Friday Night Futureposting
ASOs/siRNA & mRNA therapies are baby steps into a much broader world of tissue targeted RNA modulation
More of this gene, less of that one but only in cells with X surface marker but without Y miRNA
How much of a dinosaur genome can you reconstruct from comparative interpolation up the phylogenetic tree from more primitive birds (to a root of emus, cassowaries, &c) and down from common ancestor of crocodilians, turtles &c?
(evolutionary protein LMs, do your thing)
...and do they ever get colonized by a genetically distinct sub-unit? Are there chimeric man-o-wars?
...if siphonophores are clonal and cooperate enough to look like a single animal externally, why aren't they just considered a very compartmentalized multi-cellular organism? What's different?
Why is IPD-MHC so spotty? Where do I find a sequence collection of snake or frog MHCs? Or is this just poorly mapped biology with too few known genes/alleles to make it worth adding to a database?
If you squint at common vaccine LNPs their composition isn't dramatically different from the lipids of a cell membrane (mostly cholesterol, choline phospholipids, minority helper vs sphingolipids)
So what's the napkin math count of lipid molecules per fat blob? ~10^9 vs. ~10^5?
CLAUDE.md based on this thread: x.com/bcherny/stat...
Is PCSK9 a vestigial protein?
Which other ones are disposable in a modern nutritional context?
I’m sure this is barbarically primitive but my current coding setup is one terminal tab per repo with Claude Code (Opus high) and a Boris CLAUDE.md with some tweaks and nudges for bio research (occasionally breaking out Codex xhigh for mathier focused debugging)
Persian/Iranian book recs?
I guess a distant #3 is replacing 99% of white collar / knowledge work with subscription based intelligence, but I think that's much more commoditizable and long term less profitable than #1/#2 (so not where companies that have soaked up so much investment can dwell too long)
AI endgame is a macro "kill every human autonomous bot swarm" super-weapon and micro "kill every pathogen & misbehaving cell" generative medicine immortality box.
Unclear whether same company will own both.
(but if Anthropic is opting out of #1, they have to do #2)
I dunno, but it’s the kind of hubris that kicked our butts in Hammer Lab
“Suppose it takes a year for the clinical trials to work before you’re getting revenue from drugs”
LOL
Making myself finish the Dario/Dwarkesh podcast bc it feels important to hear a main character interview but…it’s surprisingly thin. Maybe I’m already too familiar with his essays and he’s otherwise holding cards close?
open-source the means of production
Starting to see cracks emerging all over the traditional models of drug development, clinical trials, treatment/delivery, “reimbursement”.
It’s chaotic but generally patient agency seems to be increasing alongside rate of medical progress.
Like emerging from a long dark tunnel
Emotionally, going from CS to biomed is rough.
Everything is slower, hierarchical, bureaucratized, entrained in Byzantine incentive structures, pay is bad for important roles bc of a tax on passion, public comms obfuscates behind concern for patients, &c
word of the day: eutectic ice
www.science.org/doi/10.1126/...
pubmed.ncbi.nlm.nih.gov/12448990/
Trial was revised many times, some of which look deeply confounding
eg v6 to v7 changed trial from observational to interventional and from immunotherapy alone to immunochemotherapy
@quaidmorris.bsky.social want to collab? We have a long read RNA variant extraction tool that gives me all differences from reference in long read single cell RNA seq.
I want to pull this apart into {somatic, germline, noise} by EM (alternating with cell clustering). Does this already exist?
Luckily/unluckily the trial looks very unsound
If you want any kind of say in what kinds of social rules and norms get put around a new technology you have to at least understand what it is.
Like, cars had a hideously distorting effect on the urban fabric of most countries but there’s no way you to mitigate that outcome by denying they go fast
Like, agriculture was like this (read Against the Grain), creating both oppressive social hierarchy and ecological destruction. Pastoralism / animal husbandry was even more ecologically destructive. Mining, metallurgy, industrial manufacturing, fossil fuels, plastics, &c
Yes!
We live atop a big stack of very destructive and society-rearranging technologies which are also inseparable from our material culture and standards of comfort. I guess a new one can be hard to think clearly about but there’s so much precedent.
I don’t understand why it’s difficult though.
Like, you can just try out all the tools and see what they’re good at, then think a little bit about the consequences
The social direction will be hyper-oligarchy -because- the tools are useful. If someone can’t see that it’s very weird
Moralizing AI to the point of refusing to understand it seems like such a political miss.
Biggest realignment of capital / labor / social norms & institutions in a long time…
I don’t think that’s quite right though, my Max & Pro subscriptions are squarely opex, just not wages. It’s turning labor into SaaS opex (except for the handful of companies serving the models, who have to spend a Manhattan project on capex)
I think this will be a big unlock for us.
Working on: EM alternating estimation of cluster membership vs variant category assignment
And, not just recycling cliches or circularly referencing a pile of claims based on that one time someone tried 4o and it was somehow immoral
Like, who’s got Codex running in six tabs but is also talking about the social trend lines or even organizing towards the coming challenges?
