The a16z Podcast

a16z General Partners David Haber, Alex Rampell, and Erik Torenberg discuss why 19 out of 20 AI startups building the same thing will die - and why the survivor might charge $20,000 for what used to cost $20. They expose the "janitorial services paradox" (why the most boring software is most defensible), explain why OpenAI won't compete with your orthodontic clinic software despite having 800 million weekly users, and reveal how non-lawyers are building the most successful legal AI companies. Plus: the brutal truth about why momentum isn't a moat, but without it, you're already dead.

Emmett Shear, founder of Twitch and former OpenAI interim CEO, challenges the fundamental assumptions driving AGI development. In this conversation with Erik Torenberg and Séb Krier, Shear argues that the entire "control and steering" paradigm for AI alignment is fatally flawed. Instead, he proposes "organic alignment" – teaching AI systems to genuinely care about humans the way we naturally do. The discussion explores why treating AGI as a tool rather than a potential being could be catastrophic, how current chatbots act as "narcissistic mirrors," and why the only sustainable path forward is creating AI that can say no to harmful requests. Shear shares his technical approach through multi-agent simulations at his new company Softmax, and offers a surprisingly hopeful vision of humans and AI as collaborative teammates – if we can get the alignment right.

Two venture capitalists dissect why biotech burns billions while China runs trials in weeks, and why the next Genentech won't look anything like the last one. Elliot Hershberg reveals the "three horsemen" strangling drug development as costs explode to $2.5 billion per approval, while Lada Nuzhna exposes how investigator-initiated trials in Shanghai are rewriting the competitive playbook faster than American founders can file INDs. When the infrastructure that built monoclonal antibodies becomes the commodity threatening to hollow out an entire industry, the only path forward demands inventing medicines that are literally impossible to make without tools that don't exist yet, and they're betting everything on which approach survives.

The Empire State Building took 110 days to build—today, changing a window would take two years. Alex Rampell (a16z) and Varun Krishna (Rocket CEO) expose how asset inflation turned housing from the American Dream into a wealth transfer machine where the median homebuyer age jumped from 30 to 38 in just fourteen years. While Silicon Valley burns billions on products people use daily but never pay for, Rocket quietly assembled a $10 billion profit engine and is now buying up the entire housing funnel—from Redfin's 50 million monthly searchers to one in six US mortgages—betting they can crack the code everyone else gave up on: turning a once-in-a-lifetime transaction into an everyday relationship.

Grant Lee was told Gamma was "the worst idea ever heard" by an investor who hung up mid-Zoom—yet he built it to 100 million users and $100M ARR without spending a dollar on advertising. While competitors hired aggressively, Grant's team of seven refused to grow, dedicating 25% of their tiny team to design and personally onboarding every influencer themselves. They reveal how ignoring AI for their first two years, then orchestrating multiple models in ways the frontier labs can't replicate, let them steal the presentation market from Microsoft and Google—going from 60,000 signups in eight months to 50,000 per day.

When four MIT grads decided to build a code editor while everyone else was building AI agents, they created the fastest-growing developer tool ever built. Cursor CEO Michael Truell joins a16z’s Martin Casado to discuss the deliberate constraints that led to breakthroughs: why they rejected the "democratization" narrative to focus on power users, how their 2-day work trials test for agency over credentials, and the strategic decision to own the editor when conventional wisdom said it was impossible.

Adam D’Angelo (Quora/Poe) thinks we're 5 years from automating remote work. Amjad Masad (Replit) thinks we're brute-forcing intelligence without understanding it. In this conversation, two technical founders who are building the AI future disagree on almost everything: whether LLMs are hitting limits, if we're anywhere close to AGI, and what happens when entry-level jobs disappear but experts remain irreplaceable. They dig into the uncomfortable reality that AI might create a "missing middle" in the job market, why everyone in SF is suddenly too focused on getting rich to do weird experiments, and whether consciousness research has been abandoned for prompt engineering. Plus: Why coding agents can now run for 20+ hours straight, the return of the "sovereign individual" thesis, and the surprising sophistication of everyday users juggling multiple AIs.

Priscilla Chan and Mark Zuckerberg join a16z’s Ben Horowitz, Erik Torenberg, and Vineeta Agarwala to share how the Chan Zuckerberg Initiative is building the computational tools that will accelerate the cure, prevention, and management of all disease by century's end. They explain why basic science needs $100 million-scale projects that traditional NIH grants can't fund, how their Cell Atlas became biology's missing periodic table with millions of cells catalogued in open-source format, and why their new virtual cell models will let scientists test high-risk hypotheses in silico before investing in expensive wet lab work. Plus: the organizational shift unifying the Biohub under AI leadership, what happens when biologists and engineers sit side-by-side, and why modern biology labs are expanding compute instead of square footage.