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The Generalist

Mario Gabriele
The Generalist
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  • Biological Time Travel: How Cryopreservation Could Transform Medicine | Laura Deming (CEO & co-founder of Until)
    From a child prodigy in a genetics lab to building a company that can pause life itself, Laura Deming has made a career out of chasing time. At just eight years old she became obsessed with aging. At eleven, she joined Cynthia Kenyon’s pioneering longevity lab. At seventeen, she launched The Longevity Fund—one of the first venture firms dedicated to extending human healthspan. Now, she’s tackling her boldest challenge yet: building a “pause button” for biology.As the co-founder of Until, Laura is developing reversible cryopreservation: the ability to cool living tissue to ultra-low temperatures, hold it there, and then bring it back fully functional. By achieving vitrification (the process of turning tissue into glass instead of ice), Until aims to make organ preservation, and eventually medical hibernation, a reality.We cover:• Why longevity was once stigmatized, and what changed to make it one of the most credible fields in biotech today• Why Until’s approach focuses on preserving the living, not the dead• The physics and biological challenges of scaling reversible cryopreservation from embryos to human-sized organs• How vitrification is making cryopreservation possible• How this breakthrough could transform organ transplantation by eliminating time constraints (and eventually enable medical hibernation)• The philosophical and social implications of being able to “pause” life and effectively time travel into the future• How growing up homeschooled in New Zealand shaped Laura’s unconventional way of thinking• The story of how legendary biologist Cynthia Kenyon invited 11-year-old Laura into her lab, sparking her lifelong obsession with aging• How she learned to embrace her weirdness and trust it as her creative superpower—Thank you to the partners who make this possibleGoFundMe Giving Funds: One Account. Zero Hassle.Brex: The banking solution for startups.Persona: Trusted identity verification for any use case.—Transcript: https://www.generalist.com/p/biological-time-travel-laura-deming—Timestamps(00:00) Intro(04:55) How Laura became interested in longevity at such a young age(07:40) The impact of homeschooling on Laura’s thinking(09:29) The invitation from Cynthia Kenyon that set Laura on her path at age 11(10:39) Why pursuing longevity once meant working in the shadows(14:20) Why Laura shifted into VC at The Longevity Fund(17:24) How longevity transformed from fringe science to a legitimate field(19:40) Why Laura was driven to start Until(21:08) A simple explanation of reversible cryopreservation(23:10) Science fiction’s explorations of cryo(25:38) What sparked Laura’s interest in reversible cryo(27:35) How cryonics and reversible cryo differ, and the mechanisms behind each(29:00) Until’s roadmap, beginning with cryopreserved organs for transplantation(34:00) The biggest challenges in developing preservable organs(35:53) How cryopreservation works(38:30) Until’s building philosophy(42:34) How Laura learned to trust her weirdness(49:10) Finding the right co-founder in Hunter Davis(51:17) Future applications beyond medical necessity(53:00) Unanswered questions in cryopreservation(55:05) What’s missing in Hollywood’s portrayal of genius(56:21) Laura’s unique process for exploring ideas(59:58) Personal longevity practices(01:01:30) The positive impact of Bryan Johnson’s work(01:02:38) Final meditations—Follow Laura DemingLinkedIn: https://www.linkedin.com/in/laura-deming-b255362a/X: https://x.com/laurademingWebsite: https://www.ldeming.com/—Resources and episode mentions: https://www.generalist.com/p/biological-time-travel-laura-deming⁠—Production and marketing by penname.co. For inquiries about sponsoring the podcast, email [email protected].
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  • "This feels like 1996": Why a16z's Martin Casado believes the AI boom still has years to run (General Partner)
    Martin Casado has lived through multiple tech waves—first as a founder, now as a16z’s leading voice on AI and infrastructure. He helped pioneer software-defined networking, then moved from academia to entrepreneurship, and today backs founders building at the frontier of technology as a General Partner at Andreessen Horowitz. In this conversation, Martin shares his unique perspective on the AI boom, his market-first investment philosophy, and why he believes we’re still in the early days of AI’s impact.We explore:• Martin’s path from game engines and simulations to investing at Andreessen Horowitz• Why Martin believes we’re only in “1996” of the AI boom cycle with years to run before any bubble• Why Martin approaches investing “from markets in” rather than “from companies out”• Why the AI coding market represents a potential $3 trillion opportunity• The transformation of Andreessen Horowitz from a small generalist partnership to a specialized 600-person organization• The concerning dominance of Chinese companies in open source AI models• Why Martin thinks AGI discussions encourage “lazy thinking” and obscure meaningful conversations• How World Labs is solving the 3D representation problem that could unlock robotics, VR, and more—Thank you to the partners who make this possibleAuth0: Secure access for everyone. But not just anyone.Brex: The banking solution for startups.Persona: Trusted identity verification for any use case.—Transcript: https://www.generalist.com/p/this-feels-like-1996-martin-casado—Timestamps(00:00) Intro(04:50) Martin’s early career(08:35) Martin’s shift from academia to founding his own company during an economic downturn(11:25) The story behind Martin joining Andreessen Horowitz(17:55) Ben Horowitz’s most impactful advice(19:49) How Andreessen Horowitz has transformed since 2016(22:20) Why product experience matters more than technical prowess for infrastructure investing(26:26) Martin’s market-first investment philosophy(28:39) Andreessen Horowitz’s framework for assessing founders and startups(33:14) Why Martin thinks Hock Tan may be the best CEO today(35:18) The controversy around non-consensus investing in early stages(38:42) Why today’s AI boom reminds Martin of the mid-’90s tech environment(44:38) How today’s AI boom differs from 2021’s tech bubble(47:10) Why the promise of AI in organizations remains largely unrealized(50:29) How Martin uses AI for coding and as a reading thought partner(52:56) Why Martin doesn’t use AI for writing(53:24) Martin’s interest in Eisenhower and historical parallels to today(55:33) Two equally important paths for AI’s future(58:33) Why Cursor stood out as the leader in AI coding tools(01:01:14) The lack of inherent defensibility in AI and how to build moats(01:03:30) World Labs’ mission to transform 2D images into 3D environments(01:06:42) 3D’s emerging use cases and why the VR market may expand(01:11:50) Why Martin isn’t an “AGI guy” and how the term erodes conversation quality(01:14:59) How seeing AI as a continuum creates room for future products and investment(01:16:28) The security and regulatory challenges of Chinese open-source AI models(01:19:23) Final meditations—Follow Martin CasadoLinkedIn: https://www.linkedin.com/in/martincasado/X: https://x.com/martin_casado—Resources and episode mentions—Books—• The Weirdest People in the World: https://www.amazon.com/WEIRDest-People-World-Psychologically-Particularly/dp/1250800072/• The Beginning of Infinity: Explanations That Transform the World: https://www.amazon.com/Beginning-Infinity-Explanations-Transform-World/dp/0143121359...References continued at: https://www.generalist.com/p/this-feels-like-1996-martin-casado⁠—Production and marketing by penname.co. For inquiries about sponsoring the podcast, email [email protected].
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  • How to be Agentic in the Age of AI | Cate Hall (CEO of Astera)
    Cate Hall is the CEO of Astera, a private foundation focused on AI risk and frontier technology. Before leading Astera, Cate’s unconventional career path took her from practicing law (including work on Supreme Court briefs) to becoming the world’s top-ranked female poker player in 2016. After overcoming personal struggles with addiction, she co-founded Alvea, a biotech company developing shelf-stable vaccines for pandemic response, before joining Astera. In this conversation, Cate shares insights on human psychology, agency as a learnable skill, and why she believes AI’s biggest risk may be a “soft takeover” in which humans gradually lose independence and meaning.We explore:• How Cate’s approach to poker focused on reading people rather than pure game theory, and why this contrarian strategy worked• Why people who always try to “play” high status in conversations often have psychological issues• The critical difference between ambition and agency, and why they’re often confused• How LSD helped Cate break out of her career path and discover her own agency• Why Cate believes we need a slowdown in AI development to develop the social technologies to manage it• The challenge of maintaining meaning in human life as AI systems increasingly mediate our experiences• How Astera is using investment as a philanthropic tool to help steer frontier technology development—Thank you to the partners who make this possibleAuth0: Secure access for everyone. But not just anyone.Brex: The banking solution for startups.—Transcript: https://www.generalist.com/p/how-to-be-agentic-in-the-age-of-ai-cate-hall—Timestamps(00:00) Introduction to Cate Hall(03:56) Cate’s role as CEO of Astera(04:52) Cate’s poker career and focus on live reading(07:02) The intuitive ‘people radar’ Cate has in identifying exceptional talent(11:16) Status dynamics in conversations(16:13) The parallel between poker and startup evolution(19:18) The German wave in poker and game theory(24:22) Cate’s legal career and Supreme Court experience(27:05) The difference between ambition and agency(29:13) How LSD helped Cate discover her agency(31:26) Leaving poker and dealing with mental health issues(34:26) The founding story of Alvea(38:14) The founding story of Astera(43:15) Cate’s journey into AI risk(45:50) The concept of a “soft takeover” and how AI might hollow out human experience(49:46) The overwhelming challenge of addressing AI risk(51:20) Astera’s approach to steering technology development(53:15) Astera’s investment in Last Energy(54:20) How philanthropy and investing work together at Astera(57:22) Practical ways to increase personal agency(1:07:20) Final meditations—Follow Cate HallX: https://x.com/catehallLinkedIn: https://www.linkedin.com/in/cate-hall-9a81a35/Newsletter: https://usefulfictions.substack.com/—Resources and episode mentions—Books—• Zero to One: Notes on Startups, or How to Build the Future: https://www.amazon.com/Zero-One-Notes-Startups-Future/dp/0804139296/• Impro: https://www.amazon.com/Impro-Improvisation-Theatre-Keith-Johnstone/dp/0878301178• Superintelligence: Paths, Dangers, Strategies: https://www.amazon.com/Superintelligence-Dangers-Strategies-Nick-Bostrom/dp/0198739834/• The Righteous Mind: Why Good People Are Divided by Politics and Religion: https://www.amazon.com/Righteous-Mind-Divided-Politics-Religion/dp/0307455777/—People—• Jed McCaleb on LinkedIn: https://www.linkedin.com/in/jed-mccaleb-4052a4/• Charlie Carrel on X: https://x.com/charlie_carrel• Seemay Chou on X: https://x.com/seemaychou• Ben Kuhn on X: https://x.com/benkuhnEpisode resources continued at: https://www.generalist.com/p/how-to-be-agentic-in-the-age-of-ai-cate-hall—Production and marketing by penname.co. For inquiries about sponsoring the podcast, email [email protected].
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  • Maintaining Human Intelligence in the AI Era | David Krakauer (President of the Santa Fe Institute)
    David Krakauer is a leading complex systems researcher and the president of the Santa Fe Institute, a unique institution dedicated to studying complex systems across disciplines. In this episode, David challenges conventional wisdom about AI, arguing that large language models pose a more immediate threat to humanity than commonly discussed existential risks—not by destroying us directly, but by eroding our cognitive capabilities through addictive, low-quality information.We explore:• Why David believes LLMs aren't intelligent at all and how the AI community misunderstands emergence• The three dimensions of intelligence: inference, representation, and strategy—and which one LLMs lack• How AI acts as a "competitive" rather than "complementary" cognitive technology, atrophying our thinking abilities• What makes great minds unique, from analogical reasoning to the cultivation of unconscious creativity• How Cormac McCarthy's approach to knowledge and creativity offers lessons for the AI age• Why David believes the greatest threat from AI isn't existential risk but cognitive atrophy• How to protect your mind against AI's addictive pull and maintain cognitive autonomy—Thank you to the partners who make this possibleBrex: The banking solution for startups.Enterpret: Transform feedback chaos into actionable customer intelligencePersona: Trusted identity verification for any use case—Transcript: https://www.generalist.com/p/maintaining-human-intelligence-in-the-ai-era-david-krakauer—Timestamps(00:00) Intro(04:39) The Santa Fe Institute’s approach to complex systems(06:45) Murray Gell-Mann’s ‘Odysseus vs. Apollonian’(10:35) How SFI was shaped by the legacy of Los Alamos(12:45) Traits David looks for in great minds(14:43) Cormac McCarthy on naivety and how thoughtful people treat knowledge(19:24) A simple explanation of complexity science(22:50) Why vantage point doesn’t matter when studying systems(24:36) Aesthetic preferences among complexity scientists(26:07) Films and directors with complexity science themes(29:57) Why David argues LLMs are not intelligent(32:10) What’s missing in the study of LLMs(36:40) The three qualities of intelligence and how LLMs measure up(42:19) Lessons from "The Glass Bead Game"(44:00) David’s perspective on reinforcement learning(45:38) The greatest threat of LLMs: overreliance and the decline of thinking(47:40) Competitive vs. complementary cognitive artifacts(51:55) Why exposing yourself to quality ideas matters(54:00) How to derisk LLM use(58:32) Cormac McCarthy’s legacy at SFI and beyond(1:02:40) The Kekulé Problem: cultivating the unconscious(1:05:01) Why David and McCarthy were inspired by Wittgenstein(1:09:00) What Cormac McCarthy liked to talk about(1:12:20) David’s questions to a higher being(1:14:46) Final meditations—Follow David KrakauerWebsite: https://davidckrakauer.com/—Resources and episode mentions—Books—• “The Hedgehog and the Fox”: https://www.amazon.com/Hedgehog-Fox-Tolstoys-History-Second/dp/069115600X• The Birds and The Frogs: https://www.amazon.com/Aristophanes-Frogs-Birds/dp/B000QBPUTY• The Glass Bead Game: https://www.amazon.com/Glass-Bead-Game-Magister-Novel/dp/0312278497• Frankenstein: https://www.amazon.com/Frankenstein-Mary-Shelley/dp/0486282112• Blood Meridian: Or the Evening Redness in the West: https://www.amazon.com/Blood-Meridian-Evening-Redness-West/dp/0679728759• Stella Maris: https://www.amazon.com/Stella-Maris-Cormac-McCarthy/dp/0307269000• The Passenger: https://www.amazon.com/Passenger-Cormac-McCarthy/dp/0307268993/• Pale Fire: https://www.amazon.com/Pale-Fire-Vladimir-Nabokov/dp/0679723420...Episode resources continued at: https://www.generalist.com/p/maintaining-human-intelligence-in-the-ai-era-david-krakauer—Production and marketing by penname.co. For inquiries about sponsoring the podcast, email [email protected].
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  • Building Beautiful Homes with Robots: The Future of Construction | Salar al Khafaji (CEO and Founder of Monumental)
    Salar al Khafaji is the CEO and founder of Monumental, a company building autonomous robots that assemble buildings, starting with its bricklaying system. After selling his previous software company to Palantir, Salar took time to explore big industries ripe for disruption before landing on construction—a sector that represents a significant portion of GDP yet has seen decades of productivity stagnation.We explore:• Why construction represents a massive opportunity for technological innovation• How Monumental's system of three robots works together to lay bricks autonomously• Why Europe's severe bricklayer shortage has created wages as high as €80/hour• The post-WWII shift away from beautiful architecture and how to bring it back• Why operating as a subcontractor rather than selling robots makes business sense• The challenges of building a hardware startup in Europe's tech ecosystem• How Palantir's "cult-like" culture influenced Monumental's approach to company building• The balance between structure and productive chaos in scaling a startup• Why the best robotics companies solve specific problems rather than building general-purpose machines• How to foster ambition in Europe's startup ecosystem—Thank you to the partners who make this possibleEnterpret: Transform feedback chaos into actionable customer intelligence.Brex: The banking solution for startups.Persona: Trusted identity verification for any use case.—Transcript: https://www.generalist.com/p/building-beautiful-homes-with-robots-salar-al-khafaji—Timestamps(00:00) Introduction to Salar(04:44) Overview of Monumental’s work and mission(06:25) Salar’s journey after selling his company to Palantir(11:46) Stagnation in the construction industry(14:21) The mental shift from software to hardware entrepreneurship(16:10) Salar’s funding framework(18:21) The post-WWII decline in constructing beautiful buildings(20:23) Choosing bricklaying as the first construction trade to tackle(25:20) Why Monumental operates as a subcontractor(28:38) The limitations of 3D printing and prefab construction(33:15) The technology and pricing bets Salar made(33:45) Lessons from Palantir's culture(39:35) Monumental's company culture(42:31) An overview of a construction job from start to finish(45:50) Precision and tolerances(47:50) Surprising challenges in the construction industry(49:10) The current state of Monumental and what’s next(54:00) Why humanoid robots don’t make sense for Monumental(56:16) Building an ambitious company in Europe(01:00:56) Monumental’s approach to hiring(01:03:10) The state of European tech and what needs to change(01:06:00) Salar’s optimistic take on the current state of tech in Europe(01:10:46) Final meditations—Follow Salar al KhafajiLinkedIn: https://www.linkedin.com/in/salark/X: https://x.com/salarWebsite: https://sal.ar/—Resources and episode mentions—Books—• Impro: Improvisation and the Theatre: https://www.amazon.com/Impro-Improvisation-Theatre-Keith-Johnstone/dp/0878301178• Liftoff: Elon Musk and the Desperate Early Days That Launched SpaceX: https://www.amazon.com/Liftoff-Desperate-Early-Launched-SpaceX/dp/0062979973• Seeing Like a State: How Certain Schemes to Improve the Human Condition Have Failed: https://www.amazon.com/Seeing-like-State-Certain-Condition/dp/0300078153• The Little Big Number: How GDP Came to Rule the World and What to Do about It: https://www.amazon.com/Little-Big-Number-World-about/dp/0691166528—Episode resources continued at: https://www.generalist.com/p/building-beautiful-homes-with-robots-salar-al-khafaji—Production and marketing by penname.co. For inquiries about sponsoring the podcast, email [email protected].
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