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Astral Codex Ten Podcast

Jeremiah
Astral Codex Ten Podcast
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  • Suddenly, Trait-Based Embryo Selection
    [see footnote 4 for conflicts of interest] In 2021, Genomic Prediction announced the first polygenically selected baby. When a couple uses IVF, they may get as many as ten embryos. If they only want one child, which one do they implant? In the early days, doctors would just eyeball them and choose whichever looked healthiest. Later, they started testing for some of the most severe and easiest-to-detect genetic disorders like Down Syndrome and cystic fibrosis1. The final step was polygenic selection - genotyping each embryo and implanting the one with the best genes overall. Best in what sense? Genomic Prediction claimed the ability to forecast health outcomes from diabetes to schizophrenia. For example, although the average person has a 30% chance of getting type II diabetes, if you genetically test five embryos and select the one with the lowest predicted risk, they’ll only have a 20% chance2. Since you’re taking the healthiest of many embryos, you should expect a child conceived via this method to be significantly healthier than one born naturally. Polygenic selection straddles the line between disease prevention and human enhancement. In 2023, Orchid Health entered the field. Unlike Genomic Prediction, which tested only the most important genetic variants, Orchid offers whole genome sequencing, which can detect the de novo3 mutations involved in autism, developmental disorders, and certain other genetic diseases. Critics accused GP and Orchid of offering “designer babies”, but this was only true in the weakest sense - customers couldn’t “design” a baby for anything other than slightly lower risk of genetic disease. These companies refused to offer selection on “traits” - the industry term for the really controversial stuff like height, IQ, or eye color. Still, these were trivial extensions of their technology, and everybody knew it was just a matter of time before someone took the plunge. Last month, a startup called Nucleus took the plunge. https://www.astralcodexten.com/p/suddenly-trait-based-embryo-selection
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  • My Heart Of Hearts
    I promised some people longer responses: Thomas Cotter asks why people think “consistency” is an important moral value. After all, he says, the Nazis and Soviets were “consistent” with their evil beliefs. I’m not so sure of his examples - the Soviets massacred workers striking for better conditions, and the Nazis were so bad at race science that they banned IQ tests after Jews outscored Aryans - but I’m sure if he looked harder he could find some evil person who was superficially consistent with themselves. Hen Mazzig on Twitter is suspicious that lots of people oppose the massacres in Gaza without having objected equally strenuously to various other things. Again, he’s bad at examples - most of the things he names are less bad than the massacres in Gaza - but I’m sure if he looked harder he could find some thing which was worse than Gaza and which not quite as many people had protested. Therefore, people who object to the massacres in Gaza must be motivated by anti-Semitism. An r/TrueUnpopularOpinion poster argues that No One Actually Cares About Gaza; Your Anger Is Performative. They say that (almost) nobody can actually sustain strong emotions about the deaths of some hard-to-pin-down number of people they don’t know, and so probably people who claim to care are virtue-signaling or luxury-believing or one of those things. Since 2/3 of these are about Gaza, we’ll start there. And since there’s so much virtue-signaling and luxury-believing going around these days, I assure you that what I am about to share is my absolute most honest and deepest opinion, the one I hold in my heart of hearts.  https://www.astralcodexten.com/p/my-heart-of-hearts  
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  • Your Review: The Astral Codex Ten Commentariat (“Why Do We Suck?”)
    Jul 26, 2025 Finalist #5 in the Review Contest [This is one of the finalists in the 2025 review contest, written by an ACX reader who will remain anonymous until after voting is done. I’ll be posting about one of these a week for several months. When you’ve read them all, I’ll ask you to vote for a favorite, so remember which ones you liked] Introduction The Astral Codex Ten (ACX) Commentariat is defined as the 24,485 individuals other than Scott who have contributed to the corpus of work of Scott’s blog posts, chiefly by leaving comments at the bottom of those posts. It is well understood (by the Commentariat themselves) that they are the best comments section anywhere on the internet, and have been for some time. This review takes it as a given that the ACX Commentariat outclasses all of its pale imitators across the web, so I won’t compare the ACX Commentariat to e.g. reddit. The real question is whether our glory days are behind us – specifically whether the ACX Commentariat of today has lost its edge compared to the SSC Commentariat of pre-2021. A couple of years ago Scott asked, Why Do I Suck?. This was a largely tongue-in-cheek springboard to discuss a substantive criticism he regularly received - that his earlier writing was better than his writing now. How far back do we need to go before his writing was ‘good’? Accounts seemed to differ; Scott said that the feedback he got was of two sorts: “I loved your articles from about 2013 - 2016 so much! Why don’t you write articles like that any more?”, which dates the decline to 2016 “Do you feel like you’ve shifted to less ambitious forms of writing with the new Substack?”, which dates the decline to 2021 Quite a few people responded in the comments that Scott’s writing hadn’t changed, but it was the experience of being a commentor which had worsened. For example, David Friedman, a prolific commentor on the blog in the SSC-era, writes: A lot of what I liked about SSC was the commenting community, and I find the comments here less interesting than they were on SSC, fewer interesting arguments, which is probably why I spend more time on [an alternative forum] than on ACX. Similarly, kfix seems to be a long-time lurker (from as early as 2016) who has become more active in the ACX-era, writes: I would definitely agree that the commenting community here is 'worse' than at SSC along the lines you describe, along with the also unwelcome hurt feelings post whenever Scott makes an offhand joke about a political/cultural topic. And of course, this position wasn’t unanimous. Verbamundi Consulting is a true lurker who has only ever made one post on the blog – this one: Ok, I've been lurking for a while, but I have to say: I don't think you suck… You have a good variety of topics, your commenting community remains excellent, and you're one of the few bloggers I continue to follow. The ACX Commentariat is somewhat unique in that it self-styles itself as a major reason to come and read Scott’s writing – Scott offers up some insights on an issue, and then the comments section engages unusually open and unusually respectful discussion of the theme, and the total becomes greater than the sum of the parts. Therefore, if the Commentariat has declined in quality it may disproportionately affect people’s experience of Scott’s posts. The joint value of each Scott-plus-Commentariat offering declines if the Commentariat are not pulling their weight, even if Scott himself remains just as good as ever. In Why Do I Suck? Scott suggests that there is weak to no evidence of a decline in his writing quality, so I propose this review as something of a companion piece; is the (alleged) problem with the blog, in fact, staring at us in the mirror? My personal view aligns with Verbamundi Consulting and many other commentors - I’ve enjoyed participating in both the SSC and ACX comments, and I haven’t noticed any decline in Commentariat quality. So, I was extremely surprised to find the data totally contradicted my anecdotal experience, and indicated a very clear dropoff in a number of markers of quality at almost exactly the points Scott mentioned in Why Do I Suck? – one in mid-2016 and one in early 2021 during the switch from SSC to ACX. https://readscottalexander.com/posts/acx-your-review-the-astral-codex-ten 
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  • Apply For An ACX Grant (2025)
    We’re running another ACX Grants round! If you already know what this is and just want to apply for a grant, use the form here (should take 15 - 30 minutes), deadline August 15. If you already know what this is and want to help as a funder, VC, partner charity, evaluator, or friendly professional, click the link for the relevant form, same deadline. Otherwise see below for more information. What is ACX Grants? ACX Grants is a microgrants program that helps fund ACX readers’ charitable or scientific projects. Click the links to see the 2022 and 2024 cohorts. The program is conducted in partnership with Manifund, a charity spinoff of Manifold Markets, who handle the administrative/infrastructure side of things. How much money is involved? I plan to contribute $200K. I expect (but cannot guarantee) an additional $800K from other donors, for a total of about $1 million. Most grants will probably be between $5,000 and $50,000, with a rare few up to $100,000. Depending on how much external donor interest there is, we will probably give between 10 and 50 grants. What’s the catch? There’s no catch, but this year we plan to experiment with replacing some grants with SAFEs, and others with convertible grants. That means that if you’re a startup, we (ACX Grants as an nonprofit institution, not me personally) get some claim to future equity if you succeed. If you’re not a startup, you’ll sign an agreement saying that if your project ever becomes a startup, then we’ll get the equity claim. We’re still working on the exact details of this agreement, but we intend to have pretty standard terms and err in the favorable-to-you direction; obviously we’ll show you the final agreement before you sign anything. We’re doing this because some of our previous grantees became valuable companies, and it seems foolish to leave that money on the table when we could be capturing it and reinvesting it into future grants rounds. Please don’t let this affect your decision to apply. Our top priority remains charity, and we’ll continue to select grantees based on their philanthropic value and not on their likelihood of making us money. If you’re not a startup and don’t plan to become one, none of this should affect you. And if you have a good reason not to want to sign these agreements - including “I’m not savvy enough to know what this means and it makes me nervous” - then we’re happy to opt you out of them. What’s the timeline? We’d like to have grants awarded by October 1 and money in your hands by November 1. This is a goal, not a promise. What will the application process be like? You fill out a form that should take 15 - 30 minutes. If we have questions, an evaluator might email or call you, in a way that hopefully won’t take more than another 15 - 30 minutes of your time to answer. If you win a grant, Manifund will send you the money, probably by bank wire. Every few years, we might ask you to fill out another 15 - 30 minute form letting us know how your project is doing. What kind of projects might you fund? There are already lots of good charities that help people directly at scale, for example Against Malaria Foundation (which distributes malaria-preventing bed nets) and GiveDirectly (which gives money directly to very poor people in Africa). These are hard to beat. We’re most interested in charities that pursue novel ways to change complex systems, either through technological breakthroughs, new social institutions, or targeted political change. Among the projects we’ve funded in the past were: Development of oxfendazole, a drug for treating parasitic worms in developing countries. A platform that lets people create prediction markets on topics of their choice A trip to Nigeria for college students researching lead poisoning prevention. A group of lawyers who sue factory farms under animal cruelty laws. Development of software that helps the FDA run better drug trials. A startup building anti-mosquito drones to fight tropical disease A guide for would-be parents on which IVF clinics have the highest successful rate of successful implantation. A university lab working on artificial kidneys You can read the full list here and here, and the most recent updates from each project here. Is there anything good about winning an ACX Grant other than getting money? You’ll get my support, which is mostly useful in getting me to blog about your project. For example, I can put out updates or requests for help on Open Threads. I can also try to help connect you to people I know. Some people who won ACX Grants last year were able to leverage the attention to attract larger grantmakers or VCs. You can try to pitch me guest posts about your project. This could be a description of what you’re doing and why, or just a narrative about your experience and what you learned from it. Warning that I’m terrible to pitch guest posts to, I almost never go through with this, and I’m very nitpicky when I do. Still, you can try. We’re working on gathering a network of friendly professionals who agree to provide pro bono or heavily discounted support (eg legal, accounting, business advice, cloud compute) to ACX grantees. We’ve only just begun this process and it might not actually materialize. There are occasional virtual and physical meetups of ACX grantees; these don’t always result in Important Professional Connections, but are pretty interesting. What if I want those nonfinancial benefits for my project, but don’t need money? Apply for a grant of $1. But we’re pretty nervous about giving very-low-cost grants because it’s too easy to accept all of them and dilute our signaling value; for this reason, it might be harder to get a grant of $1 than a grant of $5,000, and we expect these to make up only 0 - 10% of our cohort. You might be better off coming up with some expansion of your project that takes $5,000 and applying for that. What are the tax implications of an ACX Grant? Consult your accountant, especially if you live outside the US. If you live inside the US, we think it’s ordinary taxable income. If you’re an individual, you’ll have to pay taxes on it at your usual tax rate. If you’re a 501(c), you’ll get your normal level of tax exemption. I want to fund you, how can I help? For bureaucratic reasons, we’re currently looking for donations mostly in the $5,000+ range. If that’s you, fill out the Funder Application Form. If we’ve already talked about this over email, you don’t need to fill out the form, but we encourage you to do so anyway so we know more about your interests and needs. What’s the story behind why you have $200K to spend on grants every year, but are still asking for more funding? Some generous readers sent me crypto during the crypto boom, or advised me on buying crypto, or asked to purchase NFTs of my post for crypto. Some of the crypto went up. Then I reinvested it into AI stocks, and those went up too. I think of this as unearned money and want to give some of it back to the community, hence this grants program. I have a lot of it but not an unlimited amount. At the current rate, I can probably afford another ~5 ACX Grants rounds. When it runs out, I‘ll just be a normal person with normal amounts of money (Substack is great, but not great enough for me to afford this level of donation consistently). My hope is that I can keep making these medium-sized donations, other people can add more to the pot, and we’ll be able to drag this out at least five more rounds, after which point maybe we’ll come up with another plan. I’m a VC, how can I help? Some of our applicants are potentially-profitable startups, and we decide they’re a better match for VC funding than for our grants. If you’re willing to look these over and get in touch with any that seem interesting, fill out the VC Application Form. It will ask for more information on what kind of opportunities you’re interested in funding. I’m a philanthropist or work at a philanthropic foundation; how can I help? Some of our applicants are good projects, but not a good match for us, and we want to shop them around to other philanthropists and charities who might have different strengths or be able to work with larger amounts of money. If that’s you, please fill out the Partner Charity Application Form I’m good at evaluating grants, or an expert in some specific field; how can I help? If you have experience as a grantmaker or VC, or you’re an expert in some technical field, you might be able to help us evaluate proposals. Fill out the Evaluator Application Form. By default we expect you’ll want us to send you one or two grants in your area of expertise, but if you want a challenge you can request more. If we’ve already talked about this over email, you don’t need to fill out the form, but we encourage you to do so anyway so I know more about your interests and needs. We expect to get more volunteers than we need, and most people who fill in the evaluator form won’t get contacted unless we need someone from their specific field. I’m a professional who wants to do pro bono work for cool charities, how can I help? Fill out the Friendly Professional Application Form. If we get enough applicants, we’ll compile them into a directory for our grantees. I participated in the Impact Certificate Market last year, did you forget about me? Yes until Austin Chen reminded me last month No! Request final oracular funding by filling in the Impact Applicant Form. Sorry, I forgot, where do I go to apply for a grant again? See form here. Please apply by 11:59 PM on August 15th. https://www.astralcodexten.com/p/apply-for-an-acx-grant-2025
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  • Press Any Key For Bay Area House Party
    [previously in series: 1, 2, 3, 4, 5, 6] It is eerily silent in San Francisco tonight. Since Mayor Lurie's crackdown, the usual drug hawkers, catcallers, and street beggars are nowhere to be seen. Still, your luck can’t last forever, and just before you reach your destination a man with bloodshot eyes lurches towards you. You recognize him and sigh. "Go away!" you shout. "Hey man," says Mark Zuckerberg, grabbing your wrist. "You wanna come build superintelligence at Meta? I'll give you five million, all cash." "I said go away!" "Ten million plus a Lambo," he counters. "I don't even know anything about AI!" you say. "I'll pay you fifty million to learn." “F@$k off!”
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About Astral Codex Ten Podcast

The official audio version of Astral Codex Ten, with an archive of posts from Slate Star Codex. It's just me reading Scott Alexander's blog posts.
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