Dialectic

Patrick Hsu (X, Website, Arc lab) is co-founder and core investigator of Arc Institute, assistant professor of pathology at Stanford, and venture partner at Thrive Capital.

Patrick has always been precocious: he began college as a young teenager and contributed to early CRISPR-Cas9 gene-editing breakthroughs as part of Feng Zhang’s lab at the Broad Institute of MIT and Harvard. Today, the Hsu Lab at Arc works where genome engineering meets AI, from bridge recombinases that can rearrange up to a million bases of DNA at once to Arc's Evo biological foundation models.

We discuss Patrick’s pace and ambition, infinite games, and why he was drawn to biology. Then, we traverse power laws in biotech and the reach of GLP-1s, research taste and success, Arc’s multidisciplinary model, data limits in AI-enabled bio, and cell and bio foundation models. We also discuss how AI and new science will help us solve diseases, design life, and push the boundaries of sci-fi when it comes to human health. I hope you are inspired to raise your bar, commit to reinvention, and hold a lightness that makes the long and challenging journey fun.

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Dialectic is presented by Notion. Notion is a collaborative workspace for your life's work, and it works with whatever AI you use. New models are typically available in Notion the day they launch, you can tag agents from inside Notion, and you can tag Notion from your other AI tools. As the tools around you change, Notion stays the one place that holds your context. Notion is also hiring across product, engineering, design, storytelling, and more. Learn more at notion.com/dialectic.

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This episode is supported by Google. Gemini 4 Argon recently launched and is built for long-horizon work. I used it inside Antigravity and gave it all 60 Dialectic transcripts: more than a million words. Instead of summarizing episodes one by one, Argon synthesized across them, tracing how ideas from early conversations connect to later ones. Together we made The Dialectic Compendium, an interactive book of the themes that run across the show, with a dossier on every episode and a 3D version you can page through on the web. Gemini 4 Argon is available in the Gemini app, Antigravity, Google AI Studio, and the Gemini API.

Compendium: https://jacksondahl.com/dialectic/compendium

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Timestamps

(0:00) Opening Highlights

(1:39) Intro: Patrick Hsu

(4:29) Start: Boldness, Infinite Games, & Ambition

(12:54) GLP-1s and Power Laws in Biotechnology

(20:17) Expelled at 13 and Falling for Biology

(25:51) What Makes a Good Biologist, Research Taste, and Biology’s Data Challenges

(37:58) The Arc Model: Full-Stack Science

(52:01) Betting on People, Style, & Learning to Simplify

(57:22) Perturbation, World Models, and Evo

(1:03:27) Virtual Cell Models

(1:09:56) Designing Life: From Stem Cells to Genome Writing

(1:18:39) Testing, Bro Science, and Human Data

(1:24:26) Can It Exist vs. Will It Exist: Science Meets Markets

(1:29:59) Biofuturism: Interoception, Peptides, Muscle Modulation, Sleep, and New Forms of Life

(1:43:47) Fun, Obsolescence, Going Slow, and the Future

(1:54:27) Outro

Joe Gebbia (Website, X, LinkedIn, Wikipedia) is the first U.S. Chief Design Officer, leading the National Design Studio. He is also the co-founder of Airbnb and Samara.

The NDS and this role were created by executive order of President Trump in August 2025. I met Joe Washington, D.C, to reflect on the past year and talk about bringing the care and ambition of great product design to the digital services that every American uses. Joe & NDS just launched America.gov, their flagship project of the last year: the central entry point for how Americans get what they need from the government.

Joe believes that design is how you respect and value the people who use a product or service. At Airbnb, that meant helping strangers feel comfortable in each other’s homes. In government, it means refusing to accept a low bar for the websites and processes that Americans use to interact with the government.

We begin with CritBuns, Joe’s RISD project that taught him that design is as much about storytelling as it is about product. Then, we discuss what he learned about designing for trust at Airbnb and his initial work at DOGE, streamlining and digitizing the federal retirement process. Joe walks me through America.gov, a single, AI-powered front door to government services. We discuss the challenges of scale and designing for people who are skeptical of both government and AI, including what it means to pass the “grandma test.” We wrap up with why ambitious technologists should aspire to work in government and his collaboration with Airbnb co-founders Brian Chesky and Nathan Blecharczyk.

I hope this conversation raises your expectations for the things we’ve learned to tolerate, and inspires you to think about how you might serve your community or your country.

Full transcript & links at dialectic.fm/joe-gebbia

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Dialectic is presented by Notion. As new models and agents arrive constantly, Notion acts as a context and consolidation layer for all the ways you and your team work with AI: a command center or simply a resilience layer, so your context comes with you even if you switch models or agents. You can also work with agents right inside Notion and share skills with your team through the Skills API. Learn more at notion.com/dialectic.

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Timestamps:

0:00 Opening Highlights

1:26 Intro: Joe Gebbia

4:12 CritBuns & Why Design is Half Story

15:24 Airbnb, The Feeling of Belonging, & Designing for Trust

28:29 Public Service & Fixing Federal Retirement

42:16 Speed, Craft, and Respect

48:43 ND Studio Projects: TrumpRx, Trump Accounts, and Realfood.gov

56:18 America.gov: A New Front Door to Government

1:05:35 Trust, Privacy, and Government AI

1:15:30 America.gov’s Roadmap

1:19:54 Recruiting for ND Studio and Public Service

1:23:41 Reflecting on Year One & Passing the Grandma Test

1:31:05 A Ticking Clock Toward 2028 & Building Beyond One Administration

1:35:44 AI & Product Development

1:38:36 Closing Questions: Charles & Ray Eames, AirBnB Co-Founders, & Trust in People

Adam Mastroianni (Website, X) is an experimental psychologist and the writer of Experimental History. He earned his PhD in psychology at Harvard before leaving academia to pursue research and writing independently.

I first came across Adam through “Good conversations have lots of doorknobs,” which remains one of my favorite essays on Substack.

We talk about why psychology is stuck, why science needs people willing to look stupid, and how prestige can lead you toward a life you don’t want. From there, unpack Adam’s coffee bean test for figuring out what to do, getting “de-bogged,” and what improv teaches us about better conversations (or: create doorknobs). We also discuss writing that surprises its author, his upcoming book, The Strangest Idea in the World, and the prayer he says before publishing: “Let me be useful.”

I hope you leave a little more willing to question what seems obvious, risk looking stupid, and spend your time in ways you actually enjoy.

Transcript & links: https://dialectic.fm/adam-mastroianni

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Dialectic is presented by Notion. Notion is an AI-powered connected workspace where teams think together and create their best work. Notion AI works across your documents and context, while custom workers can automate recurring tasks and connect with your other tools. You can also explore Notion’s Knowledge Board, which evaluates how AI models perform on real knowledge-work tasks. Learn more at notion.com/dialectic.

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This episode is supported by Google. Google Antigravity is Google’s agentic development platform. Describe what you want to build, and its agents can plan the work, write and run code, and test the result, with plans and changes you can review along the way.

Gemini 3.5 Transcribe turns audio into text with a choice of verbatim and Smart modes. Verbatim mode keeps fillers and false starts, and supports speaker labels and word-level timestamps to help you check the transcript against the recording. Smart mode removes filler words and repetitions and formats speech into readable text. I used Antigravity and Gemini 3.5 Transcribe to build a Mac app for producing and reviewing Dialectic transcripts.

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Timestamps:

04:33 Start: Why Psychology is Stuck & The Focus of Adam's Blog

14:43 The Scientific Virtues of Stupidity and Rebellion & Escaping the Prestige Trap

25:08 Patronage for Weirdos

33:53 Progress in Psychology

52:15 Figuring Out What to Do, The Coffee Bean Test, and Unpacking Adam's Day-to-Day

01:03:22 Getting De-bogged and Making Ideas Land

01:14:11 Conversational Doorknobs: Giving and Taking

01:22:23 Blogging, Community, and Rules we Invent

01:28:35 Writing Advice, Thick Art, Giving The Reader an Egg to Crack

01:44:03 Adam's First Book: The Strangest Idea in the World

01:53:23 Closing Questions

Immad Akhund (⁠X⁠, ⁠LinkedIn⁠) is the co-founder and CEO of ⁠Mercury⁠. He is also a prolific angel investor and co-hosts the ⁠Founders in Arms⁠ podcast.

Mercury is a fintech banking platform used by one in three startups. It is Immad's fourth company in 20 years of entrepreneurship. Mercury is in the process of becoming an FDIC-insured bank and recently launched ⁠Mercury Books⁠, AI-powered accounting software.

Immad grew up in Pakistan, moved to London at nine, and left for San Francisco at 23 to become an entrepreneur "for real." Mercury is built on something rare in finance: a willingness to spend a disproportionate amount of energy on details, the kind of care Immad admits "seems irrational.”

We start with a simple question (what is a bank?) and discuss why banking stayed bad for so long, what stays hard as AI makes software easy to build, and why Mercury's motto is "be extremely helpful." Entrepreneurship has shaped Immad's life, and he hopes Mercury can empower a generation of entrepreneurs.

I hope you come away a little more annoyed by the mediocre things we've all learned to tolerate and inspired to put an irrational amount of care into making them better.

⁠https://dialectic.fm/immad-akhund⁠

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Dialectic is presented by ⁠Notion⁠. Notion is an AI-powered connected workspace where teams ⁠think together⁠ and create their best work. It works with all of your agents and keeps context across them and your team. ⁠Check out the new Notion Skills API⁠. You can learn more at ⁠notion.com/dialectic⁠.

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Timestamps:

(0:00) Opening Highlights

(1:50) Intro: Immad Akhund

(4:16) Start: Banks and Why Immad Was Suited to Build One

(20:30) What Traditional Banks Do Well & What Mercury Got Right

(29:33) Why Mercury Wants a Bank Charter

(35:57) What's Scarce When Software Is Easy

(49:00) Becoming the Default for New Entrepreneurs

(53:34) Product: 100 Little Things Better

(1:06:51) The Right to Win

(1:09:19) Brand as Care

(1:15:19) Culture and Being Extremely Helpful

(1:22:51) Command, Agents, and AI

(1:34:26) Ambition, Investing, and Leading

(1:46:54) Family, Pakistan, and America

(1:52:56) Money, Freedom, and Energy

(1:59:14) Outro

Independent Study is a series of bonus episodes to accompany the interviews on Dialectic. I read essays and other writing that has influenced me.

"Personal Renewal" was given as a speech by John W. Gardner to a group at McKinsey & Company in Phoenix, AZ on November 10, 1990. The transcript is available at PBS here.

John W. Gardner was a public servant, educator, and public reformer. Learn more at PBS.

This is one of my favorite things I've ever read. I hope you are similarly inspired.

Transcript and audio for the also mentioned David Foster Wallace's "This is Water" available here, from Farnam Street.

https://www.pbs.org/johngardner/sections/writings_speech_1.html⁠