Candidate gene studies are known to be pretty horrible (a vast, vast majority of them do not replicate), and the correct standard are GWASes. My understanding is that your proposed targets DEC2 and ADRB1 are both candidate gene studies, and neither of them show up in the GWAS Catalog (https://forum.effectivealtruism.org/posts/nSwaDrHunt3ohh9Et/cause-area-short-sleeper-genes?commentId=GCQf5qjG4LyEdEJov). Given that, I am quite skeptical of your specific gene targets. I am unfamiliar with the literature though and haven't read any of the references in your bibliography, and would change my mind if there has been any GWAS-based evidence in favor of DEC2 and ADRB1 recently (none showed up in the GWAS Catalog 2 years ago, according to the above EA forums). With that said, I'm very excited about the idea of sleep-reduction (and thank you for doing this work), and I'd be much more optimistic about this project if your gene targets were chosen via GWAS.

I would suggest reaching out to Andrej Karpathy: https://karpathy.bearblog.dev/finding-the-best-sleep-tracker/

wishing you many sleepless nights!

if you think about it correctly, this is the most promising life extension angle available to us

isaak is smart, tenacious, and resourceful

no brainer; fuck it we ball

Important research project! Isaak, Helena are awesome and assembling a great team that should make progress on it

incredible team, great project. we are so back 🔥

Isaak and Helena are some of the kindest and most competent people I've ever met, and I'm really excited that they're working on this.

put me in the screencap

extremely promising

Great, very promising

Accelerate humanity 🫡

seems like a very exciting and promising project

I asked Isaak to put this on Manifund as soon as I saw his proposal:

• I'm anti-sleeping-pilled: I think reducing sleep needs would be very beneficial to the world, and on a personal level have experimented with polyphasic sleep.

• Though I'm no expert in biology and have no insight on how feasible this is, I'm very impressed with the credentials of this team and their advisors.

• I strongly believe in Isaak himself, having worked with him on Future Forum and seen his trajectory since. (We asked him to serve as a Manifund regrantor in 2023.) I'd expect any project that Isaak's on to deliver extraordinary outcomes.

While it's different from the AI safety work that Manifund is mostly known for nowadays, ambitious moonshots like this are what I'm most personally interested in funding, and I'm excited to be able to support this initiative.