The Ledger
Every statement that passed quotation and attribution checks. Mix any filter with any other: certainty 1/5, debate potential 5/5, or both at once.
why aren't all 967 resolved? a statement only gets an assessment when the public record can support or contradict it. opinions and what-ifs never can, and 26 checkable ones are still open, waiting for their date. predictions held up or didn't; assertions are supported or contradicted. on every card: ▮▮▮▮▮ certainty · ▮▮▮▮▮ debate potential. speakers are clickable
Depledge: UK healthtech moves to US due to NHS procurement friction
“Most of the reason that our health tech companies leave and go to the US is not because they can't raise the money. It's because the NHS makes them jump through about a billion different hoops to get onto their, like, framework, and it's just much easier to go…”
DeWahl: Nuclear power must target premium buyers like the military and hyperscalers
“And so we believe, I believe that, you know, premium power is where you need to go with nuclear, and there's sort of like two, there's two places for that. One is what we're doing with Antares, which is go to the military, help them with mission critical need …”
DeWahl: 100% 24/7 solar and battery storage costs rival nuclear
“Actually to get true hundred percent, 24 seven coverage, the battery or the excess build out is massive. It is really expensive. It's on, it's like basically on par with nuclear costs.”
DeWahl: Antares is not using DARPA because micro-reactors lack fundamental technical novelty
“We are not working with DARPA mostly because it's actually not as technically risky as you might even think, like even. ... Like we actually, in a funny way, like it's not even really a tech problem. ... You know, I mean, it's hard to build these things, but i…”
DeWahl: Three Mile Island accident was completely overblown
“Well, it was an accident, but it was not really a big deal. Like, this much radiation came out, it was like this amount of a chest x-ray. Yes, completely overblown.”
Nadella: Neural networks and compute solve enterprise data, not complex schemas
“In fact, one of the longest time we used to always obsess about, oh, how complex do the relationships have to be, or the data model needs to be to capture the essence of an enterprise, right? And it turns out, It's lots of parameters in the neural network with…”
Nadella: Separating cognitive core from knowledge enables continual learning
“If you kind of have the model's cognitive core separated from its knowledge, then you have essentially the continual learning, you know, formula, so to speak, or the algorithm, and then you just unleash it.”
Nadella: AI agents will create their own RL environments
“Right now, for the RL loop, they are simulating our production environment, but they will ultimately be more efficient in creating their own production environments to kind of RL themselves.”
Nadella: Next IDE will be born in autonomous PR triage
“One of the things that we are experimenting with this mission control in GitHub Copilot is that, right, which is, well, the idea is you go have five, six different branches in which you fire off all these autonomous agents, they all do their work, they come ba…”
Nadella: AI infrastructure has immediate demand unlike dot-com dark fiber
“The infrastructure itself that's getting laid out. I think it's got a lot more more immediate. Like, it's not like even the, you know, the gestation period of, okay, I built up, you know, dark fiber, which, and, you know, some internet company will first scale…”
Nadella: Future companies will have their own proprietary foundation models
“The future of a company is that company has its own foundation model that captures essentially the tacit knowledge that makes the transactional costs of how knowledge gets accrued and diffused inside the organization faster.”
Nadella: The future of AI agents is ensembles with intelligent routing
“That ultimately is where, you know, the future of agents would be, right? And so therefore you want the model. In fact, you want an ensemble. Of models that then, you know, you have agents intermediating that ensemble so that it meets your needs.”
Nadella: Social cohesion is not the goal in business; winning is
“Social cohesion is not a goal, right? Winning in the marketplace is a goal. But at some level, you have to orchestrate these large organizations. In fact, you may even have two competing teams by design.”
Nadella: Non-founder CEOs can use 're-founder mode' but aren't founders
“Then mere model CEOs like us have to sort of also be, you know, you can sort of be in the re-founder mode, but don't think you're a founder. And that, that nuance I think is an important one.”
Ricks: Machine-designed drugs haven't reached clinical trials yet, but are coming
“I don't know of one that's come through the machine driven discovery process, which is really machine plus human that's made it to the clinic yet, but they're coming.”
Ricks: AI won't solve biology until we understand over 50% of it
“And today, I don't know, I would estimate we might know 10 to 15% of human biology. So the machine's not going to be good at all until we get way above 50%.”
Ricks: Claude and xAI beat ChatGPT for science because references check out
“I don't use that one for science actually. It's too, too horrible.
Patrick Collison: So which one do you use for science?
Dave Ricks: I tend to use either Claude or the XAI one. I find it more terse. And more, the references actually check out more often.”
Ricks: Lilly's industry-leading R&D ROI comes from process, not picking winners
“I think one of the reasons Lilly has probably the highest return on investment in R&D in the industry is because not the picking of winners and losers, but the, actually the process by which we run it.”
Ricks: Cardiovascular trial rules added five years to diabetes drug development
“The Evandia one, we know well, we work in diabetes, actually caused a policy change, and the policy change was you must rule out cardiovascular risk prior to market entry, and as you may know some conditions like diabetes have a more continuous variable you're…”
Ricks: Expensive cardiovascular trial mandates protect GLP-1 incumbents from low-cost competition
“Now, by happy accident, we are all now really pleased with, like, incretins, like our trisepetide to run them because they frequently demonstrate massive benefit. Uncardiovascular. And in some ways, it creates a barrier to entry for the next low-cost Chinese p…”
Ricks: ICER found tirzepatide and semaglutide cost-effective at current pricing
“They just analyzed our medicines, trisepatide and semaglutide, and they said, actually, they're both cost effective at current pricing. In fact, Zepbound or Trisepatide was, the threshold they have is to save a 100,000 dollars per person per year in downstream…”
Ricks: Lilly is considering SaaS-style recurring pricing for common gene therapies
“It's conceivable that one could create like a licensing concept, stealing from the SAS model, where you say, we'll do the procedure for free. And as long as it's working for you will deposit X amount in our bank account, and you're getting the value, and we're…”
Ricks: Medicine accounts for only 10 cents of every US healthcare dollar
“In the US, the most expensive healthcare system in the world, we spend 10 cents on the dollar on medicine. The other 90 cents go through everything else that medicine's trying to prevent.”
Ricks: Lilly's net insulin price stayed near $30 despite $275 list price
“Our actual net on insulin really hasn't changed. It's like 30 or 40 dollars, but the list price got up to two 75.”
Ricks: Early-stage biotechs pitch 80% to 100% of revenue from the US
“If you fund, if you went out and said, hey, I want to back some biotechs, and they sent you their business plan, 80 to a hundred percent of the revenue in return they'll pitch you on is the US. Meaning there is no return outside the US if you start at the poin…”
Ricks: Eli Lilly's chronic knee pain study is going to work
“We have a study reading out toward the end of this year in chronic knee pain. It's going to work.”
Ricks: Taltz plus Zepbound trial is certain to boost psoriasis efficacy
“So we're doing a study with our psoriasis drug, Taltz, and ZepBound. That will read out this fall. And I'm certain we'll show a boost in efficacy with the weight loss.”
Ricks: Pharma must invest 20-25% of revenue in R&D for double-digit growth
“I have a belief that if you're not generating, to generate double digit growth in the sector, you need to invest at 20 to 25% of sales in R&D. That's sort of a good, a positive return R&D stack.”
Abrams: US dollar stablecoins will maintain outsized dominance forever
“I think you're going to see while like, you know, fiat US dollars are x percent of the global market, stablecoin US dollars are going to be, you know, way more forever.”
Trading will shrink to 5% of the stablecoin market, Abrams predicts
“That being said, I think that the trading use, use case was like a hundred percent of the market two years ago was 80% of the market today, and, you know, will be five percent of the market in, in some number of years.”
All corporate treasuries will ultimately move into stablecoins, Abrams predicts
“So I think that ultimately all like corporate treasuries will move into stablecoins.”
Crypto transactions will soon be a large part of Stripe's business
“Crypto enabled transactions are going to be a very large part of the economy and just stripes business in the relatively near future.”
Stablecoin skeptics would not survive long at Stripe, says John Collison
“I don't think they would survive the company very long if someone's walking around like, I don't know, I don't think the stable going thing is going to be a thing.”
Stablecoins will grow 100x from their current scale, predicts John Collison
“People still have no idea how big stable coins are going to be. And I think they discount us because it feels like it's a lot of hype right now, but we're going to look back when stable coins are a hundred times bigger and just think of this moment as so cute.”
Handmer predicts Hyperloop will never happen
“Is Hyperloop ever gonna happen?
[79] Casey Handmer: No.
[80] Casey Handmer: I think I can safely say that now.”
Synthesizing natural gas from air and water is now financially viable
“The solar has gotten so cheap that you can actually kind of do the reverse process, and it makes financial sense, increasingly so over time.”
Synthetic fuel production is 100 times more land-efficient than biological photosynthesis
“Plants are great. Even this plastic one here but their net throughput efficiency is about a hundred times lower than a synthetic process like the one we're using in terms of like, Area of land into reduced carbon fuel.”
Long-range aviation, shipping, and chemicals will remain hydrocarbon-based for decades
“Fast aircraft, big aircraft, long, long range aircraft, hydrocarbons. Probably long range shipping would stay that way. Like LNG, it's just so cheap. It's gonna stay that way for a long time. Paints are gonna stay hydrocarbon based. Chemicals, pesticides, herb…”
AI data centers will inevitably scale on solar and batteries, not nuclear
“It seems pretty clear to me, I think two years ago, I've got a blog post on this saying that, like, we're going to have to go to solar and batteries for AI data centers at scale and back then everyone was still talking about, like, oh, we're going to build SMR…”
Handmer: Solar panel manufacturing costs will fall to four cents a watt
“They could probably see line of sight to, like, another two extra action in cost. So we go from eight cents a watt down to four cents a watt.”
The laws of physics allow solar panels to become 10 times cheaper
“The limit of physics on how cheap a solar panel can be is, like, at least 10 times cheaper than it currently is.”
China's electrification will end its dependence on Strait of Malacca oil
“Do you think by 2035 China is still going to be as dependent on oil through the Strait of Malacca? I don't. At the rate that they're deploying right now, they could cut off that supply if they needed to.”
Handmer: By-right permitting on private and BLM land would best accelerate solar
“The single biggest intervention you could allow is by right development of solar panels on private land and ideally even like BLM land would be great.”
Handmer: The idea the US is intrinsically uncompetitive in manufacturing is crap
“This whole idea, like, comparative advantage, that the United States should just be intrinsically bad, or, like, uncompetitive at certain kinds of things, is crap. Like, this has every advantage it could possibly want.”
Crazy but repeatedly successful decisions imply a superior model of reality
“If I see someone who is pretty successful do a series of crazy things over and over again, and yet they work out every single time, either they have root access, To the simulation. Or their model of reality is better than mine in some key way that I don't unde…”
SpaceX controls approximately 95% of the global space launch market
“In the space sector, at least, it's quite astounding the extent to which SpaceX is dominant. Right. This is not the case that, like, Apple has, what, 2030, 40% market share in smartphones, and Pixel has 10%, and Huawei and so on has a, this is like, SpaceX has…”