I'm officially ending Roote! Proud of the fellows for their relentless energy & curiosity. Proud of myself for creating the How Everything Evolved YouTube series. Grateful to have some time to focus on my health. Full post below. ❤️

This applies beyond founders. From my experience, AI is a superpower in the sense that it enhances, sometimes by a qualitative shift, skills and expertise people already have. The confused, just produce more confused stuff.

For 63 years, medicine couldn’t lower lipoprotein(a). Now everyone is trying at once. Three Phase 3 trials. Over 32,000 patients. 35 countries. Drugs hitting 80 to 94% Lp(a) reduction. The first results from 8,323 patients land this summer. But that’s the injectable chapter. Behind it: -> @EliLillyandCo is testing the first oral Lp(a) pill. No needle. Daily dose. 86% reduction in Phase 2. -> And behind that: gene editing. One infusion. Potentially permanent. -> @CRISPRTX cut Lp(a) by 73% in humans with a single dose (CTX320, Phase 1). -> @editasmed just showed ~90% reduction in primates by editing LDLR regulatory regions instead of the Lp(a) gene itself. -> @EliLillyandCo is developing its own one-time gene edit through Verve. 1 in 5 people carry elevated Lp(a). It’s over 90% genetic. Diet and exercise don’t touch it. 0.1% of Americans have ever been tested (Cleveland Clinic, 71 million records). One blood draw. $25. Once in your life.

New FRO dropping!

Holy Father the post will perform better if you append the url in a threaded reply as opposed to linking it in the tweet

After AlphaGo, the skill of human Go players noticeably improved. I suspect we will see a similar pattern in math.

I’m really excited about the Strep A Vaccine Fund we’re launching today. IMO the basic case here is a great recipe for impact: → A huge problem: ~1% of total annual deaths worldwide (>600k) → Super neglected: ~$14M/yr of R&D globally before this, ~50x less than malaria which has similar mortality → Newly tractable: new human challenge models and earlier diagnostics should speed the path to an approved vaccine Grateful to our partners Adam and Abigail Winkel, Good Ventures, Lucy Southworth, @ThePatchworkCLT, and a few anon donors for getting us to >$140M at launch. We’re continuing to actively fundraise and think we could effectively spend >$200M over the next few years. Our goal is to double the number of Strep A vaccine candidates in clinical trials and have at least one ready for Phase 3 trials by the end of 2030. And I’m thrilled to be betting on Katharine’s vision here! As a grad student, she co-invented the R21 malaria vaccine that’s now reaching millions of kids. I’m hoping to see hundreds of millions of future Strep A vaccine doses with her fingerprints on them.

One shot and you’re protected from heart disease. Imagine that for cancer, dementia and aging

Fukuyama was so prescient. In a society with strong rights and material comfort, but light on demanding shared purposes and some degree of sacrifice, thymotic energies go searching. Some quiet into bourgeois hedonism; other will seek “metaphorical wars” and eventually real ones.

effective altruism ended up being one of the most powerful political movements of the 21st century

I just sequenced a human genome to 30× coverage entirely at home. As far as I know, this is the first time this has been done. I didn’t step foot in a lab once. Every step - from saliva collection, to running the sequencer - took place in a single room with a dining table kitchenette. Six weeks ago, I had never done wet lab biology before. I used an Oxford Nanopore P2 Solo - the only commercially available sequencing device portable enough to do 30x human genome sequencing at home. Biggest takeaway - I could build something that combined software, hardware, and molecular biology far faster than I thought was possible. I can name >100 specific instances where AI helped me solve a technical problem that would previously have blocked me because I lacked access to a domain expert. For example: how do I save my sequencing run when my DNA extraction yield is 4x lower than I need it to be, and I have this limited set of reagents to hand? To make this work, I had to navigate multiple disciplines: - writing software to monitor sequencing runs and orchestrate remote GPU infra for basecalling - learning executing 5 hour long molecular biology protocols - building a hardware device to quantify DNA concentration Apologies for the hyperbole, but I feel super lucky to be living in 2026. A few weeks ago I decided to sequence a human genome to 30x at home. Then I actually did it. And I did it really quickly.

Ok, so I learned that these are called phonesthemes :)

Claude's first day at Dunder Mifflin

Been teaching 3yo to read (inspired by @erikphoel's great posts on the topic). He's into superheroes so I asked Claude to create a Batman story series that uses spaced repetition to practice sight words. His engagement is night and day. You can just dad school.

“oring theory” is true on the individual cognition level especially at high levels of skill. minor differences in energy levels, stamina, focus, emotional stability etc change what you are capable of by orders of magnitude

We're hiring 10 grantmakers and senior generalists across our GCR teams. Most of our capital is bottlenecked on a tiny number of people working to identify, vet, and generate strong funding opportunities. Apply here by May 24: jobs.ashbyhq.com/coefficient…