The Future Of Drug Discovery Is 4 Billion Years Old (Viswa Colluru, Founder & CEO at Enveda)

What America Is Missing Between Sanctions and Nuclear War (Bryon Hargis, Co-Founder & CEO of Castelion)

Bryon Hargis is the co-founder and CEO of Castelion, a defense startup building low-cost hypersonic missiles designed to be manufactured at scale. Before founding Castelion, Bryon spent more than a decade at Johns Hopkins Applied Physics Laboratory and nearly six years at SpaceX, where he worked on national security space programs and saw firsthand how iterative engineering and manufacturing speed could reshape aerospace. Castelion’s first missile, Blackbeard, is slated for integration on the Navy’s F/A-18 Super Hornet in roughly a year. — In our conversation, we explore: * Why Bryon believes building missiles is paradoxically essential to maintaining peace * The game theory behind warfare and why tit-for-tat strategies require credible middle-ground responses * How China’s 2021 hypersonic test revealed not just a capability gap but a manufacturing and cost advantage * Why traditional aerospace processes—optimized for low risk and high cost—can’t compete with rapid iteration * What Bryon learned in his first week at SpaceX (after 12 years in traditional aerospace) * Why building a carrier-based, air-launched hypersonic missile as a first product was the hard but right choice * How focusing on manufacturability and cost over maximum capability can produce more effective deterrence * Why the person who adapts faster in warfare always wins, and how that shapes Castelion’s philosophy — Thank you to the partners who make this possible .tech domains [https://go.tech/thegeneralistnl]: An identity for builders at their core. Ahrefs Brand Radar [https://ahrefs.com/generalist]: Find your brand in AI results. Persona [https://withpersona.com/generalist]: Trusted identity verification for any use case. — Timestamps (00:00) Intro (04:01) Why America needs hypersonic missiles (07:13) China’s edge in hypersonics (12:05) The missing middle ground in deterrence (18:05) Preventing warhead ambiguity (19:40) How hypersonics differ from ballistic missiles (25:05) The economics of defensive vs. offensive systems (28:21) How SpaceX differs from traditional aerospace (37:40) Why Bryon chose to build in defense over space (42:42) Key factors that drove Castelion’s success (48:28) Designing Blackbeard, Castelion’s first hypersonic missile (1:01:06) The importance of lower costs and quicker manufacturing (1:10:04) Book recommendations — Follow Bryon Hargis LinkedIn: https://www.linkedin.com/in/hargsb [https://www.linkedin.com/in/hargsb] X: https://x.com/hargsb [https://x.com/hargsb] — Resources and episode mentions: https://www.generalist.com/p/what-america-is-missing-between-sanctions [https://www.generalist.com/p/what-america-is-missing-between-sanctions] — Production and marketing by penname.co [https://penname.co/]. For inquiries about sponsoring the podcast, email jordan@penname.co.

“Our Goal Is to Build an Electrical Engineer.” (Davide Asnaghi, Co-Founder & CEO of Diode)

Davide Asnaghi [https://www.linkedin.com/in/d-asnaghi/] is the co-founder and CEO of Diode [https://www.diode.computer/], a Brooklyn-based startup using AI to design and manufacture circuit boards in the United States. Before Diode, Davide worked on Apple’s Special Projects Group and spent time in Hong Kong and Shenzhen studying Asia’s electronics manufacturing ecosystem. That experience convinced him that PCB design, despite powering everything from smartphones and satellites to medical devices and autonomous systems, remained one of the most overlooked layers of the tech stack. Since its founding just two years ago, Diode has landed Physical Intelligence and Saronic as customers and partnered with Anthropic to help Claude become a better electrical engineer. The company’s ultimate ambition: to make hardware as nimble as software. In our conversation, we explore: 1. Why the West outsourced PCB manufacturing to Asia in the 2000s and why bringing it back matters for American competitiveness 2. What Shenzhen’s manufacturing culture does better than Silicon Valley (and what the U.S. can learn from it) 3. How Diode’s models can one-shot much of schematic design and compress hardware timelines from months to weeks 4. The three-week YC pivot that transformed Diode from a design validation tool into a full-stack manufacturer 5. Why circuit boards are the “forgotten middle child” between silicon and software 6. How Diode partners with Anthropic to make LLMs better electrical engineers 7. What it takes to build a hardware company in 2025—and why the talent bar must stay incredibly high 8. How Italian, American, and Chinese cultures shaped Davide’s approach to entrepreneurship and manufacturing — Thank you to the partners who make this possible .tech domains [https://go.tech/thegeneralistnl]: An identity for builders at their core. Guru [https://www.getguru.com/]: The AI source of truth for work. Brex [https://www.brex.com/mario]: The intelligent finance platform. — Transcript: https://www.generalist.com/p/our-goal-is-to-build-an-electrical-engineer [https://www.generalist.com/p/our-goal-is-to-build-an-electrical-engineer] — Timestamps (00:00) Intro (04:15) Why Davide calls himself a copper merchant (05:53) Diode’s mission to rebuild PCB manufacturing in the U.S. (07:58) What success looks like (09:00) Growing up in northern Italy and spending a year in Minnesota (13:14) Why Italy produces fewer venture-backed founders (15:30) Why Hong Kong accelerated Davide’s learning (19:09) Silicon Valley vs. Shenzhen (22:05) What Davide learned in Apple’s Special Projects Team (24:11) Why Davide left Apple after two years (26:54) Meeting his co-founder, Lenny (29:32) How Davide uncovered the need for better PCB design and manufacturing (33:23) PCB manufacturing in Asia, and Diode’s approach (41:29) The YC pivot that changed Diode’s business (44:39) Inside Diode’s customer journey (48:10) Where the value is in electronics manufacturing, and Davide’s AGI thesis (51:30) What separates a working board from a great one (55:32) Where Diode fits in the electronics stack (59:55) Diode’s early near-death moment and long-term vision (1:02:30) Diode’s exceptionally high bar for hiring (1:04:48) Where Davide gets his best ideas (1:07:00) Final meditations — Follow Davide Asnaghi LinkedIn: https://www.linkedin.com/in/d-asnaghi [https://www.linkedin.com/in/d-asnaghi] X: https://x.com/davideasnaghi [https://x.com/davideasnaghi] GitHub: https://hexdae.github.io [https://hexdae.github.io/] — Resources and episode mentions: https://www.generalist.com/p/our-goal-is-to-build-an-electrical-engineer⁠ [https://www.generalist.com/p/our-goal-is-to-build-an-electrical-engineer] — Production and marketing by penname.co [https://penname.co/]. For inquiries about sponsoring the podcast, email jordan@penname.co.

Investing Like A Mystic: How Cyan Banister Finds Outliers (Co-Founder of Long Journey Ventures)

Cyan Banister [https://cyanbanister.com/] has built one of the most distinctive early-stage track records of the last fifteen years, with early bets on companies like Uber, SpaceX, DeepMind, Niantic, and Postmates. Today, she is co-founder and general partner at Long Journey Ventures [https://www.longjourney.vc/], where she backs what she calls “magical weirdos.” Banister describes herself as a professional daydreamer, running constant thought experiments and paying close attention to signals others ignore. In this episode, she explains how that mindset translates into investing, and why many of her best opportunities have come from observation, curiosity, and a willingness to look in unlikely places. In our conversation, we explore: * Cyan’s philosophy of treating life as a series of experiments * The strange, profound experiences that led her to question and ultimately move beyond her atheism * How scanning Wi-Fi networks in a Four Seasons café led her to Flock Safety, last valued at $8.4 billion * Long Journey Ventures’ “Biz, Tizz, and Rizz” framework for identifying exceptional founders and why the trifecta is rare * How AI will enable the age of the polymath * Why she believes brain-computer interfaces are closer than most people think * Why she says Pokémon Go was “the closest we ever came to world peace” * Why she lives part-time in a retirement community and her vision for a more connected future — Thank you to the partners who make this possible .tech domains [https://go.tech/thegeneralistnl]: An identity for builders at their core. Brex [https://www.brex.com/mario]: The intelligent finance platform. Persona [https://withpersona.com/generalist]: Trusted identity verification for any use case. — Transcript: https://www.generalist.com/p/investing-like-a-mystic-cyan-banister [https://www.generalist.com/p/investing-like-a-mystic-cyan-banister] — Timestamps (00:00) Intro (03:51) Never playing the game you appear to be playing (07:18) Practicing childlike wonder as a daily discipline (10:08) Questioning belief after her stroke (13:30) Cyan’s metaphysical experiments (23:24) Non-local consciousness and creativity (27:22) Investing with extreme openness to signals (29:05) The importance of timing in investing (32:26) Meeting Travis Kalanick (34:19) Finding Flock Safety through a chance encounter (38:23) The summer of Pokémon Go (what worked and what didn’t) (39:55) Human nature and what makes something "stick" (42:15) Brain-computer interfaces and AI’s accelerating effect (52:53) “Biz, Tiz, Riz:” her framework for evaluating founders (59:20) Why Cyan lives in a retirement community part-time (1:03:50) A unique way of finding books that speak to you (1:08:44) Final meditations — Follow Cyan Banister: LinkedIn: https://www.linkedin.com/in/cyanb [https://www.linkedin.com/in/cyanb] X: https://x.com/cyantist [https://x.com/cyantist] Newsletter: https://uglyduckling.substack.com [https://uglyduckling.substack.com/] Website: https://cyanbanister.com [https://cyanbanister.com/] — Resources and episode mentions: https://www.generalist.com/p/investing-like-a-mystic-cyan-banister [https://www.generalist.com/p/investing-like-a-mystic-cyan-banister] — Production and marketing by penname.co [https://penname.co/]. For inquiries about sponsoring the podcast, email jordan@penname.co.

The Future Of Drug Discovery Is 4 Billion Years Old (Viswa Colluru, Founder & CEO at Enveda)

For decades, drug discovery has shifted away from nature and toward biology-first approaches. Viswa Colluru believes that shift was a catastrophic mistake. His company, Enveda Biosciences, has raised over $500 million to build a “search engine for nature’s chemistry.” The mission is personal: he grew up around his father’s pharmacy in India and later lost his mother to a treatable cancer whose medicine his family couldn’t afford. Many life-changing medicines, including morphine, aspirin, and metformin, originated in nature, but there has never been a reliable, scalable way to systematically explore its chemistry. Colluru founded Enveda in 2019 with $55,000 of his own savings to change that. The company has since identified 18 drug candidates, with three now in clinical trials. In our conversation, we explore: * Why the pharmaceutical industry abandoned nature (and why that was a massive mistake) * How Enveda built a system to decode unknown molecules in nature * The deeply personal story of his mother’s battle with leukemia and how it shaped his life’s work * Why old ideas, from immunotherapy to natural products, often hold the most latent potential * How Enveda developed 18 drug candidates for about $1 million each instead of $10-15 million * Enveda’s three leading drug candidates targeting eczema, obesity, and ulcerative colitis * Why first-in-class medicines capture the vast majority of returns in pharma * What competitive table tennis taught him about building companies — Thank you to the partners who make this possible Brex [https://www.brex.com/mario]: The intelligent finance platform. Ahrefs Brand Radar [https://ahrefs.com/generalist]: Find your brand in AI results. Persona [https://withpersona.com/generalist]: Trusted identity verification for any use case. — Timestamps (00:00) Introduction to Viswa Colluru (03:57) His father’s pharmacy and early exposure to Western and Ayurvedic medicine (07:06) Early pull toward technology (09:29) His mother’s leukemia diagnosis (14:24) Studying Biotechnology (16:07) Graduate school (17:55) Studying immunotherapy when it was unfashionable (24:23) Innovation vs. novelty (27:24) Lessons from table tennis (32:05) Joining Recursion (37:10) Learning urgency and courage (40:42) What launched Enveda (45:40) The limits of reductionist drug discovery (49:53) Chemistry-first approach (52:17) Raising $225K and investing $55K personally (56:04) Initial studies and targets (1:04:30) Three categories of leading drugs: Eczema, obesity, ulcerative colitis (1:13:27) Why GLP-1s are not the whole answer (1:18:27) Enveda’s long-term vision (1:21:31) Book recommendation — Follow Viswa Colluru LinkedIn: https://www.linkedin.com/in/viswacolluru [https://www.linkedin.com/in/viswacolluru] X: https://x.com/viswacolluru [https://x.com/viswacolluru] — Resources and episode mentions: https://www.generalist.com/p/the-future-of-drug-discovery [https://www.generalist.com/p/the-future-of-drug-discovery] — Production and marketing by penname.co [https://penname.co/]. For inquiries about sponsoring the podcast, email jordan@penname.co.

How a 20-Person Startup Won Gold at the Math Olympiad—Tying With OpenAI & DeepMind (Tudor Achim, CEO of Harmonic)

Tudor Achim is the co-founder and CEO of Harmonic, a startup working to solve one of AI’s hardest problems: mathematical reasoning. In July 2024, Harmonic achieved gold-medal-level performance on International Math Olympiad problems alongside systems from OpenAI and Google DeepMind—but with a key difference: every proof Harmonic submitted was formally verified. Tudor's path to Harmonic wound through competitive piano, computational biology, and autonomous driving. He studied at Carnegie Mellon's music preparatory school, worked on machine learning at Quora, briefly pursued a PhD before dropping out, and then co-founded an autonomous driving company, Helm.ai. Harmonic's core product, Aristotle, uses reinforcement learning and the programming language Lean 4 to solve problems and verify solutions. In our conversation, we explore: * Why Tudor believes math is the fundamental toolkit to understand the world * How Harmonic uses hallucinations as a feature, not a bug * How Aristotle works and the applications beyond pure mathematics * The reinforcement learning process that lets Harmonic generate synthetic training data and solve problems humans have never attempted * Why Tudor believes AI could surpass human mathematicians on specific tasks within 2–3 years * Why the future of mathematics looks more like GitHub than academic journals * The alternating pattern between intellect leaps and data leaps throughout scientific history * How studying piano under an extraordinary teacher taught Tudor discipline and the value of sticking with hard problems — Thank you to the partners who make this possible Brex [https://www.brex.com/mario]: The intelligent finance platform. Guru [https://www.getguru.com/]: The AI source of truth for work. Rippling [https://rippling.com/mario]: Stop wasting time on admin tasks, build your startup faster. — Transcript: https://www.generalist.com/p/how-a-20-person-startup-won-gold [https://www.generalist.com/p/how-a-20-person-startup-won-gold] — Timestamps (00:00) Intro (03:34) From competitive piano to computer science (06:28) The mathematical foundations of music (and why Tudor keeps them separate) (08:24) Can AI ever create art with true intent? (09:51) Early obsessions (12:52) Defining intelligence (14:49) Discovering machine learning’s potential at Quora (17:30) Why Tudor chose computational biology for his PhD (19:19) The decision to drop out and build Helm.ai (22:55) The two breakthroughs that made mathematical AI possible in 2023 (25:28) The importance of Lean 4 (28:21) How Tudor and Vlad Tenev discovered they shared the same impossible dream (32:35) Why formal verification became the core conviction (34:21) The timeline for AI surpassing human mathematicians (35:25) An overview of Aristotle: the world’s first always-correct mathematical agent (38:12) Why Tudor says hallucinations are the engine of creativity (39:30) The translation challenge from natural language to formal proof (40:40) Reinforcement learning (42:10) Why Aristotle is both faster and cheaper than alternatives (43:34) Tradeoffs and use cases (45:34) Math in AI now and what’s next (47:38) Tying with OpenAI and DeepMind at the International Math Olympiad (49:08) Democratizing AI and correctness (53:13) Tudor’s 2030 thesis (56:02) History’s alternating rhythm of thinking and measuring (57:53) What Tudor has been wrong about (58:52) What Tudor’s best at (1:00:18) Final meditations — Follow Tudor Achim LinkedIn: https://www.linkedin.com/in/tudorachim [https://www.linkedin.com/in/tudorachim] X: https://x.com/tachim/with_replies [https://x.com/tachim/with_replies] — Resources and episode mentions: https://www.generalist.com/p/how-a-20-person-startup-won-gold⁠ [https://www.generalist.com/p/how-a-20-person-startup-won-gold] — Production and marketing by penname.co [https://penname.co/]. For inquiries about sponsoring the podcast, email jordan@penname.co.