Astral Codex Ten Podcast

https://astralcodexten.substack.com/p/links-for-november [Remember, I haven't independently verified each link. On average, commenters will end up spotting evidence that around two or three of the links in each links post are wrong or misleading. I correct these as I see them, and will highlight important corrections later, but I can't guarantee I will have caught them all by the time you read this. PS: Happy Thanksgiving!] 1: The story of Jeff Bezos' biological father, a former circus performer who didn't realize Jeff was his son until well into the 2010s. 2: New type of nominative determinism just dropped (source):

https://astralcodexten.substack.com/p/pascalian-medicine I. When I reviewed Vitamin D, I said I was about 75% sure it didn't work against COVID. When I reviewed ivermectin, I said I was about 90% sure. Another way of looking at this is that I must think there's a 25% chance Vitamin D works, and a 10% chance ivermectin does. Both substances are generally safe with few side effects. So (as many commenters brought up) there's a Pascal's Wager like argument that someone with COVID should take both. The downside is some mild inconvenience and cost (both drugs together probably cost $20 for a week-long course). The upside is a well-below-50% but still pretty substantial probability that they could save my life. (Alexandros Marinos has also been thinking about this, and calls it Omura's Wager) We can go further. The same people behind ivmmeta.com have posted this "meta-analysis" of curcumin, a common spice and oft-mooted panacea: (source) I'm going to guess it's not true, because I've become pretty critical of these people's methodology since doing the ivermectin review. Also, curcumin is a PAIN (pan-assay interference compound, ie a substance with weird chemical properties that make every test seem positive, so if you do chemical tests to see whether it activates eg coronavirus-fighting immune cells, it will always say yes). This means people are always publishing exciting papers about it and alternative medicine people are always getting really enthusiastic about it and suggesting it as the cure for everything (eg depression).

https://astralcodexten.substack.com/p/higlights-from-the-comments-on-ivermectin Thanks to everyone who commented on my recent post Ivermectin: Much More Than You Wanted To Know. Let's start with the negative comments. Leading pro-ivermectin website ivmmeta.com understandably disagreed with my fisking of them. They have a section where they respond to critics (see responses to Gideon Meyerowitz-Katz, to the BBC, to the parasitic worm hypothesis, and to someone named AT who they won't explain further). I was honored to also get a response here. They write: We note a few limitations and apparent biases in the SA/SSC ivermectin analysis. Author appears to be against all treatments, labeling them all "unorthodox" and "controversial", even those approved by western health authorities, including casirivimab/imdevimab, bamlanivimab, sotrovimab, and paxlovid. We encourage the author to at least direct readers to government approved treatments, for which there are several in the author's country, and many more in other countries (including ivermectin). While approved treatments in a specific country may not be as effective (or as inexpensive) as current evidence-based protocols combining multiple treatments, they are better than dismissing everything as "unorthodox". Elimination of COVID-19 is a race against viral evolution. No treatment, vaccine, or intervention is 100% available and effective for all variants — we need to embrace all safe and effective means.

https://astralcodexten.substack.com/p/highlights-from-the-comments-on-the Andrew writes: One word I don't see mentioned anywhere is "manufacturing." It's one thing to make enough drug for a clinical trial, it's another to make millions of commercial doses reliably. FDA approval requires inspection of and confidence in these commercial-scale manufacturing processes. Zutano adds: To expand on this more: the clinical trials only show that *that one particular batch* was safe and efficacious (the FDA thinks this, since they agreed to terminate the trial early). Pfizer must then show that the commercial batches will be identical in every relevant way to the clinical trial batches, so that they will have the same safety and efficacy. What are the relevant ways? Pfizer must decide that, and justify their decisions to the FDA with supporting evidence. Scaling up chemical manufacturing is not trivial (a regular contender for Understatement of the Year). E.g. heating and stirring work differently in different sized reactors. Heat transfer in and out of your reactor works through surface area, but heat produced/consumed by the reaction depends on volume. If your stirrer design isn't right for the viscosity of the solution, you might get hotspots and so on. Ideally, the FDA expects you to understand the chemistry so thoroughly that you know everything that can possibly go wrong, and design your commercial process so that none of these things can possibly happen. The commercial batches will therefore be identical *by design* to the clinical trial batches, and you have to prove this with science.

https://astralcodexten.substack.com/p/when-will-the-fda-approve-paxlovid https://astralcodexten.substack.com/p/when-will-the-fda-approve-paxlovid I. You thought it wasn't going to be a prediction market post, but surprise, it's a prediction market post! Metaculus predicts January 1 as the median date for the FDA approving Paxlovid. They estimate a 92% chance it will get approved by March. For context: a recent study by Pfizer, the pharma company backing the drug, found Paxlovid decreased hospitalizations and deaths from COVID by a factor of ten

https://astralcodexten.substack.com/p/highlights-from-the-comments-on-great Thanks to everyone who commented on last week's post Secrets Of The Great Families. Some highlights: Many people knew of interesting families I'd missed. Stephen Frug brings up the Jameses: Any short list of the great families (or at least the great American families) should include the James's: Henry James is one of the perennial candidates for the greatest American novelist, and his brother William James is one of the perennial candidates for the greatest American philosopher. Their sister Alice James got a posthumous reputation as a diarist. (There were two other brothers who never became famous. Their father, Henry James Sr., had some reputation as a theologian, although not in the Henry (Jr)/William James league. Kalimac writes: Another member of the Darwin family who achieved fame in a different area was the composer Ralph Vaughan Williams, who was on a slightly different branch but was 4 generations down from both Erasmus Darwin and Josiah Wedgwood. Watch out, too, for other cases where the surnames differ. I like to offer the story of Stanley Baldwin, Prime Minister and a leading figure in British politics in the 1920s and 30s. He had a particular ability to deliver powerful and effective speeches, which is perhaps partly explained by some of them having been written for him by his cousin, whose name was Rudyard Kipling.

https://astralcodexten.substack.com/p/ivermectin-much-more-than-you-wanted I know I'm two months late here. Everyone's already made up their mind and moved on to other things. But here's my pitch: this is one of the most carefully-pored-over scientific issues of our time. Dozens of teams published studies saying ivermectin definitely worked. Then most scientists concluded it didn't. What a great opportunity to exercise our study-analyzing muscles! To learn stuff about how science works which we can then apply to less well-traveled terrain! Sure, you read the articles saying that experts had concluded the studies were wrong. But did you really develop a gears-level understanding of what was going on? That's what we have a chance to get here! The Devil's Advocate Any deep dive into ivermectin has to start here:

https://astralcodexten.substack.com/p/mantic-monday-1115 Reciprocal Scoring, Part II I talked about this last week as a potential solution to the problem of long-term forecasting. Instead of waiting a century to see what happens, get a bunch of teams, and incentivize each to predict what the others will guess. If they all expect the others to strive for accuracy, then the stable Schelling point is the most accurate answer. Now there's a paper, by Karger, Monrad, Mellers, and Tetlock - Reciprocal Scoring: A Method For Forecasting Unanswerable Questions. They focus not just on long-run outcomes but on conditionals and counterfactuals. The paper starts with an argument against conditional prediction markets that I'd somehow missed before. Suppose you want to know whether a mask mandate will save lives during a pandemic. Current state of the art is to start two prediction markets: "conditional on there being a mask mandate, how many people will die?" and "conditional on there not being a mask mandate, how many people will die?" In this situation, this doesn't work! Governments are more likely to resort to mask mandates in worlds where the pandemic is very bad. So you should probably predict a higher number of deaths for the mandate condition. But then confused policy-makers will interpret your prediction market as evidence that a mask mandate will cost lives.

https://astralcodexten.substack.com/p/apply-for-an-acx-grant What is ACX Grants? I want to give grants to good research and good projects with a minimum of paperwork. Like an NIH grant or something, only a lot less money and prestige. How is this different from Marginal Revolution's Fast Grants, Nadia Eghbal's Helium Grants, or EA Funds' grant rounds? Not different at all. It's total 100% plagiarism of them. I'm doing it anyway because I think it's a good idea, and I predict there are a lot of good people with good projects in this community who haven't heard about / participated in those, but who will participate when I do it. How much money are you giving out? ACX Grants proper will involve $250,000 of my own money, but I'm hoping to supplement with much more of other people's money, amount to be determined. See the sections on ACX Grants + and ACX Grants ++ below. Why do you have $250,000 to spend on grants? Unsolicited gifts from rich patrons, your generosity in subscribing to my Substack, and the second item here.

https://astralcodexten.substack.com/p/highlights-from-the-comments-on-orban Lyman Stone on Twitter: Twitter avatar for @lymanstonekyLyman Stone 石來民 🦬🦬🦬 @lymanstoneky Here's the @slatestarcodex piece: astralcodexten.substack.com/p/dictator-boo… Overall, I agree with a lot of his assessment of Orban. But I want to quibble on two points: 1) The relationship between dictatorship and democracy 2) "Why admire Orban?" Dictator Book Club: Orban...astralcodexten.substack.com November 5th 2021 7 Likes I won't make you read it all in tweet format. He continues: 1) Dictatorship and democracy. The arguments about Orban cheating in elections might be totally true. I dunno. But that's sort of irrelevant. Neutral opinion polls nobody disputes show he would have gotten 2/3 under almost any system. Image His crude poll share was about 60% before the 2010 election, but given the threshold effects, he'd likely have ended up at a supermajority under almost any system. And as @slatestarcodex [says], a lot of the initiatives that the EU most despises under Orban are initiatives that *everyone agrees* have supermajority public support among Hungarian voters. Moreover, I agree with @slatestarcodex that if public opinion turned in Hungary, Orban would probably turn on a dime too. The dude loves power. But that should inform our read of what's going on in Hungary. *Hungarians wanted* a right-nationalist authoritarian leader, *and so they voted for one*, and the electorate has *wanted* recurrent intensifications of that regime. So is it a dictatorship? Or is it a democracy? This gets at the problem with "democracy" as a concept. Hungary is undeniably Democratic: there is widespread public support for the regime, which is selected by elections, the results of which are a decent approximation of trustworthy and neutral opinion polls. But I think it's still possibly reasonable to call Orban a dictator. He wields enormous *personal* power, there are few checks on his power, and he uses power to create a *personal* clique of supporters to perpetuate that power and enfeeble the competition. But this is the point: Democracy and dictatorship aren't opposites. In fact, they are natural companions! So much so that before the 20th century, "democracy" was often used *literally as a synonym* for "authoritarian and demagogic rule"! Orban is a great example of why the word "democracy" came into ill repute in the past: because it was widely understood that "the people" (often pejoratively "the mob") will often vote for a strongman to stomp his boot on the face of disliked others. That's not so much a disagreement with @slatestarcodex as just a comment where I think the modern western liberal mindset obscures understanding the phenomenon of populist leadership. 2) Why admire Orban? Here I think @slatestarcodex misses some important stuff, perhaps because his biographies miss it. Yes, Orban was incompetent in the 90s. So were MOST immediate post-Soviet leaders! And while Orban may have been corrupt, you can compare the personal wealth of the Fidesz clique to the cliques that looted Russia or Ukraine and realize that Hungary got a better class of corrupt leaders than much of eastern Europe. Moreover, Hungary actually had competitive elections with changes of power and leaders who *respected* those results! Maybe they were dirty but, like, it happened! This wasn't universally true! So why might Hungarians admire a dissident-cum-parliamentarian who competed for their votes and when defeated responded democratically by adapting to try to win the next election? Because.... duh?