Chris Best is the co-founder and CEO of Substack, the platform powering the rise of independent writers, podcasters, and thinkers. At Substack, Chris has reimagined what sustainable media looks like, putting creators at the center.
Andrew Mayne is the host of the OpenAI podcast and was previously the company’s first prompt engineer and science communicator, where he helped shape how people interact with and understand large language models in the earliest days of GPT-3. 3. He’s also a mystery-thriller novelist and the founder of Interdimensional, a company helping organizations deploy AI.
Together, they unpack how technology rewires culture, creativity, and even capitalism—from the birth of ChatGPT to the flood of “AI slop,” from the evolution of media business models to what makes human expression irreplaceable.
It’s a conversation that circles around the economics of culture and the future of originality as creating art becomes more and more accessible.
In this conversation, you’ll learn:
Referenced in this episode:
Where to find Andrew Mayne:
Where to find Chris Best:
Where to find The General Partnership:
Claire Hughes Johnson (former COO at Stripe) and Gretchen Howard (former COO at Robinhood) join The General Podcast for a rare, candid conversation about what it really means to operate at the highest levels inside two of the most ambitious fintech companies of the past decade.
Both left safe jobs to take bets that looked “crazy” from the outside. Both joined hyper-growth startups without the COO title, built trust with founders in real time, and ended up shaping the companies from the inside out. In this episode, they dig into what the COO role actually is, how to avoid “organ rejection” when you’re the outsider, and why the people function is the most underrated lever for scaling.
You’ll hear Claire and Gretchen swap notes on why the hardest problems are often unglamorous—compliance, self-clearing, comp plans—and why the real work is about earning trust, building velocity, and protecting the integrity of the company as it grows.
In this conversation, you’ll learn:
Where to find Gretchen:
LinkedIn: https://www.linkedin.com/in/gretchenehoward
Where to find Claire:
X: https://x.com/chughesjohnson
LinkedIn: https://www.linkedin.com/in/claire-hughes-johnson-7058
Book: Scaling People
Where to find TheGP:
X: @thegp
Newsletter: https://thegeneralpartnership.substack.com/
Dan Shipper is the co-founder and CEO of Every, a media company built around writing, software, and AI. With a tiny team, they put out a daily newsletter, build products, and run a consulting arm, all while staying weird and experimental. Dan’s one of the most thoughtful writers on how AI is reshaping creativity, business, and what it means to build.
Alex Konrad is the founder of Upstarts, a newsletter about the next breakout companies before they break out. He spent over a decade at Forbes, where he wrote 15+ cover stories, co-created the Cloud 100 list, and led Midas List coverage of the top VCs in the world.
Together, they discuss and debate building sustainable media businesses today, using AI to amplify creativity, and why legacy playbooks no longer apply.
In this conversation, you’ll learn:
1. Why being weird is often a competitive advantage
2. How thinking like a product person (and not just a writer) shapes everything they publish
3. The surprisingly tactical ways they protect time for original thinking
4. Why Upstarts and Every both resisted the pressure to “build the platform” too soon
5. How Every runs multiple AI products and a daily newsletter with only 15 people
6. Why they both believe your business model is a creative decision
7. Their thinking around independent journalism as a “tech-enabled service,” not content
8. How AI tools like Claude, Cora, and ChatGPT actually fit into their creative process
9. How to avoid burnout when your business is also your identity
10. How to stay joyful and experimental when everyone else is optimizing
Where to find Dan:
Newsletter: every.to
X: @danshipper
Where to find Alex:
Newsletter: https://www.upstartsmedia.com
X: @alexrkonrad
Where to find TheGP:
Newsletter: https://thegeneralpartnership.substack.com/
X: @thegp
Referenced in this episode:
Christina Farr, longtime healthtech journalist and now advisor, investor, and editor-in-chief of Second Opinion Media, sits down with Siddhartha Mukherjee, Pulitzer Prize–winning author of "The Emperor of All Maladies," oncologist, and founder of Manas AI.
In this expansive conversation, they explore the current and future role of AI in medicine. Sid offers a typology for how LLMs are showing up in clinical practice and scientific discovery, while Chrissy pushes on what AI can’t yet replicate: intuition, empathy and institutional memory. They discuss whether AI will replace the “intelligentsia,” what it gets right and wrong about diagnostics and drug discovery, and how clinicians can stay relevant by staying creative. This is a thoughtful, urgent discussion between two people who are both deeply familiar with the systems of medicine.
In this conversation, you’ll learn:
1. A six-part framework for how AI is transforming healthcare and science
2. How ambient scribes, LLMs, and generative chemistry are reshaping workflows
3. The difference between simulated empathy and real human care
4. What LLMs still miss: texture, taste, and tacit knowledge
5. How AI might (or might not) generate revolutionary scientific insights
6. Why the future belongs to clinicians who generate new knowledge, not just apply it
Where to find Chrissy:
LinkedIn: https://www.linkedin.com/in/christinafarr/
X: https://x.com/chrissyfar
Substack: https://secondopinion.media/
Where to find Sid:
LinkedIn: https://www.linkedin.com/in/siddhartha-mukherjee-19b6b8126/
The New Yorker: https://www.newyorker.com/contributors/siddhartha-mukherjee
Books: The Emperor of All Maladies, The Gene, The Song of the Cell
Where to find TheGP:
Referenced in this episode:
• Manas AI: https://www.manasai.co
• Richard Feynman’s “Cargo Cult Science” lecture: https://calteches.library.caltech.edu/51/2/CargoCult.htm
• Thomas Kuhn’s The Structure of Scientific Revolutions: https://www.amazon.com/Structure-Scientific-Revolutions-50th-Anniversary-ebook/dp/B007USH7J2/
• Karl Popper’s theory of falsifiability: https://www.simplypsychology.org/karl-popper.html
• Stephen Jay Gould’s “The Median Isn’t the Message”: https://journalofethics.ama-assn.org/article/median-isnt-message/2013-01
• David Fajgenbaum’s Chasing My Cure: https://chasingmycure.com/
Katie Dill, Head of Design at Stripe, and Randy Hunt, Head of Design at Notion, sit down to swap stories in the first episode of The General Podcast. This is a conversation between two of the most thoughtful design leaders in tech, covering everything from building taste into products to maintaining creative conviction inside fast-scaling orgs. They discuss how to protect what makes design great, what designers uniquely bring to the table in the age of AI, and why sometimes you just have to pick mint chip and go.
In this conversation, you’ll learn:
Where to find Katie:
Where to find Randy:
Where to find TheGP:
What is The General Podcast?