I believe that 99% of success is just the ability to outlast uncertainty. The one who can tolerate the most uncertainty will eventually win.

Somewhere right now, a person is being given a drug that doesn’t have a name yet. Just a number. And in a few years that number might be what saves your life as a cancer patient. Every cancer drug in existence went through this. Before the brand name, it was a string of letters and digits given to a few dozen people who’d run out of other options. They weren’t told it would work, they were just told that in fact nobody knew. That’s the of early trials, most of them fail or never make it to the clinic. These people signed up anyway. Some were hoping for a miracle. Many knew it was probably too late for them, and that whatever was learned would arrive for somebody else. All our blockbuster immunotherapy drugs or targeted treatments went through that process. From tomorrow onwards in Madrid at the ESMO meeting thousands of us oncologists will discuss results from trials like that. Behind every slide are a few hundred people who said yes to something unproven. We name drugs after companies or acronyms. We don’t name the patients. But every treatment you’ve ever heard of exists because someone agreed to go first.

In January 2025 my mom’s lung cancer spread to her brain. The drug with the best chance of helping her was approved in China but not here. A doctor told me, almost as an aside, that if she were Chinese she could buy it at a pharmacy. So I flew to Shanghai and came home with 26 boxes in my luggage. That was 19 months ago. My mom is still here, still working, and in her words has had an amazing three years. The drug was approved in China in 2023. The FDA approved it in July 2025. It still is not for sale here. I know of at least 30 Americans who have made the same trip. I have been scared to tell this story because I worried it could cost my mom access to the medicine keeping her alive. But the problem matters more than my silence. These drugs need to be developed and available here, and that means FDA reform. Art Allen at KFF Health News told our story this week. It also ran in The Washington Post. kffhealthnews.org/health-ind…

A watershed for FDA regulation. Every patient on the vaccine arm got a different product, with neoantigens chosen from sequencing of each person's own tumor. So FDA had no single active sequence to review. The IND pre-specified how the product would change for each patient.

Everyone's talking about AI in drug discovery, but clinical trials are the real bottleneck. I rode in a self-driving Tesla with Medable's CEO Michelle Longmire to ask: can trials drive themselves too? Her goal: 90% automated by 2030. check it out: @medableinc @LongmireMD

🌿KEEP OFF THE GRASS!

4D-Chess

Dario has written that we need to “pace the frontier,” and Sam has agreed. People may be surprised by my response: go ahead. You guys are the frontier. By any reasonable metric — market share, revenue growth, model capability — the two of you have a duopoly on frontier intelligence. You’ve also claimed the lead is widening because of recursive self-improvement. I don’t see what you see in the lab. If the unreleased models are scary enough that you think you should slow down, I support your decision to be responsible. But stop pretending you need anyone else’s permission. Stop pretending antitrust law has to be suspended so you can form a cartel. Stop pretending you need a regulatory approval process that supersedes product liability. Stop pretending METR is independent when it is intertwined with Anthropic’s investors and staff. Stop pretending you need those same evaluators to police competitors who aren’t even at the frontier. Most of all, stop pretending the motivation to slow down is purely altruistic. You face massive product-liability exposure if your products enable a truly damaging cyberattack. The market already punishes models that behave in unpredictable or unauthorized ways. After the Hugging Face episode, it is simply good business for OpenAI and Anthropic to trade some raw power for reliability and predictability. Call it alignment if you want. It is also just giving customers what they want. Pacing the frontier would also create breathing room for a more intelligent conversation about regulation than Bernie Sanders’ “shut it all down.” China is very unlikely to join a global agreement, as you know, and that has to be taken into account as well. So go ahead and pace the frontier. You are the ones setting it. The easiest way not to build superintelligence is for you to agree not to build it. Demanding your preferred regulatory framework as the price of that will look like blackmail of the public and the political system. So just do it. If you do, you’ll buy goodwill for the next conversation. If you don’t, we’ll know this was just another bid for regulatory capture — or an election-season psyop.

mes tweets un peu techniques sont pas super evidents à comprendre pour tout le monde alors je vais tenter de vulgariser au mieux pour expliquer toute la comedie qui se joue autour de l’IA en ce moment sachez déjà que nous assistons probablement à la + grande manipulation tech de notre epoque car quand je vois les dirigeants des plus grands labos de la silicon valley reclamer soudainement une pause et demander des exemptions aux lois antitrust au nom de la securitée globale je pense que nous devons regarder exactement la où ils veulent detourner notre attention mettez vous en tête que ce spectacle pseudo ethique masque une panique financière tres concrete face aux miliards engloutis dans des supercalculateurs dont les rendements sessoufflent combinee à la terreur dexposer ces pertes dans leurs prochaines formulaires d’IPO (entrée en bourse) puis je trouve que la methode brille par son cynisme sils estiment sincerement que leurs modeles non publies representent un danger ce duopole (Anthropic /openAI) possede deja toute la latitude pour freiner ses propres deploiements sans demander la permission a quiconque au lieu de cela ils nomment leurs propres organismes dévaluation soi disant independants comme METR en y placant leurs anciens employes et investisseurs & réclament une exemption antitrust officielle pour s’entendre sur le rythme de l’innovation en cherchent à substituer un tampon bureaucratique à leur responsabilite civile réelle comprenez que leur demarche vise avant tout a imposer leurs propres controleurs à des concurrents qui ne sont meme pas à la frontiere technologique… perso je pense que le calcul geopolitique qui se cache derriere ce recit s’avère tout aussi bancal car prétendre limiter le progrès aux seules nations alignées sous couvert de coordination entre democraties pour maintenir une avance artificielle relève de l’illusion pure dites vous que pendant que la silicon valley redige des chartes morales pour preserver ses rentes, verrouiller le marche americain et criminaliser la concurence exterieure, les laboratoires chinois optimisent leurs algorithmes tirent parti dune energie abordable et distribuent la puissance de calcul a une fraction du cout occidental, les batisseurs a lautre bout du monde avancent et construisent pendant que les geants americains debattent dun cartel sur mesure de même je pense que l’erreur fondamentale de ces acteurs reside dans la confusion entre la fin de leur monopole et la fin de la civilisation sachez que de l’invention de l’imprimerie au deploiement de la cryptographie moderne les pouvoirs centraux ont toujours qualifie la democratisation des outils de la pensée de menace pour lordre public le problème pour eux cnest que l’intelligence artificielle depasse la notion d’actif prive enfermé dans des coffres forts d’entreprise, elle simpose comme une propriete fondamentale de la matière et du calcul & vouloir rationner le code par decret administratif revient à tenter de breveter les lois de la physique je pense que l’avenir appartiendra inévitablement aux protocoles ouverts au calcul souverain et à l’inférence locale car la veritable resilience d’une societe emerge directement dun systeme immunitaire décentralisé ou des millions dutilisateurs inspectent, eprouvent et ameliorent la technologie en temps reel loin de la stérilité des laboratoires ultra centralisés les institutions qui tentent deriger des murs autour du savoir finissent par isoler leur propre fragilite pendant que le reste du monde batit le siecle sur des fondations libres

I reread this every year. I cry like a baby every year. Todd Beamer died a father, husband, and hero. Todd: Hello… Operator… listen to me. I can’t speak very loud. This is an emergency. I’m a passenger on a United flight to San Francisco. Our plane has been hijacked. Lisa: I understand. Can they see you? Todd: No. There are three that we know of. They have knives — razor knives, like box cutters. Someone announced from the cockpit there was a bomb. It sounded fake. Lisa: Your name?Todd: Todd Beamer. United Flight 93.Todd: They killed one passenger in first class. They forced most of us back. Fourteen of us here. Five flight attendants. The guy with the bomb ordered us to sit on the floor. Lisa: Are you okay? Todd: We’re going down… wait. No. We’re leveling off. We changed directions. We’re flying east again. Todd: A guy named Jeremy called his wife. She told him two planes hit the World Trade Center. Lisa, is that true? Lisa: I have to tell you the truth. It’s very bad. Both towers are gone. A third plane hit the Pentagon. Our country is under attack. I’m afraid your plane may be part of their plan. Todd: Oh God. Lisa, will you do something for me? Call my wife and my kids. Promise me you’ll call. Lisa: I promise. Todd: Our home number is… You have the same name as my wife. Lisa. We’ve been married ten years. She’s pregnant with our third child. Tell her I love her. I’ll always love her. We have two boys — David, he’s 3, and Andrew, he’s 1. Tell them their daddy loves them and he is so proud of them. The baby is due January 12th. I saw an ultrasound. We still don’t know if it’s a girl or a boy. Lisa: I’ll tell them. I promise, Todd.(Lisa patches in the FBI.) Agent: Todd, your plane is on a course for Washington. Best guess is the White House or the Capitol. Todd: I understand. I’ll be back. Todd: Everyone knows this isn’t a normal hijacking. We have decided we will not be pawns in their plot. Lisa: What are you going to do? Todd: Four of us are going to rush the one with the bomb. Then the cockpit. A stewardess is getting boiling water. We’ll take them out. Todd: Would you pray with me?They pray the Lord’s Prayer. Then: Yea, though I walk through the valley of the shadow of death, I will fear no evil, for thou art with me. Todd: God help me. Jesus help me.Are you guys ready? Let’s Roll.

In cognitively intact people, the level of p-tau217 in the blood tells us about the risk and timing for developing cognitive impairment and Alzheimer's disease. A new study indicates the additive effect of APOE4 carrier status on risk and timing. "Each 1-SD increase in p-tau217 concentration was associated with a 24% shorter time to cognitive impairment among APOE-ε4 carriers, compared with 13% among non-carriers." thelancet.com/journals/laneu…