The Generalist

• Why Psychedelics Might Be the Breakthrough That PTSD Patients Need | Kevin Ryan (The Godfather of NYC Tech)

  Often called the godfather of NYC tech, Kevin Ryan is one of America’s most influential entrepreneurs and investors. He co-founded MongoDB, Business Insider, Gilt Groupe, Zola, and Transcend Therapeutics, and continues to build and back new companies each year through AlleyCorp. Earlier in his career, he led DoubleClick from a 20-person startup to a global leader, taking it public before its acquisition by Google.In this episode, Kevin shares his insights on two surprising pockets of the future that he’s betting on: psychedelics for mental health and AI-powered materials science. He unpacks how psychedelics are showing remarkable success in treating depression and PTSD, and why AI may discover revolutionary new materials, from helicopter blades to smartphone glass, that humans never imagined possible.We explore:• The promising results of psychedelics in treating depression, PTSD, and addiction• How AI is accelerating materials discovery by exploring combinations humans wouldn’t try• The challenges of building successful incubators and why most attempts fail• How MongoDB lost $1 billion before turning a profit (and why it was worth it)• Why e-commerce businesses like Gilt Groupe often struggle against physical retail• How AlleyCorp plans for the future when shaping its investment strategy• What it really costs society to imprison someone for a year• The hard truth about Europe’s tech ecosystem and why it struggles to compete with the US—Thank you to the partners who make this possibleEnterpret: Transform feedback chaos into actionable customer intelligence.Auth0: Secure access for everyone. But not just anyone.Persona: Trusted identity verification for any use case.—Transcript: https://www.generalist.com/p/why-psychedelics-might-be-the-breakthrough—Timestamps(00:00) Intro(04:30) How Kevin collaborated with Scott Adams(07:11) The origins of AlleyCorp(08:33) The challenge of incubation(10:00) Why intellectual flexibility matters(10:54) What made MongoDB a breakout success(13:49) How shifting market dynamics hurt Gilt’s business(16:22) What Kevin would do differently if he built Gilt again(17:45) Juggling AlleyCorp’s long-term vision with day-to-day demands(20:26) How to make boards more productive(22:25) Why Kevin believes investors should also found companies(24:18) Future spaces Kevin is excited to invest in(25:52) Kevin’s interest in psychedelics and founding Transcend(28:20) Psychedelics for mental health(32:03) How psychedelic therapy is being conducted(34:11) Transcend’s work and the path to approval for methylone(37:47) The challenges of psychedelic research(40:28) How the Trump administration aims to accelerate psychedelic research(41:50) The size and growth of the psychedelic market(44:28) Materials science: What it is, its design tradeoffs, and how AI speeds discovery(49:02) Radical AI’s work creating new compounds(50:34) The industries Radical AI is targeting(52:50) The state of European tech and why it still lags behind(58:26) Final meditations—Follow Kevin RyanLinkedIn: https://www.linkedin.com/in/kevinryan3/X: https://x.com/alley_corp—Resources and episode mentions—Books—• How to Change Your Mind: What the New Science of Psychedelics Teaches Us About Consciousness, Dying, Addiction, Depression, and Transcendence: https://www.amazon.com/Change-Your-Mind-Consciousness-Transcendence/dp/1594204225• Breakneck: China’s Quest to Engineer the Future: https://www.amazon.com/Breakneck-Chinas-Quest-Engineer-Future/dp/1324106034• Why We Sleep: Unlocking the Power of Sleep and Dreams: https://www.amazon.com/Why-We-Sleep-Unlocking-Dreams/dp/1501144324—Episode resources continued at: ⁠https://www.generalist.com/p/why-psychedelics-might-be-the-breakthrough⁠—Production and marketing by penname.co. For inquiries about sponsoring the podcast, email [email protected].

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• The Trillion-Dollar AI Hardware Opportunity | Navin Chaddha (Managing Partner, Mayfield)

  Navin Chaddha has spent three decades at the forefront of innovation—first as a founder, and now as managing partner at Mayfield, one of Silicon Valley’s oldest venture firms. A 17-time member of Forbes’ Midas List, Navin has guided generations of entrepreneurs through waves of technological change, from the dot-com boom to the AI era. At Mayfield, he champions a philosophy rooted in the firm’s founding ethos: investing in people, not markets. That approach has shaped his perspective on what it takes to build enduring companies. In this conversation, Navin shares why $1 trillion in infrastructure spending is fueling a new hardware renaissance, how stealth startups are going from zero to billions in a year, and what it means for the future of innovation.We explore:How “vibe coding” is democratizing technology creation through conversational, collaborative, and cognitive interfacesWhy Navin believes the “vibe economy” will transform how we work, live, and playHow Mayfield’s 56-year focus on “backing the jockey, not the racetrack” shapes its investment approachThe massive opportunity in AI hardware infrastructureHow stealth AI hardware startups are going from zero to billions in under a yearHow India’s tech ecosystem has evolved and where the real opportunities are todayHow cricket taught Navin crucial lessons about company building—Thank you to the partners who make this possibleGoFundMe Giving Funds: One Account. Zero Hassle.Auth0: Secure access for everyone. But not just anyone.Tezi: The AI agent for recruiting high-quality candidates quickly—Transcript: https://www.generalist.com/p/the-trillion-dollar-ai-hardware-opportunity—Timestamps(00:00) Intro(04:52) Cricket and its parallels to venture capital(08:13) Navin’s journey to Silicon Valley(10:28) Growing up in an entrepreneurial family(12:00) Early mentors and becoming an “accidental entrepreneur”(13:46) Navin’s first company and unconventional fundraising approach(17:35) How Navin moved from founder to venture capitalist(20:11) What has worked in India’s tech market and what hasn’t yet taken off(23:31) The future of outsourcing in the AI era(27:14) How Navin landed at Mayfield(30:36) How Mayfield’s people-first approach works in practice(34:50) Why Navin sees AI and vibe coding as the next great wave of innovation(38:13) Why Navin believes AI will push humans to level up their skills rather than lose them(44:50) The hardware opportunities that excite Navin and where Mayfield is investing(48:49) An overview of photonics and why it matters now(50:06) How Mayfield balances market insight, big ideas, and the people behind them(52:50) The surprising pace of growth in AI hardware(54:54) The timeline from idea to product and scale in hardware startups(56:26) Final meditations—Follow Navin ChaddhaLinkedIn: https://www.linkedin.com/in/navinchaddha/X: https://x.com/navinchaddha—Resources and episode mentions: https://www.generalist.com/p/the-trillion-dollar-ai-hardware-opportunity—Production and marketing by penname.co. For inquiries about sponsoring the podcast, email [email protected].

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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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