The Generalist

Sequoia Capital is synonymous with outstanding performance, backing companies like Apple, Google, Airbnb, and Stripe. In today’s episode, I chat with Roelof Botha, Sequoia’s Managing Partner, about what it takes to see the future first, capitalize on it intelligently once it arrives, and help founders build enduring companies. 

Roelof is especially well-placed to discuss such matters. Not only has Sequoia navigated more than 50 years of market cycles, Roelof has personally spent more than 20 years helping shape the firm’s unique approach. From honing a philosophy rooted in clear thinking and long-term vision to asking the tough question of "What would you do with only 12 months of runway?" Roelof breaks down the mindset that’s helped Sequoia and its founders thrive, and what others can learn from it. 

In our conversation, we explore:

• The psychological biases that most frequently derail investors

• Why the first-mover advantage is often a disadvantage in technology  

• Why excess funding often undermines innovation

• The story of PayPal's near-death experience and how it sparked its most critical innovations

• How Roelof’s training as an actuary shaped his long-term thinking 

• How Sequoia maintains investment discipline through market cycles 

• Why they don’t use the word “deal” at Sequoia 

• How the US can maintain the lead in the AI race

• The thinking behind the Sequoia Capital Fund and the firm’s organizational structure 

• And much more

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Thank you to the partners who make this possible

Brex: The banking solution for startups.

WorkOS: The modern identity platform for B2B SaaS.

Explo: Customer-facing analytics for any platform.

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For a full transcript of the episode, please visit: https://thegeneralist.substack.com/p/lessons-from-20-years-of-vc-roelof-botha

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Timestamps

(00:00) Intro

(04:50) Roelof on the AI bubble

(07:26) Sequoia’s Monday tracker and investment tools

(09:25) AI's role in business growth

(11:55) The challenge of spotting unicorns in a climate of rapid growth

(14:48) Roelof’s critique of capital-heavy AI startups

(19:30) A glimpse at how partners work at Sequoia

(21:43) A lesson from PayPal

(24:09) Roelof’s interest in decision-making and biases

(27:19) Two key biases: loss aversion and anchoring

(30:55) Examples of anchoring with Square and Twitter

(36:30) The case for long-term thinking

(41:00) Sequoia’s culture and commitment to winning

(48:38) What Sequoia looks for in founders

(51:39) How new technology enables less technical founders to succeed

(54:06) Why AI may favor incumbents over startups

(57:12) Where the US stands in the AI race

(1:01:16) The risks of government overspending

(1:03:54) Sequoia’s journey from idea to IPO

(1:10:44) How Sequoia uses AI

(1:15:05) Final meditations

Performance numbers shared in this interview are as of March 24, 2025. Past performance is not indicative of future performance.

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Follow Roelof Botha

X: https://x.com/roelofbotha

LinkedIn: https://www.linkedin.com/in/roelofbotha/

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Resources and episode mentions

—Books—

• Decisive: How to Make Better Choices in Life and Work: https://www.amazon.com/Decisive-Make-Better-Choices-Life/dp/0307956393/

• Leading: Learning from Life and My Years at Manchester United: https://www.amazon.com/Leading-Learning-Years-Manchester-United/dp/0316268100

• A Tale of Two Cities: https://www.amazon.com/Tale-Two-Cities-Penguin-Classics/dp/0141439602

• Man’s Search for Meaning: https://www.amazon.com/Mans-Search-Meaning-Viktor-Frankl/dp/0807014273/r

—People—

• Don Valentine: https://en.wikipedia.org/wiki/Don_Valentine

• Daniel Kahneman: https://www.nobelprize.org/prizes/economic-sciences/2002/kahneman/facts/

• Brian Chesky on X: https://x.com/bchesky

...Episode resources continued at: https://thegeneralist.substack.com/p/lessons-from-20-years-of-vc-roelof-botha

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Production and marketing by penname.co. For inquiries about sponsoring the podcast, email [email protected].

Josh Wolfe is a co-founder of Lux Capital, where he funds the kinds of ventures that change everything: think gene-edited pig organs and technology that lets you “record” smells. His approach? Relentless curiosity. He reads dozens of newspapers daily to identify patterns, always staying a few steps ahead. In this episode of The Generalist, Josh shares how his firm backs companies that don’t just predict the future, but create it.

In our conversation, we explore:

• The revolutionary development of genetically modified pig organs being transplanted into humans and what this means for the future of organ transplantation.

• The recent achievement of "teleporting smell" across space and why computers that can replicate scents will open up entirely new industries.

• Why Lux is investing in the search for real-life "X-Men" — genetic outliers in isolated populations whose DNA could lead to life-saving medical advancements.

• How Josh evaluates macro trends to make smarter micro investment decisions and why ignoring the big picture is a mistake.

• The three tech sectors that Josh believes will define the geopolitical balance in the decades ahead.

• How Josh stays current on macroeconomic trends.

• Much more

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Thank you to the partners who make this possible

Brex: The banking solution for startups.

WorkOS: The modern identity platform for B2B SaaS.

Generalist+: Essential intelligence for modern investors and technologists.
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For a full transcript of the episode, please visit: https://thegeneralist.substack.com/p/shrinking-the-gap-between-sci-fi-and-sci-fact-josh-wolfe

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Timestamps

(00:00) Intro

(04:38) A brief overview of Josh’s work at Lux Capital 

(05:57) The science fiction to science fact pipeline 

(09:11) Xenotransplantation

(12:10) Proven transplantations with modified pig kidneys, and what’s next 

(15:38) Ethical questions around xenotransplantation 

(17:48) Lux Capital’s investment in eGenesis

(19:34) The theory of persistent cellular memory 

(23:35) Why eGenesis began with kidneys

(24:30) Digitizing smell

(32:24) Commercializing digital olfaction technology

(38:26) The potential applications for a “Shazam for smell” 

(43:16) Variant Bio’s work studying genetic outliers 

(52:00) Variant Bio's two primary clinical focuses

(53:46) How Josh stays current on macroeconomic trends

(59:44) Josh’s thoughts on the critical areas the U.S. should invest in

(1:14:00) How to win the talent war

(1:18:53) Final meditations

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Follow Josh Wolfe

X: https://x.com/wolfejosh

LinkedIn: https://www.linkedin.com/in/josh-wolfe-7883/

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Follow Mario Gabriele

Newsletter: https://thegeneralist.substack.com/

LinkedIn: https://www.linkedin.com/in/mariogabriele/

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Resources and episode mentions

—Books—

• 20,000 Leagues Under the Sea: https://www.amazon.com/000-Leagues-Under-Wordsworth-Classics/dp/1853260312

• War of the Worlds: https://www.amazon.com/War-Worlds-H-G-Wells/dp/8175992824/

• In Search of Lost Time: https://www.amazon.com/Search-Lost-Time-Library-Classics/dp/0812969642

• Perfume: The Story of a Murderer: https://www.amazon.com/Perfume-Story-Murderer-Patrick-Suskind/dp/0375725849/

• Poor Charlie's Almanack: The Wit and Wisdom of Charles T. Munger: https://www.amazon.com/Poor-Charlies-Almanack-Charles-Expanded/dp/1578645018

—Other Resources—

• eGenesis: https://egenesisbio.com/

• Xenotransplantation: https://egenesisbio.com/xenotransplant/

• Surgeons Transplant Engineered Pig Kidney Into Fourth Patient: https://www.nytimes.com/2025/02/07/health/fourth-pig-kidney-transplant.html

• CRISPR: https://www.genome.gov/genetics-glossary/CRISPR

• Can an Organ Transplant Change Someone’s Personality? https://www.psychologytoday.com/us/blog/the-leading-edge/202402/do-organ-transplants-cause-personality-change-in-recipients#

...Episode resources continued at: https://thegeneralist.substack.com/p/shrinking-the-gap-between-sci-fi-and-sci-fact-josh-wolfe

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Production and marketing by penname.co. For inquiries about sponsoring the podcast, email [email protected].

Science fiction has long warned of AI's dark side. Think: Robots turning against us, surveillance, and lost agency. But in this episode of The Generalist, Reid Hoffman, co-founder of LinkedIn and AI pioneer, shares a more hopeful future. His book Superagency argues for AI optimism, grounded in real-world experience. We talk about how AI can fuel creativity and how to ensure technology works for us, not the other way around.

We explore:

• Why Reid wrote Superagency—and his belief that AI leads to more human agency, not less

• The philosophical questions raised by AI’s reasoning—can machines truly think, or are they just mimicking us?

• How generative AI promotes collaboration and creativity over passive consumption

• Preserving humanity's essence as transformative technologies like gene editing and neural interfaces become mainstream

• Reid’s optimistic take on synthetic biological intelligence as a symbiotic relationship

• How AI agents can actually deepen human friendships rather than replace them

• A glimpse at how Reid uses AI in his daily life

• Reid’s “mini-curriculum” on science fiction and philosophy—two essential lenses for understanding AI’s potential

• And much more

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Thank you to the partners who make this possible

Vanta⁠: Automate compliance and simplify security.

Brex⁠: The banking solution for startups.

WorkOS⁠: The modern identity platform for B2B SaaS.

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For a full transcript of the episode, please visit: ⁠https://thegeneralist.substack.com/p/how-ai-will-enhance-human-potential-reid-hoffman⁠

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Timestamps

(00:00) Intro

(06:10) Why Reid wrote Superagency

(11:30) Reid AI—and using tech to highlight human agency

(13:55) The book Amusing Ourselves to Death, and the pros and cons of any new technology

(18:55) A brief overview of Reid’s career

(25:16) An explanation of Reid’s belief system as a ‘mystical atheist’ 

(27:47) Reid’s term ‘homo techne’ and how technology makes us more human

(33:54) Preserving genetic diversity to safeguard humanity

(39:05) Reid’s optimistic take on synthetic biological intelligence

(42:34) Why Reid wants more optimistic science fiction

(45:40) The value of literature—and potential future mediums for creatives

(49:12) The importance of thoughtful regulation

(59:35) AI’s impact on human friendships

(1:03:49) Platforms for AI agents 

(1:05:50) How Reid uses AI in his daily life 

(1:09:28) Final meditations

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Books

• Superagency: What Could Possibly Go Right with Our AI Future: ⁠https://www.amazon.com/Superagency-Could-Possibly-Right-Future-ebook/dp/B0D886ZQHY⁠

• Impromptu: Amplifying Our Humanity Through AI: ⁠https://www.amazon.com/Impromptu-Amplifying-Our-Humanity-Through/dp/B0BYLSCPPV⁠

• 1984: ⁠https://www.amazon.com/1984-Signet-Classics-George-Orwell/dp/0451524934⁠

• Amusing Ourselves to Death: Public Discourse in the Age of Show Business: ⁠https://www.amazon.com/Amusing-Ourselves-Death-Discourse-Business/dp/014303653X⁠

• Brave New World: ⁠https://www.amazon.com/Brave-New-World-Aldous-Huxley/dp/0060850523⁠

• On Bullshit: ⁠https://www.amazon.com/Bullshit-Harry-G-Frankfurt/dp/0691122946⁠

• Culture series: ⁠https://www.amazon.com/Iain-M-Banks-Culture-anniversary/dp/0356502090/⁠

• Klara and the Sun: ⁠https://www.amazon.com/Klara-Sun-Ishiguro-Kazuo/dp/0571364888⁠?

• Ulysses: ⁠https://www.amazon.com/Ulysses-James-Joyce/dp/0679722769⁠

…For a complete list of books and all other resources mentioned in this episode, check out the show notes at: ⁠https://thegeneralist.substack.com/p/how-ai-will-enhance-human-potential-reid-hoffman⁠

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Follow Reid Hoffman

• Website: ⁠https://www.reidhoffman.org/⁠

• X: ⁠https://x.com/reidhoffman⁠

• LinkedIn: ⁠https://www.linkedin.com/in/reidhoffman/⁠

• Podcast: ⁠https://www.possible.fm/⁠

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Follow Mario Gabriele

• Newsletter: ⁠https://thegeneralist.substack.com/⁠

• LinkedIn: ⁠https://www.linkedin.com/in/mariogabriele/⁠

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Production and marketing by ⁠penname.co⁠. For inquiries about sponsoring the podcast, email [email protected].

Welcome to The Generalist – a podcast about the future brought to you by Mario Gabriele. This isn’t your typical innovation podcast. Each week, we go beyond the headlines and into the minds of the founders, investors, and thinkers who are building tomorrow’s world. From AI to space exploration, nuclear fusion to new media, stablecoins to semiconductors, these are the people living in the future today.

In just 60 minutes each episode, we’ll dive into the ideas, technologies, and strategies that are shaping industries and societies in real-time.

Production and marketing by penname.co.