2025-04-24 21:17:29
“Some of the best analytical work out there - we learn something new from every post!” - Peter, a paying subscriber
Friends,
If you want to, you can divide the world into two tribes.
There are the People of Certainty and the People of Doubt. I belong to the latter camp. There is no opinion I hold unequivocally. Everything looks probabilistic if I inspect it closely enough.
This posture means that when I encounter someone from the other tribe, a Person of Certainty, I find myself a little stupefied. How can anyone believe something so fully? How can they know, in themselves, so many things with such clarity?
Providing they are not weak-minded or boorish, these people make the best conversationalists. They do not hedge or waffle, they are unlikely to backtrack; they emblazon the air with their opinions. Hearing them is an invitation to a different kind of thinking, into a strangely vivid reality.
Keith Rabois is one of these conversationalists, a high priest among the People of Certainty. Though you might not agree with his battle against the evils of stretching or share his veneration for Margaret Thatcher, his mind undeniably fizzes with inventive ideas colored by a trademark surety.
That mind, combined with a ferocious drive that still animates him 25 years into his tech career, has made Keith one of the most consistent hitmakers in the industry.
Arguably, no one else has succeeded so completely as an operator, investor, and founder. As an operator, Keith helped build PayPal, Square, and LinkedIn into multi-billion-dollar behemoths. As an investor, he’s backed a steady stream of unicorns, including Ramp, DoorDash, YouTube, Airbnb, Stripe, Webflow, Checkr, Faire, Palantir, Udemy, Trade Republic, and Affirm. As an entrepreneur, Keith is best known for launching real estate company Opendoor, which hit an $18 billion valuation as part of its public market push before fading in the following years. He is now back in the founder’s seat (while also investing at Khosla Ventures), serving as CEO of OpenStore, an e-commerce rollup.
All of which is to say that there are no guarantees in tech, a land governed by the Power Law, but Keith Rabois comes ludicrously close.
In this edition of Modern Meditations, Keith and I discuss his passion for EDM, how he identifies exceptional talent before they’ve proven their abilities, what Reid Hoffman said about Max Levchin, why he believes in “input-driven” management, and why he believes everyone should increase their stress levels.
To unlock The Generalist’s full library of interviews, case studies, and tactical guides, consider becoming a premium subscriber today. For $22/month, you’ll discover breakthrough startups, hear from investing legends like Keith, Reid Hoffman, Kirsten Green, Ho Nam, and Vinod Khosla, and access the playbooks of elite founders.
Possibly politics. There are attractive aspects to it, like the potential impact you can have. But there are significant downsides, too.
Politics is more of a zero-sum game. By definition, if one person is appointed to a role, it means a hundred people are not. Technology, by contrast, is almost never zero-sum. If I build a successful startup, that doesn’t foreclose your ability to build one, too. Working in a non-zero-sum field is exciting.
I didn’t always know I would work in technology, of course. Up until 2000, I had followed a pretty canonical legal trajectory: I attended a top-tier law school, clerked for Edith H. Jones, an extremely well-known federal appellate court judge, then spent three-and-a-half years as an associate at Wall Street’s most prestigious firm, Sullivan & Cromwell. I was going down the most conventional, credentialist path possible, with politics looking like the road ahead.
Then, in February 2000, I dropped out completely to jump into the technology revolution. It was right at the height of the dot-com bubble and six weeks later, the entire market collapsed. My choice of direction might have been right, but the timing was disastrous. Twenty-four years later, with the benefit of hindsight, it worked out fine.
It was a radical switch for me – I had been a litigator, not a transactional attorney. And law is, in many ways, the antithesis of entrepreneurship. You spend your time mostly thinking about what can go wrong, not what can go right.
Instead of taking an intermediary role by joining a legal department at a tech company, I switched cold turkey, joining Voter.com to do business development before heading to PayPal. Just, “I’m jumping out completely, and I’m going to be 100% a business person.” I wanted to grow revenue lines and learn how to do that, even though I’d never used an Excel spreadsheet in my life. Fortunately, I’m past the point where I have to use Excel now, but the first five years were rough.
Talent spotting. There’s a common denominator between building a company and being an early-stage investor – it’s identifying the alpha in people.
The technique differs when applied to founders versus employees, but in both cases, you’re trying to identify the highest-potential people on the planet as early as possible in their trajectory. That’s the art of venture capital, and to some extent, it’s how you scale a high-tech company.
At Khosla Ventures, our mantra is to be “bold, early, and impactful.” “Early” means I want to be the first institutional capital in every single company of note. The only way to do that is by having an unfair advantage in attracting and assessing undiscovered talent.
It’s easy to state that conceptually, but extremely difficult to do. Even meeting those people is hard, let alone assessing them before they have any proof points. But if you do it well, it’s very rewarding financially and psychologically.
One of the reasons it’s so hard? Because there’s no common pattern. What makes Mike from Traba special is very different from what makes Eric at Ramp compelling and unique. They’re both going to build iconic companies, though. Because there’s no formula, it’s rare to be a proficient talent spotter, and even if you are, it’s challenging.
The most common denominator, at an abstract level, is that the person is between the top 1 basis point and top 10 basis points at something. To simplify it, when I walk out of a meeting with a founder that has that kind of high potential, I usually say to myself, “Wow, I’ve never met anybody like that before.”
What I mean is that the founder is the best I’ve ever seen on a certain dimension. They could be the smartest person, most tenacious, most analytically rigorous, or have the greatest sales ability, best design instincts, or the strongest reality distortion field. But on some dimension, I have to feel like they are in the top 1 basis points. If you don’t feel that, they’re probably not going to be a super successful founder.
There is a slight variation on this to look out for. Sometimes, you find someone with an overlap of traits that are rarely combined. I remember Reid Hoffman sitting me down in December 2000 and explaining to me why Max Levchin was so special. “Max is a first-rate technologist. Max is a first-rate business mind. There are less than five of those people in the world.” This was long before Max had proven his talent, but Reid understood that he had this unusual Venn diagram overlap.
Jack Dorsey is another example of this: a first-rate mind, a first-rate business strategist, and a reasonably good technologist. That’s an incredibly rare combination. His design talent showed up in different ways. For example, at Square, he spent so much of his time recruiting Robert Andersen. Simply knowing that Robert was the single best person in the world to recruit takes talent.
Inputs versus outputs. When I started my career at PayPal, we were an outputs-driven organization. Now, I’ve flipped pretty much 180 degrees to believing in inputs-driven organizations.
There are successful examples of both approaches in technology. Apple and Amazon are more input-driven, while Meta and Google are more output-driven. I don’t think it’s impossible to succeed with either approach, but I’ve found that one style works better for me.
My experiences at Slide and Square informed my opinion here. Slide was output-driven and not successful, while Square was 100% inputs-driven and very successful.
In terms of newer companies, I would say that Basis, which does AI accounting, is very inputs-driven. They spent two years building the perfect product. They really obsessed over it, believing that customer adoption and revenue will take care of themselves once you have a high-quality product.
Meanwhile, Traba is a bit of a hybrid, though probably a little further on the output side. They manage through OKRs very aggressively, which is a classic part of output philosophy. The reason it’s a bit of a hybrid is that they’re also strict on the input side with their 9-9-6 culture and expectation of being in the office 80 hours a week.
There’s a great book on input-driven company building by football coach Bill Walsh called The Score Takes Care of Itself. It perfectly captures the methodology for building an input-driven, successful organization. I recommend that book to all of the entrepreneurs I work with. It has some overlap with Andy Grove’s High Output Management, but as the title implies, it’s output-driven. Over my career, I’ve transitioned from high-output mode to high-input mode.
Margaret Thatcher. Almost everything important you need to learn, you can learn from her career. She’s been my idol since I was in junior high school, maybe even earlier. To me, she’s an example of principled leadership, not accepting the status quo or inertia, and always doing the right thing, even when that wasn’t popular.
The reality is that the UK was basically falling apart. It was a corrupt, socialist, non-egalitarian, elitist world. Thatcher reinvigorated the country in many, many different ways through her force of will, energy, and intelligence.
I’ve adopted some of Thatcher’s expressions so thoroughly that I forget they derive from her. It’s only when I watch a movie about her life or reread her autobiography that I realize. My favorite expression of hers is “No, no, no.”
There are many good applications of that phrase – both of my kids like to mimic me, saying, “No, no, no” all the time. It’s turned into a bit of a caricature with them already. But there’s real value in it – it represents good discipline. There’s the famous Steve Jobs speech that describes focus as saying no to a thousand things to excel at just one. There’s also the sense in Thatcher’s words of not going along with the crowd or accepting conventional wisdom. It’s my favorite expression – maybe in the world.
As rough introductions go, the recent seasons of The Crown are pretty good, though they’re a little bit distorted by left-wing biases. If you want to read more rigorous materials, there’s a great chapter in Kissinger’s last book (Leadership: Six Studies in World Strategy); for political types, her collected speeches are worthwhile, and the first volume of her autobiography charts her political career amazingly well. It also captures the weakness of other people – those from elite and entitled backgrounds who were envious of her success and conspired to depose her. Thatcher never lost an election; in fact, she technically never lost a leadership election within her party. Still, the insiders, with their envy and jealousy and pettiness, combined to force her out of power.
The Conservative party has never really rebounded, in my opinion. It’s been a bunch of mostly bland politicians, which is why they’re out of power. Because Labour is so bad, I think there will eventually be a fresh face that re-energizes the Conservatives, just like what happened in the United States with Trump.
Unfortunately, my views are moving into the mainstream so fast that I don’t know what to choose anymore. All my pseudo-conspiracy theories are becoming accepted wisdom. A decade ago, I had between 5-15 ideas that were pretty out there. All of them are now somewhere between 90% and 99% accepted. So, I have to go back to the drawing board.
I remember that in March 2013, I got about 10 friends together for my birthday. I went through all these kinds of crazy “Keith precepts,” trying to convince people to form a Rabois Institute with me to publish studies supporting my ideas. One of the major ones for the Rabois Institute to study was going to be the importance of sleep. I had this long-standing view that the most important thing you could do to improve your happiness, health, and wealth was to sleep better. Even in 2013, that was incredibly controversial; now, I think it’s almost banal.
Two other ideas I’d cite:
First, I think stretching is bad for you. I’m starting to get some real traction around this and beginning to marshal some evidence.
Second, I believe the best thing you can do for yourself is to increase the stress in your life. Basically, everything we’ve been taught about stress is wrong. If you want to be happier, you want more stress in your life, not less. You want to embrace stress. I’ve lived my life that way for 50 years.
That was highly controversial in 2013 and still generates a fair amount of heat in the public domain today.
My two favorite art forms are books and music. I read voraciously and consume EDM music constantly. I also collect old school art, but I don’t tend to obsess about what’s hanging on my walls as much as music or reading.
I don’t listen to EDM while I do traditional work. It’s probably the wrong genre for deep concentration, but for mood and energy enhancement, it’s excellent for me. I walk around constantly with AirPods while listening to EDM, and I enjoy going to shows. A few companies I’m involved in give people “walk-on” songs when they’re speaking at an all-hands meeting, which I like. My go-tos would be “Heroes” by Alesso and “High on Life” by Martin Garrix.
Beyond mood enhancement, music is also great for improving athletic performance. It’s a pretty well studied topic. As a starting point, there’s a reason why no athletic competition in the world allows competitors to listen to music. If you want to improve your performance in the gym or running or swimming, you need to find the right music, optimized for the activity. I have my playlists pretty dialed in.
Dedication. It combines resilience, consistency, and a lack of excuses.
I try to model this myself. I have a philosophy – #nodaysoff – because I believe you should never take a day off from anything important. I’ve literally missed only seven days of workouts in the last seven years. I track it meticulously and occasionally post screenshots. I’m still frustrated that its seven days, not two or three.
Last year, I missed one and a half days, and Sam Lessin asked me on Twitter what caused me to miss a day. It was because I had a severe back injury. Sam responded, “You only missed a day with a severe back injury?”
It was true. It was a severe injury – borderline hospitalization level. When I told my regular doctor, he said, “You know you’re going to have to take a month off.” So, then I went to my other doctor and said, “How can I start working out tomorrow?”
Fortunately, it happened in San Francisco. I was able to get access to an incredible sports medicine doctor who is truly outstanding at what he does. Maybe there’s someone on par with him in New York, but if it had happened in most other cities, I don’t think I could have recovered as fast. Between his ability, creativity, and access to technology, we were able to make it happen.
We used different cutting-edge technologies; the most advanced was a dual-wave laser. In high school, most of us learn how sunlight stimulates plant growth through photosynthesis. We work similarly, except for the fact that getting light to penetrate the skin and reach our cells is difficult. Lasers are strong enough to penetrate deeply, but they tend to burn your skin; the average laser has approximately a 30% burn rate, which is way too high-risk for the FDA to approve.
They created a dual-wave laser to get around these issues. Its effective power is deep enough to penetrate relatively deeply but with zero burn risk profile. As of July 2024, there were only something like 10 of these in the world.
Directionally, I’d probably go into the realm of Bryan Johnson’s work – exploring how to extend our healthy lifespans. I don’t think I’d approach it exactly the same way, and I don’t subscribe to all his views or recommendations. But I absolutely believe that avoiding dying – maybe not forever, but deferring it – is a very realistic objective, and I don’t think traditional medicine or research are really trying.
However, I’m way too distracted with my day job right now. I don’t have a lot of spare cycles to think about it. But if an entrepreneur who’s passionate about extending human life span with a venture-scale business crossed my desk? That would be great.
We should revert to raising children the way we did 20, 30, 40, 50, 60 years ago.
My parents gave me an incredible degree of freedom that would be almost unfathomable today. From my recollection, I walked to school by myself at the age of six years old – plus or minus a couple of years. My school wasn’t that far in the grand scheme of things, but I had to cross major streets with the help of a crossing guard. Today, if I suggested my kids do the same thing in two years, my friends would think I was crazy.
Insulating kids from the world is not healthy. The faster they absorb real-world lessons, the better. In my house, for example, we don’t have traditional gates for kids around stairs. Instead, from a very early age, we taught them that navigating the stairs can be dangerous and showed them how to do it safely. Because of that, they’ve been able to navigate the stairs successfully since the age of two.
Similarly, in Miami, many houses have pools – we have one in our backyard. It’s not really possible to completely isolate the pool from kids, so from three months old, my children were taught to swim. Now they’re better swimmers than I am. Both kids can swim an entire pool length and get in and out completely comfortably.
These are both simplified examples, but I think they illustrate how we should be raising kids to deal with the modern world. We shouldn’t be insulating them from these things but teaching them how to confront and manage challenges.
The Upside of Stress by Kelly McGonigal.
I think that would be the most transformative for most people. It’s incredibly persuasive. There’s no way you can read it and not have it affect your behavior.
I think we’re in a new era starting this year. The last 20-30 years were the “era of excuses” – that’s over. Now, I think we’re entering an “acceleration era,” where we make things better and faster and stop whining.
It’s very exciting. The next ten years are going to be volatile and unpredictable, but very exciting and thrilling at the same time.
2025-04-17 21:15:54
“I think your Substack contains simply the best writings about venture out there. You provide a kind of storytelling and thoroughness that no one else does. Thanks :)” — David, a premium subscriber
Friends,
Successful serial entrepreneurs are a special breed. Though these founders might not have the unifying pleasure of working on one singular company across multiple decades, they get to test themselves in different environments and learn what works, not just once but repeatedly. Was how they structured the team at their first company smart or sloppy? Did they grow 300% year over year because they architected a high-output organization or because they happened across a hot space?
Building an enduring company requires both luck and skill; the serial entrepreneur has the opportunity to distinguish between the two with unusual precision.
In this edition of the "Letters to a Young Founder" series, I’m thrilled to share wisdom from Marc Lore, one of this generation’s best serial entrepreneurs. Over the past 25 years, Marc has created, grown, and successfully sold multiple businesses – including Quidsi (Diapers.com) to Amazon for $545 million and Jet.com to Walmart for an astonishing $3.3 billion. Marc led Walmart’s e-commerce push over the following 4.5 years, driving America’s biggest retailer into the digital age.
Today, Marc is applying his organizational genius to Wonder, a “new kind of food hall” that’s raised nearly $2 billion to reimagine how we experience restaurant-quality meals. It’s an ambitious undertaking that requires orchestrating countless moving pieces—from real estate and inventory management to culinary excellence and logistics—in an industry known for razor-thin margins and operational complexity. From the outside, at least, Wonder has the potential to become a generational player and the culmination of Marc’s remarkable career.
Throughout our correspondence, Marc reveals the frameworks and systems that have enabled his repeated success. His VCP (Vision, Capital, People) methodology is at the core – a systematic approach to translating audacious visions into concrete metrics, organizational structures, and accountability systems.
What’s particularly striking is Marc’s mathematical precision. Where many founders rely on intuition, Marc has developed quantitative systems for weighting priorities, assigning ownership, and measuring impact throughout his organizations.
For founders grappling with how to scale effectively while focusing on what truly matters, Marc’s insights offer invaluable guidance from someone who has repeatedly mastered this challenging transition.
Why Marc spends 90% of his time on VCP. Marc reveals how his Vision, Capital, People framework has guided his entrepreneurial journey across multiple billion-dollar exits, and why he believes founders who neglect these foundations are destined to fail.
The “ownership points” system Wonder uses to clarify everyone's impact. Marc's quantitative approach to measuring each role's impact creates transparency about value creation throughout the organization.
What it means to have “fat” in the organization and how Marc keeps Wonder lean. The systematic process Marc uses to identify where Wonder is over-investing relative to business impact and how he gradually rebalances resources.
Why Marc hired a Chief People Officer before almost anyone else. Against conventional startup wisdom, Marc made this critical hire during Wonder's earliest stages. He explains why most founders get this timing wrong.
How Marc builds a company that SOARs. Marc’s organizational structure is designed to maximize Speed, Ownership, Accountability, Results (SOAR). Optimizing for those traits creates a high performance and efficient machine.
…and much more. To unlock the full correspondence and everything else The Generalist’s premium newsletter has to offer, join today:
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Subject: The architecture of an org
From: Mario Gabriele
To: Marc Lore
Date: Thursday March 27, 2025 at 12:38 PM GMT
Marc,
I am so excited to be starting this conversation with you, and I'm grateful for your willingness to share your wisdom with me and The Generalist’s readers.
Before turning to your far more formidable accomplishments, I hope you’ll allow me a brief opening gambit. My hope is that it helps frame why I think you’re such an interesting entrepreneur. And, that it leads us into this first correspondence.
When I was first trying to get into the world of startups, I had no concrete skills. I’d studied political science as an undergraduate, worked at a boutique law firm, started trying to write a novel, and then experimented with becoming a chef, attending culinary school and cooking at a modern French restaurant in New York. I’d followed that up by going to grad school to study International Development without a real plan for what I might do afterward.
While I was there, a germinating curiosity in technology turned into an obsession. But as that trajectory suggested, I had no obvious marketable abilities. I couldn’t code, had no design skills, and didn’t really understand what people meant when they said they worked in “product.” I asked a business school professor who had taken a shine to me how, with those limitations, someone like me might break in. (As you can sense from that question, I was still thinking in a very tracked, credentialed, un-startup way in those days.)
“You should be an athlete,” my professor told me.
Sensing my confusion, he explained what he meant. He wasn’t suggesting I don a pair of sprinting spikes and hot tail it to my local track, but be a business athlete. These kinds of people weren’t good at one specific thing but were sufficiently sharp and flexible to be useful across a few different functions. They might start by helping on a marketing task before hopping over to operations or pulling together a spreadsheet for an upcoming board meeting. They were, in effect, competent generalists rather than functional experts.
As you know much better than I do, in the early stage of a startup's life, almost everyone has to be an athlete to some degree. The best engineer might have to help out on customer support during a surge, and the CEO should be prepared to moonlight as an office manager, accountant, janitor, recruiter, and a dozen other roles. (As a company grows, the CEO has to maintain that level of mental dexterity, even as others on the team specialize, adding skills to keep a company growing.)
You have always struck me as one of the current generation’s great business athletes. I say that not because of your sporting connections, though they are considerable. For those who might not know, you ran track and field in college, are the incoming owner of the NBA’s Minnesota Timberwolves and WNBA’s Minnesota Lynx, and founded a venture firm with baseball’s Alex Rodriguez.
Rather, it’s because you seem to approach your work as a business builder with the same craft and dedication we expect from elite athletes. And while I piddled around in the rec leagues throwing up cinder blocks, you’ve been competing at an NBA level for over two decades, scaling massive, operationally complex companies from Quidsi (owner of Diapers.com) to Jet.com to Wonder. Along the way, you’ve landed massive exits, selling Quidsi to Amazon for $545 million and Jet to Walmart for $3.3 billion.
With Wonder, you’re taking another big swing, raising nearly $2 billion in venture and debt capital to build a “new kind of food hall.” (As my history suggests, it’s a concept I’ve always been fascinated by – I briefly helped a friend run a ghost kitchen serving burritos.)
More specifically, Wonder operates physical brick-and-mortar locations and a digital service. From a location on the Upper West Side or Wonder’s app, customers can order from multiple restaurants simultaneously – getting a starter from Marcus Samuelsson’s Streetbird, a pizza from Di Fara, and a cookie from Hungry Gnome.
It’s an audacious mission, requiring you to wrangle real estate, perishable products, beloved brands, temperamental customer preferences, and logistical complexities – in a category known for low margins with established competitors.
With that in mind, I was hoping to use this first correspondence to unpack how, precisely, you architect an organization to take on a challenge of this magnitude. Where do you begin? How do you stage what to focus on and when? How do you ensure that each function within a company is firing at the same time?
In researching your work, I came across a framework you like to refer to: VCP or Vision, Capital, People. When starting a new company, how do you think about turning a vision—which can often feel vague and amorphous—into a methodology that impacts how a business runs? At Wonder today, how do you translate your vision into day-to-day operations?
I suppose I am asking something like: how do you avoid “shipping your org chart?” For those unfamiliar with that phrase, it’s the idea that your product will follow the shape of your organization. If you’re shipping a frivolous mobile game, the consequences might be relatively low – perhaps there’s an inconsistent visual language across the app because your design and product teams barely talk. But when we’re talking about shipping food in all its logistical, emotional, and culinary complexity, the challenges seem undoubtedly greater. (I do not think I’m overestimating the intricacies of turning out consistent truffled mashed potatoes, but correct me if I am wrong.)
With much gratitude,
Mario
Subject: The architecture of an org
From: Marc Lore
To: Mario Gabriele
Date: Monday April 14, 2025 at 9:52 AM PST
Mario,
Thanks for kicking off this conversation. I can’t believe it, but it’s been 25 years of raising money and building companies. You learn lessons with each one, but it always comes back to Vision Capital People. Without exaggeration, I spend 90% of my time as a founder thinking about some aspect of VCP.
Why? Because you need to get the foundation right. Everything else follows from there.
You asked about Vision and how I translate that down to the business. Let’s start there and walk through how the right vision leads to picking the right strategies, which we measure with success metrics.
First, the vision. Explain what you’re going to build in detail, painting a picture of the future. This isn’t something you write once and then put away. You have to constantly come back to it and analyze it. Come back to the words you wrote down and interrogate them.
Maybe you wrote you wanted to build “the best Italian restaurant.” Ok, well, what do you mean by “best?” Is that actually what you mean? Do you want to be truly the best, number one in the world? Or do you just want to be better than your competitor? You have to flesh it out in detail and paint a picture of what the future looks like.
Once you have a vision, you must consider the strategies that get you there. When I say strategies, I don’t mean initiatives over a one-year period but 3-5 pillars that you’re building over the next 10 or 20 years. Strategies are the how: how you and your company will make your vision a reality. These will change more often than the vision, adapting alongside the business.
How do you know if you’re delivering on your vision or that your strategies are working? You need to pull each one down into success metrics.
2025-04-15 20:03:08
Friends,
What if you could record the smell of your grandmother’s kitchen or detect diseases with a breath? Josh Wolfe, co-founder of Lux Capital, is funding the breakthroughs that are turning these concepts into reality.
In this episode of The Generalist, Josh discusses how Lux Capital is backing companies like eGenesis, which is transplanting gene-edited pig organs into humans; Osmo, pioneering digital olfaction technology; and Variant Bio, which is studying genetic outliers in indigenous populations whose DNA could lead to life-saving medical advancements.
Science fiction doesn’t just predict the future, it creates it. Josh’s investment approach is deeply influenced by speculative fiction, which has inspired many of the groundbreaking companies in his portfolio. This visionary thinking has driven Lux to fund startups working on technologies once considered impossible.
Josh also shares how stories shape his worldview, how he stays on top of macro trends, where America is trailing China in the AI race, and how we can catch up.
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
Brex: The banking solution for startups.
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Generalist+: Essential intelligence for modern investors and technologists.
(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
LinkedIn: https://www.linkedin.com/in/josh-wolfe-7883/
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
George Church on LinkedIn: https://www.linkedin.com/in/george-church-2b86301/
David Deutsch on X: https://x.com/daviddeutschoxf
Karl Popper: https://en.wikipedia.org/wiki/Karl_Popper
Feng Zhang on X: https://x.com/zhangf
John Maraganore on LinkedIn: https://www.linkedin.com/in/john-maraganore/
Vicki Sato: https://en.wikipedia.org/wiki/Vicki_Sato
Robert Nelson on X: https://x.com/rtnarch
David Shenkein on LinkedIn: https://www.linkedin.com/in/david-schenkein-md-45342476/
Alex Wiltschko on X: https://x.com/awiltschko
Richard Axel: https://www.nobelprize.org/prizes/medicine/2004/axel/facts/
Andrew Farnam on LinkedIn: https://www.linkedin.com/in/andrew-farnum-4b180a1/
Chris Hohn: https://ciff.org/team/chris-hohn/
Charles Darwin: https://en.wikipedia.org/wiki/Charles_Darwin
Isaac Asimov: https://en.wikipedia.org/wiki/Isaac_Asimov
Neil Gaiman: https://en.wikipedia.org/wiki/Neil_Gaiman
Terry Pratchett: https://en.wikipedia.org/wiki/Terry_Pratchett
Neal Stephenson’s website: https://www.nealstephenson.com/
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
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#
Personality changes following heart transplantation: The role of cellular memory: https://www.sciencedirect.com/science/article/abs/pii/S0306987719307145
Kallyope: https://kallyope.com/
Letter from the founder: https://www.osmo.ai/blog/letter-from-the-founder
Plum 1.0: https://osmostudios.ai/products/plum1o
IFF: https://www.iff.com/
Firmenich: https://www.dsm-firmenich.com/en/
Variant Bio: https://www.variantbio.com/
Gates Foundation: https://www.gatesfoundation.org/
23andme: https://www.23andme.com/
Genentech: https://www.gene.com/
PCSK9 gene: https://medlineplus.gov/genetics/gene/pcsk9/
Leonardo da Vinci DNA Project: https://www.jcvi.org/research/leonardo-da-vinci-dna-project
CBGB: https://www.cbgb.com/
Coney Island High concert history: https://www.concertarchives.org/venues/coney-island-high--5
Community Notes: https://help.x.com/en/using-x/community-notes
Chinese Missile Destroys Satellite in 500-Mile Orbit: https://www.npr.org/2007/01/19/6923805/chinese-missile-destroys-satellite-in-500-mile-orbit
Logic Pro: https://www.apple.com/logic-pro/
GarageBand: https://www.apple.com/mac/garageband/
NVIDIA: https://www.nvidia.com/
Trump pulls $400m from Columbia University, saying it failed to protect Jewish students: https://www.bbc.com/news/articles/c4gp979w055o
Cuban Missile Crisis: https://en.wikipedia.org/wiki/Cuban_Missile_Crisis
Josh’s post on X about Islamic extremists in Africa: https://x.com/wolfejosh/status/1241912312493215744
Africom: https://www.africom.mil/
I’d love it if you’d subscribe and share the show. Your support makes all the difference as we try to bring more curious minds into the conversation.
Production and marketing by penname.co. For inquiries about sponsoring the podcast, email [email protected].
2025-04-10 19:54:43
"Venture is a somewhat obscure craft that mostly lies in the minds of great investors and is hard to access. Thanks for your incredible longform content that teases out a lof of this and is a guiding light to those of us who are early in the journey of investing. Cheers!" - Sumangal V, a paying subscriber
Friends,
I’ll keep it brief: today’s piece is a me…
2025-04-08 20:04:20
Friends,
For decades, science fiction has painted AI as humanity's downfall. Think: Killer robots, surveillance states, and the end of human agency. In this episode of The Generalist, I'm joined by someone who's been actively architecting a different AI future: Reid Hoffman.
Reid isn't just theorizing about AI, he's building it. As co-founder of LinkedIn, card-carrying member of the PayPal Mafia, former OpenAI board member, and founder of multiple AI startups, he's had a hand in shaping our technological landscape for over two decades. His latest book, Superagency: What Could Possibly Go Right with Our AI Future, makes a compelling case for AI optimism that's grounded in deep thinking and practical experience.
In our conversation, Reid shares why he’s optimistic about what’s to come, how we can use AI to foster human creativity, and what we need to do to ensure a world where 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
Vanta: Automate compliance and simplify security.
Brex: The banking solution for startups.
WorkOS: The modern identity platform for B2B SaaS.
(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
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
The Player of Games: https://www.amazon.com/Player-Games-Culture-Iain-Banks/dp/0316005401/r
Look to Winward: https://www.amazon.com/Look-Windward-Culture-Novel-Book-ebook/dp/B001D20270
Excession: https://www.amazon.com/Excession-Iain-M-Banks/dp/0553575376
Startide Rising: https://www.amazon.com/Startide-Rising-Uplift-Saga-2/dp/1504064720
The Murderbot Diaries Vol 1: https://www.amazon.com/Murderbot-Diaries-Vol-1/dp/1250389828/r
Ender’s Game: https://www.amazon.com/Enders-Game-Ender-Quintet-1/dp/1250773024/
Greg Beato on LinkedIn: https://www.linkedin.com/in/gregbeato/
Reid Hoffman meets his AI twin: https://www.youtube.com/watch?v=rgD2gmwCS10
Humanity’s Hegelian Golden Braid speech: https://www.reidhoffman.org/perugia-speech/
Aldous Huxley: https://en.wikipedia.org/wiki/Aldous_Huxley
Idiocracy: https://www.imdb.com/title/tt0387808/
Ludwig Wittgenstein: https://en.wikipedia.org/wiki/Ludwig_Wittgenstein
Language game: https://en.wikipedia.org/wiki/Language_game_(philosophy)
Gareth Evans: https://en.wikipedia.org/wiki/Gareth_Evans_(philosopher)
Reid Hoffman and ChatGPT | Talking AI with AI : Introducing Fireside Chatbots: https://www.youtube.com/watch?v=t1kSfVO1YJ0
NotebookLM: https://notebooklm.google/
Turing test: https://en.wikipedia.org/wiki/Turing_test
Harry Frankfurt: https://en.wikipedia.org/wiki/Harry_Frankfurt
Logical reasoning: https://en.wikipedia.org/wiki/Logical_reasoning
Bayesian inference: https://en.wikipedia.org/wiki/Bayesian_inference
Reid Hoffman’s ‘homo techne’ post on X: https://x.com/reidhoffman/status/1619368528695668736
Roger Penrose: https://en.wikipedia.org/wiki/Roger_Penrose
Fyodor Dostoevsky: https://en.wikipedia.org/wiki/Fyodor_Dostoevsky
Leo Tolstoy: https://en.wikipedia.org/wiki/Leo_Tolstoy
Disco Elysium: https://discoelysium.com/
Marcel Proust: https://en.wikipedia.org/wiki/Marcel_Proust
Seatbelt laws in the United States: https://en.wikipedia.org/wiki/Seat_belt_laws_in_the_United_States
The American Academy of Arts and Sciences: https://www.amacad.org/
Inflection AI: https://inflection.ai/
Pi: https://pi.ai/
Alain de Botton’s website: https://www.alaindebotton.com/
Ron Chrisley on X: https://x.com/RonChrisley
David Chalmer’s website: https://consc.net/
Website: https://www.reidhoffman.org/
LinkedIn: https://www.linkedin.com/in/reidhoffman/
Podcast: https://www.possible.fm/
I’d love it if you’d subscribe and share the show. Your support makes all the difference as we try to bring more curious minds into the conversation.
Production and marketing by penname.co. For inquiries about sponsoring the podcast, email [email protected].
2025-04-07 23:16:03
Subscribe to make sure you don’t miss our first episode, launching tomorrow:
Friends,
Today marks the start of something I’ve wanted to create for a long time: The Generalist Podcast.
There’s a saying – usually attributed to science fiction writer William Gibson – that I think about with inordinate frequency: “The future is here. It’s just not evenly distributed.” Our goal with The Generalist Podcast is to help distribute the future more evenly through conversations with the people who see it first.
Look around, and you can see this dynamic everywhere. We have robots that fold clothes, dance, do kung fu, and build houses. We have AIs that write, paint, make films, fold proteins, and demolish us at chess. We have humans living in space and people on Earth walking around with genetically modified animal organs or brain-computer interfaces that allow them to navigate the web. We have money that travels instantly from one corner of the world to another and satellites that bathe entire landscapes with high-speed internet.
These technologies aren’t impacting everyone yet but exist in pockets that might one day grow to span our civilization.
All of which is to say that the best way to predict the future isn’t to prognosticate blindly but to find the pocket in which it already exists and extrapolate outward.
The oldest living person today is the nun Inah Canabarro Lucas, age 116. When Lucas was born in 1908 in rural Brazil, today’s innovations would have been unimaginable. Awaiting her were the television, the printer, commercial aviation, space travel, microwaves, refrigeration, barcodes, GPS, PCs, video games, the internet, the browser, the mobile phone, social media, and artificial intelligence. The world leaped from spotty mechanization to near-total connectedness in a single lifetime.
As technological progress accelerates, we may experience the scale of change Sister Lucas did within a decade or two. In our lifetimes, we should expect to know someone who emigrated to Mars, fell hopelessly in love with a digital companion, radically extended their lifespan through biohacking, and works alongside affable automatons. In some fashion, all of these are already happening – they are simply waiting for wider distribution.
These possibilities, and others like them, are much closer than many of us believe. I want more people to understand what the future might look like so they can choose how to participate in shaping it.
With The Generalist Podcast, I’m bringing you thoughtful, differentiated interviews with visionary founders, far-seeing investors, and provocative thinkers who live in these pockets of the future that we can already see today.
What does that look like, tangibly? Here’s a teaser of our upcoming slate:
Reid Hoffman on the cognitive industrial revolution, AI agency, mystical atheism, and gene editing
Josh Wolfe on xenotransplantation, digitizing smell, searching for genetic mutants, and learning from science-fiction
Roelof Botha on cultivating the mindset to weather bubbles, how Sequoia navigates investment cycles, and why AI may favor incumbents
Chris Best and Hamish McKenzie on creator economics, what AI means for the art of writing and a volatile media landscape
Trae Stephens on innovating in defense, arming super soldiers, and Great Power conflicts
Chris Miller on semiconductor strategy, Chinese AI companies, and Southeast Asia’s growing importance in the chip war
Bob Mumgaard and Vinod Khosla on nuclear fusion’s potential, why it’s been a “holy grail,” and how close we are to limitless clean energy
…and many more!
In just 60 minutes each week, I hope you’ll be introduced to ideas, technologies, and people before you might have discovered them otherwise—and that this will make you a little bit more prepared for tomorrow’s world.
This is very much an experiment and a work in progress. I’ve loved recording the first few episodes and have personally learned so much. Though I was optimistic about what we’re building with this podcast, the process has made me increasingly convinced that we’re onto something special. That said, there’s still lots for us to learn and improve (I’m still getting my sea legs as a host, for example). I hope we can do that together, using your feedback, to steadily design the highest-value, signal-dense hour of your week.
To that end, I hope you’ll join us by subscribing to the show, listening to our upcoming episodes, and sharing your feedback. The journey officially begins tomorrow, when we’ll release our first episode with Reid Hoffman. I hope you enjoy it, and I can’t wait to hear what you think.
To the future,
Mario
I’d love it if you’d subscribe and share the show. Your support makes all the difference as we try to bring more curious minds into the conversation.
Production and marketing by penname.co, artwork by Ibrahim Rayintakath.
