D W

Timelines for scooping good data is a long one - that is still the fundamental role of the VC. Now I believe you'll need to be in the lab with entrepreneurs; seeing the data for yourself (and funding the work that creates it) More risk, more reward for being right - know where the puck is going

i’ve been reflecting on how much my own behavior has shifted from reading scientific papers to asking AI to interpret the literature. as LLMs get better, more of our interaction with knowledge is mediated through generated summaries rather than primary sources. that shift is not just about how we consume information. it undermines the economic layer that has historically funded truth generation, across both journalism and science. in news, if LLMs can produce infinite “journalism-like” articles, the marginal value of content collapses. subscriptions erode, ads weaken. when anyone can generate something that looks like reporting, the institutions that fund actual reporting, including investigation, sourcing, and verification, start to break. the traditional business model was already cracking, and AI may collapse it entirely. in science, the same dynamic plays out. if LLMs can generate “paper-like” PDFs, the supply of plausible research explodes and signal is lost in the noise. journals and citations, already imperfect proxies for truth, become even less reliable. when publishing is cheap, it stops being a meaningful filter for correctness. the incentive shifts toward producing more papers, not more correct ones. the core issue is that our systems reward the production of content, not the generation of truth. journalists get paid to publish, not to be right. researchers are rewarded for output, filtered through peer review systems with no skin in the game. reviewers do not profit from identifying important work or lose from endorsing weak work. prediction markets offer a different architecture, one that shifts incentives from output to accuracy. instead of rewarding publication, markets reward correct forecasts. if you uncover a scoop, generate a dataset, or replicate a result, you can monetize that knowledge directly by taking a position in a market tied to the truth, then revealing the information. this changes the unit of value. it is no longer a paper or article, but a resolved question, such as whether a clinical trial succeeds or a result replicates. anyone who can answer these questions early, including journalists, researchers, labs, and AI agents, has an incentive to do the hard work of discovery and verification. this is particularly powerful for science. today, novelty is rewarded over correctness. replication is undervalued, and null results never get published. in a market system, the incentives flip such that shorting a flashy result or replicating an overlooked finding are profitable. the broader shift is that journals, news outlets, and preprint servers become oracles feeding into markets, rather than the primary locus of value capture. the economic reward flows to whoever is most accurate about reality before it is obvious. AI makes content cheap, which makes correctness more valuable. prediction markets may be one of the first mechanisms that directly reward it.

@Biohazard3737 that was fast

@docrodwong Just listened to John on Invest Like the Best - biotech not mentioned but an obvious cognitive dissonance around how he views regulations in other industries - rules for thee but not for me mindset

this is the first major mention i've seen of arnold venture's influence on this fda. arnold is said to be have been a major backer of prasad's research (i don't have proof of this, have just been told many times), and as wsj notes, szarama worked at arnold before prasad brought her in. most aren't aware arnold ventures was the major backer of ICER, the group that defines the value of medicines for the UK (which is set at a cap of roughly 30k pounds per human life year). it is also the reason the UK has dropped below basically all other developed countries when it comes to access to rare disease medicines. in short, arnold doesn't believe rare disease medicines are worth it, and it's natural to conclude prasad and others were bringing that philosophy to fda. now it's fine to have that view as a society (as the UK chooses to), but the trump administration represented the opposite, which is to accelerate access to rare disease medicines. wsj.com/opinion/one-ex…

@PersimmonTI A bad time in eight words or less!

post hoc analyses and modified intent to treat yay

@Biohazard3737 Good flag, big challenge of parenthood is managing fears of your kids - no matter how real the risks are, it’s never easy. Hope you were able to alleviate it. I had some pretty irrational fears as a kid - I was given self help books to manage, hopefully you did better.

@davidycli i see, you’re suggesting scale will overpower biology and inadvertently create novel compounds as exhaust This would be a shift for sure (and no doubt coming) from the current style of only creating “novelty” on things that have shown to work in the US - not quite copycat, not quite new target biology exploration

Don’t disagree that clinical proximity helps drive novelty, but Chinese companies can 1) crank out more mlcs on riskier, early discovery / non clinically validated targets or 2) apply combinations of targets to existing modalities eg trispecifics or 3) bring novel modalities to validated targets / mechanisms In next 5 years they will develop capabilities to do deep sequencing and biology exploration to find truly novel targets at scale (already seeing happening one off)

the one unequivocal advantage that US biotech has over China biotech is proximity to clinical practice in the largest, deepest payor market in the world we know exactly what the treatment paradigm is. we know what the patients with most unmet need actually need. we know what the delta is between being successful in a 2nd or 3rd line therapy in every signfiicant market. in short, we know the clinical target product profile and the exact patient population that needs it the path to domination in the biopharma world still runs through the clinic (as always). we need to double down on this advantage

@davidycli @tjparker Honest question; how do China assets come to novelty without proximity to the clinic? Clinical challenge is what originates novel solutions to problems -

@tjparker The problem is the majority of assets coming out of China on a go fwd basis will not be look-alike molecules at all, they will have novelty of some form, either target or modality wise

@orrdavid @SowingAlphaSeed We all hit that phase where it’s about maintenance and injury prevention - don’t learn that you’re in that phase by hurting yourself lifting too heavy!

@SowingAlphaSeed I really need to get more consistent back in the gym. I don't think I"ll lift super heavy again in my life though.

My office is just a little less elegant than @orrdavid's. Finally got the rack set up. First time benching with a barbell since my latest kid was born in July. Gonna be sore...

WE ARE GOING TO WIN!

one dictator is luck two dictators is skill

@WillManidis Societal curse of wanting the promise land without doing the work…. The work is the middle game, but it is also where all the salvation, joy, and peace is found

AI will fail at messaging to their consumers in a similiar way to the failure of the biotech/pharma industry

@Biohazard3737 I think they are very constrained by their ability to generate novel modalities/functionality in biologics - improving affinity and half-life ain't gonna cut it in the market

@Biohazard3737 not reported

@Biohazard3737 a faster lap time

Information we generate with just a few movements of the thumbs (AI), will always be inferior to information created through understanding the liturgy

@sharkbiotech The volatility is opportunity - it isn't easy but I think it is a completely different game to be played to make money these days. You've got to be tax inefficient and ruthless!

was just thinking that we are used to good markets or bad markets this is neither its just a very difficult market

@WillManidis I leave a few in here arnd there just so people have proof of life

typos are increasingly proof of work for humanity

@dalibali2 I thought nobody drank booze anymore

Vibe code this nerds