2025-09-18 10:55:02
Please enjoy this transcript of my interview with Pablos Holman (@pablos), a hacker and inventor and the bestselling author of Deep Future: Creating Technology that Matters, the indispensable guide to deep tech. Previously, Pablos worked on spaceships at Blue Origin and helped build The Intellectual Ventures Lab to invent a wide variety of breakthroughs, including a brain surgery tool, a machine to suppress hurricanes, 3D food printers, and a laser that can shoot down mosquitos, part of an impact invention effort to eradicate malaria with Bill Gates. Pablos hosts the Deep Future Podcast, and his TED talks have been viewed more than 30 million times. He is also managing partner at Deep Future, investing in technologies to solve the world’s biggest problems.
Transcripts may contain a few typos. With many episodes lasting 2+ hours, it can be difficult to catch minor errors. Enjoy!
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Tim Ferriss: Where to begin, Pablos? I don’t even know where to start. But I will start perhaps with my first glimpse of Pablos, which was circa 2008. I think it was the O’Reilly Emerging Technology Conference. It could have been Google at Night, but it was a demonstration, and I remember watching you.
Let me actually take it to Wired magazine for a second. So this is what they wrote about this particular event.
“San Diego, California — Your credit card, the lock on your front door, your cell phone’s voicemail, your hotel television, and your web browser are all not as secure as you might like to think, as Pablos Holman, a hacker clad in all black, gleefully demonstrated on stage Wednesday like an evil Las Vegas magician.
“Holman used caller ID spoofing to break into the AT&T voicemail of the organizer of the O’Reilly Emerging Technology conference being held this week in San Diego.
“Using the speaker phone, Holman changed the outgoing message of the target, Brady Forrest, while he sat helpless in a back row.”
“Maybe that’s why I’m confusing with Google at Night, because Brady also did Google at Night at one point.
“Don’t chuckle too much. The hack works for all many AT&T users, including anyone with an iPhone.
“Holman continued on to show how Schlage…” is that how you say that?
Pablos Holman: Schlage.
Tim Ferriss: “…Schlage locks — the kind that is likely on your front door of your house — can be quickly opened by banging a filed down key with a small mallet.
“Likewise, Holman used a snippet of Javascript to create a link that forced CNNMoney.com to load a modified Onion story saying that the iTunes store would soon be selling Tim O’Reilly’s home movies for $1.99 a piece.”
Then I’m just going to paraphrase here in the interest of time, called up a volunteer, this one, a young man sporting a headband. also had an RFID-enabled credit card. Holman waved a magic reader over the kid’s pocket. Up popped the kid’s credit card number and expiration date on the projection screen with a few digits Xed out. Turns out that after months of trying to figure out how to break the encrypted information transferred by the card, Holman just bought a merchant card reader on eBay for $8. Now, the only reason I think I may have been at a different event is because my memory, and maybe I conjured exaggeration for dramatic effect, is that you actually walked along the front line, the front row of the attendees and then put all of their credit cards up on a screen.
Pablos Holman: It was wild times.
Tim Ferriss: Wild times. So I just want to read some notes from a mutual friend of ours to give people a taste of where we’re going.
Pablos Holman: Oh, man.
Tim Ferriss: I put shorthand here, “Password-stealing robot? Keychain unlocking REDACTED within a square mile? Hardware in a car in Seattle downloading and uploading hard drives from unsecure Wi-Fi. Printing food, things that taste like steak?”
Pablos Holman: Oh man,
Tim Ferriss: So, so far that’s all. Is that all facts?
Pablos Holman: I mean, there’s —
Tim Ferriss: Ish?
Pablos Holman: There’s something factual about all of them, but certainly something must be exaggerated, I guess. Yeah.
Tim Ferriss: Certainly something must be exaggerated. Well, we will find out. Let’s begin with a question around this term hacker.
Pablos Holman: All right.
Tim Ferriss: What is a hacker to you and do you consider yourself a hacker?
Pablos Holman: Well, I’m a hacker because my early life was all around reverse engineering a computer. And that was out of necessity because I grew up in Alaska and there was nobody around who’d ever seen a computer. But I got one when I was like nine years old, one of the first couple thousand Apple IIs ever made. So I had a computer in the cold, in the dark, in the basement, in Alaska, and nobody to show me anything about how it worked. So I had to learn by reverse engineering, what we would call reverse engineering. You break things and see what they do and then try to learn from that. And so I learned the hard way.
And then for the first, I don’t know, couple decades of my career, it was all about trying to do new things with computers and advanced computers. And I didn’t have any formal training. I didn’t go to college. Software development was invented long after I got started. So there’s a lot I didn’t get that most people get. And so a hacker is somebody who I think is attracted to puzzles. They are attracted to computer security, because it’s a bottomless pit of puzzles. And I am trying, at this point, hack everything but computers, and I’m trying to rescue hackers out of the computer security department and get them into helping go attack bigger problems.
Tim Ferriss: How did you end up acquiring a computer in Alaska?
Pablos Holman: So my dad had put some of the first mainframes in the oil industry in the early 70s, let’s say. And so he wasn’t really a computer guy, but he had a notion that these things might be interesting. And when Apple needed customers, at the beginning of Apple, they went to the oil industry, because that was the big rich industry at the time. My dad said, “Sure, we’ll take one.” So I got one of the first Apple IIs. So I’m like nine, 10, 11 years old. I had an Apple II, I had a skateboard. People were sure that neither of them was a good waste of time, but it was a fair fight. It was just too early.
And I was lit up about this thing. Apple II isn’t very powerful, and in those days computers weren’t useful. It didn’t have hardly any memory. It was super slow. But I was lit up. And so I tried to convince everyone around me that this computer was going to be amazing someday, and no one believed me. They’d never seen a computer, but they were sure they weren’t cool. And so, I was inviting girls over to my basement to show them my computer and —
Tim Ferriss: Is that what they called it back then?
Pablos Holman: It made an impression, just not the one that maybe I was going for. So I’m still doing that. I’m still trying to convince people that these technologies are important.
Tim Ferriss: I’m trying to pull from your book, which I’ve been devouring.
Pablos Holman: All right.
Tim Ferriss: Deep Future: Creating Technology That Matters, about three-quarters of the way through, and I’m going to do something dangerous, because I just got off of opioid painkillers from my arm surgery, try to pull from memory.
Pablos Holman: Way to go.
Tim Ferriss: But let’s give it a good college try. Do hackers ask some version of not what does this do, but what can I get this to do?
Pablos Holman: The way I described that before, in the book, is just a simple way of thinking about the mindset of a hacker. Most people, if you get a new gadget, like your phone, and give it to your mom, she’ll ask you, “What does this do?” That’s a totally normal question. “iPhone, Mom. Says on the box.” If you give a new gadget to a hacker, then the question is, “What can I make this do?” And they’re starting from a completely different position. They’re going to take out the screws, break it into a lot of the pieces. You’ve met Samy, he’s the poster child for this. He’s violating the warranty before he got the shrink wrap off.
Tim Ferriss: Can you, just for entertainment value, people can listen to my conversation with Samy Kamkar to hear about his amazing adventures and his crime and punishment involving MySpace.
Pablos Holman: Oh yeah.
Tim Ferriss: He wasn’t allowed to touch computers for a while.
Pablos Holman: Samy is just —
Tim Ferriss: But what did you —
Pablos Holman: He’s just the most delightful hacker.
Tim Ferriss: He is a super delightful human. What did he do with Google Maps?
Pablos Holman: Oh, Google Maps is one of my favorite things he did. Early on, Samy was finally allowed to use computers again. Google colors the roads for traffic, based on where everybody’s phone is, just reporting to Google when you’re stuck in traffic. And so Samy figured out he could just lie to Google. He just sent a bunch of fake data to Google. And he figured out how to structure it so that he could make all the roads he’s about to drive on, just clear out, because they look like they’re all log jammed.
Tim Ferriss: Just ramped all the way.
Pablos Holman: Yeah, they all look like traffic jams. And so Samy could manipulate the traffic. I mean, Google’s since fixed this. But I often like to show off Samy on stage, and so I’ve shown his exploits a bunch of times and that’s one of them.
Tim Ferriss: What makes for a good hacker?
Pablos Holman: So I think the hackers have one way or another ended up being the people who start from that position I described. They’re the ones who don’t take the conventional wisdom of what something is for.
Tim Ferriss: Masters of off-label use.
Pablos Holman: Yeah, off-label. And so they’re creative, in a sense. They are the people who figure out what is possible. You can’t invent a new technology by reading the directions. That’s just never happened, ever. So a hacker, I’m interested in their minds as inventors. I’m interested in their minds as creative people who are going to figure out how to elevate what humans can do. And so a good hacker is somebody who is willing to do that.
I learned a little bit about hackers, because I was, like you described, I was doing this bizarre kind of hacker magic show stealing people’s passwords. But some magicians, actual magicians, showed up in my audience one time. And they explained to me like, “Hey, you kind of suck as a magician.” And I’m like, “Oh, yeah, you could probably tell me what I should do.” And what I realized is magicians, getting to know them, are like these people who will spend an obscene amount of time, more than anyone can imagine, focused on the most useless thing. And they’ll figure it out. They’ll figure out something no one else could imagine ever figuring out. And that’s part of how their capabilities, their tricks come together, the things they invent.
And you could say maybe what magicians are inventing is useless. And you could argue that a lot of what hackers are inventing is useless. It’s like, why are you spending all of your time trying to figure out how to fuck with Google Maps? They’re just going to fix that bug and then it’ll be useless. But to Samy, it’s no problem at all. That is what he wants to do with his time.
And so I think a big part of it too is this, you could say as a class, maybe hackers have ADHD, but they can focus on what they’re interested in. And when they get interested in a puzzle, they’ll just go deep. And so you have to do that as well to get somewhere that no one’s gotten before. This is actually the reason I think I’m here is because I want you to know that you are the hacker. You’re like a very important hacker. And you don’t think of yourself that way, but the reason is you are the one who showed people that what hackers are doing can be taken places that are not computers. And you did that with all the things in your books. That’s what the Tango thing is, and the wrestling thing is, and all those examples, swimming and all the things that you showed in your books, that’s the exact same thing hackers are doing. And you’re showing them that it can go somewhere else. And that means a lot to me because I’m trying to get hackers to see that they could go somewhere else besides computers.
Tim Ferriss: Right, outside of software.
Pablos Holman: Yeah.
Tim Ferriss: Well, thank you for saying that. That’s a huge compliment coming from you. And it’s also a very smooth segue, because you mentioned two things that were of questionable value when you were a kid, computers and skateboards. Rodney Mullen. Could you describe for people who Rodney Mullen is?
Pablos Holman: Oh, man. So Rodney Mullen, I don’t have to describe for anyone who ever touched a skateboard, because Rodney is the godfather of street skating. He’s the guy who invented every single thing you’ve ever seen a kid do on a skateboard, and including he’s the first one to ollie a skateboard, which is the fundamental basis of all street skating. I’m a shitty skateboarder. But Rodney is one of my favorite people on earth. He’s such a delightful human. And we spend all night hanging out together talking about everything but skateboarding. But I’ve used him as an example of an inventor, again, because I’m trying to show people that an inventor is a valuable and important thing. Hackers are one source of inventor, but skateboarder is inventor. There’s a difference between Rodney and every other skateboarder. And that difference is that Rodney will imagine something in his mind that’s never been done before, maybe impossible. He can spend months every night trying to make it happen on a skateboard and then finally get it.
Tim Ferriss: Now, did he grow up in Santa Monica?
Pablos Holman: No. He grew up in rural Florida. So we have this kind of odd parallel childhood. I mean, Rodney is way more important than me. But Rodney’s childhood was in rural Florida, no neighbors, like a farm. And he had a little patch of cement in the driveway. His entire skateboarding life started there. No one around him could skateboard. He didn’t have any influences. He just had his brain and the skateboard. So he invented what was possible. And so I think that is so important. So it’s analogous to my Apple II in Alaska thing.
But what’s so cool about it is that once Rodney does a new trick, puts it on YouTube, two weeks later, kids in Kazakhstan are doing it better than him. And so it’s a very important contrast, I think, to show people the difference between what an inventor does the first time. The zero to one, that first time is incredibly hard. It takes lifetimes, it takes careers, it takes everything you’ve got to do something the first time that humans have never seen before. Every time after that, the second time to the nth time, that’s craft. That is not invention, that’s not art, that’s craft. You need a skill to do it. Rodney needed to be able to skate to invent. But I want people to understand how important inventors are. And we throw them under the bus. You don’t know anybody, probably besides me, whose business card says inventor. It’s not a legitimate career choice.
Tim Ferriss: I only know one person, a guy named Stephen Key who’s just prolific in the toy world. But —
Pablos Holman: Okay, cool. You know one.
Tim Ferriss: But he’s literally the only one.
Pablos Holman: But how many music artists could you name?
Tim Ferriss: Yeah.
Pablos Holman: Or painters, or —
Tim Ferriss: A hundred. A hundred
Pablos Holman: Yeah. Or actors. I mean, and it’s just the contrast is extreme. It’s our most important creative class, inventor, and they don’t count. And I think we got to fix that.
Tim Ferriss: I want to dive into some of the personal, because some of the magic tricks, so to speak, I want to try to unpack a bit.
Pablos Holman: Sure.
Tim Ferriss: And it might be pearls before swine because I’m not technical.
Pablos Holman: It’s okay.
Tim Ferriss: Do not know how to program. But I am curious, for instance, this robot, I don’t remember its name.
Pablos Holman: Oh, the Hackerbot.
Tim Ferriss: The Hackerbot with a printer attached, right? Did I —
Pablos Holman: Oh, yeah.
Tim Ferriss: Okay. What did this do —
Pablos Holman: No, it had a screen, not a printer.
Tim Ferriss: Had a screen. Okay. How did that work?
Pablos Holman: Okay. So —
Tim Ferriss: And what did it do? Maybe you could describe it.
Pablos Holman: So, it’s like a long time ago. So Eric Johanson is my co-conspirator on a lot of hacking stuff. He and I were hanging out. We went to one of those first robotics competitions, which are huge now it’s teenagers making robots that they turned into a spectator sport. And we realized, like, oh, these kids are making robots. If they can do it, we should be able to do it, because super geniuses with a machine shop. I had the Blue Origin machine shop. So I figured we could build a robot. So we started — Eric is amazing. You come up with an idea, he’ll smoke cigarettes and stay up all night and get it done while I go to sleep. And so Eric —
Tim Ferriss: A great friend to have.
Pablos Holman: Yeah, great friend to have. So Eric starts trying to get PWM controllers and all this stuff to build a robot. I bought the wheels, because I’m good at buying wheels. So we started building this thing, assembling it as it goes. And then —
Tim Ferriss: These are robots for a competition?
Pablos Holman: No, we just were making a robot for no good reason.
Tim Ferriss: Okay. I got it. I got it.
Pablos Holman: And eventually, we figured out it should have a reason. So we’re like, “Well, what should our robot do?” Neither of us drink beer, so it didn’t need to fetch beer. We’re like, “Well, we could make it do some hacking since that’s what we’re normally doing.” So it became the Hackerbot. And everything that robot can do, a nerd with a Linux t-shirt and a laptop can do. So we made the robot, so it would drive around and it would find people, kind of like triangulate Wi-Fi users —
Tim Ferriss: At a conference or —
Pablos Holman: Anywhere.
Tim Ferriss: Anywhere.
Pablos Holman: Yeah. It’d drive up to them and then show them their passwords on the screen. Because we had all the tools for cracking Wi-Fi.
Tim Ferriss: This is a Wi-Fi password?
Pablos Holman: Yeah, we’re cracking Wi-Fi at the time. One of our buddies had made a tool called AirSnort to crack Wi-Fi, and we were cracking Wi-Fi and stealing passwords for fun. But the cool thing about the Hackerbot was it was just this insanely mediagenic kind of thing where everybody thought it was cute. It’s a nefarious robot stealing your passwords, but people thought it was cute. So we realized we could — in those days, we were just trying to raise the alarm about how insecure everything was, and nobody gave a shit about it. No one wanted to hear from hackers. But the Hackerbot got on television and that kind of thing. So we learned something from that, how to contextualize the lesson. I made a lot of friends stealing passwords too.
Tim Ferriss: Yeah. They’re like, “Wow.” Got to keep your prospective enemies as close as possible.
Pablos Holman: I came unarmed.
Tim Ferriss: Well, honestly, I’m not going to lie, when I saw that demo at whichever conference, I was like, “I don’t know how close I should get to this guy, because if he decides that I’m a pain in the ass, I really am defenseless.” I feel like I would just be bringing a butter knife to a gunfight. And so I was simultaneously incredibly curious, but I was very, very nervous —
Pablos Holman: Fair enough.
Tim Ferriss: — at the same time.
Pablos Holman: You’re not the only one.
Tim Ferriss: Is it fair to say, and I tend to tilt a little dystopian, so I’ll just disclose that in advance, that if you are a legitimate target who is non-technical of a very competent hacker, that your goose is cooked? I mean, and I’m sure there are basic digital hygiene things that you can do.
Pablos Holman: Yeah. You’ve heard them all.
Tim Ferriss: But what are your thoughts? Because I’ve talked to people, for instance, in the intelligence community, and they’re like, “Oh, yeah. If you’re the target of a state actor and the entire machine behind it,” they’re like, “They’re going to get your stuff.”
Pablos Holman: Yeah, that’s true. The problem is it is a moving target. So there’s this war of escalation between attackers and defenders. And a lot of what people are familiar with, it’s just kids in Romania screwing around trying to try an attack against every IP address of the internet and see what falls in their lap. That’s stealing credit cards and Bitcoin wallets and stuff. So that you could say it doesn’t really count. I mean, it sucks, but that’s all the recommendations you’ve heard of, use a password manager and stuff, will help you with that.
But if you are the target of a sophisticated, mostly nation state actor, it would just be an extreme lifestyle change to insulate yourself against that. And there’s a very sophisticated game of finding new exploits, selling them mostly to governments, and then they sit on them. They don’t use them. Because every time you use a new exploit, like say I’ve got a way of hacking an iPhone, that is so valuable, I’m going to save it for a really, really, really good use. The day I use it, I risk someone figuring out that it exists. So I want it to be what’s called zero-day. So you don’t use those lightly. So most people don’t have anything to worry about because governments don’t give a shit about you. And so I think you’re fine. If they start to, then you’re going to have a problem.
Tim Ferriss: What does the marketplace look like for zero-day exploits? Because I’ve heard of, say, Israeli developers formerly of Intelligence developing these exploits, these zero-click exploits, if I’m using the term correctly, and then they sell it for like a million dollars a pop or $2 million a pop for specific targets or something like that. But how does that transaction actually take place?
Pablos Holman: Well, so I don’t play this game anymore, but friends do. Say I were to discover a way to make a zero-click exploit for iPhone, that’s probably the most valuable thing in the world right now.
Tim Ferriss: Which means you don’t have to click on anything.
Pablos Holman: Right. It means I send you a text message or something and I’m in and I control your phone. That is very hard to do. Apple’s trying to keep that from happening. But if I have that, then I sell it to a broker. And so there are certain hackers whose job is to vet these things.
Tim Ferriss: Those are the brokers.
Pablos Holman: Yeah, the brokers.
Tim Ferriss: Do you find those people on the dark web or is it like a referral number, a referral?
Pablos Holman: Actually some of them, I think these days they’ll hang out a shingle. I’m not going to name any here. But the point is hackers who are finding exploits know who they are. And so then you sell it to a broker. And those guys have relationships with the shady folks at governments around the world. And that’s only people they’ll sell to, because otherwise they risk getting prosecuted in different jurisdictions. So you can get away with selling to a three-letter agency in the US, but you can’t get away with selling it to even a corporation in the US. Because to use an exploit like that for corporate espionage, you’re getting into very risky turf.
American hackers don’t want to play that game because they can make more money doing legit stuff. If you’re a Romanian hacker, there’s no six-figure job for you, so you might play with seeing how I can use that to get Bitcoin wallets or something. Love Romania, by the way.
Tim Ferriss: I do too. Love.
Pablos Holman: Amazing.
Tim Ferriss: I was just there a few months ago.
Pablos Holman: Amazing hackers.
Tim Ferriss: Go to Brasov if you have the chance, folks. Also, little known fact, lots of bears in Romania.
Pablos Holman: Not compared to where I come from, but —
Tim Ferriss: I find that to be an appealing draw, but —
Pablos Holman: Their bears are little, though.
Tim Ferriss: — that’s just me. In any case, are there pockets of incredible hacker density, geographically speaking, for whatever reason? You see this with all sorts of things where there’s a particular tennis school in Russia that produces just an absurd percentage of top tennis players for a decade or two. Or there’s a million examples from a million disciplines.
Tim Ferriss: So does that exist for hacking?
Pablos Holman: Yeah, there’s —
Tim Ferriss: Is it like, oh, this particular city in China, oh, this particular place in Uzbekistan or wherever?
Pablos Holman: Yeah. Well, there’s two things that caused that. So one is a center of gravity of technical excellence. And so you could say places like Hungary put out amazing mathematicians, which translates to pretty good understanding of computers. Some of those Eastern European places had that and/or still do. And so there’s a center of gravity there. Germany had these extraordinary hackers that would blow our minds. We would go over there and just wonder why we were —
Tim Ferriss: You say had, past tense?
Pablos Holman: I don’t know now, because again, I’m hacking other things. But I used to go to the Chaos Computer Congress in Germany, which is the big hacker convention. And we could blow their minds a little, but they could blow our minds a lot. So that was cool. But what happened is, in the early two thousands, Microsoft started to get serious about computer security. And they started to import hackers to Seattle from everywhere. I was in Seattle at the time, again graduating out of hacking and computer stuff into other things. But all my friends were hackers. And what was great is we had this critical mass of hackers from all over the world, including Germany and all these places, that Microsoft imported. So that was a center of gravity for a while. I don’t —
Tim Ferriss: Must have been fun grabbing dinner or drinks with that crew after work.
Pablos Holman: Yeah, that’s what we were doing. Actually, it was funny because it was at the same era Dodgeball came out, which is like this pre-iPhone location, SMS app.
Tim Ferriss: Oh, I thought you were talking about the movie with Ben Stiller.
Pablos Holman: Not the movie, this is an app. Before Foursquare. It’s like the predecessor to Foursquare. And so you’d send a text to this one number and then it would go to all your friends. And so you’d send this text and like, “I’m at the bar.” And immediately a hundred friends would get the text. And they’re like, “I’ll go to the bar.” So the drinking rate amongst hackers just went off the charts. But we were hanging out together all the time, and that was actually a really cool community vibe for hackers. And we had some hackers that were good at getting people together. So that was a good era. I think it’s hard to say where the center of gravity is. Hackers have conventions that they go to now.
Tim Ferriss: What are the most interesting to you?
Pablos Holman: DEF CON got a little out of control. I think it’s a little too big. And then we did ShmooCon for 20 years. This is the last year though, so that one’s over. But you could still go to Germany for CCC. That would probably be the best thing to do. In the US —
Tim Ferriss: I’d leave my phone in the hotel room.
Pablos Holman: — ToorCon if you — oh, yeah, don’t take any computers to these things. But go naked and you’ll be fine.
Tim Ferriss: Naked and afraid.
Pablos Holman: There you go.
Tim Ferriss: CCC edition. Let me just pull on this geographic thread a little bit and then we’re going to move to other things. But this is from another of our mutual friends. So questions around geopolitics from a tech angle. In other words, who is leading and what? Do you have any thoughts on that?
Pablos Holman: Oh my God. Geopolitics.
Tim Ferriss: It’s a promising start.
Pablos Holman: Here’s how I would try to think about it. Technology in general, especially computers, especially computer security, these things are a war of escalation. You cannot win that war. You can lose very easily by not playing. And so for better or worse, I think it’s important to think about these things this way. You can see it, if you’re going to say geopolitically on technology in general, China and the US are definitely trying to play. And you can see a lot of places that I won’t name, like Europe, that you absolutely could say are not playing. And so you’ll see how that plays out. You can see how it plays out with lots of technologies.
Tim Ferriss: What are the main technologies?
Pablos Holman: Well, these days —
Tim Ferriss: I mean, are we talking semiconductors and AI? Are we talking about —
Pablos Holman: These days, those are the biggest ones. And the reason they’re so big is they’re generally applicable. So computers can be applied to everything. If you haven’t got one in your pocket by now, you will. I mean, they go everywhere. So computers are very important. Technology that’s generally applicable. You just can’t ignore it. You could hang out in Copenhagen and draft off China and the US if that’s what you want to do. But I think it’s dangerous not to play the game. You want to get to the point where you can at least wield these technologies to whatever extent you think is important. So that’s as much as I think people really need to know.
Now, there’s a whole stack. The software relies on the chips, which rely increasingly on energy. All these hyperscalers have woken up this year to the fact that a chip from Nvidia needs a shit ton of energy and we’ve been burning gas to get it, so maybe we should find something better. So now there’s a lot of intention on improving energy. I’m so excited about that because —
Tim Ferriss: Do you think the hyperscalers will actually help resurrect nuclear energy in the US?
Pablos Holman: I think hyperscalers are going to save us. It’s a crazy thing to say.
Tim Ferriss: Wild to say, huh?
Pablos Holman: It’s a crazy thing to say. But you can thank Meta and Microsoft and Google. And the reason is that we don’t make enough energy on this planet. Now you could say we make enough energy for Americans, because we’re not very price sensitive and we can just keep throwing money at it. But you will watch, even not counting AI, you will see that energy demand is off the charts. Try to remember when Shell or Chevron advertised to get you to buy more gas. It’s the biggest market in the world. They don’t have to advertise their product.
I mean they advertise to get you to buy it from them instead of —
Tim Ferriss: Well, speaking of dodgeball, I think in your book you wrote that at one point, was it the Senate, was switching players on a dodgeball team between Chevron and someone else?
Pablos Holman: Well, yeah. I mean, I would say the oil industry probably staffed Congress for most of our lives. Now, it’s hyperscalers. And so we are getting the legislation that we need. Last year, the most bipartisan bill I know of was called ADVANCE. That was to build nuclear reactors in the US. Now, Trump has signed multiple executive orders to build nuclear reactors and free it up. And it’s working. The overhaul of the NRC, which regulates nuclear, has been amazing. They’re supportive and helpful in my lifetime. They were usually an anti-nuclear activist group. It’s been crazy how — because we started, we invented one of the most advanced nuclear reactors at the Intellectual Ventures lab where I was before. And for the last 18 years, you’ve seen me on stage telling people nuclear reactors are awesome and they’re coming and they weren’t coming.
And that is because the NRC regulated them into oblivion. That has all changed now. And as of this year, this is crazy, as of this week — so we have now a nuclear reactor company I should describe, which has invented a reactor that fits in a borehole. They bury it a mile deep. So this reactor is unquestionably safe.
Tim Ferriss: It’s the size of a small car or something like that.
Pablos Holman: It’s the size of a Toyota, not more complicated than a Toyota. And the thing can be made in a factory like a Toyota, but it’s buried under 10 billion tons of rock. It’s something that if anything went wrong, there’d be no radioactivity at the surface. It’s a mile from anyone’s backyard.
Tim Ferriss: And when you retire it or when it stops functioning —
Pablos Holman: Fill the hole with dirt.
Tim Ferriss: Just bury it.
Pablos Holman: Yeah. Leave the uranium where we found it. It’s a really exciting way of making nuclear reactors.
Tim Ferriss: How do you cool it?
Pablos Holman: So there’s water in the borehole that goes down and cools it. What’s so fascinating is if you look at a Fukushima type problem, there’s these pumps that are supposed to be pumping water through the reactor core to cool it. And those pumps could fail. Well, that pressure, the water pressure in the borehole from gravity creates enough pressure to cool the reactor.
Tim Ferriss: Gravity has been pretty reliable so far.
Pablos Holman: Pretty reliable so far. So then that makes steam, that goes back up and you run a turbine in a generator like everyone else. So the reason I’m describing this is that that company was on a track to get the reactor approved in a couple of years, build a test core at a national lab over a couple years, then build a commercial reactor in 2029. The Department of Energy is pushing them to do all of that by July. They will deploy their first reactors in July. It’s insane. It’s awesome.
Tim Ferriss: Is it?
Pablos Holman: And then we’ll make thousands in a gigafactory.
Tim Ferriss: Do you think the US is kind of a day late and a dollar short in terms of waking up to the reality? Because my understanding, and I’m not going to get the number right —
Pablos Holman: That’s okay.
Tim Ferriss: But looking at China, they have how many functional reactors?
Pablos Holman: I think they have about 130 reactor projects and they tend to get them done on time, on budget. There’s different technologies. They’re trying them all. It took them about three years to build a reactor. And those are big ones. They’re smoking it. It’s amazing.
Tim Ferriss: And is that legacy, well maybe it’s cleaned up, but mostly legacy technology in terms of —
Pablos Holman: Yeah, so there are different kinds of reactor technologies, and I won’t weigh in on that because I think we need a thousand silver bullets and I kind of want them all to succeed. Obviously I invest in the ones I think are the best. But the future of reactors involves a bunch of advanced reactor technologies and they’re — so like the TerraPower reactor that we invented at the Intellectual Ventures lab, which we can’t build because it’s new technology, not because there’s any other reason.
Tim Ferriss: That’s a regulatory hurdle?
Pablos Holman: It’s a regulatory. But just because the US has never figured out how to approve any advanced reactor technology. Once they do, we could build something like that. That reactor is powered by nuclear waste. It literally recycles nuclear waste inside the reactor. So that’s where we want to go. That might take a while. So the deep fission reactor that I described, that goes in the borehole, no new technology, just a simple design. And you get the containment for the price of a hole. And we have a whole industry that’s real good at holes.
Tim Ferriss: So if you were, I’m not saying you would agree to this, but if you were brought in by people you trust to advise the current administration on what the US needs to do to remain globally strategically advantaged or at least not lose, what are some of those pieces of advice that you would give?
Pablos Holman: Wow. Well, I’d say the number one thing is going to be energy. In energy, the number one thing is fission reactors. Love fusion. Hope we get it someday. Don’t hold your breath. We have other technologies that I think could happen sooner than fusion that we could talk about like space solar, but I would say aggressively deploy nuclear reactors, make that as easy as possible. Take on the — I mean the biggest problem remaining is the litigious nature of the US. So you start a nuclear reactor project, you get a thousand lawsuits. We’ve got to squelch that because we’re competing with China and China doesn’t have that problem. And so make a clean regulatory track that makes it possible to deploy these things at scale. So that’s the most important thing. If you get nuclear reactors, you solve a lot of other problems for free. And so I think that with limited attention span, that would be where my focus would be. Commercially, we can take care of the chips and everything after that.
Tim Ferriss: Maybe just patting myself on the back here in a self-congratulatory way. But when you talk about sequencing, picking the proper sequence of problems to solve, it just makes me so happy because I feel like —
Pablos Holman: That’s your mantra.
Tim Ferriss: Right. There are quite a few people who are good at defining, say, the constituent parts of a given problem. There are a lot of people who are good at applying some type of an 80/20 analysis, but it seems like the secret sauce that is kind of self-evident when you really peer closely at it that gets ignored a lot is the sequencing. Where it’s like, yeah, you can try to fix these 18 separate issues, but if your lead domino is solving for energy, then those either become irrelevant or they become a lot easier to solve.
Pablos Holman: The great example to me was how recycling played out in the US. We’ve been recycling our whole lives. Right now it’s kind of a wash. You’d probably burn less gas making fresh plastic than if you try to recycle these plastic bottles and things. And we’re 50 years into that. And so it’s just putting the cart before the horse. Recycling is going to work great once you have a nuclear reactor to power your recycling plan.
But we’re not there. We’re burning gas to do it. And you watch out your window when the truck comes, it’s going to pick up the trash and the recycling and throw them in the same truck. It’s not working and we’re not being honest about that. And it placates people. They feel like they did their part, separating stuff out. So I think it’s one of the things I’m trying to convey to people with technologies is you can’t keep putting the cart before the horse. We don’t have time to keep scaling the wrong thing. We got to pick something that’s going to work and then go build that. And you can just do basic arithmetic to get those answers a lot of the time.
Solve energy first, then you can solve — if you want to go do carbon captured, pick co-to molecules —
Tim Ferriss: 400 parts per million.
Pablos Holman: 400 parts per million means 400 needles in a haystack with a million pieces of straw. That’s what we’re talking about. So good luck. I think you want to find a less entropic source of carbon, leave the coal on the ground if that’s what you want to do. It’s very highly concentrated there. So if you had energy that was cheap and basically free, then you could go pump all the air through a filter and go get those carbon molecules. But we’re really not being honest about the basic arithmetic for a lot of these things. And so I can be a little harsh on these ideas, but it’s not because I don’t want them to work, it’s just that I want them to be done in logical order.
Tim Ferriss: And tell me if I’m off base here, but I don’t want people to misconstrue what you’re saying. It seems like what you’re saying, if I’m understanding it correctly, as much as people sometimes say “It’s the economy, stupid,” it’s the energy, stupid. But in the sense that that is the biggest lever we have to pull. What you’re not saying is everyone should stop recycling if their municipality actually sorts and so on.
Pablos Holman: I mean, maybe they should stop. Some of them are working. Copenhagen in one neighborhood, they figured it out.
Tim Ferriss: I guess product would mean more microplastics and there are issues with a larger volume of plastics besides the energy equation, I guess. But I don’t know how you think about that.
Pablos Holman: So again, something like plastics are part of the reason we all exist. They are very, very useful for saving lives in a lot of ways. But yeah, you want to use the plastic where it belongs, not where it doesn’t belong. So yeah, keep it out of your testicles and keep it out of the ocean and keep it out of the places where you don’t want it. But there are places where it can be very, very helpful.
Tim Ferriss: The inventions that you describe in your book are really compelling. And as I believe you described them, please fact check me if I’m getting this off, but that with deep tech, and you should probably define what that means —
Pablos Holman: Sure.
Tim Ferriss: — the risk isn’t so much, it doesn’t seem to be market risk or a need risk. People could read about the description and say, “Of course we should use that.” There’s technical risk up front, but I’m wondering how you think about and assess as an investor regulatory risk and all of the red tape and bramble bushes that entail getting something like that to launch or adoption.
Pablos Holman: Okay.
Tim Ferriss: Because you have built or indirectly funded people who have built much better mousetraps.
Pablos Holman: Right.
Tim Ferriss: Quite a lot. And been involved with Nathan Myhrvold’s lab and building technology for, say, reducing the likelihood or severity of hurricanes, simple tech, which we could get into. And it’s like why the hell isn’t it being used?
Pablos Holman: Yeah. Okay. So there’s a few things there. I usually get involved when I see a technology that I think is 10 times better than state-of-the-art. If you go to Hewlett Packard, there’s somebody there. There’s an engineer that’s super smart figuring out how to make inkjet printers like one percent better, which is awesome. But I want the guy who’s figuring out how to make whatever comes after inkjet. So two times better. There’s probably not enough margin there to ensure that you can go the distance, but 10 times better. That’s a real window. It is 10 times cheaper, 10 times faster, 10 times more efficient, 10 times on any metric could be a good window. So that’s kind where I see deep tech breakthroughs as becoming sort of contenders. And then we try to invest in them and help get them out of the lab or out of the garage and into a startup.
That’s what I’m looking for in the world. Now that’s a much different thing than what we’re both very familiar with startups and venture capital and probably audiences too. The last couple decades of Silicon Valley, let’s say, have evolved a very impressive machinery for funding iPhone apps to have weed delivered to your dorm room by a drone. They’re not going to take on nuclear reactors. You can’t take a nuclear reactor and go knock it on doors in Silicon Valley and expect to get a response. Maybe this week it’s getting better. But the point is we’ve been funding these SaaS holes for decades instead of actual technologies.
And that’s okay. That’s cool to make software and it’s a good, I think good practice run. If you’re an entrepreneur and you made an app. Cool practice. Now take on a new technology that’s a 10X multiplier in some hundred-year-old industry where nobody in Silicon Valley has touched it. To me, that’s where the action is. And I think I can prove that.
Tim Ferriss: Does it need to involve hardware?
Pablos Holman: It doesn’t need to. We have a small percentage of things we backed that are exclusively software, but by and large, they don’t need our help. They probably don’t need your help because those are easier things that other people are going to do anyway. I do things like say new algorithms in AI, but I wouldn’t do applied AI, things like that. So things that move the needle along, what’s possible. New chip architectures, I do. But anyway, the point is, let’s get back to hardware in a minute. When you’re investing, you’re looking at risk as you described. So all of Silicon Valley, you could say, is fixated on market risk. So we have milestones like MVP, product market fit, those kinds of things because that’s a way to reduce market risk.
Technical risk. You never heard of it. If I can draw an iPhone app on a napkin —
Tim Ferriss: Except in my biotech investing.
Pablos Holman: Okay, that’s different. Yeah, we’ll leave Boston out of this. But for software investment, there’s really not technical risk that much these days. If you can draw it on Canva, then we can make it. Okay, so what I’m doing is the opposite. I take a lot of technical risk. Can we build this nuclear reactor? Can we put solar panels in space? Can we do whatever? But the day that I get through that, the day we get through that, the day the first reactor goes in the ground and lights up, there’s no more technical risk. It works. You can see it. And there was never any market risk because I just have vast industrial markets, trillion dollar markets. And that’s very important to understand. So I actually get — our companies, on average, will graduate from Venture earlier.
We’re not selling equity to make more nuclear reactors. There’s project financing and debt for that. So I think investors are missing what’s possible in deep tech. Basically no market risk once we get through the technical risk. And so the size of the markets, if you’re one of these SaaS investors and you see a TAM of 10 billion, let’s say for a Zoom or a Slack or something, that sounds good. If you add up all the software companies in the world, including Microsoft and Meta and everybody combined, their combined revenue is about $2 trillion a year. The global GDP is over a hundred trillion dollars a year. So Silicon Valley is doing two percent of what humans rely on. That other 98 percent is my TAM.
Tim Ferriss: Is top-line revenue and GDP a fair comparison?
Pablos Holman: I mean, you could nitpick over the details. It’s actually, if it’s unfair, it’s unfair in my advantage. It’s unfair to my advantage. So I’m trying to be generous here. And so just rough numbers, we can nitpick later. Fact-check me, guys, 98 percent. If you fact-check me, I’m going to win. Okay. 98 percent of what’s left is that’s energy, but it’s shipping. Shipping is a $2 trillion Industry as big as software. We could talk about that. Durable goods.
Tim Ferriss: And by shipping, you mean mostly ocean based.
Pablos Holman: Right. Durable goods, all your sinks and bicycles and light fixtures and chairs, that’s $4 trillion a year. Automotive is another four, five, six trillion. I mean we’re just talking about massive industries bigger than the entire tech industry and we’ve completely ignored them in Silicon Valley. That’s what deep tech is. That’s what we’re going after.
Tim Ferriss: What about the regulatory implementation piece? Because for instance, I was reading the book and I’m fascinated by containers and how the standardizing of containers revolutionized activity on the planet. And learning through your book about the different types of fuel and just the congestion at ports caused by extraordinarily large seaborne container ships, cargo ships, which is a necessity to reduce drag because they’re optimizing for fuel.
And the alternative that you propose seems like a no-brainer. But then I’m like, well wait a second. Is it like the Greek and Chinese cartels, so to speak? The sort of —
Pablos Holman: So you’ve named two more kinds of risk.
Tim Ferriss: Yeah. Yeah. I mean what are we talking about?
Pablos Holman: All right, well, so just to make it clear for the audience, we have a team that’s developing cargo ships that are autonomous. I don’t think it’s that hard. You duct tape a Tesla to the front and it can drive across an ocean. Probably anybody listening would believe that’s possible. There’s nothing to hit out there. One documented pedestrian ever.
Tim Ferriss: Are we talking about JC? Is that —
Pablos Holman: Yeah. And so other than that, it’s probably going to work. I don’t think it’s — not very questionable at this point. The other important advancement is it’s sailing, so it doesn’t need a crew, but it doesn’t need fuel. Those two trillion spent in the shipping industry every year are spent. Five out of six of those dollars is burned.
Tim Ferriss: You said sailing. What if there’s no wind?
Pablos Holman: If there’s no wind, we have electric backup to get out of the dead zone.
Tim Ferriss: I see.
Pablos Holman: But we’re actually really good at weather prediction because even cargo ships now need to avoid storms. And so the weather prediction has improved so much. We’re really good at that. But yeah, your worst-case scenario is you’ve got a ship full of bananas and they’re stuck in a dead zone. So we have electric backup to get out of the dead zone and then they sail themselves.
Tim Ferriss: Why aren’t these things everywhere?
Pablos Holman: Exactly. So they’re not everywhere because look at how we’ve all learned about disruption. You’ve seen what happened. Any taxi company in the world could have made an iPhone app. None of them did.
Tim Ferriss: Instead, they ended up suing Uber everywhere they launched.
Pablos Holman: Any shipping company in the world could make this ship. None of them will. So that’s what we have to do. That’s what the tech industry needs to do. That’s why deep tech matters. That’s why I want your fans who are listening, once they graduate from software, come help us build this ship. Help us take on — you don’t need to be a physicist. I’ve got physicists. What I need is entrepreneurs who want to build these industries. And when you look at what happened with Uber, that playbook is incredible. What happens the day my first ship sails? Do we sell this to Maersk? That would be like Uber selling to Yellow Cab. No, we build the next Maersk. That’s the opportunity.
Would you have rather built Uber or Maersk? That’s where —
Tim Ferriss: I mean, Maersk just might take it into hospice.
Pablos Holman: Risk of assassination is high. I grant that. Maybe higher than even in taxis because there are a few big cabals globally that run the shipping industry. You might need to partner with one of them, but that’s a tomorrow problem. The truth is we can do this.
Tim Ferriss: Pablos, one day I’m going to ask you for a favor.
Pablos Holman: Yeah, might need one myself after this airs. So the point is you could identify, I don’t know, risk of assassination as a fourth kind of risk. But look, we have to build these things. The regulatory risk in different industries in shipping you’re dealing with, look, teamsters and ports, I mean that’s where labor unions come from. Read about the Wobblies having shootouts with the sheriff’s office. I mean this is crazy stuff in the history of labor. So you’ve got to be careful about who you put out of a job. But I think it’s one of these exciting things.
What you mentioned is the reason ships are so big is because you get a drag advantage, you get improved drag. When you double the size of a ship, your drag only goes up by 50 percent. So you’re incentivized to build the biggest ship you can.
Well, those ships are clogging up ports. So if you look at what’s happening in shipping, your happy meal toys start out in China, it takes 50 days to get them to Los Angeles. Only 14 of those days are on the water. The rest of the time they’re just hanging out at port waiting to get loaded or unloaded. So that 14 days is a little slower when you’re sailing. 30 percent slower. But overall it’s faster. But we can make smaller ships and lots of them.
Tim Ferriss: I mean, I guess you need to get to a certain position of dominance in order to clear the congestion at ports. You need to start replacing a lot of the container ships that are clogging.
Pablos Holman: I mean that would be great, but we will start out with tiny ships that move a few containers to islands. I mean there’s all these islands that you can’t even get a ship to. And we could just do that. Sail your happy meal toys to islands.
Tim Ferriss: Is Pablos a common name in Alaska?
Pablos Holman: Pablos is a totally fake name because all hackers have fake names.
Tim Ferriss: Is the last name fake too?
Pablos Holman: No, I mean I’m not trying to fly below the radar at this point. I got that username on a mainframe when I was like 12 and I don’t even remember how. I’ve been called Pablos for longer than anyone can remember.
Tim Ferriss: And I have to ask, I know we’re taking a left turn here, but on the cover of your book, you have your glasses. In every video I’ve ever seen, I see you in the glasses. What is the story behind the glasses?
Pablos Holman: I’ve been wearing the same glasses for 20 years, which is kind of why they ended up on the cover of the book and people associate me with the glasses. These are the best glasses ever made, which is why I started wearing them and because in labs all the time, I kind of need safety glasses that wrap around.
Tim Ferriss: Are they prescription?
Pablos Holman: Yeah.
Tim Ferriss: Okay.
Pablos Holman: And I’ve been wearing glasses since I was four, but I started wearing these. They’re made of titanium alloy.
Tim Ferriss: What are they? Are they Oakley?
Pablos Holman: Oakley made them in their heyday. So back before Oakley got sold out, they had these designers who were little gods. They could do whatever they wanted. And they built this factory in Nevada to make titanium frames. But this is intensive to do. 425,000 watts to make one pair of frames. And they have all these volatile gases in the casting process. And so eventually the factory blew up and nobody will ever make glasses this way again. But I’ve been wearing the same ones for 20 years.
Tim Ferriss: One pair?
Pablos Holman: You can’t break them. Oh, I have a few pairs that I cycle out because the nose bridge gets loose and I got a guy who will tighten them up, but two pairs would’ve lasted this long. Yeah, I have more just in case I live a couple extra lifetimes. I’ve been stockpiling them.
Tim Ferriss: Are you optimistic? Would you describe yourself as optimistic?
Pablos Holman: Well, people cast me that way and I think it’s probably fair. But what I wrote in the book about that is that I think I’m not a pollyannish optimist. I don’t think everything’s going to be awesome. What I think is the future could be awesome that we have some volition in this, that we build that future ourselves with the toolkit we have. That toolkit is largely the technologies we have. And so I think it’s up to us to try. It’s up to us to decide where we want to go, what we want to aim for, what future we want to build and do that. I call it possible-ist. I think a future that’s awesome is absolutely possible. A shitty future is also possible, but the balance is up to us. And so that’s how I would describe that.
Tim Ferriss: Yeah. Let’s talk about the B word for a second. Billionaires. So I know of at least three, you don’t need to name names, although you mentioned a few publicly who just find you to be the shiniest, most attractive hire. And I want to know why you think that is? Because they’re not looking for script kiddies in Romania. There are a lot of people who can steal passwords and who are capable hackers of various types, but you just seem to pop up again and again on these teams. Why is that?
Pablos Holman: Okay, so first of all, lots of hackers that are way smarter than me and way more potent, so nothing to worry about. I think that the heart of what you’re getting at is probably what you could say about me is I do have a kind of extreme risk tolerance. My whole career, I’ve only worked on things that I thought were cool or interesting. I’ll optimize for that over everything else. I’ve gone broke a bunch of times because I worked on things that were way too soon or way too cool or way too expensive. But I’m okay with that because I want to do the thing —
I’m not going to do that anymore. But I’m okay with that because I’m good at doing things I’m interested in. I think people are optimized for that. I don’t find that I’m effective if I’m working on something that’s not interesting. I’ve always optimized for that. I took on things a decade before other people would see them as rational. That’s how I ended up in some of those unusual situations in my career. As far as billionaires go, I think — look, I don’t think I’m just a shiny object. They can hire whoever they want.
Tim Ferriss: Not my words, by the way. It’s one of our mutual friend’s words. Shiny meaning attractive, by the way. Not just a crow collecting buttons or something. I’m just saying.
Pablos Holman: Yeah, I mean some of these are very — just circumstances that I ended up being open to when most people wouldn’t. I’d say that’s the biggest thing and I think it’s replicable. Other people could do that. Think about your worst case scenario. Probably your startup fails, you end up on your mom’s couch, regroup. Try again. For most people, you and I know most people in the US, most people in tech, that’s what it looks like. It’s not so bad. So why are you over-optimizing on safety? Why are you going to work for a big tech company or Goldman Sachs or whatever? That’s optimizing for safety.
Tim Ferriss: So let me ask you this, do you think people are under-optimizing on location? Because you mentioned Seattle, I’m not sure how you got to Seattle, but when I think Nathan Myhrvold, Bill Gates, Jeff Bezos, all Seattle, right? So is there some engineered serendipity placing yourself in the right location? Or is that less of a factor?
Pablos Holman: Okay, so I was in Silicon Valley before that and I would say the main reason I left is that sock puppet attack. In 2001, everything in Silicon Valley got shut down because of the.com bubble. So it was a wasteland.
Tim Ferriss: Sock puppet attack.
Pablos Holman: It was this —
Tim Ferriss: What does that mean? I like it. I want to use it. So I need to understand what it means.
Pablos Holman: Because the poster child for .com bubble was pets.com and they had this ad campaign, they spent like a billion dollars on ads, like Super Bowl ads with a sock puppet. And it was just the most ridiculous thing.
Tim Ferriss: You’re like, the end is nigh.
Pablos Holman: The end was nigh, and it’s because everything was over-hyped. Too much money was put into too many dumb things. I have a bad attitude about this because we had real technologies, and we got shut down too. I don’t like what I see in Silicon Valley. It’s too much crap. Not enough actual technology. We overindexed on entrepreneurs and we threw the inventors under the bus. It’s time to course correct. I want the guy from WeWork and I want to give him a nuclear reactor. Let me arm you. If you are an entrepreneur that wants to build a company, great. Let me arm you with IP, with an invention, with a CTO, I can hook you up. Only the good ones. So that’s kind of where I think this goes.
Tim Ferriss: Now the WeWork founder is a controversial choice.
Pablos Holman: Okay, whatever.
Tim Ferriss: No, no.
Pablos Holman: I’ll take the Uber founder. Any founder. Controversial or otherwise —
Tim Ferriss: Those are the two strong ones.
Pablos Holman: Okay, fine. But good entrepreneurs. No tech. So let’s arm those guys with some actual technology. That’s what I think — but that’s not your question. The point is, in 2001, everything got shut down. Silicon Valley was a wasteland. You couldn’t start companies, couldn’t do hardly anything. So I ran out of excuses to pay rent and go broke in San Francisco. And so Seattle was like, for the price of rent in San Francisco, I could rent a whole neighborhood. And I was like, “Oh, let’s try that.” And —
Tim Ferriss: How did you choose Seattle over every other place?
Pablos Holman: Because I’m from Alaska, Seattle’s like the default next, so I knew more people in Seattle than anywhere. And so I was just hanging out in Seattle during the summer funemployed and looking at real estate prices thinking, “Oh, this could be okay.” And then I got an email from Neal Stephenson who —
Tim Ferriss: I was going to bring him up, so I’m glad you did. Yeah.
Pablos Holman: So, look, Neal, if you’re any kind of nerd, Neal is a demigod.
Tim Ferriss: Yeah. Snow Crash, Metaverse. I mean, when did Cryptonomicon come out? Which I loved.
Pablos Holman: ’98.
Tim Ferriss: Okay, so early glimmers of crypto.
Pablos Holman: Yeah. So I was working on cryptocurrency in ’98 when Cryptonomicon came out, so I’m a closet Neal Stephenson fan. And so I got an email from Neal and he’s like, “Hey.”
Tim Ferriss: How did he find you?
Pablos Holman: Mutual friends. Jeremy Bornstein introduced us and he was the founder of the company I’d been working for, doing AI stuff that got shut down in dot-com bubble sock puppet attack. So anyway, so Jeremy introduced me to Neal, Neal said, “Hey, we’re building a lab to do some cool stuff. Come check it out.” So I went down to this lab. So Neal and an astrophysicist named Keith Rosema had gotten this old envelope factory and turned it into a machine shop that they bought a machine shop on surplus, and actually the crusty old machinist kind of came with it.
So they were trying to build what was called Blue Operations. And I went down there and they’re like, “Hey, we’re trying to go to space.” I’m like, “Cool, whatever. Space is good, I’ve got nothing else going. Let’s do it.” And they needed help with computer stuff, of course. And so I started helping on that, and we were trying to figure out alternative ways of going to space besides rockets. And eventually we hired a couple other machinists and some other super nerds and tried all these experiments. And that was the origin of Blue Origin.
Tim Ferriss: Wow. What were the alternatives that you guys were exploring?
Pablos Holman: So rockets are like 90 percent fuel. So when you light up a rocket, you’re just burning fuel to get out of Earth’s gravity.
Tim Ferriss: Cargo ship plus.
Pablos Holman: Yeah, right, totally. So you can’t make rockets sail, but we thought maybe you could. So what if you could just take the payload, the craft, the part you want, people or the stuff or the satellites, and then beam power to it from the ground, which sounds kind of crazy, but every day gets easier and easier. We have the technologies that could do that now, so I think eventually we will do these things. But the problem was Jeff Bezos was the one who started Blue Origin. He’s the one funding it. And in those days, Jeff was worth like $7 billion and our job was to figure out what we could do with one. So —
Tim Ferriss: That’s a ballsy bet. He’s done pretty well since.
Pablos Holman: He’s done all right and now it’s putting a billion or more every year in Blue Origin. But the point is we could get further faster by standing on the shoulders of NASA and Russia than starting in a $50 billion hole, inventing some new propulsion scheme. So we have a bunch of ideas that were really cool, but in the end — so this, again, started in 2001. I’m going to go to Blue Origin next week for the 25th anniversary, and I get to meet some of the staff. I don’t have anything to do with it anymore, but hopefully get to meet some of the folks who are taking that and running with it. But the last thing I worked on was we built this terrifying craft with four Rolls Royce jet engines that we retooled to operate vertically and made like a quadcopter out of them.
Tim Ferriss: Sounds safe.
Pablos Holman: It’s totally not safe. This is before you could buy a quadcopter at Walmart, so we had to write all the code to do self-balancing and stuff on these microcontrollers and get it working and do thrust vectoring and all this. Anyway, we drug this thing out into the desert in central Washington, we fire the thing up, and it goes up and flies around like a UFO and then it comes back down and does a vertical landing. And so we proved that it could be done, and that was the day we decided go do it with a rocket, and Blue Origin got started on a track to go build a rocket and that’s when I left. You don’t need me to build a rocket, so yeah.
Tim Ferriss: Yeah. Amazing. All right. This is going to be out of left field, but I like out of left field. But I don’t want to leave this question of why you get hired for these projects too quickly.
Pablos Holman: Sure.
Tim Ferriss: Because for whatever reason, I feel like there’s more there. How do you look at the world or what toolkit do you have? What are you able to provide that —
Pablos Holman: Honestly, I think there’s probably somebody better at everything than me.
Tim Ferriss: You’re very multidisciplinary.
Pablos Holman: Yeah. At this point, I’d say I’m kind of the canonical T-shaped person. I went real deep in computers and so I can appreciate and communicate with people who are experts in other things because I’m kind of a generalist. So I don’t write much code, I mean I’m fucking vibe coding for fun, but no one cares about any code I’m writing. I’m not that guy. But because my depth of knowledge is deep, I can appreciate another expert’s depth of knowledge and I think that that helps me to work with folks. A lot of people get pigeonholed into just the thing. We see that with scientists or engineers a lot. They’re specialized too much. And if you look at millennials, they’re kind of typically very flat. They just — “I could do anything,” but they can’t do it too well.
Tim Ferriss: An M-dash-shaped person?
Pablos Holman: M-dash. Yeah, M-dash for millennial. I like that. So I think that my suspension of disbelief, my willingness. Also, I think one of the other things that works to my advantage is most of my colleagues and friends are legitimate scientists or engineers, and they’re formally trained and they know what they’re doing. Those folks get stuck with kind of some professional liability. If you’re a scientist, you can’t say crazy shit because that could be professionally damaging for sure.
I’m a hacker so I can ask all the dumbest questions in the world because they think I’m a little bit smart, a little bit dangerous, but if I don’t actually know about shipping or rockets, I mean I had to learn physics on the job. I’m working with actual astrophysicists who know about rockets, and I have to understand what does delta-v mean, and I’m Googling that shit on the side. So I had to learn those things on the job, and I’m more fluent now, but I’m not formally trained in those things, but it’s okay for me to ask a dumb question about rockets. And so I think that helped me a lot.
Tim Ferriss: Yeah, that’s my job to ask dumb questions.
Pablos Holman: Yeah. And you get away with it too.
Tim Ferriss: Yeah.
Pablos Holman: So that’s really cool. And you’re doing such a good job of that because you’ve been able to bring in people, whereas someone else, and you can see this when you see experts interview people, it’s not interesting. It doesn’t go anywhere because they can’t ask those dumb questions. Ask me some dumb questions. We’ll prove it right now.
Tim Ferriss: Okay, Zero Effect.
Pablos Holman: Oh, man.
Tim Ferriss: What is Zero Effect? You and Elan Lee are both fans of Zero Effect and I’ve never seen it. What is Zero Effect?
Pablos Holman: I thought I got this from him, but he says he got it from me. So this is a philosophy that drives me. So there was a film called the Zero Effect. It was like Ben Stiller made it 20 years ago.
Tim Ferriss: 1998. Yeah.
Pablos Holman: Okay. The main character is the world’s greatest private detective. And at one point in the film, he’s articulating his philosophy of being the world’s greatest private detective, and he’s a private detective who never leaves his home, so he stays home and he cracks every case.
Tim Ferriss: It’s like the fantasy of every millennial on screens right now.
Pablos Holman: Yeah, right. Well, here’s how to do it guys. If you lose your keys and you go looking for them, of all of the things in the entire world, you’re only looking for one of them and your odds of finding it are very low. But if you go looking for something in general and you don’t set such a specific target, you’re bound to find something. And so it’s a way of thinking about like, “Oh yeah, if I’m open, if I’m open to what’s possible…”
So for example, why I say that’s a philosophy that matters to me. I’m running the most wild venture fund ever. We invest in things that sound crazy and I have to be open. Most of them, even I don’t like them at the beginning. Even I’m like, “That sounds crazy,” but I have to force myself to stay open, let the founders try and explain why it’s not actually crazy. And by the time we invest, I’m convinced and I understand enough that it’s like, “Okay, it sounds crazy, but it isn’t.” You know by now I’m in the business of things that sound like complete bullshit but aren’t. I have to be right enough times that they’re not, but I got to be open. So I think the Zero Effect is how I think about staying open to finding anything.
So people come at me with perpetual motion devices every day now, and it would be crazy to invest in one of these perpetual motion devices, but it might be genius if you invest in all of them, so I do. Well, or at least a lot of them. So if one of them works, I’ll have it. So that’s kind of the game. And I think more people would get something out of that approach to life than the opposite, which is much more common, which is people are trying so hard to be so sure and be right all the time, and they really aren’t any way. They’re spectators in the world, they’re not building something anyway. So I think be open to things and be supportive.
One of the best things about Silicon Valley in the ’90s was the way everybody was like that. You could just walk down the street, find a homeless dude, start telling them about self-sailing cargo ships or nuclear reactors. He’d be like, “Oh, cool, man, my college roommate is an astrophysicist. He might be able to help you with that.” Everybody was in on it, and I think they get a bit of that now with AI. People are supportive, but it’s hard to find a critical mass of that dynamic anywhere else, so I try to be that for the deep tech folks.
Tim Ferriss: Is the movie worth watching or is it really just the philosophy?
Pablos Holman: Oh, yeah. Oh, totally. Good movie. It’s a good movie. It’s awesome. Go watch it. Yeah, I mean, I don’t even watch movies, but trust me, this one’s good. And WarGames, those are the two movies in the world to watch. Everything else, you can ignore.
Tim Ferriss: WarGames, the only defensible movie on hacking?
Pablos Holman: Only defensible hacker movie ever. I keep trying, Hollywood calls me to put hackers in a movie. I keep trying to help them put legit hacking in the movies and I explain everything, I show them exactly how to make it go so that real hackers will get on board. And then by the time the movie comes out, my influence is completely lost. It’s just fake access, control, override again.
Tim Ferriss: “Enhance photo.”
Pablos Holman: “Enhance photo.”
Tim Ferriss: That’s one of my favorites.
Pablos Holman: I know enhance — it’s such bullshit. Although enhance photo is working pretty well now.
Tim Ferriss: Yeah, yeah. Now it’s a thing. So perpetual motion folks, it’s coming.
Pablos Holman: There you go.
Tim Ferriss: You mentioned looking for keys. I just have to ask because I know that you’re focused on deep tech, but still it seems like you have occasional side projects. So the key with duct tape, at least as it was described to me, where you were like, “Oh yeah, this one opens my car, closes my car, and this one unlocks every REDACTED in a one or two-mile radius.” Is this just a fairy tale?
Pablos Holman: It’s not a fairy tale. It was figured out by a hacker named Major Malfunction in England.
Tim Ferriss: Great handle.
Pablos Holman: And so those keyless remote or the remote key buttons that you have for your car, they’re kind of like RFIDs. They have a battery in them, so they can emit a signal, and then the car is listening for that signal. And when you build almost anything, you build it to do the thing, but you almost always build a little back door. Watch board games. So Major Malfunction, not through hacking, but by calling tech support for his REDACTED, because his wife was locked out in a sketchy situation, was told, “Oh, do this, manipulate the key.” So he’s able to manipulate the key to open any REDACTED and he explained this to me. And I don’t know if he was drunk or what, but he probably shouldn’t have. And so —
Tim Ferriss: Pablos on the loose.
Pablos Holman: — go by the dealership and you can open any REDACTED. So at the time, I wasn’t going to say the name of the brand, but you did. So yeah, it was —
Tim Ferriss: I mean, we can bleep it out.
Pablos Holman: — one brand of cars can open any car from that manufacturer. I think they probably have fixed this by now, but you would have to, or at least in modern cars, I sure hope so. I’m not going to say how to do it, but yeah, so look, that’s a vulnerability that has poor foresight because in those days, this is an old attack, so I don’t mind talking about too much, but you don’t have a system update. Those cars are not online. Now a Tesla and modern cars almost all have an internet connection and they can run system update, which is a very important way of reducing attack surface for vulnerabilities. So now that cars have system update, we could fix something like that remotely, but in those days you couldn’t. And so it was a pretty wild attack for a while. Yeah.
Tim Ferriss: Well, I guess it still is if you’re going after vintage vehicles, potentially.
Pablos Holman: Maybe, yeah. I’m not going to tell you how to do it.
Tim Ferriss: Yeah, yeah, no, that’s all right. I’d be curious to know, and there was another friend who popped up in your book, Chris Young.
Pablos Holman: Oh, yeah. Oh, good.
Tim Ferriss: I’ve spent a ton of time with Chris Young —
Pablos Holman: Great.
Tim Ferriss: — for the book that I wrote about learning and cooking and so on, and had a blast. And that’s also the first time — I think I bumped into him twice now, but met Neal Stephenson —
Pablos Holman: Oh, yeah, good.
Tim Ferriss: — who is one hell of a diversified polymath. I mean, that guy is up to a lot more than writing. I mean, he certainly is a prolific –
Pablos Holman: Neal’s delightful. We got to obviously do Blue Origin together. He helped us start the Intellectual Ventures Lab. He and I started a sword fighting school one time.
Tim Ferriss: He’s really into Victorian-era exercises, right?
Pablos Holman: Yeah, right. No, you got all the club bells and for a while was training with a Sherlock Holmes-esque cane, I forgot what’s that called? Bartitsu. Oh, man. Yeah, Neal, it’s great. I mean I really love Neal. He’s delightful, but he would spend about half his day writing in the morning and then the afternoon working on some crazy project, and I got to work on a lot of those with him.
Tim Ferriss: What are some of the characteristics or mental frameworks, anything at all, that distinguish some of these people who have employed you? So for instance, and I think you might’ve written about this, certainly I’ve thought about it a lot, but the advantage that, for instance, Jeff Bezos was able to create even before he created his empire with longer time horizons than anyone else, just changing the timeframe of thinking and planning. What else have you gleaned from these folks?
Pablos Holman: Well, that one, I think it’s a very important one because like you said, you sort of flippantly mentioned billionaires, and people get off about these folks as soon as they’re rich just because they’re rich or successful. But often what I see is it’s blinding them, it’s blinding people to learning what is it that made those people successful? What is it that’s good? What is it that’s replicable? What are the lessons? And that’s why I think we kind of need you to pay attention to them because for better or worse, more people will probably listen to you than these billionaires. And so you can —
Tim Ferriss: That’d save us.
Pablos Holman: — get those lessons, yeah. So for example, what I learned working for Jeff that really made a big difference to me personally was that if you think about Blue Origin, what is really going on there? It’s not a way for Jeff to get rich. That’s covered. So why make Blue Origin? Well, Blue Origin’s vision is to build a future for humans off of this planet and turn Earth into a wildlife refuge that maybe you would visit once in a lifetime because this is an awesome, amazing, and beautiful place and we don’t want to fuck it up too badly. So that sounds crazy, and none of us are going to be around for that, but it might take thousands of years to craft that future for humanity.
In the best case scenario, Earth just melts into the sun and that’s if nothing else wipes us out in the meantime. So if you believe in the sanctity of human life, you believe humans are something special, and I do, then in the long run you want to build kind of a plan B if not planet B. So that’s what Blue Origin is about. Now, that’s going to take generations, maybe millennia to do, but even so it would start with one small step. Blue Origin is that one small step. Can we get it started? And it’s actually a really amazing thing.
And so I learned to start by thinking on longer-term horizons, and that’s not super — like a thousand-year project to build space colonies is obviously not very relevant to me. I run a 10-year venture fund like everybody else who’s an investor. So what does that mean for me? Well, it gives me a way to think about new technologies. If I look at this nuclear reactor that goes in a borehole as an example or this cargo ship, and I say, “All right, 100 years from now, are we going to be burning nasty bunker oil to move those happy meal toys around or would we make these self-sailing cargo ships?” It’s like such an easy thing to answer. Anybody could do it. You don’t need to be smart, you don’t need to know anything about tech to answer that question.
Tim Ferriss: As soon as you extend the horizon.
Pablos Holman: You extend the horizon. In 100 years, anything could happen. In 100 years, the regulatory environment could change, Maersk could be out of business, all the cabals could be out of business, whatever, all the things, any objection you have probably could be solved in 100 years. So then ask yourself, “Does it have to take 100 years or could we do it in 10?” And if you can start to craft a vision for how to do it in 10, then you align with a lot of the machinery in the world that works. Venture funds are all 10-year funds. I can’t invest in things that take 20, but I can invest in things that take 10. So all the money is in 10-year funds. So people’s careers, they could sign up for a 10-year project, but a 20-year project might be too much. So that’s the kind of thing that helps me craft a vision for what I could invest in.
Okay, ships, yeah, we could do that in 10 years. The nuclear reactor, totally we can do it in 10 years. We’re going to do it by July. So all these crazy-sounding things that we do, I looked at them as things that definitely will get done in 100, but we’re going to try and do it in 10. And I learned that from Jeff. And you look at what even Amazon is doing, they’re taking on a whole bunch of projects that they could prove a success in less than 10 years. They’re like a giant venture fund internally, basically. Silicon Valley is thousands of million dollar experiments. We just try all these things that could be done in 10 years or less. And in 10 years you could do a lot. I think people don’t realize Google, Apple, Microsoft, all companies that were successful in less than 10 years. But not just that, the Apollo program was less than 10 years. The Space Shuttle program —
Tim Ferriss: Hoover Dam.
Pablos Holman: The Hoover Dam, the Panama Canal.
Tim Ferriss: The Empire State Building was like 18 or 24 months or something insane.
Pablos Holman: Right. So what are we sitting on our thumbs for, making more iPhone apps?
Tim Ferriss: My friend gave me that number when his remodel in Santa Monica took five years. He said, “Come on guys, what is happening?”
Pablos Holman: There you go. So the answer to that question is the answer to every question about the future, about what’s happening in the world around us. We need to solve all the things in that window. Let’s build in less than 10 years everything.
Tim Ferriss: Do you think that Elon actually wants to colonize Mars or is that a clever visual and story to tell to marshal public interest and support and so on? Or do you think that whether it’s Jeff, or Elon, or someone else, that the most practical future we’re looking to off-planet is something closer to Elysium where it’s in sort of a self-contained large-scale ISS city of some sort?
Pablos Holman: All right. Well, two things there. One, I do know Jeff, I don’t know Elon, so I know as much as you, I’ve seen publicly what he has done. I don’t know if it’s just because of Blue Origin, but I’m a little more on the space colony side of things than on the Mars thing. You only get one Mars anyway and so it doesn’t seem like that good of a destination.
Tim Ferriss: Yeah. Well, I remember somebody said to me, they’re like, “If you think you want to live on Mars, go spend a month in the winter in Antarctica.”
Pablos Holman: Yeah, which I have done for my entire childhood, so Mars doesn’t exactly appeal to me. I’ve had enough of that. I want to be in a city with people. But I think it goes back to the thing that matters to me is what I said before. People are blinded. They’re pissed off about Elon for one thing or another, and it blinds them to learning. That guy is showing us, “Here’s how you make modern industries.”
Tim Ferriss: Yeah, I mean, he’s a phenomenon.
Pablos Holman: It’s phenomenal. And look, if you don’t like Elon, fine, go show us how to do it better.
Tim Ferriss: Well, you also don’t need to like everything about someone.
Pablos Holman: Yeah, that’s true.
Tim Ferriss: Or admire everything about someone in order to recognize and potentially model some of the things that really do work.
Pablos Holman: Well, I appreciate you demonstrating that by hanging out with me today. I mean, I think there was this thing I learned a little, I got a glimpse of this from this thing that a bunch of music artists did called the ONE Campaign, like U2 was doing it, and the idea behind the ONE Campaign was because they wanted to solve malaria, they wanted to solve HIV, they wanted to go after some big global scale problems. And the reason it’s called ONE is that they wanted to get all these constituencies from around the world to focus on this problem, and they only had to agree about this one thing. We only have to agree about this one thing, which is that we need to solve HIV.
Yeah, we don’t agree about all this other stuff. We don’t even like the same music. We need the Republicans and the Democrats and the autocrats all together for this one thing. And that had a big impression on me because I think it is important. We don’t all agree about everything. I’m a cypherpunk. We don’t agree about a lot of things, okay? That’s okay. And most of my friends, I want them for what they’re good for and what we can work on together. So yeah, I’m with you on that. And that’s why I can work for people who, I mean, I probably don’t agree with everything people I work with are about, but yeah, we need like 1,000 Elons. Maybe they don’t all need X accounts, but we need 1,000 Elons and we need them to go after all these things and that’s how we’re going to build the future.
Tim Ferriss: So this is from a New York Times article from 2018.
Pablos Holman: Oh, man.
Tim Ferriss: So this may not be relevant anymore, but I have attended a lot of conferences. You’ve been to a lot of conferences. I’ve heard of most of them, but one popped up, Mars, the conference. I don’t even know if it still exists, but what was it like to attend that?
Pablos Holman: Oh yeah. Well, Mars is —
Tim Ferriss: And what is it?
Pablos Holman: So that’s just a small event. So Jeff Bezos has that event annually. It’s for machine learning, automation, robotics, and space. And so Jeff and Amazon organize it. It’s a really delightful event because we bring in the world’s experts in those four things, and we’ve been doing that for like a decade. And so it’s a way to make a peer group out of people who often are siloed because they’re researchers in a lab somewhere. They wouldn’t necessarily party together otherwise. And so it’s a very important thing. I’m oddly probably the one person who’s worked in all four of those things. Everybody else is usually a Nobel Prize winner in something, but it’s otherwise like a normal conference. We come hang out together for a few days. Thankfully, Amazon or Jeff is paying for it, which is great.
And we get to cross-pollinate these folks who really often are peerless in a sense, because they’re world-class experts in their thing. You’re surrounded by people who are smarter than you. We’ll have five or 10 Nobel Prize winners and we don’t even put them on stage, so it’s a rarefied group. And I am convinced that these things are so important because people need a community. And we have like a WhatsApp group where we sort of stay in touch with each other the rest of the year, and people are very supportive and helpful. And it’s just wherever you are, I mean, look, you don’t need Mars, but you do need a community. And so one cool thing about Silicon Valley, if you’re into, I guess right now, AI-type stuff, you could definitely find a community there. The deep tech founders are having a harder time because there’s no geographic center of gravity. So we’re trying to, at least for our founders, help them get that going. But, man —
Tim Ferriss: Well, this is a good —
Pablos Holman: — community matters.
Tim Ferriss: — good time to explain why the hell we’re sitting where we’re sitting. What is this location? Where are we?
Pablos Holman: This place is so cool. So we are at the Newlab in the Brooklyn Navy yard, and this is like nothing else even I know about. It’s actually kind of like my lab or the Intellectual Ventures Lab. It’s about the same size, maybe a little bigger. There’s a machine shop here, there’s labs of all different kinds, and it’s an incubator for deep tech startups. They have like 100 of them.
Tim Ferriss: Beautiful space.
Pablos Holman: It’s a beautiful space. It’s I think kind of a public-private partnership with the city to build this thing. And they’ve been at this for like a decade. I’ve been friends with the founders for that whole time and just so impressed with what they’ve done. I actually don’t have anything to do with it. I’m pimping Newlab because if you have a deep tech startup, these folks can help. And I think it would be great to attract more deep tech founders to these things because they built this one, and they built one in Detroit that’s even bigger, and it’s so cool and it’s got space. So if you’re trying to build something, go see Newlab. And I thought this would be a cool place to record the podcast because it’s cool. And in New York it’s hard to find a cool space that’s not tiny. Yeah.
Tim Ferriss: Yeah. This is anything but tiny. And I was pulling up my phone because we haven’t spent much time together, and I’m pulling up to this location that I have no familiarity with. And so I just want to read our text exchange for a second. “Pulling up now.” “Enter through building 77.” I’m like, “Where the hell’s building 77?” Okay, you drop a pin. Apparently the main gate is under construction. I’m like, “Okay.” So I walk over and then you’re like, “Walk all the way through that building. There’s a turnstile with a guard, but he’s easy to PSYOP. Then go out and left.” And I’m like, “Building 5? PSYOP completed. I’m out walking left.” We’re going to come back to the PSYOP.
But then you say, “The big building straight ahead is your target. Get to that and then go left. No number on it. Entrance is at the far corner of the building.” And then I said, “Am I being set up for a podcast kidnapping? Very elegant,” ’cause I’m like, “Where the hell am I going?” Then you said, “I’ll come out and meet with the black van.” And there was actually a black van. And I’m like, “Wow, this is just…”
Pablos Holman: Now you know why Elan Lee and I are friends.
Tim Ferriss: Yeah, yeah. I was like, “This is a coin toss. I have no idea what this — this could be the long con.”
Pablos Holman: Yeah, it’s a bit —
Tim Ferriss: This would be an amazing long con.
Pablos Holman: Well, my dating life has been very colorful because of every girl who’s dating me ends up meeting me at some strange warehouse in the industrial district with wires hanging out of metal. And yeah, it’s —
Tim Ferriss: So I remember ages ago when it first came out, someone recommended that I read Kevin Mitnick’s The Art of Deception, which — you made a face.
Pablos Holman: Oh, I did? Shit.
Tim Ferriss: Yeah. Okay. Tell me what that’s about.
Pablos Holman: Well, look, I mean, Kevin’s a delightful human, you could say. He’s dead now, so we don’t want to say anything bad about him, but hackers kind of rallied around him ’cause he was one of the first hackers to get thrown in jail.
Tim Ferriss: Yeah.
Pablos Holman: But most hackers, I don’t know, if you’re elite, Kevin is kind of a joke because he was a good social engineer.
Tim Ferriss: Well, that’s why I bring it up, because you mentioned PSYOP. And as far as I could tell, 90 percent of the book was social engineering.
Pablos Holman: Yeah, that’s his thing.
Tim Ferriss: Right.
Pablos Holman: And it’s worth learning. I mean, that’s a totally great thing. It’s different than hacking.
Tim Ferriss: Okay. But PSYOP, was that a joke or is that something —
Pablos Holman: Oh, just because — no, I had gone through building 77 and I’m like, “Hey, going to new lab,” and he just waved me through.
Tim Ferriss: Yeah, okay.
Pablos Holman: So I’m like, I think this —
Tim Ferriss: Supremely easy to PSYOP.
Pablos Holman: — will be an easy challenge for you.
Tim Ferriss: Yeah, okay. All right.
Pablos Holman: Yeah. Anyway.
Tim Ferriss: I want to ask you a bit more about China. So I lived in China for a period of time. I went to two universities there, studied Chinese, the whole nine yards. Spend about, oddly enough, right now, 20 percent of my time probably speaking Chinese, resurrecting my Chinese right now.
Pablos Holman: Wow.
Tim Ferriss: And that’s actually an exaggeration, but it’s like 10 to 20 percent probably. And I’ve been so simultaneously impressed and terrified by China on so many different levels.
Pablos Holman: You and me both.
Tim Ferriss: And there was a book, Tyler Cowen recommended, great, amazing guy, everybody should check out. There’s a book called Breakneck.
Pablos Holman: Oh, yeah.
Tim Ferriss: And I haven’t yet read it, but one of my employees is reading it and recommended it. He said, “It’s an amazing page turner. Really well researched.” And the reason I mention it is that in that book, they describe some of the differences in government planning and efficiency based on the fact that a lot of leaders in the US have backgrounds as attorneys, whereas a lot of leaders in China have backgrounds as engineers. And I have been chewing on that. I just learned about this yesterday, but I’m wondering what impresses you about China ’cause they really seem to have their act together. The homogeneity, relatively speaking, of the country helps. The speed with which the CCP can execute top down helps tremendously. But anything else come to mind?
Pablos Holman: So look, I could learn a lot about China from you. I’ve been there some, but probably not as much. I don’t speak the language. My way of learning was to start sleeping with a Chinese woman. So I’ve been doing that for five years.
Tim Ferriss: Sounds more fun than memorizing characters, frankly.
Pablos Holman: It’s helped a ton. I really opened up my eyes to China. So yeah, my fiance is Chinese, but been in America long enough that she’ll put up with me. And I think the insight from that book, I haven’t read Breakneck yet, it’s a relatively new book. I am also just kind of a spectator on what’s happening in China.
Tim Ferriss: But you have a unique multidisciplinary technical lens that includes deep tech.
Pablos Holman: Yeah. So what I can tell you, I think there’s a couple of major factors and the insight about the preponderance of lawyers I think is huge and really important. So I’m excited about reading that book. The reason we invented LLMs is to put lawyers out of business so we can fix this country, and I think that’s going to work. So if you are a parent right now, don’t send your kid to school to become a lawyer ’cause we’re going to replace all the lawyers with AI. I think where this goes, I’m optimistic. I know I’m taking it aside here, but I’m only half joking about that.
Right now —
Tim Ferriss: I use LLMs on a weekly basis for legal first passes already.
Pablos Holman: For lawsuits. Good.
Tim Ferriss: Not for all my lawsuits. No. Well, I’ll give you an example. I mean, this would be no surprise to you, but with just off-the-shelf basic ChatGPT or fill in the blank for your favorite LLM, I was selling a property in rural New York and it was taking kind of forever to get done. There are a lot of arcane local laws and so on. And I wanted to protect the land from overdevelopment. So I wanted to create deed restrictions —
Pablos Holman: More laws.
Tim Ferriss: Yeah. Well, I wanted to create deed restrictions, which are very tricky. Make the sale complicated because it’s encumbered in a way the resale value is reduced, blah, blah, blah, blah, blah. But I just threw in, this county, this is what I’m trying to do. This is the contract that I need to add to, like, draft me some basic language. And it drafted the language, explained exactly why it drafted that way. When it was eventually reviewed by a lawyer to do the finishing touches on it, maybe two or three words were changed and then it was copy and pasted right in.
Pablos Holman: So that’s a great example of what’s happening. Obviously a lot less lawyers were needed to get that job done. When Congress passes a bill, no congressman has ever read it. Collectively, all the congressmen have not read it. And so what the future we’re getting to here is one where if you’re running a business, we build a computational model of your business now, not an LLM, but still an AI, where you can run simulations of your business and you can figure out how to optimize your business. That’s all happening right now. If you’re in business and not doing this, be terrified ’cause by next year your competitors will be doing this. So I take heart because what I think is it means a hundred years from now, governments will do that too.
Tim Ferriss: So if you haven’t seen this, it didn’t get as much airtime as I would’ve expected, but Abu Dhabi is implementing that right now for legislation.
Pablos Holman: That’s right. It’s unbelievable. And if you go —
Tim Ferriss: And it seems like there were a lot of people who poked fun at it, where I saw a lot of people who were like, “Ah, this is nonsense.” As someone who has spent some time in Abu Dhabi with the people who are implementing this stuff, what they already have is science fiction.
Pablos Holman: That’s right.
Tim Ferriss: It’s remarkable what they’re already doing.
Pablos Holman: These are tools to help humans make better decisions. Now, an LLM is the wrong tool for lots of kinds of decisions, but AI overall can be applied to help make better decisions and that is where we’re going. And so when governments figure this out, and it’s great to see that some of these countries are leading the charge. When you see a country like the UAE and you see what good leadership can do, it’s kind of embarrassing. Democracy needs a little maintenance work, and I’m hoping that this class of tools is going to help us level up and fulfill our potential. So that is where that goes. What I think about it is, China has done a great job of a lot of things, and it would be great to have a Netflix series where every episode shows something amazing from China that sucks in the US. I just think that’s the kind of story people need to get in their head just to see that contrast and realize we’re not playing in the major leagues in a lot of things.
So we need to step up. And I think there’s a lot that’s impressive about China. I obviously am an Alaskan, which is a super charged American. So look, I think that there’s a lot of dumb shit going on in China that I can’t stand, I don’t want to live there. But I think you got to give them credit for the things that they’re good at. Now, the thing that’s missing here is a respect for that engineering mindset, a respect for, like you described, putting the dominoes in order, a respect for building thoughtfully, respect for basic arithmetic, a respect for building the future that we want.
We need to work on that. China’s problem, no respect for me, for the hacker mindset, for the renegade, for the creative person, for the crazy ones. They don’t make room for that. And it’s hurting their ability to do new things. Now, they’re kicking by just waiting for us to figure shit out and then implementing it faster and better than us. So we’ve spent most of our life worried about China copying us. We need to figure out how are we going to copy China. And I think that’s a wake-up call where we’re at right now.
Tim Ferriss: Yeah. I’m very curious to see where it all goes.
Pablos Holman: Yeah, me too.
Tim Ferriss: They’re moving at remarkable speed with implementation on so many fronts.
Pablos Holman: Yeah. And it’s great for humanity.
Tim Ferriss: Yeah.
Pablos Holman: I mean, it really is. I mean, they should get a Nobel Prize for bringing their country out of extreme poverty. We should probably get one for, I don’t know, making global trade possible with our Navy or something. But there’s also a lot of accolades that I think we’re not giving to China that we should.
Tim Ferriss: So I want to get your take. I wasn’t planning on asking this, but I’m curious about, since you’ve looked at autonomous shipping vessels, you have familiarity in that domain. I’d like to talk about, for instance, Taiwan for a second. So I’ve spent time in Taiwan. I love Taiwan. Absolutely adore that place. Incredibly friendly. Food is amazing. The culture has been preserved in a way that was not true through the culture revolution in mainland China and everybody should go visit. It’s just an amazing place. Now, it’s also a tiny speck of an island that happens to be incredibly valuable for a number of different reasons, primarily chip production. And there’s a lot of discussion around what say an amphibious assault might look like, how China might exert pressure on Taiwan non-violently, which I think is the most probable path. But on one side you have these statistics that are related to shipbuilding capacity, and China has, I’m going to get this wrong.
Pablos Holman: All of it. Basically all of it.
Tim Ferriss: It’s like 30x, 300x —
Pablos Holman: Yeah.
Tim Ferriss: — the US capacity. And I believe they also require that any commercial vessel over a particular size needs to be manufactured or built to military spec just in case they need to be requisitioned or otherwise enrolled in an attack. Now, we’re not going to catch up with that in the next two years, just it’s a logistics impossibility.
But you do have some startups like Anduril for instance, that talk about the only path forward to create a counter-attack in such a scenario would be lots and lots of small autonomous weaponized marine vessels. Do you think there’s a there there?
Pablos Holman: Well, I do think the nature of ballistic warfare is changing. I think the case Anduril would make is fairly compelling. I think we probably need a lot more Anduril. I’m not the guy who should weigh in on the geopolitics of Taiwan, but I think it’s not hard to look at that and say, “All right, why can’t we do that?” Now, one of the criticisms often made of American schools is that the whole structure was invented to make factory workers after the war. Well, now that we need some factory workers, where are they? We don’t have them. What we’ve got are OnlyFans, creators. So could some of them maybe help us out in a factory? We need to build a lot of things. And I think if you look around, we’re just miscalibrated. You and I barely have to work. You don’t know — anybody you know hasn’t worked a day in their lives, we’re not digging coal out of a mine. We’re sitting in front of a laptop wondering how long is the line at Starbucks?
It’s just not even close. So I think we need to recalibrate on our expectation of what it means to work. Look, I think we’re optimized for work. We’re evolved to work. You wonder about why are people depressed? I mean, not everyone, I don’t want mean to disparage anybody who is dealing with something like that, but you’re evolved to be useful to the world around you, to the people around you. And if you can’t see how your work is useful, yeah, you’re going to get depressed. I mean, I think that happens a lot. I’m not saying it’s the only reason, but when you have a whole society that doesn’t really do anything where you can see how anyone gives a shit about what you do, that’s not going to be very healthy. So I think we just need to recalibrate in our society and recognize like, okay, everybody needs to do something that matters, do something where they can see how it matters. I’m good at connecting dots, so I can do things where I see how it matters in a thousand years and I’m good.
But most people might be better off if they’re like a nurse where you can see, “Yeah, I helped that person today.” Are nurses depressed? They might be depressed about having to do a lot of paperwork, but they’re probably not depressed about their work —
Tim Ferriss: The meaningfulness of their work.
Pablos Holman: Again, I don’t mean to belittle anyone who’s depressed. I’m just saying as an example, we could be a much happier, healthier society if we’re doing things where we can see how it helps our world, helps our society. So building stuff is a good example of that ’cause you can build a thing and you can see I built that thing and somebody’s using it and that’s awesome. Are Tesla factory workers depressed. I don’t know. Or maybe swap out depressed for disgruntled or apathetic or something. You can solve some of these things. So I want to see us build, and I think Anduril is an example of we’re going to build these things that help us. I want to build those ships. We can build ships in the US.
Tim Ferriss: And Palmer Luckey is a machine. I mean, he’s an impressive —
Pablos Holman: Yeah. And we can build —
Tim Ferriss: — founder.
Pablos Holman: And so are other people there. We can build chip fabs. You don’t necessarily need tiny fingers. It’s not a lot of bullshit stories we’ve been told. We can build chip fabs, we can learn to work.
Pablos Holman Anyway, I’m ranting, but you get the idea. Let’s build some cool shit. And I don’t know why you wouldn’t want to do that. And we could build ships, we can build chips, we can build all these other things.
Tim Ferriss: Yeah. So how do you find wild inventors? Or do they just come to you and you act as kind of a honeypot for the forlorn, the crazy, the people into the DeLorean with the crazy hair, as I heard you say once.
Pablos Holman: Honeypot means something else to hackers. So I’ll go with lightning rod.
Tim Ferriss: Yeah.
Pablos Holman: You just look for the crazy hair and the DeLorean and that’s how you find them. Yeah, I’d say I attract some of them because I’ve worked on some of the kinds of projects they want to do, and hopefully they believe that I’ll at least hang in there long enough to understand what they’re trying to do and maybe believe in it and maybe invest in it. So that’s where I’m at. There are times when I find out about a technology or an invention that we might’ve been really helpful with, but it’s too late. That is frustrating. So if you do invent —
Tim Ferriss: Too late in terms of stage?
Pablos Holman: Meaning, yeah, we’re basically helpful at the beginning. We’re helpful in the early stages when you’ve got to get out of that garage or get out of that lab and become more, maybe, venture compatible so that you could go, we’re trying to help people co-opt the machinery of venture capital and aim it at deep tech. And so if you’re kind of on that track, we could maybe be helpful. Not for everyone, but that’s what I’m looking for. And so yeah, I would love to see these, especially the breakthroughs, really early.
Tim Ferriss: But I guess is your game to attract them to you or do you go out and search in the —
Pablos Holman: I do still, like —
Tim Ferriss: — dark corners of nerddom.
Pablos Holman: Yeah, but I still need help. I need to deputize my friends. There’s probably VCs hanging out at Starbucks by MIT, but those professors call me when they have something that their post-docs want to spin out, and I’m like, “Yes, that’s the help I need because I can’t hang out at every lab.” I go and I visit and I try to be helpful. So some of its labs. About a third of it, I’d say, about another third is rogue engineers who are working at some company that’s got their head up their ass and not doing the coolest thing. So I like that. And then my favorite third is the crazy hackers who are in a basement. You just can’t find them. They’re not going to TED or whatever. Yeah.
Tim Ferriss: Yeah, yeah, right. Rodney Mullen wasn’t going to TED when he was a teenager.
Pablos Holman: Yeah, Rodney’s not going to TED. That’s right. He spoke at a couple of TED events, I think.
Tim Ferriss: Okay. But I mean, when he was the undiscovered —
Pablos Holman: Oh, yeah, no, right. Yeah.
Tim Ferriss: Yeah. Where does salsa enter the picture?
Pablos Holman: Oh, my God.
Tim Ferriss: Because it seems to be important to you.
Pablos Holman: Well, it is important to me, actually. So I remember the Tango thing that you did that I read about, and you and I have a radically different relationship to dance. So I can’t do things that are choreographed. I can’t memorize things. I can’t focus on a structured plan for learning something like you do. I’m all reverse engineering. So when I show up to salsa, what I’m doing is, yeah, there’s a teacher and they’re showing me a thing I’m supposed to learn. I have to try everything and throw out the stuff that doesn’t work.
Tim Ferriss: Yeah.
Pablos Holman: That’s literally how I learned to dance. So I’m a really good salsa dancer now ’cause I started 20 years ago, but very unorthodox salsa dancer, which to be fair to my partners, I should say that ’cause I don’t dance like everyone else, and I can’t learn to dance like someone else because I can only — I have to try this stuff and then converge on what works, and that’s a really great thing. So I danced differently than ever else. But salsa for me was very important partly ’cause too much of my life was hanging out with hackers who fit a demographic that’s a little too homogenous in its way.
Maybe not intellectually, but certainly by all other metrics. And so I had trained in aikido for a decade, which is a Japanese martial art, very structured, very disciplined, very traditional. And I love, I’m obsessed with the physical communication. I love that part of it. And what’s cool about aikido is you’d always train with a partner. And that’s not true for a lot of martial arts. I’d done a lot of punching and kicking in the air with karate and stuff before that, and it just didn’t land for me. With aikido, you always have a partner, and so they’re attacking you and without words, you’re trying to communicate that you want them to shove their head in the ground or something like that. And I love that. I love that feeling of physical communication.
And I’m not great at aikido, and I was trying to learn that through reverse engineering as well, which also has its unorthodox problems. But eventually, short version of the story is I figured out that it was an upgrade to train instead of with sweaty, old Japanese guys, sweaty young Latin girls. So I’m still basically doing the same thing as aikido, but in salsa. And I can do it any night, anywhere in the world. There’s salsa dancers. You just got to know where to find them. You don’t need to speak the language. And so I got a lot out of dancing salsa ’cause I got a community of people in all walks of life. I’m not a rock star in salsa. I get out ranked by the Mexican dishwasher every night. It’s good for my ego ’cause I’m at the bottom always. And I think that’s good for me. And you learn something. My way of moving through the world is so heavily affected by aikido and salsa. Yeah. So anyway, I’ve been doing that for a long time.
Tim Ferriss: Salsa has a huge advantage over Tango that you can find it anywhere. Tango is pretty —
Pablos Holman: Yeah, it’s more niche.
Tim Ferriss: — narrow.
Pablos Holman: Yeah.
Tim Ferriss: Unless you’re in Argentina, in which case you have an embarrassment of riches. But anywhere else, even in Argentina, outside of the capital, you can find more salsa.
Pablos Holman: The salsa’s everywhere. And the reason I defected from Tango, I tried to do Tango first for a month, but it takes advantage of none of my natural talents. You can’t do reverse engineering in Tango. It’s too structured and disciplined and minute, and salsa, you can just wiggle your way through it, so —
Tim Ferriss: So to actually implement the trial and error of trying everything and throwing out what doesn’t work for you, how do you even figure out the menu of options that you need to run through from A to Z?
Pablos Holman: Yeah. Well, again, you’re going back to the Tim Ferriss learning style. I’m not trying to codify the menu. I’m discovery mode. So what’s cool —
Tim Ferriss: Okay. I’m just wondering, when you went in and you decided that that was your approach, innately, maybe just instinctually, you’re like, “This is all I know how to do.” What does it actually look like in class for you?
Pablos Holman: So in salsa, the first year and a half, you’re in class, you’re being shown a move. You’re learning the move, you’re learning the basics, you’re learning the timing, learning the steps. You have to do that. There’s just no way getting out. It’s excruciating for me because I kind of suck at that. But the day I got through that, and what that meant for me was the day I could get out of anything I could get myself into ’cause in salsa, you’re turning a girl into a pretzel and then untying her at 180 miles an hour. Once I realized, okay, I know how to get out of every possible thing that I can get into —
Tim Ferriss: Every failure mode I know how to get out of.
Pablos Holman: — then I became dangerous because then I could just play. And in salsa, you get a different partner for every song. So you go out at night, you dance with a different girl every night, and it’s a different track, it’s a different girl, it’s a different, you know, and you’re just making it up and you’re leading. So I could just play and play and try things and see what works. So I have this vocabulary of bizarre salsa moves that I can do with a partner who’s never learned those moves ’cause I’m leading her through it and I know what I’m — I can feel it all. That’s what happened to me. And that’s pretty heterodox, but that’s what I meant. Yeah.
Tim Ferriss: We may have more overlap than you realize. Just in the sense that I had, when I first got to Argentina in late 2004, maybe early 2004, I had zero interest in Tango, absolutely zero. I in fact wanted to avoid it because my reference points were Scent of a Woman, True Lies, flower in the teeth. I’m like, “Who would ever want to do that? It looks so stiff.” I did not have any interest in the choreography. My only dance background at that point was that I had co-founded the first hip-hop dance troupe at Princeton University.
Pablos Holman: Wow.
Tim Ferriss: And so breakdancing —
Pablos Holman: All right.
Tim Ferriss: — that’s all I had, which was improvised.
Pablos Holman: Yeah, okay, cool. Right.
Tim Ferriss: And did not do any kind of set routines. It was all improvised depending on the songs and stuff. And it was that physical improv that appealed to me. Like, the improv jazz aspect of needing to be not just fast on your feet, but mentally fast enough to improvise in that way. And then I was walking down Avenida Florida in Buenos Aires, which is a very famous pedestrian area, no cars. And it was hot as balls. I mean, it was just so, it gets very humid and hot. And the only place I could see I was waiting for a friend to get out of a Spanish class was this Tango music shop, total tourist trap. Just had, it had all of this cold air. I could see it just billowing out the AC.
And so I walked in there and I was just killing time. And this older woman, middle-aged woman chain-smoking, bleach blonde hair, in Spanish was like, “Hey, asshole.” She’s like, “I know you’re not going to buy anything, but if you’re going to stick around, you have to at least give me 10 pesos for the class upstairs.” And I was like, “Okay, what’s the class?” “Tango.” And I was like, “Ah, okay, fine.” And meanwhile, for the first month or so there, a half Panamanian, half Argentine friend had convinced me to go to Argentina from Panama, because he had said that Argentina has the best red wine in the world, the best steak in the world, the most beautiful women in the world, and you can live there for a king on pennies. And I was like, “Sold. Let’s go.”
So I found the steak, I found the wine. It was cheap. And I was like, “Where are all these beautiful women?” And then I walked upstairs to this class. It was like 3:00 p.m. or something, and it was like nine smoking hot women and one bored-looking guy who was like a husband who had been sent there on assignment. And I was like, “Oh, okay.” And then throughout the course of that class realized, “Oh, this is all improvised.”
Pablos Holman: Yeah.
Tim Ferriss: Now this is interesting.
Pablos Holman: Yeah.
Tim Ferriss: Now this is interesting.
Pablos Holman: Yeah.
Tim Ferriss: And it was actually not for me, aikido, but wrestling, believe it or not, and judo that helped because it’s the same same.
Pablos Holman: Yeah.
Tim Ferriss: I mean, you’re shifting weight, you’re changing balance, you are directing the motion of someone else. The only difference is in dance, the person’s trying to cooperate instead of choke you out —
Pablos Holman: Sometimes.
Tim Ferriss: — or break your arms or throw you on your head. Yes, sometimes. Exactly. I did get shamed off the dance floor by some old Argentine ladies when I first tried to go out into the wild.
Pablos Holman: I still do.
Tim Ferriss: Oh my God.
Pablos Holman: Yeah.
Tim Ferriss: Practicing, it’s —
Pablos Holman: It’s such a good story.
Tim Ferriss: It’s a good, very humbling experience.
Pablos Holman: For me, it was exact same thing ’cause I went to this Argentine steakhouse, and there was these pros direct from Argentina that —
Tim Ferriss: Oh, man.
Pablos Holman: — danced between the tables and up on the bar, and I saw he’s leaving her. But the communication was so subtle, I realized that’s what aikidoka are trying to do, and they’re better at it.
Tim Ferriss: Yeah.
Pablos Holman: And so I went to try and learn from them, and then —
Tim Ferriss: Yeah, it is for people who haven’t really been exposed to dance, at the very least, you should go to a Tango or salsa dance hall to see good dancers who are strangers, dance with one another because if I took you to La Viruta or Niño Bien or one of these milonga in Argentina during kind of prime time, which would be like 2:00 a.m. or 3:00 a.m. I don’t know how they —
Pablos Holman: The good dancers don’t show up until after midnight. Yeah. I never go out until midnight.
Tim Ferriss: They show up really late. And, I could show you a pair dancing and you would say, “Wow. They must have been practicing and rehearsing this choreography for six months.” And, I’d say, “No. This is the first time they’re dancing.”
Pablos Holman: There you go. There you go.
Tim Ferriss: It’s so unbelievable. And, I don’t know if this is true — it’s such a different type of dance. It may be very different, but the best female dancers or a lot of the best female dancers in Argentina will dance with their eyes closed.
Pablos Holman: Yeah.
Tim Ferriss: For that sensory —
Pablos Holman: I’ll do that to salsa dancers. Salsa is super fast, but —
Tim Ferriss: Salsa is a lot. Well, Tango can get fast, but salsa is dependably fast.
Pablos Holman: So, very fast music, the steps are fast and there’s a lot of spinning and shit. And so, I’ll close a partner’s eyes because I can lead her —
Tim Ferriss: Sleek.
Pablos Holman: And, she doesn’t need her eyes because I’m leading everything. I’m tracking every moving object in the room. I’m putting her feet where they go. And so, you can sometimes, especially for some dancers, especially if they’re uptight, because a lot of salsa dancers will train for the stage, so they’ll train choreography and all this crap. And, I’m trying to get them out of that mindset. So, I’ll get their eyes closed and you won’t know. She can spin with her eyes closed.
Tim Ferriss: And, I remember also one of the aspects of my Tango immersion — because I went 110 percent. I just fully committed. I mean, I was doing three to six hours a day and my feet ended up so bruised because the shoes are these really thin shoes. They’re basically suede slippers. It was a lot of fun to dissect that and explore and try everything. And, one of the aspects I so loved, and I imagine this is true in salsa maybe, is that you’d go out to these different milonga, these different dance halls. Every one had its own personality, right?
Pablos Holman: For sure.
Tim Ferriss: There’d be one I remember, La Viruta, I think it’s in the basement of the Armenian consulate filled with smoke, which I can actually tolerate in that environment. Everyone’s sweating and it’s got kind of an illegal speakeasy type of feel.
Pablos Holman: Yep. Totally.
Tim Ferriss: Definitely a fire hazard.
Pablos Holman: Totally.
Tim Ferriss: And then, there’s another one, Sundaland, which was basically in a high school gymnasium on a basketball court, just blindingly bright lights and a totally different crowd. And, by crowd, I mean almost every age you can imagine. I mean, it’s like 18 plus. But, you would have older ladies, you would have 70-year-old guys dressed to the nines in a three-piece suit. I also got screamed off the dance floor by a few of those guys.
Pablos Holman: What was your violation?
Tim Ferriss: Well, my violation was very basic, and it is the most common mistake I would say that men make because in the classes when they’re teaching you the basic eight step, which is the first boot up sequence that everybody gets, almost always in every school where I’ve seen it taught, the first step is a step backwards. And so, you’ve got your partner and you step backwards. So, male, right foot back.
And, in a dance hall, you cannot do that. Why? Because you don’t have a bicycle helmet with mirrors on it. You can’t see where you’re going so you just end up smashing into people when you do that. So, when you go into a live environment in the wild, typically you’re going to take that first step out to the side because you can see where you’re going with your peripheral vision. So, I would get screamed off by the men because I would bump into them. And, Argentines, they are, at least in the capital city, very much like Italians. They are passionate gang of folks, very wild gesticulating, very high volume. And, if you bump into their lady, they’re going to give you an earful.
With the women in the beginning, this probably happens in salsa, but in Tango, at least, if you’re always practicing with the same partner especially if, in my case, that woman is a really good dancer, she will develop a sixth sense to read what you are intending her to do even if your lead or the mark is weak.
Pablos Holman: Of course.
Tim Ferriss: And then, you’re like, “Wow. I’m a Jedi. I’m doing so well.”
Pablos Holman: Totally.
Tim Ferriss: And, you go out and you do it with a stranger. And, literally I had women say to me, they would throw their arms down in disgust in the middle of a song, which is quite a show in the Tango world, and just be like, “I don’t know what you’re trying to do. I do not know what you’re trying to do, how you’re trying to move me.” And, they would just get furious. And then, I would put my tail between my legs and scuttle off and recover.
Pablos Holman: That’s why I say it’s important to do. It’s humbling. Even now, I mean, I’ve been dancing for 20 years, but if I show up, there’ll be incompatible dancers. And, my problem is, so I’m trained in what’s called essentially L.A. style, West Coast salsa. Salsa actually comes from New York City —
Tim Ferriss: New York City. Yeah.
Pablos Holman: So, I live in the epicenter of salsa but they dance what’s called Mambo and they can see me coming from miles away. I’m like an invasive species. They’re like, “Oh my God. What is this trash?” So, I’m having a hard time. I have to now reorient. And, it’s just a minor change in how you do the timing and it’s actually super cool but man, I have to somehow whitewash myself of this filth from the West Coast salsa scene.
Tim Ferriss: The Tango world also has its factions since every subculture needs its infighting.
Pablos Holman: Exactly.
Tim Ferriss: So, there’s definitely a fair amount of that. And, I brought up the older guys, the 70-year-old guys in part because I remember going to these dance halls and I’m a healthy red-blooded male, and I’m looking for the most attractive women to dance with, which was not worth it in the beginning because I was just going to make an ass of myself. But, of course, you’re looking around and taking a gander, and more often than not, they would be dancing with the old guys. And, the reason for that is that you get these young bucks who are 30 or whatever, professional stage dancers, they want to show off every tool in the toolkit and it ends up just being a melee. It’s like they’re a weed whacker, and it’s not fun for these women necessarily to dance with them if they’re just trying to showcase everything they know. Whereas the older guys, they can’t do that physically. They also have a very clean classical style and they listen to the music —
Pablos Holman: Yes. The musicality.
Tim Ferriss: The musicality —
Pablos Holman: Exactly.
Tim Ferriss: — is what matters.
Pablos Holman: And, same in salsa and its derivatives.
Tim Ferriss: Yeah.
Pablos Holman: Yeah.
Tim Ferriss: So now, 20 years in, you started salsa, it seems, in part to get away from the homogeneity of the hacker world but you’re still doing it. What do you get out of it?
Pablos Holman: I do it less. I want to. COVID kind of damaged the salsa scene. It’s mostly back, but I don’t have a salsa community anymore. And, the problem with that is it takes me a while to sort of brainwash my partners into doing the thing I want to do. And, you got to find a certain special kind of partner that can hang in there for that. What I do because I travel so much and I dance salsa everywhere I go, it’s kind of like the first conversation when you meet somebody. It’s like, “What do you do? Where do you work? Where’d you grow up?”
And, it’s just that I have the dance version of that conversation over and over again. It’s not very rewarding. I need a pretty rarefied partner now, and if you learn to dance, you should get good as slowly as possible. And, I did do that and I was able to have fun for a long time but now it’s really hard for me to have fun unless I have a pretty rarified partner that will put up with my flavor of bullshit. So, yeah. It’s an evolution.
Tim Ferriss: Yeah. Pablos, we’ve covered a lot of ground. We could, of course —
Pablos Holman: Keep going. Yeah —
Tim Ferriss: — cover a million other things for another five hours, but is there anything that we haven’t touched on that you would like to bring up?
Pablos Holman: Oh, wow.
Tim Ferriss: Anything at all? And, I have a few closing questions as well —
Pablos Holman: Okay. Yeah.
Tim Ferriss: But, I’m just wondering if anything comes to mind.
Pablos Holman: I guess the thing I maybe alluded to but didn’t articulate very well is that you could see how I kind of, in my career, I got the software out of my system young because I got early start and then maybe by 2001 or something, I was able to sort of say, “Okay. Did all this stuff with computers, but maybe I could go beyond that and bring other technologies to life.”
And, when I look at Silicon Valley, I see a lot of people who might want to do that. They got to do the software stuff. They may be 10 or 20 years into their career now and so maybe we can win some of them over and help us come bring these other technologies to life. Like I described, I think the opportunities are bigger, the impact is bigger.
And, why would you want to do that? Well, I think there’s a meaning in it. There’s an opportunity here to see technology as a force for good, to make the world better. We build this toolkit that we’re going to use to build the future, and you get to add something to that toolkit. So, yeah. I just think if you put that framework to use, you could kind of get a sense of where technology can go and get a lot more excited about it. It’s really sad for me to see people that are pissed off about technology in general or even pissed off about their phones or whatever. I’m like, “Yeah. Okay. Well, what are you using it for? Are you just doomscrolling, because we could do a lot better than that.” And so, yeah. So, I think, if I had a chance to try and share something, it would be that there’s a lot left to do.
Tim Ferriss: That is a military helicopter that just flew over us.
Pablos Holman: Oh, yeah. You’re trained in military helicopters. Great. We can rewind.
Tim Ferriss: Yeah. No. No. I’m good. I’m good. I just wanted to say this is a lively environment. I like it. Those people, let’s say there are at least a handful listening who resonate with what you just said. What should they do? Should they fill out a form on your website? Should they check out anything online related to you? Send you an email? I mean, what would you want those —
Pablos Holman: Careful what I ask for?
Tim Ferriss: Yeah. I’d be careful with the email, but —
Pablos Holman: Yeah. I don’t know. I mean, look, I try to read every email already. I can’t reply to all of them so I don’t know the right answer. With or without me, I think these are important things to do. We can take on some fraction of things and help out a little bit. I think that what I’m trying to do is convince not just those founders but also those investors like, “Hey. You could steer what you’re doing to bigger opportunities. Look at deep tech. You don’t have to be a physicist to do it. You could find some important things and some really, really lucrative things to invest in deep tech and you won’t be competing with all the other usual suspects.”
Tim Ferriss: I’ve made that shift largely in my own investing in the last five years.
Pablos Holman: Wow. Cool.
Tim Ferriss: Oh, yeah.
Pablos Holman: Yeah. I heard of, I know we can cut this out, but you’re an investor in Holobiome.
Tim Ferriss: Yeah.
Pablos Holman: Yeah. That’s one that we did. Super cool.
Tim Ferriss: Holobiome is amazing.
Pablos Holman: It is. That’s right.
Tim Ferriss: I mean, I think that’s going to be such, hopefully, fingers crossed, we can talk about it, a service to humanity. I mean, building a proper library is step number one, right? It’s coming back to the — it’s like, yeah, sure, you can create probiotics with six widely available commercial strains, but ultimately you have thousands.
Pablos Holman: Yeah. What people don’t realize is that, well, just to make it clear to the audience, when you eat food, you’re not feeding yourself. You’re feeding a thousand different microbes in your gut, and then what they spit out feeds you. So, there’s this layer of indirection that we have no measurement for. Mine’s different than yours, everybody’s different. We’re tuned for different things and we don’t even have a way of understanding that. And so, that’s microbiome. We’re going to learn about it. Every one of those microbes is probably a few PhDs that need to get done, but Holobiome is crafting the machinery to do that, the mechanism to do that. And, it’s exciting because they’re figuring out cool stuff already.
Tim Ferriss: It’s a super cool company. I’ve been getting very involved with aqua culture and algae feed additives for cows to reduce methane production which is, frankly, very far outside of my comfort zone. I hope to have a positive return on investment, but I tend to get myself sometimes into trouble. For instance, I invested in a company that was developing in inhalable insulin. So, insulin that you could effectively use an inhaler for. And, the tech was super solid but due to a bunch of regulatory issues and other factors that I have much less familiarity with, puzzles that I’m not accustomed to solving for, I end up with a lot of zeros when I stray outside of stuff that I can directly promote to my audience. Because I can increase the value of equity in a company very clearly if it’s —
Pablos Holman: For a certain thing.
Tim Ferriss: ,,, in Uber or a Blue Bottle coffee or fill in the blank.
Pablos Holman: That makes sense.
Tim Ferriss: But, nonetheless, I have been as an intrepid deep tech investor because a lot of it just seems more meaningful if it works.
Pablos Holman: Right. So, the trick there, I am sure by now what most investors would do is get a portfolio, try to get a big enough portfolio to offset those failures with hits and that’s a shots on goal game. That’s why we do so many. That’s why we focus on being the first check. We’re doing pre-seed stuff, actual tech, but we will do hundreds of these things and we’re going to hope to get a couple hits.
Tim Ferriss: Over the course of a single 10-year fund.
Pablos Holman: In one fund, we’ll do about 60. So, we’ll do another fund and we’ll do another 60 in the future. But, yeah. We’ll do multiple funds, but most VCs would kind of graduate from pre-seed to seed to series A. We don’t do that. We just stay —
Tim Ferriss: Super early.
Pablos Holman: Lots and lots of pre-seed.
Tim Ferriss: Yeah. If you could only place one bet in fusion, where would you place it?
Pablos Holman: Oh, boy. Don’t get me started. Okay. I’m started. Yeah. Okay. Fusion. Look —
Tim Ferriss: Or, would your answer be zero?
Pablos Holman: It’s not zero. So, here’s the thing. So, as you know, fusion is like rattle these molecules and get them to break apart and get a bunch of energy out. That’s fission. Fusion is push these molecules together and get them to become one. Plasma fusion is the biggest branch of fusion research in history. And so what that means is you’re going to heat up these molecules so much that they kind of expand and open up to the possibility of getting stuck together.
Tim Ferriss: Just create a miniature sun, no big deal.
Pablos Holman: It is temperatures that rival the sun because that is what the sun is doing. It’s doing fusion. But, what you need that we don’t have on earth that the sun has is you need a lot of pressure as well. Now, the pressure you could get if you could make a vessel that would hold the plasma, but the plasma’s so hot, it’d melt anything on Earth.
So, the way we do it now is — the best idea so far has been what’s called a magnetic confinement. So you create a giant super magnet and use the magnetic field to push the plasma together, and it’s far enough away that it won’t melt. That’s using force to do it. So that’s a super cool idea but it has been very difficult to make it work. And, scientifically we didn’t even really know if it would work and that’s why people make fun of fusion all the time and say that it’s 20 years away and always will be. That changed.
So, the cool thing is, a few years ago, the team from MIT called Commonwealth Fusion Systems now, published a series of, I think, seven papers that explain exactly how they can make magnetic confinement fusion work. And, the real breakthrough was a new superconductor. It’s a superconductor that allows them to make the world’s most powerful magnet, which they have done and it’s awesome, crazy cool magnet. But, now they got that working, we’re out of the science risk window into the technical risk window, which means can they engineer a fusion reactor?
So, I’d say Commonwealth is probably the most well-funded, most advanced plasma fusion reactor company. They’re building what’s called a toga mac, which is like the giant doughnut shaped thing you see pictures of, and I wish them a lot of luck, but they have extreme engineering problems. It is really hard to build that thing. And, once they get it built, then they’re going to need tritium. And there’s about enough tritium on earth left to make it go one time. And, the only way to make more tritium is, you guessed it, in a fusion reactor where they’ve got to get 99 percent efficiency on getting the tritium out. And, we don’t know if that’s going to be possible. So, there’s just a zillion of these really hard engineering problems. So, anyway, that’s the long version —
Tim Ferriss: Can’t just source the tritium from gun sites?
Pablos Holman: You can source it from the moon. So there are people who want to go to the moon and grab tritium and bring it back. The stuff in gun sites, there’s very little of it left.
Tim Ferriss: Yeah.
Pablos Holman: It has tritium paint and in your old Swiss watches and things, and that’s why they glow. You need tritium. But, anyway, the point of all this is to say, in the best-case scenario, fusion is very difficult. I really hope we get it. The upside of that is, once it really does work, you’ll get more energy out than you put in. So, think of a gas tank, you’ll have to fill once and it runs the rest of your life.
Tim Ferriss: What is that? Q greater than one?
Pablos Holman: Q greater than one is the metric.
Tim Ferriss: Has anyone ever crossed that?
Pablos Holman: No one has ever actually achieved that if you count the entire energy for the system. There are projects and once in a while you see fusion headlines where it’s like, “Fusion works from Livermore,” or whatever. And, what they’ve done is, on system level one, which basically means the energy going into the fusion from the 192 giant lasers is less than the energy coming out of the fusion, but they’re not counting the energy going into the lasers.
Tim Ferriss: Yeah. Right.
Pablos Holman: And, the problem with all this, the reason I’m explaining is so people can understand, a lot of these fusion projects are very expensive to do research on. They’ve figured out that it’s hard to get that money from academic research financing. They’re trying to co-opt venture capital to do it. So, I think a lot of these teams are overstating what they can do, how fast they can do it, because they’re trying to attract that capital and I think they’re being a little disingenuous about it. I’m not going to name names. And, the problem with that is it poisons the well for the people who do have something that could work. So you’ve got to be very careful about whether you think it’s going to map to that 10-year venture time horizon.
I have seen a lot of the fusion companies. I haven’t evaluated all of them. I’ve not invested in any of the plasma fusion companies. I will tell you because I am a crazy venture capitalist who invests in wild ideas. I did invest in one and it’s called nanoconfinement fusion.
So these guys have figured out a very simple way to cause fusion by putting deuterium together with carbon nanotubes that cause a fusion. And, if it works, it’ll be fucking amazing. There’s work to do to prove it. Got it working in the lab, but they’re working on advancing that now. NASA has done the same kind of fusion using metal lattices. So, this is a very fringe area in fusion. Probably any physicist will tell you that Pablos is full of shit, which is fine but that’s the kind of wild ideas that we think are worth pursuing if we can. And so, there’s an important inflection point there where we were able to see this works in the lab, can we commercialize it is an open question.
Tim Ferriss: Also, as long as you are not completely insane and you have some degree of technical due diligence given the way you’re investing — if you were investing at series D —
Pablos Holman: No, I can’t do that —
Tim Ferriss: Then it would be a very dangerous game indeed. But, if your maximum loss is a check, which doesn’t need to be exorbitant in size at the precede, that’s your maximum downside res.
Pablos Holman: That’s right.
Tim Ferriss: Then it’s like, “Okay.”
Pablos Holman: Yeah. So I’m along for that ride. I’m going to get it wrong sometimes but, if that works, the upside is fucking utopia. So we’re going to do a few of those and we have a few.
Tim Ferriss: I’m not going to ask you to pick one because that would put you in a tight spot, but could you name one, of I’m sure quite a few or several from your portfolio, that you feel is likely to be a winner? And, the reason I’m asking is that I want to know what the characteristics are that give you that conviction.
Pablos Holman: Yeah. I think the heart of what you’re getting at, one thing worth articulating here is, I attract those technical founders, those inventors. A lot of the time I can’t invest. And, the reason is I love the technology, but there’s no entrepreneur, there’s no commercial animal, there’s nobody who can sell some shit. And, a lot of times the homework I have to give them is go find a frat buddy or a cousin or a roommate or somebody who can sell something because you need that to build a business. And, I can only take a few bets where I don’t see that hoping that it’s going to come later
Tim Ferriss: It’s interesting because you have the opposite problem of a lot of venture capitalists, right?
Pablos Holman: That’s right. I do. And, I know —
Tim Ferriss: You’re not looking for technical co-founders.
Pablos Holman: Every other VC will tell you, “We back the best founders.” That’s their mantra and I get it. And, increasingly, I’m sympathetic. I have backed founders because I loved the tech but they spent their career on the tech. They’re only making a business because it’s the next logical step.
Tim Ferriss: I mean, the other issue is that if you have someone who’s very technical, let’s say that they happen to be a unicorn and they’re also really good at business. If they try to spearhead both sides of that coin, they’re going to burn out.
Pablos Holman: Totally. I think we have a fucked up mythology in Silicon Valley. We imagine this amazing, smart person who invented something and then became a patent lawyer and patented it, wrote the code to launch the first version, and then hired the genius team, and then chose an HR policy and took the company public. That is not actually what’s going on. It’s always teams. And we might have the quarterback out in front that is the focal point that the whole world looks at and says, “Oh, that’s the founder,” and that’s the one that you see on YouTube. But, that is a person who is doing an important job of being the human face for a company, but there’s a team behind them.
And so, as a founder, I think you’ve got to find the people who are good at the things you suck at. My founders often suck at marketing. They suck at business development. They suck at the kinds of things that — and that’s okay. You can suck at that. I don’t need you to be good at that. I don’t believe in personal growth like every other podcast host probably does. I believe in do the thing you’re good at, hire friends or people who are good at the things you suck at.
So what I don’t know how to do is scale up on co-founder dating for deep tech. I want that solved desperately. There are more entrepreneurs than there are inventors. I’ve got the thing that’s precious here, but I want to figure out how do I get them to party with entrepreneurs and team up? And, I don’t know how to scale that, but I really want to.
Tim Ferriss: Pablos, where should people find you online? What are the best websites or otherwise?
Pablos Holman: So, I have, deepfuture.tech is our website. There’s a podcast there, which is mostly just long conversations with nerds. That’s how I learn. So, I pick the brains of nerds and I record some of them. And then, I’m on all the stuff. I’m Pablos on X, but nobody listens to me there. LinkedIn, more people listen. But, yeah. So, you could do those things. Oh, I have probably the best email list in the world because the only things I send out are super inspiring and amazing technology. So, join that or whatever.
Tim Ferriss: They can find that at the —
Pablos Holman: Deepfuture.tech. Yeah. That’s there, there’s a WhatsApp group with propaganda, you can join that too.
Tim Ferriss: And, if people are interested in the book, which I have in my backpack right now, it’s Deep Future: Creating Technology That Matters. A lot of good stories and a lot of head-spinning statistics.
Pablos Holman: Oh, no. Don’t say that.
Tim Ferriss: Well, I shouldn’t say statistics — that makes it sound too sterile — but just facts and figures that underscore a lot of important points that are pretty jaw-dropping, such as the $5 out of every $6 associated with shipping going to fuel or whatever the number might be and so on. I mean, it’s really remarkable.
Pablos Holman: The statistics, those are meant to be drop-kicks.
Tim Ferriss: Well, Pablos, thank you for taking the time. So great to hang.
Pablos Holman: Oh, man. No. This is awesome. I’m glad we finally got to do it.
Tim Ferriss: Yeah. It’s super fun.
Pablos Holman: After all these years. And I came unarmed, so I wouldn’t intimidate your sensibility about getting hacked.
Tim Ferriss: Yeah, black van’s still out front, so it ain’t over until it’s over. And, for everybody listening, and we will link to all the things we mentioned, including Pablo’s website, the book, newsletter, et cetera at tim.blog/podcast.” I can guarantee you that Pablos will be the only Pablos, so just search Pablos —
Pablos Holman: That’s true. Sounds plural, but there’s only one.
Tim Ferriss: — and you will find him immediately. So, that is where you can find all the resources. And, as always, be a little bit kinder than is necessary until next time to others, but also to yourself. And, thanks for tuning in.
Pablos Holman: Well, thank you. This is a real treat and I appreciate — I mean, you’ve done something really special with your whole career, and I’m really thankful that we got to hang out.
Tim Ferriss: Yeah. Thanks, man. To be continued. I feel like this is the beginning.
Pablos Holman: Good. Yeah.
The post The Tim Ferriss Show Transcripts: Pablos Holman — One of the Scariest Hackers I’ve Ever Met (#827) appeared first on The Blog of Author Tim Ferriss.
2025-09-17 04:05:15
Pablos Holman (@pablos) is a hacker and inventor and the bestselling author of Deep Future: Creating Technology that Matters, the indispensable guide to deep tech. Previously, Pablos worked on spaceships at Blue Origin and helped build The Intellectual Ventures Lab to invent a wide variety of breakthroughs, including a brain surgery tool, a machine to suppress hurricanes, 3D food printers, and a laser that can shoot down mosquitos, part of an impact invention effort to eradicate malaria with Bill Gates.
Pablos hosts the Deep Future Podcast, and his TED talks have been viewed more than 30 million times. He is also managing partner at Deep Future, investing in technologies to solve the world’s biggest problems.
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“I think a future that’s awesome is absolutely possible. A shitty future is also possible, but the balance is up to us.”
— Pablos Holman
“I tried to do tango first for a month, but it takes advantage of none of my natural talents. You can’t do reverse engineering in tango. It’s too structured and disciplined and minute, and salsa, you can just wiggle your way through it.”
— Pablos Holman
“Most people, if you get a new gadget, like your phone, and give it to your mom, she’ll ask you, ‘What does this do?’ That’s a totally normal question. ‘iPhone, Mom. Says on the box.’ If you give a new gadget to a hacker, then the question is, ‘What can I make this do?'”
— Pablos Holman
“You can’t invent a new technology by reading the directions. That’s just never happened, ever.”
— Pablos Holman
“I had a computer in the cold, in the dark, in the basement, in Alaska, and nobody to show me anything about how it worked. So I had to learn by reverse engineering.”
— Pablos Holman
I do have a kind of extreme risk tolerance. My whole career, I’ve only worked on things that I thought were cool or interesting. I’ll optimize for that over everything else.
— Pablos Holman
“Pablos is a totally fake name because all hackers have fake names.”
— Pablos Holman
Want to hear another episode with someone who asks “What can I make this do?” Listen to my conversation with legendary hacker Samy Kamkar, in which we discussed creating the fastest-spreading computer virus of all time, accidentally taking down MySpace, getting raided by the Secret Service, hijacking drones with custom hardware, optimizing online dating through reverse engineering, opening locked cars, manipulating Google Maps traffic data, and much more.
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The post Pablos Holman — One of the Scariest Hackers I’ve Ever Met (#827) appeared first on The Blog of Author Tim Ferriss.
2025-09-11 00:43:25
Please enjoy this transcript of another in-between-isode, with one of my favorite formats: the good old-fashioned Q&A.
I answer questions submitted by the small-but-elite group of test readers of my upcoming THE NO BOOK. The community is closed for new members, as we have the right number of people now, but I hope to potentially expand it, once the book comes out.
Transcripts may contain a few typos. With many episodes lasting 2+ hours, it can be difficult to catch minor errors. Enjoy!
Listen to the episode on Apple Podcasts, Spotify, Overcast, Podcast Addict, Pocket Casts, Castbox, YouTube Music, Amazon Music, Audible, or on your favorite podcast platform. Watch the conversation on YouTube.
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Tim Ferriss: Well, greetings from the East Coast, everybody. I figured we’d just hop right into it. And I thought we would make this simple to start with by simply going through the questions that were submitted and trying to answer as many of those as possible. And then we can go to some live questions if that works for you guys. I’m going to take a sip of my incredibly strong decaf coffee. One sec.
All right, the first question is from Sasha, “What’s an obstacle or challenge that you’re currently facing? How are you approaching it?” This actually, I could combine with the second one as well, which is Rasheeda, “How is your recovery from elbow surgery? What procedure did you have done? Have you seen The Wonderful Story of Henry Sugar?” I had to look that up. It looks amazing. A Wes Anderson short film adaptation of a Roald Dahl short story, which I’m very excited to see. So thank you for putting that on my radar.
That is on my to-watch list for Netflix, particularly since I just finished listening to Charlie and the Chocolate Factory by the same author. So let’s hop into obstacle or challenge. I’ll give you a couple. So the first is actually a retail distribution and placement question, and that relates to Coyote, the game that’s now in 8,000 or so retail locations.
And as you might expect, there are some variables that can affect sell-through. And the Coyote itself is one of the smallest games that Exploding Kittens has ever made. And it is their first game that is on a hang tag. So it’s intended to be put on one of those metal prongs that sticks out on the wall. And this was part one in terms of addressing it, trying to figure out why different stores or regions have varying levels of sell-through.
The first thing you have to do is gather information. So rather than just speculate at every turn, trying to gather as much information as possible, and this actually makes me think of Dale Carnegie in How to Stop Worrying and Start Living. Often step number one is more information. Do you have enough information or even partial information upon which to base this fear/goal/fill in the blank?
So right now went to a Discord server that hosts a lot of fans of Exploding Kittens games, and also with the help of the EK team and separately have gone out to some of the families who play tested to ask them to go to local Walmart stores and Target stores to send back photographs, close up and then zoomed out of actual retail placement. And so that will then help to inform possible strategies for improving sell-through for all of those stores, which produces a long list at this point, and every item on that list is premature.
And this is also where the scientific method comes in really handy in so much as not fooling yourself because can you even know, for instance, if the game is affecting sell-through at retail? Is that knowable? Can you actually parse data in any compelling statistically significant way to say yes or no? If not, you can just ignore it. But that’s an open question. Then you have box size, you have box placement. Can you increase just, say, adherence to agreed upon placement? Or do we want to potentially boost the size of a box? Of course, there are cost considerations with that, et cetera, et cetera, et cetera.
So that’s one that I’m contending with. And then tying into what came up as the second question, Rasheeda, “How’s your recovery from elbow surgery? What procedure did I have done?” I had a repair for lateral epicondylitis. I’m not sure if you can see that. I’ve got a nice incision right there where the entire elbow was opened up and the lateral epicondyle, which is that nice little bump on the outside of the elbow, which is associated with tennis elbow as opposed to the inside, the medial side, which is golfer’s elbow.
And this is an injury from 20 years ago, probably 20-plus years ago actually in New York City where I had my elbow popped and bent the wrong direction in a jiu-jitsu practice by a black belt, which in retrospect, was totally unnecessary. Black belt has no need to exert that kind of force. But every few years it comes back and has bothered me. And then particularly after doing a lot of rock climbing last winter and getting to, for me, tougher climbs like 5.11 plus on big walls, much bigger walls than Texas can provide.
The elbow effectively just became unusable and it was in constant pain and got to the point where even picking up a glass of water was excruciating. So that was all tacked back where it should be, sewn back together. But you can see, let’s see, this is about a week and a half out and I’ve got almost full extension. This is 80, 90 percent of the way there. And then on this side, I still have a lot of pain in the anconeus when I flex the arm towards my face for brushing my teeth or something like that. But that’s a week and a half.
And so how did I approach that? Well, a big part of how I think about solving problems or challenges is sequencing. That won’t surprise anybody who’s read The 4-Hour Chef, which is confusingly a book about accelerated learning. But sequencing is the magic sauce, I think, for a lot of things. So you’re going to deconstruct something to break it down into its constituent pieces.
So what does healing look like? In fact, when you break it down into its constituent pieces, let’s just say those LEGO pieces, then how do you select the 20 percent for this 80/20 analysis to get the highest yield out of the few levers you decide to pull? Because you probably can’t address all of them with the time that you have as a non-professional athlete or Major League Baseball pitcher, for instance.
Then how do you sequence those things? How do you solve in the right order? And I’ll actually be interviewing someone very soon, Pablos Holman, who talks a lot about this. He is one of the world’s most fascinating hackers. And a lot of problems can’t be solved until you solve for energy expenditure in the context of a lot of what he discusses. And similarly, with healing, a large part of clearing the highway for productive work is decongestion.
So I was using a device called a Marc Pro device, M-A-R-C, which provides, effectively, stimulation through electrodes to pump the tissue for decongestion and lymphatic drainage. I was also doing lymphatic drainage massage, which is much lighter than you might expect and does not involve any type of incision. And then there were a number of peptides like BPC-157, not medical advice, for information purposes only, that I was consuming to hedge my bets. And that was based on a number of recommendations and I’ve used that as far back as 15 years ago.
So for surgical repair, it’s somewhat interesting. Lots of supplementation. So along the lines of, say, Keith Baar, who I had on the podcast from UC Davis, consuming particular types of collagen plus vitamin C plus a few other things prior to any type of, say, range of motion stretching or working or isometric strengthening, not of the extensors that I had repaired. I’m not doing any isometrics on that just yet, but for bicep and tricep.
And then once the acute phase of congestion was somewhat addressed — it’s still inflamed, but that’s to be expected given how much remodeling is going on in the elbow. Now I’m applying blood flow restriction, BFR training. And this was recommended to me and it’s been around quite a long time, but by Kelly Starrett, who’s an amazing performance coach, PT, works with Delta Force and many others. And the BFR allows you to effectively not only flush the tissue but also maintain muscle mass on some level without the ability to, say, concentrically or eccentrically handle much load.
And I think that BFR is very, very interesting, not just for rehab but for training while minimizing the likelihood for injury. And by training, I mean resistance training. So those are a few of the tools in the toolkit. Of course, sleep is mandatory, so doing anything and everything necessary to get good amounts of restorative sleep. Deep sleep is super critical. And off we go. So I am planning on resuming actual flexor grip strength training around week five. And for some people, the risk is that they don’t do the rehab. The risk for someone like me is that I do too much too soon and blow the whole thing apart. So sitting still and just not fussing with it is my great challenge. It’s continually a challenge in every context.
Okay, let’s hop back to the questions, and I’m happy to answer more questions about the surgery as we come along and might as well pick up one. Let’s see. So following a protocol. I am following a protocol with a PT. I have multiple PTs. So I’m not just DIYing this. I’m definitely relying on professionals for every step of this, even though I would like to think I’m pretty well-versed, but frankly, the accountability and structure and the third-party expert observation and assessment is really critical.
I just had my first follow-up assessment by the surgeon today, who has also had this identical surgery performed on his own elbow as a former high-level tennis player. So I like to choose surgeons, when possible, who are former athletes or current athletes. Call me biased. But I do try to look for those folks because they tend to understand the bizarre programming that I have in my own mind.
All right, let’s hop back to a question from Jake, “Do I still think California is the place to go for builders or is Austin viable as a place for a mechanical engineer to find a job, build some momentum, and make a go at a startup? I know you’re not in the space anymore, but I’m curious what trends you see in Austin versus, say, the Bay Area.” So this is a very good question and it’s top of mind for me because one of my best friends just moved from Austin back to San Francisco, and his reason for doing so was related, I would say, largely to the focus of his new startup that he hopes to launch for which he will probably need to find a technical co-founder.
And it is in, broadly speaking, the AI space. And I will say that AI, as yet another example of — I suppose, I’m not sure it ever died entirely, I don’t think it did, but is another kind of Lazarus resurrection for Silicon Valley. And if you want to build something that is sophisticated in the AI space, which I know is a broad umbrella, then I do think the top talent, the density of talent is highest in a place like San Francisco.
So if you hope to not only build, but learn and hire, particularly if you’re going to play the venture-backed startup game, then you got to fish where the fish are. And from a talent perspective, that’s going to have the highest density. Can you do it in Austin? It depends a lot on what you’re building. There are some really interesting FinTech companies. There are some very interesting hardware companies. There are headquarters for a lot of large companies, or at least large outposts, Oracle, Google, Meta, et cetera, that exist in Austin.
So I think it really depends on specifically what you are trying to build. But what I would add to that is that perhaps you don’t have to choose one. Maybe they’re not mutually exclusive. Perhaps you just treat a month or two or three in Silicon Valley as your MBA that you get to pay for with respect to any type of domain expertise you’re trying to develop or frankly networks and relationships. And then you take that and you port it back to Austin potentially. These are all possibilities. So you could straddle both horses in a sense.
That, I think, is my answer on California. I’m happy to answer more specifics on California and Austin, but there are reasons why people are willing to pay astronomical taxes in California. This is true of a lot of places with high taxes generally. There are pretty good reasons they can get away with it.
All right, let’s go back to the questions I have here. Pete, “How are you currently using AI for personal medical advice and what’s your typical workflow?”
I will say in advance of answering this that I am not a doctor, nor do I play one on the internet. So I’m not providing medical advice. I’m simply, for educational and entertainment purposes, only telling you what I do. I use a few different tools and I always cross-reference and I talk to professionals. So this is really important as a way to lead into this conversation because much like the person who is his or her own lawyer has a fool for a client, I think that could apply to PT, I think it could apply to medicine certainly.
And you really want to interrogate and cross-reference your own opinions with someone who’s very experienced. But there are a couple of different tools I use. So one is the off-the-rack ChatGPT and so on. I also use something called Consensus.app. Consensus.app is specifically tuned for reviewing published scientific literature to answer a given question. So for instance, in my case, if I wanted to do a preliminary run at a few questions before speaking to a very in-demand, very busy surgeon, i.e. the person who just fixed my elbow, I would look at the literature around BFR.
So I have two tabs open on my computer right now related to blood flow restriction and accelerating or otherwise affecting positively or negatively surgical recovery in upper extremities in humans. But that will often give you nothing or something that is too narrow. So I will expand that to include animal models, which are imperfect but helpful. And so then I get a read on, say, Consensus.app, and it will give you a conviction rating effectively. So it’ll give you a red, there’s no evidence to support X, a yellow, results are mixed, or a green where there seems to be a compelling majority of evidence that has been published in support of X.
So I use Consensus.app quite a bit. And then I will often ask the same question of, say, a ChatGPT or a Claude or Perplexity, fill in the blank, and then cross-reference those. So those are how I will then do a first pass on a question or topic of interest. After I have that, I will typically take the germane paragraph or two and copy and paste it. Send it, in this case for instance, to the surgeon and say, “What is your opinion of BFR for A, B, or C? Here’s what I found.” So that he or she, referring to the expert in question, knows you’re not being a lazy son of a bitch and just throwing something at them that you haven’t even thrown into Google or an LLM.
So I’ll make sure that I indicate I’ve done a bunch of lifting on my own first, here’s my tentative conclusion. Do you have anything at all you could add? Even a sense or two would really be greatly appreciated. And by the way, you don’t need to have fancy people on your SMS to do that. Reddit is a great place to do this. Again, not medical advice, but there are some very smart people on subreddits and various other places. So those would be a few of the ways that I currently use it.
And I might use it to, for instance, take something that has been mentioned to me. A genetic screening company reached out to me after one of my recent podcasts, and one of my former podcast guests is a scientific advisor to them, a credible scientific advisor. And they indicated that the APOE3/4, which I have, which predisposes me somewhat. Somewhat. Well, 2.5 times more than APOE3/3, at least based on current understanding, to Alzheimer’s disease. They said, “Well, there are probably 30 to 40 other factors that you would want to weigh pretty heavily.” And so I would use something among the suite of AI tools to explore that for myself and ask for some type of weighting, not only to get a better understanding of what they’re suggesting, but to fact check it before I go too far down to any road of exploring someone who is offering a product for free because generally things that are offered to you for free are the most expensive things you’ll ever receive. Not always, but very, very often. All right, so that is that question.
Kevin: What supplements are you currently taking? Is PAGGs or AGG still in the mix? I’ll explain what that is for people who don’t know the reference, and then I’ll combine that with a question from Steve, do you still take magnesium L-threonate? And an additional question around supplements. So right now I’m using a ton of stuff because of the surgery and surgical recovery, but I’ll answer the PAGG/AGG quickly.
I am still taking the AGG component of that, which would be alpha-lipoic acid, which can be helpful for liver health. So as I’m consuming, for instance, ketone monoesters, there’s some evidence to suggest that chronic use could have a negative effect on liver function. I’m taking alpha-lipoic acid, I’m also taking N-acetylcysteine or NAC, and then the two Gs refer to green tea extract and garlic allicin extract. I still find value in those.
Policosanol is the only thing, the P of PAGG that I would put on the question mark chopping block if I were to update The 4-Hour Body. That’s the only thing in the entire book where I’m like, evidence was split. I made the decision to include it. I would want to go back and revisit.
Coming back to other supplements, I do take, let me give you my roll call for let’s just say today. Today, I’m taking a number of prescription medications for, it’s really preemptively avoiding issues that are common in my family. I’m taking something called Uloric for, febuxostat, for managing uric acid levels to avoid future problems with gout for instance. I’m taking something called Nexlizet. Do not just copy paste this type of stuff for your own use. Please, God, don’t do that. But this is very personal, requires lots of good medical supervision. Nexlizet, which is a combination of ezetimibe and bempedoic acid for various lipid profile variables or biomarkers that I care about since most of the males in my family on both sides tend to die of some type of vascular or cardio complication. So I’m taking those.
I’m also taking famotidine, otherwise known as Pepcid, for possible anti-COVID applications. You should look up the research on that, it’s actually pretty fascinating. It may also be a mild vagal tone improver or vagus nerve stimulator, which appears to be through indirect means, but it’s pretty interesting. Again, talk to your fucking doctors. Do not just copy me on this, but it is pretty fascinating.
Then I’m taking the BPC-157, which may or may not be orally available, but since it was recommended to me by a top performance coach and I want the placebo effect to work for me, I have not bothered to look that one up because I’m quite certain that the downside risk is nil, but the GI tract might render that completely inert. Who knows? Back in the day, like 15 years ago, I was injecting that locally, which I really don’t recommend either unless you have professional supervision. So I’m taking that.
I mentioned N-acetylcysteine, which I’m taking in the morning, typically taking that between meals, and then throughout the day I’m taking the supplementation, which I mentioned, which is the collagen, often with whey protein and vitamin C prior to any type of straining or training or stretching of the elbow, which is my top priority at the moment.
I am also taking maca root extract, which I found to be beneficial for a host of different things and almost acts like a androgen, like a mild anabolic and seems to have some pretty interesting results based on some reports on reproductive health. I still need my twins to work if I want kids, which I do. So keeping those happy and healthy, hopefully.
Then as we move through the day, I’m not taking much in the middle of the day, and then at night right now, because keep in mind I only had surgery a week and a half ago. I am 100 percent off of any opioids. I really minimized my use of that, but the elbow still hurts. It hurts at night so I’m taking a combination of THC and CBN to help with pain, which it does in my case quite dramatically. Then I’m taking a few other prescription meds I’m not going to get into because people love taking prescription meds for sleep. I’m probably going to modify that.
I’m looking very closely at, I believe it’s the DORA class, D-O-R-A class of sleep medications because there may appears to be some evidence to support that it could help prevent or clear amyloid plaque buildup and tau associated with Alzheimer’s. So if I can get a two for one, help me sleep and also perhaps mitigate some risk with the neurodegenerative disease, then I am interested in taking a closer look.
There’s that, and I’m taking the mag threonate, and then I am also taking two other things. I take it back for my first meal of the day, which is around two or 3:00 p.m. because I’m intermittent fasting right now. I’m taking fish oil, good old fish oil, pure encapsulations. The ONE, O-N-E, has been tested by Kevin Rose and Rhonda Patrick as being quite pure so I’m taking that.
And I am also taking AREDS 2, A-R-E-D-S 2, which is a supplement that is produced by Bausch & Lomb based on clinical research into helping to improve some types of ocular degeneration, meaning visual problems. It shouldn’t technically work in my particular version of presbyopia, which is the stiffening of the lens. Shouldn’t technically help but I do know of a few patients who claim that after six weeks they saw some type of dramatic reversal, even when it shouldn’t have by the letter of the book help them out. So since the downside is very low, I would say for me that’s a pretty easy possible upside, limited downside. It contains quite a bit of zinc, so you just have to be careful not to overdose on the zinc if you’re also taking a multivitamin and so on. Okay, talk to your doctor since I’m not one.
All right. Going to answer a question that just popped up here real quick. In the past, you’ve mentioned the desire to start a family, would California, Texas be states you would consider raising children in? Are there factors that might influence you to consider somewhere else? Yeah, I could consider many other places entirely. California, possibly. Texas, I just don’t know from a political, legal, regulatory perspective how family friendly. That might sound funny to say. Some people are going to get that, some people won’t. But I’m not sure that I would want to raise a family in an environment also where access to immersive nature is as challenging as it is in Texas, which is almost entirely privately owned as a state. So California, possibly. There are many, many places that are more rural perhaps, but within striking distance of a decent airport all throughout the country. So I’m not wedded to Texas, California, or either coast for that matter.
All right, so this is a question from Cindy. What are some recent examples of saying “No” to good things that allowed you to have “Hell, yes” moments? Bonus if you have examples of when you should have said no but didn’t and the consequences. Fortunately, I don’t have any examples that hopped to mind of when I should have said no and faced the consequences, although I could pull from my life with many of those and if and when THE NO BOOK gets published, which is currently an 800-page draft, there will be many, many such examples but recent examples of saying no to good things that allowed you to have hell yes moments.
The one that jumps to mind is I was invited to speak at a great event in Europe and they were willing to pay me a substantial sum of money and I had always been tempted to go to this event and I said no so that I could go to Montana and spend a week in the woods with a number of my closest friends learning outdoor survival skills with a fantastic teacher who’s going to end up on the podcast in the next couple of months. I would take that trade, especially having experienced it now a hundred times out of a hundred. And being gone off the grid, I mean entirely off the grid, like, phone left many, many miles away in my bag has costs.
There are always costs, but I would, for those who have not seen, it’s an oldie, but I think it’s as relevant, probably more relevant now with every passing year than when I published it, “The Art of Letting Bad Things Happen.” It’s a blog post that was published a long time ago, but this is very much how I live my life. So “The Art of Letting Bad Things Happen,” and I’m sure that you can find it if you just Google that.
All right, this is from JC. My question, thinking back to before you started Saisei Foundation, that’s my foundation that funds a lot of different things mostly related to mental health therapeutics and science that would form the basis of those therapeutics, what’s the one piece of advice you’d give your younger self on how to best prepare beyond just the money to be a truly effective and focused philanthropist?
I’ll give a few pieces of advice. The first would be, and I wrote about this quite a long time ago in a blog post called “Karmic Capitalist,” something like that. But effectively, I would’ve told myself, don’t wait. You don’t have to wait until you have a ton of money. That’s because a lot of these problems are compounding. So if you can intervene earlier, less money can be worth just as much, if not more than a lot of money 10, 15 years later. I would say don’t wait, number one. I would say number two, don’t do it out of some type of burdensome guilt. A lot of people I think give back to try to cleanse their conscience of some type of guilt or other issue that’s generally been imposed on them by some de jour social narrative. I don’t think that’s clean fuel and it’s not very good fuel for the long haul if you’re planning on trying to do a lot of good or any good.
So I would say that, and then last I would say treat it like for-profit investing or at least be very clear about distinguishing between and having separate budgets for feel good philanthropy is like, I’m doing this, it feels good. Disaster recovery is a good example of that for a lot of reasons, or do good, which might be mitigating future disaster scenarios and wildfires and so on as an example. And just being very clear on what is objectively impact driven. And that doesn’t mean it needs to affect a million people could affect 10 people in a small pilot trial.
A lot of the science I’ve funded is incredibly early stage where you can do more with less money because it’s at least in the world of say, psychedelic therapies, it wasn’t derisked, it was still stigmatized when I was involved, which opened up a lot of interesting opportunities in the same way that Uber was turned down by 300-plus investors when I was getting involved with it in the very beginning, and that actually proved to be very advantageous because when things aren’t popular, they’re not as highly valued and there’s a lot more room to maneuver.
I don’t know if that is a satisfying answer, but I would say don’t wait, treat it like for-profit investing. If you wouldn’t invest in it as a potential company, you have to make certain allowances for this strained metaphor to work, but it’s actually very, very analogous to how I approach angel investing, which includes the real world MBA approach of focusing on learning and relationships, so skills and relationships, even if the project fails. I’m still applying that same heuristic to my non-profit work, not just the for-profit angel investing that I do.
Rose, here’s a question from you. Recent thing I’ve changed my mind about. Honestly, the value of intermittent fasting. I was very skeptical of intermittent fasting because based on conversations with owners of DEXA facilities and so on, there seemed to be a pattern of a lot of people trying intermittent fasting where you’re limiting your feeding to say an eight-hour window between 2:00 p.m. and 10:00 p.m. That’s generally what I’m looking at. I try to squeeze it in and limit it to 2:00 or 3:00 p.m. to let’s call it 9:00 p.m.
I was very skeptical because there seemed to be a number of inherent problems. Number one, people were losing based on data from owners of DEXA facilities, a lot of lean muscle tissue when they were going on these experimental phases of intermittent fasting. And there were a lot of open questions that I didn’t have great answers.
For instance, and this is a question that is also one that was submitted from, and I am going to butcher this and I apologize, but Ludek, and there’s a little upside down caret on your E, so I don’t know how to pronounce that, but how do you actually pull off getting all the protein you need within just an eight-hour window? This is a good question, and I have in the process of seeing a number of my relatives disintegrate physically and mentally in large measure, I think due to metabolic dysfunction, insulin and sensitivity, incredibly screwed up glucose metabolism, overtaxed pancreases, et cetera. I began doing intermittent fasting after, let’s call it two to four weeks. I want to say it was three to four weeks of strict ketogenic diet. And about two months after that, had the best blood work that I have seen for myself in more than a decade.
That includes incredibly high testosterone and other things, so it’s not just can you starve yourself into living a very long and miserable life. There were other metrics, performance metrics including workout journal and strength improvement and muscle mass improvement. So I think there are a couple of key elements, and I’m not the first person to say this, but there are a few key elements that form a productive cocktail for intermittent fasting.
One is you have to do resistance training, you must do resistance training. And my experience is you can absorb a lot more protein than you would expect in single settings, right? There is this myth that has been propagated just by repetition along the lines of you can’t absorb more than 30 grams of protein in a single sitting, I don’t think that’s true, and I don’t think the literature supports that at all. And in fact, as you get older, there is some published literature to suggest that as one gets older, this is humans, that you absorb more protein, let’s just say over the course of the day, more effectively in fewer settings.
I’m having in my eight-hour window, basically two larger meals. My 2:00 or 3:00 p.m. like today, right? For those might be wondering, nothing super fancy, right? I had a bunch of doctor’s appointments and surgeon checkups and so on today, and I just went to Chipotle, had a huge burrito bowl. I mean I think it was gigantic with barbacoa, so I don’t know, a thousand plus calories right there. Then come back and it’s 5:40 p.m. right now. I’m going to eat after this and have another proper meal, but I will almost certainly have one or two protein shakes. If I hadn’t been running around the city all day today, I would’ve already had one of those protein shakes, which would’ve added, let’s just call it 30 grams of fast acting protein. If I could just wave a magic wand and have everything that I wanted, yeah, sure, I’d be eating cottage cheese or maybe micellar casein or something that’s more slowly digested, but whey is just easy. I want to get the collagen that other stuff anyway. And when you add all that up, it’s a decent chunk of protein.
You don’t need to force-feed yourself. But what I have tracked meticulously is body weight, body composition, and a good proxy for a lot of that is just strength. Are you gaining strength or are you maintaining strength or are you losing strength? And so intermittent fasting would certainly be, if you were to ask me, if you could only add one chapter to The 4-Hour Body, what would it be about? It would be about intermittent fasting. And then if I had to add a second chapter, which isn’t really something I changed my mind on, but it would be on vagus nerve stimulation probably. And I encourage you to listen to my Dr. Kevin Tracey episode that came out not too long ago.
In how many ways could you finish this sentence? Actually, I still have all of my… all of my Dungeons & Dragons hardcovers and modules and dice from when I was a kid. That would certainly be one. And all my books on marine biology that I started accumulating when I was age six or something like that.
Do I have any bucket list multi-day hikes or treks to complete? That’s David. I wouldn’t say there are any specifics, but I try to do two or three of those a year. I already have another one, actually two more on the books. One in Mexico and one in Japan, but they don’t need to be that far-flung. We were in Montana, which is beyond gorgeous. So I would say no individual hikes or routes come to mind, but definitely plenty. I think Glacier National Park would be high on my list of dream locations.
All right. It’s from Tim, if you had to pick one specific moment that felt like disaster at the time, but later became the most catalytic gift, what was it and what chain of events turned it into that gift? Some of you will know this, but I’ll say it anyway because it’s the most standout example. That is when The 4-Hour Chef, this book on accelerated learning really, really underperformed when it was published. And I put my heart and soul, there’s so much blood and tears that went into that literally and super proud of that book. But because it was published through Amazon Publishing, it was the first mega title that was used to announce the existence for the launch of Amazon Publishing, where they went head-to-head against their publisher partners, in effect, for scouting author talent and putting out their own titles. It was boycotted by everybody. And I expected Barnes & Noble. I did not foresee Costco and all these other big box retailers and indies of course, and that smashed the book on The New York Times.
It still hit number four, but it should have been number one. And during the launch of The 4-Hour Chef, as with the launch of anything I do, I’m always looking for a channel that I can learn a lot about that is undervalued and quickly growing. And at the time, in 2012, that was podcasts. So I fell in love with podcasts and then when I was completely demolished and my ego is shattered to pieces by The 4-Hour Chef performing so poorly relative to my other books, even though still I went to one of the top restaurants in Austin and the maitre d came out after the meal and said, “The exec chef just wanted to say a huge thanks to you because the first cookbook he ever bought was The 4-Hour Chef.” This is one of the top restaurants in Austin, which is a major food town.
So there are these examples that are really incredibly rewarding, and there are a lot of them actually. But if it had not been for that burnout, I would not have decided to take a cold turkey break from books and launch my own podcast as a test, right? As a test with a graceful exit. I think I committed to six to 10 episodes and here we are more than a decade and 800 episodes later.
All right, Cindy, “Would love to hear how it feels to be in a season of life when you’re inspired people towards high performance and learning over 15 years. Now with Coyote, you’re bringing absolute delight and laughter to people’s lives.” It feels great because frankly, what the hell are we doing here on this spinning rock, right? We’re on a one-way trip as far as we can tell. Productivity is important and having a sense of purpose and meaning, these are important. But they are, I would argue, and maybe this is just the voice of someone who’s non-religious speaking, but somewhat arbitrary.
You’re picking a story that works for you. Much like Seth Godin has said, “Money is a story past a certain point, so pick one that you can live with.” It’s like, yes, all of those things are true and important, but they’re pretty subjective. And the more you study history, the more you realize the idea of leaving your legacy by putting in an extra 10 hours a week in your Microsoft Teams or whatever is probably not going to matter in the grand scheme of things.
If you just listen to the Fall of Civilizations podcast and you’re like, “Oh, wow, yeah, the Assyrians used to be a really big deal. Oh yeah, Babylonians too.” “How many Sumerians do you know?” as Naval Ravikant would ask. None, right? So the more you let go of this heavy rock of being preoccupied with legacy, the more you realize. Also when you do a past year review, as I always do, when you do a past year review and you look back over the year at your peak emotional experiences, your peak positive experiences, a lot of them are just hanging out with friends or family doing something, engaging, right? Sitting around a fire, going fishing, going on a hike. None of which tend to cost that much money, or they could be replaced with something very similar that doesn’t cost a lot of money.
So I feel like that realization is very freeing and nourishing and is something you can cultivate very quickly. But for, I mean, millions of people who have been type A for too long, including yours truly, you’re used to sixth gear and you don’t know what any of the other gears feel like unless you burn out and then you’re in park. So you know park, when you blow up, your wheels go flying off. And you know sixth gear. But showing people that it’s like, “Hey, you actually, five other gears.” Is something I had to learn, I hate to sound like an old bastard, but the hard way, through just lots of self-inflicted wounds.
And it feels really great to have something that costs 10 bucks, takes 10 minutes to play that you can reliably inject into a family evening or something like that where — I don’t know if you guys have seen one of the more recent videos that I put up on Instagram that a family put up with four or five kids just going completely fucking bananas, having so much fun, they’re all interacting, no screens, and it feels great. Yeah, it feels really, really, really fantastic, which is part of the reason why I keep talking about it. Because I’m just like, “Guys, if you take yourself and your work too seriously for too long, the really serious stuff isn’t going to get done. You need recovery. And fun is a great way to recover.”
This is from Nicholas. “What interesting ideas from people of the past do you think could be important in the future? For instance, Charles Babbage’s work on computing machines would later be picked up as a reference for the first computers in the US. Lots of machine learning research from around the ’50s was later useful once hardware caught up.” I don’t have a great computer science example to respond with, but I will say that I have done a lot of reading of very old research related to extended human fasting. And for a lot of reasons in the US with the IRB approval and ethics board approvals and so on, it’s incredibly hard to do extended fasting in humans.
I don’t know when and why exactly that happened, but there was a point where it just stopped and I guess it was just deemed cruel and unusual punishment or something. And that’s a shame because I do feel like fasting is the oldest cure. If you look at pretty much any mammal, and this probably applies to creatures well outside of mammals, if they’re sick, if they’re injured, what do they do? They fast. That is the instinct that. That is the evolved instinct. And I really look forward to, and may end up if I have to, funding that type of science.
I literally have a printout in my hotel room that’s about 40 pages written up in English describing the findings of a Soviet psychiatrist who was the executive director of this center that fasted thousands of patients with schizophrenia and other psychiatric disorders for 30 plus days. Some of the mechanisms they propose are wrong, we know that now. But in a culture in a modern world where most people, and that includes all of us probably on this Zoom, are incentivized to add things, we’re also sold in a — and look, I think capitalism is the best of the worst systems that we have. So I’m obviously an avid participant in capitalism.
But when you are constantly sold things, people want you to buy more stuff, not less stuff. And therefore, I think even in or perhaps especially in medicine, there are a lot of incentives and unfortunately a lot of large incumbent regulatory capture players who perpetuate an ecosystem that relies on recurring revenue through taking medicine forever. But I think the subtractive approach is more interesting.
In part it’s more interesting to me because it’s less discussed and more neglected. And there are compliance issues. How do you actually get people to fast? Which is where the fast mimicking diet, say some of the research of Valter Longo, and something coming out tomorrow on the podcast with Dominic D’Agostino, sardine fasting, you should check that out. It’s pretty wild. And also medications that might in some way provide you with the cellular repair and self-cleaning, the autophagy and mitophagy and things like this that are associated with fasting.
So could you do that with some combination of medications, like rapamycin and others? Could you do it with exogenous ketones or the ketogenic diet? What are alternatives that are nonetheless overlapping with fasting? So long answer to a short question, but I would say fasting was — there was a lot of research being done and then it just kind of disappeared. And then what you’re left with is private clinics that have some shit to sell you who are doing their own kind of self-funded “studies” that are ultimately being used to drive more people to sign up for their programs or become vegan or whatever the agenda happens to be. That’s a real example.
All right, let’s see. Rose, most magical experiences in New Mexico would’ve been a Zen meditation retreat at Henry Shukman’s Center in Santa Fe. Just incredibly beautiful and I think magical is the right word for it. Small group, six to eight people. Mountain Cloud Zen Center for anyone who wants to look it up. It is gorgeous.
All right. Okay. This is a question on two meta skills that would be disproportionately valuable in the AI era. Honestly, and this is going to sound like I’m trying to prop up the book I told you it didn’t perform the way I wanted it to, but The 4-Hour Chef has got it all. I mean, I think the only insurance you have is being hyper-adaptable and a world-class learner.
I don’t think there’s any other answer I can confidently provide. Because even the people at the top of the game who are at the absolute apex of the AI world, who are working on these products every day, all day, don’t know what it’s going to look like in 18 months. They really don’t. If they’ve had a few glasses of wine and they’re being honest, they’re like, “Yeah, impossible to predict. Look at the rate of change.” All right, let’s see.
Okay, there were a couple of questions. I’m going to hop back to the written questions now based on the CØCKPUNCH mentioned because there are a couple of questions about CØCKPUNCH stuff. And that’s also Jack and a bunch of others who asked about this. So the CØCKPUNCH side of things is fascinating, right? Because the NFT world is, on some level, I would say on life support. So it’s very hard to predict what’s going to happen with NFTs.
But with respect to the actual world building that I did and Varlata, particularly the last few chapters that were published on the podcast with Tyrolean, I have a very, very clear vision for what I think an incredible film would look like, whether that’s animated or live action or some blend or AI-produced for that matter. And I have a very, very clear storyline. So what I’m trying to do right now on the East coast is corner a number of my friends who spend all their time on these tools, that’s what they get paid to do all day long, so that I can put together a movie trailer.
And that’s just mostly for my fun. I really want to do it because I think it’d be incredibly exciting and fun to do, at least the way I see it in my head, which is like a comic book penciler or director, I guess. I very naturally, because of my obsession with comics for so long and wanting to be a comic book penciler, think in terms of cuts and angles and framing and everything. Which is part of the reason why I put up that giant coffee table book, which is a collector’s edition of Sin City by Frank Miller, because you get to see underneath the finished inking a lot of the pencil marks and the rubber cement and all the white-out and so on. You get to see the process that’s hidden underneath.
So that for me is kind of the next step, is hopefully creating a movie trailer. And if that gives me the kind of quickening and that wellspring of energy that makes me feel like I’ve grabbed a productive third rail of chi or something, then I’ll be like, “Okay, yeah, let’s see how other people respond to it and show a couple of friends.” And if they’re like — if I get that response, then I’ll probably push a little harder. But as I mentioned earlier, I do have a couple of other things on the plate, including that 800-page book. So you can only do so many things in parallel.
But that’s one that I think over a weekend or two or three days, if the tools are good enough and I have people sitting right next to me who are good enough with the cutting edge of say, animation/video production using AI tools, I feel like it should be, at least to my muggle mind, pretty straightforward. But I don’t know how good these models are at following literal explicit directions, right? Like, “This for a half second, this for a quarter second.” I don’t think they’re actually going to cooperate. I think they’re going to be petulant little two-year-olds and make a mess of things and throw their construction blocks all over the floor. Then I’ll have to clean it all up. So I think it’ll be harder than I would like, but we’ll get there. So that I think is next up.
So, Guido, I don’t have any thoughts on the Johnny Depp and Ridley Scott’s Hyde comic collaboration. Honestly, it’s the first time I’m hearing of it, so I will need to check that out to see what I can pick up from the creative process. All right, designing small experiments, what’s one experiment you’ve run in the past year that gave you outsized returns personally and professionally, and what made it work? I don’t want to beat a dead horse here, but it would’ve been Coyote for sure, just as a creative unlock and energy tap, sort of fracking your psyche for increased energy.
What made it work was finding someone I would pay to spend time with anyway, and that’s Elan Lee. And certainly there are many other people on the team for Exploding Kittens who made the entire Coyote project incredibly worthwhile. So many amazing folks on that team. But fundamentally it was my first contact and conversation with Elan where I was like, “Okay, this guy is so hilarious, so smart, so technical, which a lot of people do not realize, and just so gifted in so many things as a polymath, I would just pay to hang out with this guy.” I think that’s what made it work.
All right, let me answer another just quick question on the, like, Varlata movie. Do I see the film as something that can belong to the emergent long fiction model or would that shift the project into a different creative framework? I think it would be a different creative framework. And for me, I just have such a clear vision on what this entire story looks like. I think it would be fucking nuts. If someone was like, “Tim, you’re the benevolent dictator of Hollywood. You can just tell everybody what to do,” I would cast Tom Hardy and I would cast someone who’s a younger version of Timothee Chalamet, and that would be the father and son pair. And I would — Sasha, did you raise your hand?
I mean, it’s actually not a bad fit. And then I see exactly how this thing would unfold. It would be a fucking incredibly exciting, fun film. I have the utmost confidence. But alas, I do not have the ability to force people with a hundred million dollars of budget just to do what I want. So we’ll see. I don’t think I’m willing to bet the farm on it, which is why I want to play with these AI tools first. Let’s do a proof of concept at a very low cost and see if it gets a couple of people to hold their breath or go, “Holy fucking shit.” Can I make someone speechless with it for a couple seconds or just make them lose their composure in an interesting way? That’s going to be my test.
All right, so I’m going to butcher this name, I apologize. Jilca? “All right, I’m getting back into competitive chess after having been away from it for many years. If you treated it like a mental sport, how would you train recovery focus and stamina? Expensive ketone esters are sadly out of my budget.” Yeah, they add up. All right, so I would treat chess as a mental sport. It’s also a physical sport depending on how long the games last. And I wish I had my friend Josh Waitzkin here with me right now to take a stab at this.
But I think you can treat it like a sport, just like esports. You can’t play esports 24 hours a day. You’re going to run out of sufficient levels of certain neurotransmitters and glycogen and all that, just like a Tour de France athlete. So there are biochemical or biological limiters like rate-limiting steps. Okay, so how would I think about it? Well, first I would just make a huge list of options.
And as a competitive chess player, I would basically go through and document on a piece of paper, maybe you do this first, but your failure modes, right? When have you made mistakes? When have you lost games that you feel like you should have won? What were the causes? Was it not enough sleep? Was it too long of a game? Was it emotional dysregulation because someone was playing dirty or otherwise fucking around with you? And that definitely happens in chess. What was it, right? So what are your top 10, top 20 kind of like failure modes or failure stories? So you could dissect that.
But in my case, I would say a few things. One is getting your glucose metabolism and glucose energy management as stable as possible. And I think I really feel like intermittent fasting on a 16/8 format. So eight hours of eating between, let’s just call it for simplicity, like 2:00 p.m. and 10:00 p.m. is a great way — it takes about a week of being pissy and grumpy to acclimate, but after about a week to 10 days, everything stabilizes and you end up having a lot more energy consistently. You just do not have the ups and downs.
Be careful with too much coffee also, which spikes insulin, even if it doesn’t spike your glucose levels. Although it very often will also spike your glucose levels with the release of glycogen. So just be aware of moderating your caffeine intake. Because part of the reason, I at least, crash after too much caffeine, like 30 to 45 minutes later, it’s not that the caffeine itself by itself is fast metabolized, and I am a caffeine fast metabolizer, it is the effect on insulin and glucose. And I and many others have tracked this.
Then there’s all sorts of stuff you can play around with. So for instance, even if exogenous ketones are out of your budget, MCT oil may not. Definitely be close to a bathroom when you first start experimenting with MCT oil. But MCT oil, whether it’s oil or powdered, make sure you check the expiration date. Do not consume out-of-date oil. Don’t play that game, it’s not going to be good for you. But MCT oil does have some very interesting case studies and I think also clinical trials that you can look at in terms of cognitive enhancement, typically done in older subpopulations. But I do think that’s interesting, right? It’s certainly a lot cheaper than a ketone monoester.
There are other ketones that are less expensive than the ketone monoester, like Keto Start made by Dom D’Agostino, which is a electrolyte and ketone salt combination, right? But forget about exogenous ketones for a second. You could also play with a ketogenic diet. That can be done inexpensively. If you have macadamia nuts, sardines, and some oil, you’re pretty much set, in some salad greens. The ketogenic diet doesn’t need to be expensive.
If that’s too much of a pain in the ass, as I mentioned, I feel like stabilizing your glucose metabolism is priority number one. We were talking about sequencing and putting problems in order. You will end up throwing a lot of band-aids on the problem if you don’t have that checked off first, right? You’ll be consuming all sorts of smart drugs and caffeine and nicotine and blah, blah, blah, which is like pissing in the wind if you haven’t fixed the underlying system first. So I would probably suggest speak with your medical professional, yada, yada, yada, but that’s an easy kind of on-ramp to addressing that.
And then there’s all sorts of stuff that can help, but there’s no free lunch, right? So I’m sure that modafinil is used by some competitive chess players. I don’t know what the doping protocols are, I don’t know what is banned, if anything, for competitive chess, I don’t know if they test, but I’m sure people are using things like modafinil, just an anti-narcolepsy drug that was very popular among Olympic sprinters before it was banned. It was like, “Wow, what a coincidence. All of the finalists for the gold medal run are diagnosed narcoleptics? Wow, what a crazy coincidence.” Because then they could sort of legally use modafinil as a stimulant.
I’m sure there are many, many other things. I would look at archery, right? So I’m sure just as people use it for music auditions, things like beta blockers. I’m not recommending you use any of these drugs, by the way. I’m just saying these are things that are probably in the mix. I’m sure people are using nicotine. And Andrew Huberman’s talked a lot about this. Peter Attia also has talked a lot about nicotine. A lot of my friends are now hooked on nicotine, and I would just say it is very addictive. It’s kind of like, in my mind, sort of second in place to heroin. So just know what you’re signing up for.
And then there are the old-school smart drugs, like hydergine or the racetams. A little known fact, hydergine I believe was created by Albert Hofmann, who also created LSD. Fascinating drug. That guy was super genius. And so on and so forth, right? I imagine there are also people who are microdosing. I could see there being advantages to that. If you overshoot, you’re going to be in a world of trouble and it’s not going to be very pleasant, but I’m sure there are people who are microdosing using something like 50 to a hundred milligrams of dried psilocybe mushrooms plus caffeine at the right time, plus ketones at the right time. That’s a pretty interesting stool of a cocktail.
But fundamentally, I would say glucose management, and just like an endurance cyclist, depending on the duration of the event, how are you going to fuel, how are you allowed to fuel. If you’re not allowed to fuel, I don’t know the rules, but if you’re not allowed to fuel across multiple hours, then some version of ketosis is probably going to be very helpful. And I’m going to stop there, but this could be applied to just about anything, including podcasting, by the way.
Kate. “Are you working on any unexpected projects that people wouldn’t instantly associate with you?” You know, behind the scenes I have been working on all sorts of stuff that I haven’t talked about that much related to trying to incentivize humans to un-fuck the planet a bit and hopefully head off some of the problems that are coming our way at high speed over the horizon with technology. So I’ve been very involved going back at least five years, but in fusion, looking at different types of different nuclear options for clean energy. And when I give credit where credit is due since I’m reading his book right now, but Pablos Holman talks about this and he said basically people conflated nuclear weapons with nuclear reactors and the wrong one got banned.
So fusion is a place that I’m spending a bunch of time. I’m looking at ways of addressing emissions in various ways, like algae feed additives to reduce methane production from cows. It sounds funny maybe, but actually a pretty big lever. Meat alternatives for scalable protein, even though I’m an avid meat consumer and one of the largest investors in Maui Nui Venison, which is the sort of most nutritious red meat you can purchase on the planet arguably. And yet, depending on how things swing, I really do think that having scalable, easy-to-harvest, space-efficient protein is going to be increasingly important.
So those are a few of the things that behind the scenes I’m involved with that I haven’t talked too much about because I don’t want to sound like some self-congratulatory eco-warrior who’s just patting himself on the back because he has too much time. You know, like there’s so many of those people, I just don’t want to be one of them. So I don’t talk too much about that stuff, but I do think it’s really fucking important.
David. “What’s one country you wished you visited earlier or can’t believe you haven’t been to yet?” One country, now this is going to be controversial depending on who you ask as far as country status, but I would say Taiwan. Taiwan is just one of my favorite places on Earth. I went there for the first time around ’99, I guess, 1999, and fell in love with it, was there for two or three summers, and then had no opportunity or didn’t make the time to go back until a few months ago.
And I just love Taiwan in part because Taiwan really preserved a lot of the culture that was demolished during the Cultural Revolution in Mainland China. People are very friendly, very polite, the food is fantastic, tons of natural beauty. It is a speck of an island. It is very small, which on the plus side means that you can explore a whole hell of a lot of it very, very easily. There’s incredible nature and waterfalls and rivers and rainforests within less than an hour drive of Taipei. I just love that place. So if that’s on your wish list, I would suggest visiting sooner rather than later.
And I’m sure there are tons of other places where I haven’t spent time. I haven’t spent time in all sorts of countries that are interesting to me for a bunch of different reasons, like Estonia, these smaller countries, Lithuania, that all punch above their weight class in certain ways, like Lithuanian basketball. Go look up Lithuanian basketball history. It’s completely bananas. Look up Lithuania basketball and the Grateful Dead if you want an amazing story. True fact. Check it out. And there’s just a bunch of little tiny countries sprinkled around that I have never had the opportunity to visit that I would like to check out. So who knows?
I would say it’s tough because there are so many other places I have visited which are confirmed awesome for Tim, and they’re just guaranteed bets. It’s like how many speculative kind of missions do I want to go on versus just doubling down on the things I know are going to be absolutely fantastic, the Japans and the Italys and so on, right? Argentina, even though they can’t seem to, like every three or four years they just light their whole country on fire, but I do love Argentina. Too bad about that whole crypto thing with Milei. Come on. What a mess. Anyway, they just can’t help themselves.
So I would say those are a couple that come to mind.
All right. Let me look at — this is a comment/question from Jiho who couldn’t make this because she’s on a plane, but I’ll just read the kind of relevant part here, the most relevant for the group. “Saying ‘No’ is important, but I believe there are moments in life when ‘Not yet,'” in quotation marks, “is wiser than no, especially in the early stages of growth before reaching any kind of summit. I think we need a phase of openness, a time to welcome an experiment rather than reject. What do you think about that?”
Yeah, I agree with that. I think in part, and this is certainly in The 4-Hour Workweek as well, you need to figure out what you’re good at, what you’re good at what, and part of that is like what do you find easier to do than other people? Or is there anything that other people really dislike doing that you happen to love doing or at least tolerate doing, right? And then what do other people seem interested in, right? What are other people going to value? But at the very top of that is what are you good at? And to figure that out, you do have to throw a lot against the wall, and I think that engineering for more serendipity rather than less is a good idea because your ability to predict that is going to be terrible generally speaking.
So yes, I think that — but I would say that for every example of someone who has radical openness, there’s also somebody who figured out. They tend to be people who figured it out reasonably early, either something they absolutely wanted to do and that was it, like Frank Miller, I think Frank Miller when he was like age five. He’s one of the top five or he’s one of the top comic book artists and writers of all time, right? Sin City, Batman: Year One, like the list is super long, 300, et cetera, and he decided when he was five years old that’s what he was going to do, right? Or you take a Michael Phelps or whatever. But that tends to correspond to someone finding something that they are good at or that gives them effectively an unending supply of energy, which then provides you with the fuel to get really good, right?
So those are the two things that I would look for if you’re throwing a lot against the wall. But once you figure that out, even partially, I think that going through a period of having a closed-door policy, which is just like there’s my summit in the future and anything that gets me closer is a yes and anything gets me off to the side or causes me to divert is a no, I think, is a good practice.
And again, coming back to the discussion around Austin, San Francisco, they don’t need to be mutually exclusive. You can alternate and it doesn’t need to be one forever, it doesn’t need to be one for a year. It could be one for a month. And certainly if I’m going to focus on, say, a movie script, or a book, or Coyote, right? Why did I shelve THE NO BOOK? Because I wanted to single task on Coyote and the game and maximizing everything about it in the early stages, the development, and the play testing, and the tweaking, and the iterating, and all of that, and then now more the retail distribution, optimization, and things like that. So until I feel like I have seen that to escape velocity or at least taking it as far as I can within reason, I’m not going to say yes to things that cause me to deviate off of that.
“Congratulations on Coyote. Are you already thinking about another game to make the most of the skills and knowledge you’ve gained?” Not yet, not yet. I’m tempted to because that’s the fun brainstorming fantasy land side of things that is always the most fun for me, but I recognize that that is going to pull Tim the beast of burden away from the yoke that it needs to push around in a wheel, you know? So I haven’t thought about it, to be honest. I’m disallowing myself. I’m forbidding myself from thinking about it until I do as much as possible with Coyote.
All right. Cindy. “Love The 4-Hour Chef and still use it regularly.” Thank you.
All right, this is Hugo. “Do you prefer doing a podcast with big headphones versus in-ear AirPods? Why?” I do, and that is because these AirPods, which I’m holding up, run out of battery and also sometimes have connectivity issues and so on via Bluetooth, so I prefer to have a hard connection, which is what I’m using right now, an Audio-Technica headset with this as backup audio at highest fidelity via QuickTime. Two is one and one is none, so good to have backup.
Okay, Life Olsen. “What do you think the uncrowded channel is right now? Is it still in-person?” I do think in-person is still reliably uncrowded. I think a lot of legacy technologies are uncrowded as newer things get shiny and are made shiny and sold as very sexy. So email, possibly older platforms. It’s something I’ve been looking at very closely, like could we, for instance, use Pinterest and Quora and other sites or platforms that are not currently like the youngest, hottest girl at the dance, like whatever latest short-form social media thing has happened to show up, right? What are some tried-and-true, proven platforms that just aren’t getting the air time of the latest and greatest? Not saying that is the answer. It’s an open question for me that I’m looking at pretty closely.
Stephanie. “Monopoly Deal, great game, and Coyote, I’m biased, I think it’s also a great game, are my go-to card games with family and friends. So much fun.” Thank you for that.
Let’s see. Okay, Rashida, you’re recommending Dr. Mindy Pelz, The Resetter Podcast. She wrote Eat Like a Girl and Fast Like a Girl, all about fasting. That’s interesting to me also because women tend to have a harder time with fasting, and particularly, depending on if you have family planning imminently, that’d be good to speak to proper medical professionals about. But that is interesting, I mean because there appear to be some pretty heavily gendered differences in how men and women respond to fasting or adapt to a ketogenic diet for that matter. So that’s a great recommendation. I’ll check it out.
Kevin Rose’s Zero fasting app, yes for fasting, great one.
And I do know Robert Rodriguez. Great studio and in Texas, so yes, at some point — Robert has been, to his credit, busting my balls about being a lazy-ass MFer about not biting the bullet with doing something in film. So I appreciate Robert for pointing out the obvious, which is like he can do 12 projects at once and I’ve yet to even do a short film. So I appreciate that, and yes, he’s right in my backyard and a friend and just an awesome human being.
All right.
I have looked into fast neutron reactors, David. Thank you for asking. Yeah, there’s a lot of interesting stuff in that area, also, just frankly, building more legacy designs with water cooling and so on, I mean just putting more reactors in play. If you want a really great wake-up call, you can just type into ChatGPT like, “What is the status of nuclear power in China versus the US?”
And somebody asked about the Bugatti of ketones that I mentioned on The Random Show and if I would be willing to disclose. I’m not willing to disclose yet because there is the possibility that chronic use of an alcohol-bonded monoester could negatively affect liver function, and I want to do the homework on that. There seemed to be some ways to mitigate that, so number one, just don’t become a ketone addict and take them all day.
Secondly, maybe consuming with MCT oil has some beneficial effect. Certainly some of the supplements I mentioned, NAC, ALA, et cetera, I mean there are whole suite of other things you might take for liver support might also mitigate some of the risk, but I want to do more homework because I realize what will happen if I recommend this particular thing, is that a lot of people are going to buy it and that’ll be the last time they ever listened to me, and if they don’t hear my findings later, which are like, “Hey, guys, remember that thing? Cut back, only take this much per day, or stop taking it,” they may not hear that disclaimer after the fact. So I’m trying to do more heavy lifting on my side in terms of due diligence.
I have not watched The Four Seasons. I’m assuming that’s not related to the hotel. Let’s see.
Okay. It would’ve been some of the best locations for when you’ve taken your extended family places. Yeah, anything that is built for family outings, honestly, makes it so much easier. So if there’s something with outdoor activities for the youngsters, some hiking, a pond, then I think there’s a lot to be done. For instance, there’s a beautiful place in Upstate New York called Mohonk Mountain House. It’s absolutely stunning. It’s been around, it’s basically like Dirty Dancing in Upstate New York. It’s been around for like a hundred years. Somebody puts a baby in a corner. It’s a fantastic spot, and you have activities for anyone and everyone, and they can accommodate people in wheelchairs and so on, right? So for an extended family outing, that would be very high up.
Taking my family, and of course location would vary on person, but taking my family on basically a family tree trip and going to different countries where we can trace our bloodlines. Bloodlines, honestly. I mean, what a mutt. I mean as European a mutt as you can possibly imagine. But picking kind of the top percentages on ancestry.com or something like that and going on a trip like that was really fun. The list could go on and on. But for an extended family, I would say choose a place that’s accustomed to dealing with extended families.
“Any NO BOOK meetups at some point?” Yes, I would plan on some NO BOOK meetups for sure. Once this thing is done and people can actually get together and compare notes, I would say almost certainly. We could do them ahead of time as well if you guys wanted to meet up. I mean, there’s nothing preventing that. Just I would say let me know how I and my team can facilitate that.
Hopefully that was interesting. I appreciate all the questions and participation. Thanks everybody, and hope you had a wonderful Labor Day extended weekend for those of you who are in the right country for that, and even if not, I hope you enjoyed your last weekend. And I am going to leave it at that. But always appreciate you guys. Thanks for all the engagement, and the questions, and the thoughtful follow-ups and everything else, so have a wonderful night. Take care, guys.
The post The Tim Ferriss Show Transcripts: Q&A with Tim — Supplements I’m Taking, Austin vs. SF, Training for Mental Performance, Current Go-To AI Tools, Recovering from Surgery, Intermittent Fasting, and More (#826) appeared first on The Blog of Author Tim Ferriss.
2025-09-10 05:40:00
Welcome back to another in-between-isode, with one of my favorite formats: the good old-fashioned Q&A.
I answer questions submitted by the small-but-elite group of test readers of my upcoming THE NO BOOK. The community is closed for new members, as we have the right number of people now, but I hope to potentially expand it, once the book comes out.
See below for show notes, links to everything discussed, and more!
Please enjoy!
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Listen to the episode on Apple Podcasts, Spotify, Overcast, Podcast Addict, Pocket Casts, Castbox, YouTube Music, Amazon Music, Audible, or on your favorite podcast platform.
(Disclaimer: I’m not a doctor, and I don’t play one on the Internet. I emphasize multiple times to consult a doctor.)
(Disclaimer: I’m not a doctor, and I don’t play one on the Internet. I emphasize multiple times to consult a doctor.)
Want to hear another Q&A episode with listeners? Check out my recent Q&A session in which I discussed changing my mind about parenthood, identity diversification, how to find joy and live with urgency, career reinvention in the age of AI, avoiding complacency, getting unstuck, and much more.
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2025-09-06 04:58:59
Please enjoy this transcript of my interview with Dr. Dominic D’Agostino (@DominicDAgosti2), a tenured associate professor in the Department of Molecular Pharmacology and Physiology at the University of South Florida Morsani College of Medicine and a Visiting Senior Research Scientist at the Institute for Human and Machine Cognition.
He teaches medical neuroscience, physiology, nutrition, and neuropharmacology, and his research focuses on the development and testing of nutritional strategies and metabolic-based therapies for neurological disorders, cancer, and human performance optimization. His work spans both basic science and human clinical trials.
He has a strong personal interest in environmental medicine and enhancing the safety and resilience of military personnel and astronauts. In this capacity, he served as a research investigator and crew member on NASA’s Extreme Environment Mission Operations. His research has been supported by the Office of Naval Research, the Department of Defense, the National Institutes of Health, private organizations, and nonprofit foundations.
He earned his B.S. in Nutritional Science and Biological Sciences from Rutgers University in 1998, followed by a predoctoral fellowship in Neuroscience and Physiology at Rutgers and the University of Medicine and Dentistry of New Jersey. He then completed postdoctoral training in Neuroscience at Wright State University’s Boonshoft School of Medicine in 2004 and at University of South Florida Morsani College of Medicine in 2006.
Transcripts may contain a few typos. With many episodes lasting 2+ hours, it can be difficult to catch minor errors. Enjoy!
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Tim Ferriss: Dom, nice to see you again. It’s been a few years. Thanks for making the time.
Dr. Dominic D’Agostino: Yeah, it’s great to see you, Tim. Yeah, we’ve stayed in contact here and there with texting, but yeah.
Tim Ferriss: Lots of texts. And why not? This is one of the text threads I could probably actually make public in my life without some type of mutually assured destruction with many of my friends.
I have been revisiting everything ketogenic and certainly looking at exogenous ketones for a number of reasons.
And one of which we were chatting a little bit before recording, is that I have a number of relatives who are deteriorating from neurodegenerative disease, including Alzheimer’s. And one of them is APOE33, and my siblings and I are APOE34, which would seem to indicate we would have potentially a, let’s just call it two and a half X, higher probability of developing something like Alzheimer’s, even though data might change. Who knows?
Nonetheless, I’m looking to throw as much possible at this from a preventative perspective. What data do we have, and if there’s a little bit of speculation of all them, fine with that too in terms of future directions for research and what might come up for applications of, say, the ketogenic diet and, or exogenous ketones to something like Alzheimer’s, whether it’s from a preventative perspective, a mitigation of, or slowing of, progression of symptoms or anything else.
Dr. Dominic D’Agostino: Yeah, that’s a rapidly emerging area of research, and I think you’re aware, we talked previously of the case reports that are out there that got put this on everybody’s radar. I would say the early adopters of this idea were the people who understood that brain energy metabolism was pretty central to Alzheimer’s disease.
Tim Ferriss: Sometimes called type 3 diabetes, if I’m getting that right.
Dr. Dominic D’Agostino: Yeah. That was coined back in 2005 or ‘6, I think, and that was brought to my attention actually by Dr. Mary Newport and her husband, Steve Newport, was the subject actually in the case report for the use of the beta-hydroxybutyrate monoester for that. Dr. Richard Veech of the NIH was also on that. And Mary was near and dear to my heart. I actually coincidentally hosted her for dinner last night at the house and had her over here. And she’s a close friend of mine. We co-teach together at USF. She’s a guest teacher.
Interestingly, I saw Steve Newport in 2008 or ’09, and I witnessed the observation. He’s a 3/4. He has Alzheimer’s. He was 3/4 for APOE4. And he also had, he had Lewy body dementia, but confirmed Alzheimer’s disease too when they looked at the brain. And I observed — I was still pretty — I was questioning this idea of ketones rescuing the brain in the context of Alzheimer’s disease.
Symptomatically, there was no doubt in my mind that it did, because I witnessed him. He wasn’t using the ketone ester at the time, but we quickly transitioned to that after meeting, but he was taking coconut oil and MCT oil. And he would bring these little shot glasses. Mary taught my class. We went out to dinner. He did the shot glasses. His tremors stopped. He became animated, and he talked. And after about four hours, he started to decline and started getting fine tremors again. And then he would become reanimated upon increasing his ketones to about one to two, which we’d give him a 30 milliliter shot of MCT plus coconut oil that was mixed in there. So she was really — and doing that three to four times a day with meals.
So that was my first observation. And it was clear to me that there was at least a metabolic — within the Alzheimer’s spectrum, I just like to — Alzheimer’s is kind of a fuzzy diagnosis and —
Tim Ferriss: Sure. Very fuzzy.
Dr. Dominic D’Agostino: Yeah. And I just like to call it dementia, cognitive dementia. There’s vascular dementia and there’s Aβ and tau. And my wife was working on tau at the Alzheimer’s center when we met. She was working under a guy who studied tau. Then there was people there who studied amyloid beta, and there was the tauists and the beta. And there was an argument as to what was more profound.
But a universal feature of Alzheimer’s is amyloid plaque accumulation. But also now we know that glucose hypometabolism is central to that. And as we age, our ability to use glucose as an energy source decreases over time due to they thought maybe vascular reasons. But come to find out, it’s really, it’s a constellation of things, including the glucose transporter, the GLUT3 is on neurons. Pyruvate dehydrogenase complex, which is really the governor or the rate limiter of glucose metabolism in neurons. That’s PDH, pyruvate dehydrogenase complex.
And the production of — if you look at that protein for that decreases over time, as does the catalytic activity of that enzyme over time. So we know that. And then there’s neuroinflammation, there’s a vascular component. So all these things kind of contribute to metabolic dysregulation, but also a big driver is neuroinflammation.
And I do believe, as does Dr. Mary Newport, who is the author of that paper with a case report and a number of other leaders in the field, including, I’m blanking on his name, the chair of neurology at Harvard just gave an NIH seminar on infection as an etiological agent for Alzheimer’s disease. So Epstein-Barr virus, cytomegalovirus, herpes simplex virus. We do know — yeah, HPV — know can contribute to things like —
Tim Ferriss: So we’re probably talking about —
Dr. Dominic D’Agostino: — cancer.
Tim Ferriss: — if, I mean, 50, 60 percent of the population having one of these things.
Dr. Dominic D’Agostino: Sure, yeah. Well, Steve Newport, the subject in that case report, had bouts of herpes, HSV, around the eyes and got hit pretty hard with that. But also people who have shingles that I think they’re at risk too. We know Epstein-Barr virus, you’re four or five times more risk for things like MS. It’s triggering the immune system.
So I think there’s a renewed interest in looking at Alzheimer’s disease, looking at the root cause. And I think metabolism is central, but the metabolic hit that may be contributing to dysregulated metabolism and neuroinflammation could be an infection. And I think there’s accumulating evidence for that. I was skeptical 10 years ago, probably, when we talked. However, this kept putting on my radar. And then I was in an NIH sponsored workshop on this looking at various aspects, and the data presented by a number of different labs was very compelling for this.
So what does that mean? Our immune system is — there’s the four horsemen that our friend Dr. Peter Attia talks about. I think the fifth horseman is really the immune system. I like to add a sixth horsemen as our physical form, our skeletal structure, so our bones, and that will give over time too. But the immune system is really central to longevity. And the metabolic control of epigenetic regulation and metabolic control of immune system function is of very high interest. I know the Buck Institute has refocused on that, and many longevity clinics are now looking at that.
Tim Ferriss: What is your preferred device for measuring ketones these days?
Dr. Dominic D’Agostino: For publications, we’ve used the Abbott Precision Xtra because historically we’ve used that. However, when I recommend a meter to people, I generally recommend the Keto-Mojo device because that —
Tim Ferriss: Keto-Mojo.
Dr. Dominic D’Agostino: — has the glucose ketone index. And so the glucose ketone index is the millimolar concentration of over ketones, and the strips are about, nowadays, still less — I was going to say, I don’t know, a few years ago, they were about half the price. And we’ve tested the Keto-Mojo. We have a human clinical trial where we did breath, we did urine, and we did Precision Xtra and Keto-Mojo all together. Then subjects go into the chamber and we did metabolomics and everything else. But the Keto-Mojo consistently gives us numbers that are more in line with our biological assays that we run in the lab.
Tim Ferriss: Okay, interesting.
Dr. Dominic D’Agostino: Like the [inaudible] on that.
Tim Ferriss: Yeah, yeah. Let me just tell you what I’m up to and you can tell me how ridiculous I am in off base or fact-check as needed. Can you remind me of how to pronounce this Dr. Thomas? Is it Seyfried? Am I getting that right?
Dr. Dominic D’Agostino: Yeah. He’s a good friend and colleague. Dr. Tom Seyfried.
Tim Ferriss: Tom Seyfried. All right. So in terms of fasting, we’ve talked quite a bit about fasting. It still is very interesting to me. And I’m wondering just in brief, if you could, without getting too much in the weeds, but I’m wondering what the ketogenic diet does that exogenous ketones do not achieve? And then I’m wondering what fasting does that the ketogenic diet does not do.
But the way I want to get to that is to ask you, because for a long time I was doing a one week, we could call it a water-only fast, but let’s call it a calorie-free fast, right? Black coffee and black tea and stuff I was consuming, but a week-long, water long fast a year, and I was doing maybe a three-day fast every quarter. I didn’t really want to do three to four week-long fasts a year, just didn’t want to do it. But in terms of potentially purging precancerous cells and so on, I was like, you know what? I like the aesthetic practice — seems like a bit of autophagy and cellular cleanup is a good thing. Why don’t I do that?
Do you do any fasting anymore or is that something that you have omitted from the current version of Dom’s schedule?
Dr. Dominic D’Agostino: Yeah, I do it situationally and I think there’s situations where I think I’ll benefit from fasting or from just inducing a state of an energy deficit. So you could do caloric restriction, time restricted feeding, dietary restriction. You could do a restricted ketogenic diet, a cyclic ketogenic diet, modified, a modified supplemented ketogenic diet, which is what I do. I like to do what I call, I mean I coined it. It’s like sardine fasting. And I had a cancer patient a long time. One of the first that I sort of engaged with, actually his name was Dr. Fred Hatfield. So he was kind of a famous —
Tim Ferriss: This is Dr. Squat?
Dr. Dominic D’Agostino: Yeah, yeah, Dr. Squat.
Tim Ferriss: Back in the day. Wow.
Dr. Dominic D’Agostino: Yeah, we were good friends. He was a mentor to me in many ways. But he had advanced metastatic prostate cancer, and it went to the bones where they did a PET. And I was just getting into this area of research and I was like, “Here’s what I would do.” And I would go to his house and I’d bring him things, and he was testing things. And he loved sardines. So I think he steered me onto sardines in maybe 2007 or oh eight or something like that. So that was my love for sardines was probably from him.
But he would do low-carb. He called it ketogenic, but I think it was just more of a low-carb diet. And then he would do five days, he would do a fasting mimicking diet that Valter Longo has advanced, but he has more of a plant-based approach. But Dr. Hatfield would do, Fred would do one or two cans of sardines, maybe one can of sardine per day for a week. So we called it sardine fasting. And that was just as I was getting into this. And essentially what happened is that he went into rapid remission and the doctors didn’t really know. Fred ended up passing away maybe eight years later of something completely unrelated to his cancer.
Tim Ferriss: As a non-oncologist, I have to pause and just say, I mean, it seems like prostate, for a lot of people, they hear that, they think “Death sentence.” Metastasized prostate cancer, they think, “No way, you’re done.” Am I exaggerating? I mean, how frequent is it that people have complete remission of something like that? Maybe I’m exaggerating things.
Dr. Dominic D’Agostino: Yeah, there’s a lot of factors like the Gleason score and his was not good in a number of factors. So he was given, I think he told me three months to live, but he went years and years —
Tim Ferriss: Wow.
Dr. Dominic D’Agostino: — after that. And he was like, no evidence of disease.
Tim Ferriss: How often was he doing the sardine fasting? Was that once every month? What did his cadence look like?
Dr. Dominic D’Agostino: Yeah, he stayed ketogenic, and then I would go over there and encourage him to do that, and he loved to do it. He was like, “Okay, I do this and now I feel better when I’m doing it.” Fred also surprisingly, would smoke a little bit, and I got him to maybe stop that too. So we got him to dial back on some other behaviors and maybe he would drink a little bit too, but not that much. But his health improved dramatically when he adopted a low-carb and then ketogenic diet. And then for years, he did the sardine fasting and we communicated and I just encouraged, “Hey, keep sending me your medical reports.”
And I was like, “Maybe there is something to this.” So that actually steered me into just like the Alzheimer’s, we did started Alzheimer’s research because of Dr. Mary Newport. I studied seizures because of Mike Dancer. Just Google Mike Dancer, epilepsy, and you’ll find some remarkable stories. I steered him to the ketogenic diet and it was a remarkable. He got off all meds and it worked way better than the meds. So Fred, but that was prostate cancer. But then I started engaging with other patients and then connected with Thomas Seyfried soon after that.
Tim Ferriss: How frequently was Fred doing the week-long sardine fasts, if you had to guess?
Dr. Dominic D’Agostino: Once a month. Sorry. Yeah, I meant to —
Tim Ferriss: Once a month.
Dr. Dominic D’Agostino: Yeah, it’s analogous to the fasting mimicking diet. I think Valter Longo can do that. He advises patients based on, situationally, their situation. But I encourage Fred to do it every month. And his feedback to me was that he would do it once every month to two months. He enjoyed doing it, so it was something that he kind of looked forward to doing.
Tim Ferriss: Sardine fast. I can’t wait for that to become a thing. That’s going to spread. I don’t want to gloss over what you personally do. So for you, for instance, I found out recently — and everybody get your checkups. Do not skip colonoscopies. Do not skip. In my case, I got an endoscopy because I was having some trouble swallowing every once in a while. I thought it was like, ah, maybe it’s just like I’m eating too quickly with dried chicken or something. And suffice to say, putting that aside, that was sort of the symptom that catalyzed it.
But I ended up having very unexpectedly a hiatal hernia. Hiatal, I think also related to the word hiatus etymologically. I’m going to get the definition wrong, I’m sure. But basically from your esophagus to your stomach, typically there’s a nice kind of sphincter or ring, and basically the stomach is kind of pushed out of that ring. And there’s actually a lot of scarring in my throat from acid. And so I was told that maybe not this bluntly, but that puts me at some increased risk of throat cancer or esophageal cancer, some type of cancer.
And I was like, “Shit, that’s not typically what kills people in my family. Usually it’s the cardiac stuff.” And I feel like I have that. My lipid profile is very well under control, which is why going back and doing research for this conversation, and I’ve also done fasting over the years, I’ve thought, “Okay, well, in addition to taking the proton pump inhibitors and everything so that I’m not accumulating more scarring, is there a place for doing the fasting, since I don’t mind doing it anyway? Just to further hopefully decrease the risk.”
And you were saying you fast episodically, was that the word that you used?
Dr. Dominic D’Agostino: Yeah. Situationally, episodically.
Tim Ferriss: Situationally. Situationally. What does that mean?
Dr. Dominic D’Agostino: If my wife is traveling and it prevents me from being antisocial and I have a lot of work to do, and I have a grant deadline that’s five days away, okay, I’m starting fasting for five days until I get this grant submitted. If I’m traveling by myself, I’ll do it. Occasionally I’ll get sort of an inflammatory flare up and I don’t know what it’s — I’ll feel a little bit off like brain fog or my joints or something like that. It’s pretty rare now because my HSCRP is like non-detectable, right? Before I did, it was always one or two on a higher carb diet.
Tim Ferriss: So people might recognize CRP, right? I mean, C reactive protein is a marker of inflammation. I mean, if you get your annual blood test or whatever, chances are it’s on there somewhere.
Dr. Dominic D’Agostino: Yeah, I’d like to draw attention to that real quick because HSCRP is a better indicator of cardiovascular disease than LDL cholesterol. We know that now. If someone said that 10 years ago, they’re just like, “We think you’re crazy.”
But yeah, HSCRP is what we call a cardio metabolic biomarker, including triglycerides and insulin and things that should be included. But that is a really important biomarker, I think, to keep low for Alzheimer’s and cancer and all the other, I call it six horsemen. No. The things that I mentioned. But yeah, so occasionally I will use it situationally just if I feel my body, if I feel like something is coming on, I’m getting a flu. But the sardine fasting is, and I advise it for cancer patients too. I want them to avoid a water-only fast in the context to prevent cancer cachexia.
Tim Ferriss: Muscle loss or muscle wasting.
Dr. Dominic D’Agostino: Yeah. And omega-3 fatty acids are very potent mitigators of cancer cachexia. And so you have the omega-3s and basically you have everything your body needs, especially nutrition-wise in sardines. You might want to add a little bit of vitamin C or magnesium or something. But essentially it’s like you have adequate nutrition and then you create a caloric deficit, you create caloric restriction, and then with caloric restriction come a whole host of beneficial things. The protein’s low enough that you’re suppressing insulin, mTOR, and probably activating AMP kinase. And if you do that in a protracted way and you can achieve a glucose ketone index of one to two for about three to five days, that the constellation of things that if you measure that would correlate with inducing and maximizing autophagy. So that was the rationale for me to do that. A lot of people talk about autophagy and it’s kind of a nebulous term. We measure it. We look at the autophagosome. So we’re a lab that actually does look at things like that. There’s p62 and other things that you can measure, but there’s no commercially available — I think the best way to measure to suggest you’re in autophagy is a glucose ketone index after a period of fasting.
Tim Ferriss: Which Keto-Mojo will do automatically. It’ll do the calculation for you. I did have a quick question.
When I compared my Keto-Mojo to an oral glucose tolerance test where I was having blood drawn every 30 minutes, the glucose readings I got from the Keto-Mojo were substantially higher than the blood test, than the blood draw itself and I was wondering if that’s something you’ve observed. I mean, who knows? Maybe it’s a bad device. Maybe I had too much alcohol still on the finger and I didn’t dry it properly. I mean, who the hell knows? Maybe it doesn’t matter so much, but it seems to matter because regular spikes above a certain nanogram per deciliter seem to be indicative of all sorts of things. Have you run into any issues with the device or any caveats related to specifically the glucometer side? What I do like that’s nice about it is it does give you that glucose ketone index, the GKI as a readout right there on the device or in the app at least that accompanies the device.
Dr. Dominic D’Agostino: Are you talking about measuring glucose at the exact same time point that a phlebotomist pulled blood.
Tim Ferriss: That’s exactly what I’m talking about. Yep.
Dr. Dominic D’Agostino: Okay. What was the difference between what was measured there?
Tim Ferriss: Let’s say the peak at 30 minutes out after drinking this not-so-delicious dextrose water. It’s something like this. I was bumped up to probably 140 on the phlebotomist drawn blood and it was like 165 on the Keto-Mojo. The return was much faster and much better on the phlebotomist drawn blood than it was on the Keto-Mojo device, which not to throw them under the bus. It could be operator error or just a single bad device. I have friends who have used it very successfully on the ketogenic diet, which is why I ended up buying it because Precision Xtra is kind of a pain in the ass to get a hold of, at least on Amazon. So that was my experience and I was like, “Okay. Well, tricky, tricky, tricky,” because if I’m really trying not to pop above a certain level, if the device I’m using day to day is 20 points above where maybe it should be, then that’s a problem.
Dr. Dominic D’Agostino: What’s your hemoglobin A1C?
Tim Ferriss: I’d have to go back and look. It’s trending down, but I would have to go back and look.
Dr. Dominic D’Agostino: If you wear a CGM, you’re under maybe 100 with the CGM. So the meters tend to trend a little bit high, about 10 percent high. I think they were 10 to 20. Keto-Mojo was 10 percent higher than our assays, and the Precision Xtra was 20 percent higher than the assays that we do when we pulled blood from the animal. So if that helps, I think you want to at all. You want to look at your insulin levels, your hemoglobin A1C, hs-CRP.
Tim Ferriss: Yeah, we got it all. Just for people, public service announcement, do an oral glucose tolerance test, ask your doctor, talk to them, get your insulin measured, because my relatives metabolic dysfunction was missed for a very long time, in part because they were looking at fasting glucose. You can get really lucky with fasting glucose depending on when you get that snapshot and the docs weren’t great to begin with who were tracking these relatives, but as soon as we looked at OGTT, the oral glucose tolerance system, insulin, oh my God, it was like sky-high out of range.
Dr. Dominic D’Agostino: Or put a CGM on them. That’s what motivated me to be, I guess, one of the first advisors for Levels. I’ve worked with them on a research front. I think you’ve interviewed Sam, right?
Tim Ferriss: Yeah.
Dr. Dominic D’Agostino: But Levels, I mean, that’s —
Tim Ferriss: Yeah, Sam Corcos.
Dr. Dominic D’Agostino: Yeah, Sam. I mean, that’s like the ultimate kind of metabolic optimization platform. I mean, there’s others emerging too, but simply wearing — I mean, now they have the Stelo device that came out, so CGM’s are over-the-counter now, but the analytics from that and also the biomarkers that if you’re part of that program that you can measure, which include many things that we could talk about, but that would capture your relatives if your relatives put a CGM on. That’s really important, but what you observed is pretty normal and not to probably be of concern, like your —
Tim Ferriss: Yeah. Okay. Cool. Yeah, I just wanted to check it out. Just to tie this up for me, and I maybe just missed it, if someone is using ketones on a continual basis, are there longer term adaptations? Part of the reason I’m asking is that in the most recent set of experiments, let’s just say, I was strict keto for three weeks, and then frankly just got bored to death of the diet.
Dr. Dominic D’Agostino: It’s hard.
Tim Ferriss: Yeah, I did three weeks of let’s just call it kind of textbook — protein also quite low, like 10 to 15 percent let’s say, so maybe I bump it up next time, but just got so bored of it after three weeks, but I want to do enough that there might be some upgrade of the metabolic machinery. We could talk about that because I know for athletes it might be like six months to 12 months, but went from that to then 16:8 intermittent fasting, still in ketosis for maybe a week, so 16 hours off eating between, let’s say, 2:00 p.m. and 10:00 p.m. Then I went to a more paleo-ish diet, let’s just call it, within that feeding window. Then I did that for a few weeks and then started layering in exogenous ketones in my fasting state, typically 11:00 a.m., 1:00 p.m. if I’m doing podcast recordings and things like that.
Part of what I’m trying to figure out is given I’m APOE3/4, scared to death of Alzheimer’s, and maybe there’s nothing to be done about it, but if there is something to be done in addition to exercise rights and kicking out the Klotho and BDNF and all that good stuff, from a dietary perspective, trying to figure out, okay, how long does keto memory last if there is an expiration date? If you were in my shoes, how you would think about not just the exogenous ketones, but fasting and ketogenic diet? Do you have any thoughts on that?
Dr. Dominic D’Agostino: Well, yeah, you’re doing a lot of stuff there, and I would recommend following a protocol that you could do day in and day out that should ideally almost be effortless and mesh with your schedule, which may be variable if you have podcasts and things like that. I’m of the opinion that you could follow a baseline diet, which is a low-carb Mediterranean-like diet. Mediterranean is kind of a fuzzy term, I hate it, but low-carb Mediterranean style diet that essentially keeps biomarkers in check and then situationally going the ketosis now and then to just optimize it. But you want to follow an approach therapeutically that keeps your GKI into that one to four range. Tom Seyfried is very adamant about one to two, but the normal GKI of a person in the US is like 50, or 25 to 50.
So just living in a state of having a GKI of even five would be, I think, trending towards being more metabolically flexible and having greater fat oxidation. Then you want to, as it sounds like you’re doing, just keeping check of your metabolic biomarkers, so comprehensive metabolic panel, CBC, of course, if you’re using different agents on that, but insulin HSCRP, hemoglobin A1C, triglycerides, ApoB you want to measure too, Lp(a) it’s good to know.
Unfortunately, 30 percent of people — this is probably important when navigating what protocol to use. I have a mutation. I did GB HealthWatch, which looked at my genetics for dyslipidemia. So GB HealthWatch, Dr. Spencer Nadolsky reached out to me because I was posting my numbers online and he was like, “Hey, you need to do this test.” He’s a very smart, aggressive or proactive kind of guy and suggested this test. He’s like, “I think you’re a hyperabsorber.” I was like, “Isn’t one percent of the population hyperabsorber?” But come to find out about 30 percent of the population hyperabsorb cholesterol.
Tim Ferriss: That’s me too. I’m in the same boat.
Dr. Dominic D’Agostino: Okay. I have an NPC1L1 receptor mutation that’s a gain-of-function mutation. I use an ezetimibe monotherapy for that. Ezetimibe was sold as Zetia, and I can get by with half of a tablet, which is five milligrams, and half my ApoB. It put my ApoB — it cut it in half, and also half my LDL. So I can follow a ketogenic diet. I had the skyrocketing LDL ApoB, but then I put that back in check. I am of the opinion that I need more data to come out. There’s a group of people that think LDL in the context of optimal metabolic biomarkers that it’s not to be concerned about, but that data is emerging and there’s groups of people that I believe are credible and then working on that front, looking at the lipid energy model. With the lipid energy model, LDL and ApoB is a carrier for fat to peripheral tissues, but we don’t have to go there.
Tim Ferriss: Dodge it for now.
Dr. Dominic D’Agostino: Yeah. If your LDL pops up, then a pescatarian Mediterranean-like diet that’s low-carb that’s ideally under 100 grams of carbohydrates per day, and that’s no sugar, no starch, fibrous vegetables and fruits. So my rule of thumb is 25 percent of what carbohydrate you consume should be fiber, and then that’ll essentially make it non-glycemic, right?
Tim Ferriss: What percentage did you say?
Dr. Dominic D’Agostino: What I do personally is about 50 to 100 grams of carbs a day and ensuring that the carbohydrates that you’re consuming, about 25 percent of that carbohydrate is fiber, so for example, broccoli, asparagus, of course, cauliflower, green, leafy vegetables, but even fruits, I trend towards wild blackberries, raspberries, blueberries, and buy them in combination. Then wild blueberries are about half the size and they have more fiber, less sugar, so I have a cup of that per day. My carbs come from mostly broccoli, wild berries, dark chocolate, and maybe a few other odds and ends.
Tim Ferriss: Where do you get wild berries? Is that something you buy or do you have to go out and steal from your neighbor’s patch?
Dr. Dominic D’Agostino: Well, yeah, we have a blueberry — surprisingly, blueberries grow great in Florida — but we have a blueberry farm right by us. It’s a winery, so they grow blueberries and then make blueberry wines and things like that and have huge festivals, but we get from there. But yeah, you can go to Walmart and get the Walmart blueberries, which are the size of grapes. Then next to that, now Costco and Sam’s and even Walmart now have the wild blueberries.
Tim Ferriss: No kidding? Okay. Just because you mentioned LDL, I might be hallucinating this, so please correct me if I am, but didn’t you at one point dramatically cut down your LDL labs by swapping dairy out, I think maybe heavy cream and using coconut cream or something else in its place, or am I making that up?
Dr. Dominic D’Agostino: I took out heavy cream, but put sour cream back in, but maybe about half of the sour cream, but also just switched out the eggs. I think the eggs were getting to me because eggs have a lot of cholesterol, and I was eating a dozen a day.
When I prepare my food in the morning, my dogs get my food. So I’ll make 10 eggs, but I’ll have three yolks, and then I divide the other yolks between my two dogs. Then instead of ground meat, which I was eating a lot of, I get chub mackerel. I do sardines, occasionally tuna fish, but I get cases of chub.
Tim Ferriss: Chubb like the insurance company, C-H-U-B-B? No. How do you spell that?
Dr. Dominic D’Agostino: Yeah, C-H-U-B. Unlike a king mackerel, which are bigger, chub mackerel are small fish.
Tim Ferriss: Yeah, don’t bioaccumulate as much garbage or —
Dr. Dominic D’Agostino: Yeah. So they’re really low on the heavy metal list, which I tend to check because I eat so much of it. One can is almost a pound, and there’s three fish in each. I take a fish and give my two dogs each a fish. It’s got a lot of fatty water in it full of omega-3s, and I pour that on their food and they love it.
Tim Ferriss: Where do I sign up to be reincarnated as one of your dogs?
Dr. Dominic D’Agostino: Yeah, this morning they got — my wife has an Audacious canine supplement, so we give them a — that’s got spirulina, ketones and a few other things. We give them that, creatine monohydrate.
Tim Ferriss: Hold on, I can’t skip over that. Why give ketones to your dogs?
Dr. Dominic D’Agostino: Yeah. Well, the brain-boosting effects, the anti-inflammatory effects, the neuroprotective effects, and the anti-cancer effects, so these are all things I worry about with my dog. They are fixed. I do give them a SARM, surprisingly, after they got injured.
Tim Ferriss: This is an anabolic, right?
Dr. Dominic D’Agostino: I do, yeah. I transitioned. They got attacked by a big pit bull and they kind of immobilized for a while. I was going to use it for a cancer cachexia study, and it’s ostarine, I think. So I started giving it to them and it seems like they are leaner, stronger. We have a Great Dane that’s 12 years old. That makes him 90 to 100 human years, and he runs 35 miles per hour. He has no sign of slowing down.
Tim Ferriss: What?
Dr. Dominic D’Agostino: Yeah, he’s a Great Dane that should have passed away years ago and he’s just like a machine.
Tim Ferriss: You mentioned Audacious Nutrition. Just for the purposes of transparency, you do have family in the business involved with Audacious, right? Just to confirm?
Dr. Dominic D’Agostino: Yeah, I can’t have any company. I don’t sell anything personally, but my wife decided to create a product that used the ketones that we actually used in research. So it evolved out of that was various salts, and the idea was that if that product was created, then we can use it for research. And that was the initial part.
Tim Ferriss: Cool.
Dr. Dominic D’Agostino: I was using it anyway. I was like, “Well, why don’t you just make a product out of this? I can’t do it.” But it actually was an I-Corps NSF program through the university that got that started.
Tim Ferriss: Question, do you give rapamycin to your dogs or to yourself. Do you currently take or give your dogs rapamycin?
Dr. Dominic D’Agostino: I’ve gone back and forth. I follow Matt Kaeberlein’s work pretty closely and go back and forth. I’ve decided not to just because of the immune suppression. I know I got about a handful of people that use it, and I would say half of them get sores in the mouth. That can’t be a good thing.
Tim Ferriss: That’s super, super common, the mouth sores.
Dr. Dominic D’Agostino: Yeah. The data’s too early for that. I think the same thing can be achieved in a greater — a bigger lever would be sardine fasting for one thing and just beta-hydroxybutyrate and well-formulated low-carb supplemented ketogenic diet, by definition, a diet that elevates ketones and exercise, so exercise and a whole host of other lifestyle things. I’m not ready to pull the rapamycin trigger on my — anything I do with my dogs, excluding the SARM, I haven’t used that, but seeing the effects and looking at their blood work, it looks perfect. So there are no side effects with that and it seems to be helping with their advanced age.
Tim Ferriss: Can you take just a paragraph, explain what this SARM refers to for people?
Dr. Dominic D’Agostino: Yeah, there’s a specific androgen receptor modulator that hits the androgen receptor but doesn’t have the androgenic-like qualities.
Tim Ferriss: It’s not going to give you a third Adam’s apple, but it’ll help with muscle growth.
Dr. Dominic D’Agostino: It helps to stimulate skeletal muscle protein synthesis, and then the context of this drug also bone metabolism. Both of our male dogs are fixed too. We have discussions with various vets that are of the opinion — they’re more progressive that your dog should be on like TRT or testosterone if they’re fixed, because that will increase the quality of their life, especially as they age. Our dog look — I can’t detect any loss of skeletal muscle mass even when I look at pictures —
Tim Ferriss: For clarity, your dogs are all male?
Dr. Dominic D’Agostino: Yeah, we have two male dogs and both of them are considered advanced age, and the black Lab is showing it a little bit. He has hardware in his two back legs. We had two knees put in with him, but he was a little bit heavier and now we’ve dropped his weight with what I feed him now, which is essentially fish, meat, eggs, ketones, and we give him a mushroom supplement. That’s a mushroom kind of lion’s mane and a reishi, maybe cordyceps and a few other things, and then I give them creatine monohydrate. Yeah, they’re pretty optimized as dogs. I think the big thing is that we live on a farm and they get a lot of activity too. They get two non-negotiable walks every day. I do that for me too. That’s part of my creative downtime is to do a non-negotiable walk morning and night. So they get a lot of that and they chase our animals around too.
Tim Ferriss: What are your current feelings on — let’s just say on the sardine fast, when you’re doing a week-long sardine fast, and maybe you’re so adapted at this point that you don’t experience this, but certainly when I’ve done water fasts, and even if I’m following a lower calorie ketogenic diet, I can have a really tough time sleeping, at least for a handful of days, right? I have just rapid heart rate. I don’t know if that’s trying to compensate for lower blood pressure because I’m just losing so much water and electrolytes. Who knows? I have found supplemental electrolytes to help a bit with that. But what type of supplementation do you take or advise people take if they are trying a ketogenic diet for the first time or fasting? Maybe the answers are different. Let’s just say it’s a sardine fast like, man, Valter Longo coming for you with a sardine fast. What supplementation makes this easier or more productive just from an adaptation perspective?
Dr. Dominic D’Agostino: Yeah, I will use sardines and also KetoStart, which is essentially the electric sodium, potassium, calcium, magnesium, beta-hydroxybutyrate and that will be used two to three times per day. At nighttime, when you go with a caloric deficit, your sympathetic nervous system is activated a little bit, especially with the water-only fast, so you get a little bit hyper or dysphoric even for some people.
Tim Ferriss: Yeah, I feel like you just ran up three flights of stairs when you’re trying to go to sleep. Yeah, it’s unpleasant.
Dr. Dominic D’Agostino: Yeah. Yeah. So that’s less with a sardine fasting instead of zero calories. So the sardines would then be eaten at nighttime typically. I remember doing this repeatedly, and what I would do is take a little bit of GABA at night, and on one or two fasts I took just 25 milligrams of diphenhydramine.
Tim Ferriss: I think that’s the exact or close to the exact dose of one or two Benadryl, right? I’d have to look at it, but isn’t diphenhydramine Benadryl?
Dr. Dominic D’Agostino: Yeah, diphenhydramine is — yeah, it’s a histamine. It’s tends to be lipophilic, which means when you take diphenhydramine, it quickly crosses the blood-brain barrier. You could be a little bit groggy the next morning. The studies show that 50 milligrams of diphenhydramine can decrease memory recall if taken acutely, but 25 milligrams, there’s no effect of that. I’m comfortable with taking 25 milligrams of diphenhydramine at night and then giving a lecture the next day in the morning. I feel razor sharp and because also it enhances — it reduces sleep latency, so I get better sleep, but I would not use it more than once a month or something. Yeah, I do think diphenhydramine and these over-the-counter sleep aids used every night by various people that are emailing me, I mean, it’s creating dementia, I think. I mean, the data’s pretty clear on that. You have an older person getting 50 milligrams every night, every week is bad.
So melatonin, magnesium, a small dose, I guess for my size, it would be a half dose of diphenhydramine, and then GABA. So you could take GABA in the form of GABA that you can get over the counter, or there’s also phenibut GABA, which I have but tend to haven’t used in a while.
Phenibut I would just want to put out there can be a really nasty drug for people. It could be addictive. You build a tolerance real fast, and coming off of phenibut can be very problematic for people. I mean, it’s like coming off of GHB, I think, but it could be a tool in the toolbox because — I mean, we’re talking about taking two, three grams of phenibut can give you euphoria.
It’s like a benzodiazepine, kind of, but if you take 250 milligrams or 200 milligrams of phenibut, which is a small dose — I mean, theoretically, you could take that two or three times per week and never really build a tolerance or get, but I would not advise people to do that. But if you’re going to fast, say, once a month, one way to avert that, and I get the same exact thing, I get super hyper and my brain just goes on fire when I do the first day of fasting, a little bit of GABA or phenibut, diphenhydramine, magnesium. I’ve always done melatonin, five to 10 milligrams of melatonin.
Tim Ferriss: Oh, that’s a solid dose.
Dr. Dominic D’Agostino: Yeah, we went on vacation and I forgot it.
Tim Ferriss: Do you still use melatonin continually? Because I remember there was some conversation floating around the ether and never looked too closely into it because I don’t use melatonin all the time about some possibility of endocrine disruption, or can you speak to that?
Dr. Dominic D’Agostino: Yeah, I’ve been using melatonin probably when I started using creatine in 1993, the old phosphagen when I was in high school.
Tim Ferriss: Back in the day.
Dr. Dominic D’Agostino: Yeah. Yeah.
Tim Ferriss: Yeah. EAS is that way back in the day?
Dr. Dominic D’Agostino: I was a beta tester for that. Yeah, I was a beta tester when phosphagen came out. Then 1993, I think I started using creatine. I was an early adopter of creatine. But to get to your question in melatonin, I studied melatonin on the hippocampus on brain slices. You can slice the brain like a piece of bread and applied melatonin, looked at reactive oxygen species and things like that. We used it for oxygen toxicity. It wasn’t good for that because it did make the rats sleepy. Melatonin doesn’t really make me sleepy, it makes me more calm than anything else. I went on a vacation where I forgot melatonin and I slept like a baby probably because I was up every morning. The sun is the ultimate circadian synchronizer. I got off of melatonin to check my endogenous melatonin, and there was no suppression. Melatonin in animals that are hibernating, like little gerbils and things like that, if you give them melatonin, it can suppress endocrine function including testosterone production.
Huberman talked about it. I love Huberman. So I was following him and he was talking about melatonin. So I went to the primary literature and I was like, “Man, he’s right. It is an endocrine disruptor and suppressor.” But then I dug into the literature more and it was not the case for humans. So there was no evidence in human. I think when he talks about it, I don’t think he references a human study, but he does reference legit studies. Yeah, Andrew Huberman is an amazing scientist and he puts out awesome information out there, but it did get me concerned about it. So I got off of melatonin, and then I confirmed that my body does make normal amounts of melatonin, so I measured that. I also confirmed that five milligrams of melatonin, if I go and measure the next day, my melatonin is off the charts, meaning that I take five milligrams at night, the next day in the morning at nine o’clock or 10 o’clock in the morning, my melatonin is super physiological.
Tim Ferriss: Is that good or bad?
Dr. Dominic D’Agostino: I think it’s good. So I take melatonin not to sleep, but as a neuroprotective agent that has a whole host of beneficial effects for the brain, also Alzheimer’s disease and also cancer, especially breast cancer. So, use it for that. I also mega-dosed 20 or 30 milligrams and then checked my LH and FSH.
Tim Ferriss: Milligrams?
Dr. Dominic D’Agostino: Yeah.
Tim Ferriss: Okay. Yeah. 20 to 30 milligrams.
Dr. Dominic D’Agostino: 10 milligram tablets are like the gorilla tablets for melatonin. So I chewed a bunch of them and then held it under my tongue and I didn’t really feel any more sleepy. I just slept like normal. My aura ring was normal. But then I went and I got lab work done and I did testosterone, LH, FSH, and there was no suppression. Actually, my LH and FSH were trending high end of normal, which is another topic that I can get into. But the thing is that it did not trigger an endocrine response in me. I do not think there’s any data in humans, although specific animals are very sensitive to melatonin, and if you give it to them, it can cause endocrine suppression, some sex hormones. So it is a hormone. Yeah.
Tim Ferriss: Yeah. Okay. All right. Well, that’s good to know because I actually benefit from taking melatonin, but I largely cut it out because of some of the murmurs, but it does help me sleep. Is this a true statement that you do not do any fasting currently or recurrent pure water fasting, but instead do this situational sardine fasting? I mean, is that sort of 99 percent of the bang for the buck and there isn’t really any reason to go beyond something like that as a fast-mimicking diet, or are there benefits that you think are compelling of doing a more restrictive, say, water-only fast where you’re allowed black coffee and a few other things perhaps, but are otherwise really not consuming calories?
Dr. Dominic D’Agostino: For me, personally, it’s very context dependent. I was talking to someone the other day that was getting shingles. As soon as the first sign of tingling, which is the precursor of getting shingles, they start fasting and it never actually surfaces. So only when they situationally pull the trigger and start water-only fasting does it completely mitigate — it’s a massively effective countermeasure for herpes simplex flares or things like that.
Tim Ferriss: Yeah, I was going to ask, I don’t know anything about shingles, so what’s happening there? Do endogenous ketones, and therefore, could you just take a bunch of shots of exogenous ketones, or what’s actually happening to have that suppression?
Dr. Dominic D’Agostino: I think we’re augmenting metabolic control of immune regulation in the context. You have the innate immune system, which is always kind of running around. Then research work we’re doing now with the Moffitt Cancer Center is basically using ketone metabolic therapy to augment the adaptive immune system. So the adaptive immune system is more specific. It’s kind of like that B-cell and T-cell, augmenting the B-cell and T-cell, things where it’s like the adaptive immune system is like the Navy SEALs of — there was a human study that used a vegan diet versus a ketogenic diet, and this got put on my radar by numerous people who then wanted to research this. A vegan diet actually augments and enhances the innate immune system and a two-week ketogenic diet, and this was published in Nature Medicine, augmented the adaptive immune system and partly through the gut and partly just through changing metabolic physiology. This happens when we fast. If we’re fasting, our gut is relaxing. I think it’s restoring or preventing. When we eat something, we have things going into circulation that’s keeping our immune system kind of active, right? So if we’re not eating anything, our immune system becomes hypervigilant and then in a way that it becomes hypervigilant to attack things, but at the same time, it’s suppressed.
So inflammatory markers go down and because the immune system is like an army, you have a hundred thousand guys in an army in the immune system and they’re all working if you’re eating and you’re stressed and environmental toxins and things like that. When we fast, we allocate more of that immune system to be more vigilant to attack things. But at the same time, our general inflammation state goes down. It becomes more vigilant, but inflammatory cytokines, chemokines kind of go down.
So I think that’s part of it in that it’s stimulating, I think cancer-specific immunity but also just generally suppressing inflammation. And that’s happening for a number of different reasons. In part due to elevating beta-hydroxybutyrate, which is an endogenous metabolite that plays a role in inflammasome suppression.
So I know guys, maybe Eric Verdin and like the guys at the Buck Institute, they had kind of looking at that. And then our colleagues, Dr. Deep Dixit at Yale, sort of formulated a diet to specifically elevate BHB because he had showed previously that fasting suppresses the NLRP3 inflammasome and the metabolite that’s off the charts with beta hydroxybutyrate. So the next study was giving that as a supplement with a normal diet to see if that could then also suppress the inflammasome and it did. And that was published in Nature Medicine, 2015.
So I formulated the diet for that study and I’m a middle author on that. So I think that plays a role in that. But I think it’s multifactorial and I think it’s just one of these things that needs to be studied because it’s kind of universally accepted. It’s kind of happening, but you also have to be in a good, healthy state.
If your nutritional status is low, it depends on your baseline characteristics, your therapeutic response to fasting, and I think that’s really important, especially for people who have cancer, maybe getting chemotherapy where they have compromised nutritional state in some ways, then you have to approach it very cautiously.
Tim Ferriss: How many meals per day do you eat now? How old are you, Dom, at this point?
Dr. Dominic D’Agostino: 50s. Yeah. I just turned —
Tim Ferriss: Yeah. 50s.
Dr. Dominic D’Agostino: In my 50s. Yeah.
Tim Ferriss: All right. Well, congrats. What does your diet look like now? Just kind of the set it and forget it version of Dom’s diet. What does that look like?
Dr. Dominic D’Agostino: Yeah. It’s situational, but always probably three meals per day that I do and I did —
Tim Ferriss: And you weigh about how much at this point?
Dr. Dominic D’Agostino: I just did a DEXA this weekend, actually. I did a DEXA two weeks ago and I did another one after I got off creatine and then did another one. So I just hover right at 218 to 220 and body fat last was 9.4 so —
Tim Ferriss: Yeah. You got some muscle to feed. All right. So three meals a day. What does it look like?
Dr. Dominic D’Agostino: This morning it was eggs and chub mackerel and that’s it. So basically just protein and fat. And for lunch, I typically have beef, chicken, or fish, usually fish. Lately I’ve been eating a David bar. So Peter sent me some of those and I have kind of mixed opinions about it. It pops up on the CGM a little bit, but I think it’s kind of an interesting direction to go into. I enjoy them, they taste really good. So I’ve been doing that.
And then for dinner, we went out for Mexican the other night and last night hosted Mary Newport and usually have beef, chicken, or fish with a vegetable, like always broccoli. I’m a huge fan of broccoli. It worked. I could eat three pounds of broccoli has no gas or bloating effect for me at all. So somehow my body is just broccoli. My body loves broccoli, so our dogs do too. So I give them a little bit of that, salads, but usually about a pound of beef, chicken, or fish at dinner. So that’s my big meal.
Tim Ferriss: Wow.
Dr. Dominic D’Agostino: And over the years we have transitioned. Instead of eating at 7:00, we eat at 5:00 — 5:00 or 5:30, so we eat earlier. And then I do physical activity after that. So if it’s squats or deadlifts, I have to do it before I eat. But for pressing movements and activity, I do after that. And I do farm work for an hour or two in the evening after that.
And I typically have, every other night, wine. So I’ll have a bit of wine, lower alcohol, non-sugar Dry Farm wines, which has less than one gram of sugar. I would never drink wine without doing some kind of activity after. If wine at nine o’clock and then try to go to bed, I would never do that because I see that on my aura. But if I do a glass of wine in some form of physical activity, we always do an evening walk. I think I sleep better, I think.
I don’t do two glasses, but I just do one glass. I know the current consensus on alcohol is that it’s — but I would push back because none of that is specifically studying wine. If you go to the studies on wine, actually, shows once, the first one that came up is actually decreasing cancer risk.
And then I noticed that when I take wine and measure my blood, it’s less viscous. So wine also decreases platelet aggregation. So it makes your blood less viscous. And that is well known. I observed it and was like, “Something’s going on here.” And then I went to PubMed and it’s actually well known. I didn’t know it at the time that it decreases platelet aggregation, so less potential for clotting, for stroke and things like that.
So I think that may factor into — we just got back from Greece and they had the ouzo and everything, then we went to Sardinia. So we went to these blue zones and they just, at night after their dinner, the males will do a shot of alcohol, usually wine, but sometimes ouzo and they’re all in their 90s and hundreds, they’re in the blue zone. So it’s a universal characteristic. That’s my protocol.
Tim Ferriss: Well, there may be a genetic component too. I remember there was this book that was like, Why French Women Don’t Get Fat or something and way back in the day, I remember before his passing, I was talking to Charles Poliquin, he’s like, “Yeah, MTHFR.” He is like, “That’s why. It’s none of the other stuff in the book.” And he mentioned a couple of other things, like, who knows? I think —
Dr. Dominic D’Agostino: Yeah. Living by the water, activity, and social. So the social interaction is probably the biggest lever. I mean, I just see them, they’re all out and about walking around and yeah, that’s probably the biggest lever. And getting sun. So they’re outside in the sun, everybody, it’s multifactorial, but it doesn’t seem to be hurting them, let’s put it that way.
Tim Ferriss: If someone is, let’s just say they want to test out the ketogenic diet, and certainly they will note, they’ll be like, “Wow. Dom doesn’t eat a lot of vegetables except for a pound of broccoli at dinner — “
Dr. Dominic D’Agostino: I can tolerate that but I have, probably it comes out to 30 to 40 grams of fiber a day, which is pretty high, but that’s broccoli. And I usually have a small apple too. Sometimes we have apples and then a cup of wild blueberries. So it comes out to about 30 grams. That’s maybe a higher, sometimes 10 or 20 but I try to shoot for about 30 grams of fiber.
Tim Ferriss: Yeah. Got it. Okay. If people want to kickstart the ketogenic diet, any tips for getting over the hump in the beginning? It can sometimes have a bit of a hard time before they kind of click over. I’m not sure. For me, it’s like once I’m above 1.2 millimolar I feel totally fine. That’s just me on a Precision Xtra. But for people who are looking to give it a shot and maybe haven’t given it a shot, any tips for novices?
Dr. Dominic D’Agostino: Yeah. I would do fasted low-intensity cardio. For me, that would just be going for a long walk. Waking up in the morning, and if you’re going to start your ketosis experiment or whatever you’re doing that morning, getting out in the sun, staying well hydrated, you could take MCT and also ketone electrolytes like KetoStart or something like that. And then that will ease the transition because it takes a little while for your ketogenesis to ramp up due to you got to deplete liver glycogen and ramp up beta oxidation fat enzymes.
And then as ketones get into circulation, over the period of a couple weeks, you’re going to upregulate the ketolytic enzymes, which are basically the enzymes and the tissues that are able to utilize and leverage those ketones for energy over time.
Tim Ferriss: How long does that adaptation take, would you say?
Dr. Dominic D’Agostino: I don’t know if anyone has unambiguously answered this question in humans, but in rodent models you could see the MCT transporter, not to be confused with MCT oil, but the monocarboxylic acid transporter, now there’s one, two, three and four. That protein is 50 percent higher after two weeks in a rat, for example.
I think the point for most people is that if you start fasting or ketogenic diet and to avert the keto flu, you want to hydrate, get in electrolytes and also elevate ketones as much as possible. And to do that with MCT, if you can tolerate it or ketone electrolytes. I would not be guzzling a ketone ester because you’re going to spike ketones up, you’re going to inhibit your own ketone production, especially if it’s a dose-dependent thing. But my advice would be low intensity cardio, hydrate electrolytes, and then small amounts of ketone electrolytes with MCT. So MCT will stimulate your own Ketone production too so it kind of —
Tim Ferriss: Yeah. Now are you just taking tablespoons of liquid MCT? Are you using a powder and mixing it in? What do you personally do or what would you recommend?
Dr. Dominic D’Agostino: For the liquid, sometimes what I do if I’m eating tuna fish, which is packed in water. I’ll pour the MCT on the tuna fish and stir it up and then deliver it that way. If I’m having coffee, I can put in the MCT powder in the coffee and mix that up and that would be 10, 20 upwards of 30 grams and work by Stephen Cunnane actually showed that if you take MCT in the context of caffeine or coffee, you can boost your ketone production by 20 or 30 percent. So there’s a bit of a ketogenic synergy when you deliver caffeine with MCT. It’s stimulating lipolysis and also fat oxidation in the liver so you’re ramping out —
Tim Ferriss: What type of powder do you like to use?
Dr. Dominic D’Agostino: People send me things but actually the powder that I have is actually, it’s Keto Brainz. It’s MCT powder, Alpha GPC theanine, and it has lion’s mane mushroom. So it goes under the brand name of Keto Brainz, and that’s the MCT powder that I use. The base of it is MCT, but then it has sprinkled onto that theanine, which has a nice calming effect, which probably good to use on the first day of fasting. Alpha GPC, if I take too much of it gives me a headache so I only do one or two.
Tim Ferriss: Yeah. I got to be careful with Alpha GPC. I also get a headache.
Dr. Dominic D’Agostino: Yeah. Oh, really? Okay.
Tim Ferriss: Yeah.
Dr. Dominic D’Agostino: So you’re the first one. I don’t know if I was creepy. But yeah, when I first got Alpha, when I first got Keto Brainz and did like six scoops and I was like, “Oh, my God. I got to have a bad headache.” But one or two scoops.
Tim Ferriss: I love that your first go was six scoops. If I just want it off the shelf, MCT oil, because I feel like there’s only so many medicinal mushrooms that I can cram into my diet also, but no offense to the mushrooms, but I actually have some interesting thought on some of them additional mushrooms. Some of them are very strongly antiviral and immunomodulatory. And so when I’ve talked to a number of very credible mycologists, so like, “Yeah. It’s probably best not to take that stuff every day. You should cycle on and off.”
Dr. Dominic D’Agostino: Yeah.
Tim Ferriss: But if I just wanted MCT, for purposes of travel, because MCT liquid can create such a goddamn mess when you’re traveling.
Dr. Dominic D’Agostino: And their pants too. Yeah.
Tim Ferriss: And in your pants too. And for people who are novices do not do creatine, caffeine and MCT oil out of the gate. You’ve got to prove to yourself that you can handle that.
Dr. Dominic D’Agostino: Unless you’re constipated.
Tim Ferriss: It depends on the airplane. Yeah. What other just MCT oil, powders might you recommend or have you used?
Dr. Dominic D’Agostino: Quest MCT powder. I think you can get that in like CVS and Walgreens now too. And Amazon, just the Nutricost. So I bought just straight up MCT. They also have a C8 powder and I’ve tested both of them wearing a continuous ketone monitor. And I saw a nice elevation over time and then I combined that MCT powder with KetoStart, and basically I was in ketosis for half the day. So just dosing twice a day with that.
Tim Ferriss: I mean, I’m going to break my own rules here, but I’ve done enough test drives. I’m about to go to, not super high altitude, but I’ll be coming from sea level to about 8,000 feet on average and we’re going to be doing a lot of intense exercise. So maybe my morning dose of coffee, which I’m sure will be some shit instant coffee, but it’s going to taste delicious when you’ve been freezing your balls off all night, maybe I’ll add some KetoStart and MCT powder to that because those would be easy to travel with I would imagine.
Dr. Dominic D’Agostino: Super easy. Yeah.
Tim Ferriss: I’m not sure how KetoStart tastes in coffee.
Dr. Dominic D’Agostino: No. No. Don’t do that. No. They have KetoSpike coffee. So Audacious Nutrition has KetoSpike cocoa, coffee and tea. So in the afternoon I don’t do caffeine after 12:00. So I will brew. I’ll just boil hot water and just put, and the KetoSpike coffee is a good Colombian coffee and it just has the BHB electrolytes in it. So I’ve been doing that.
Tim Ferriss: Yeah. All right. Cool. I’ll check it out. I’m just trying to figure out, because I went back through all of our conversations, which covers a lot of technical detail as you would imagine. And I’m just wondering what you are most excited about. And right now, I mean, just to volunteer this. I’m very interested in neuroinflammation and the inflammasome, the interplay with the microbiome and how the microbiome can seemingly influence or mediate some of, for instance, the anti-seizure effects of the ketogenic diet. If you get rid of Akkermansia or a few other strains.
Dr. Dominic D’Agostino: Yeah. Yeah.
Tim Ferriss: Lo and behold, doesn’t really work. And I’m wondering if that applies to other, say, conditions that metabolic psychiatry might be applied for, like schizophrenia and others, I don’t know, but seems interesting as a question. What types of questions or projects or realizations, findings, anything have captured your interest or excitement these days?
Dr. Dominic D’Agostino: Yeah. I think just quickly go down the list. Ketone metabolic therapy for cancer, so is one. And we have a pretty comprehensive review that describes the framework for ketone metabolic therapy for glioblastoma, which is a cancer that’s largely resistant to the standard of care. So way much to talk about. It was actually like a 200 plus page paper that was going to be submitted. And we had to basically put a lot of data and things as supplementary figures.
I think there’s like six supplementary figures that tell specifically all the different metabolic drugs that target glucose, glutamine, GKI calculator and a lot of things. So yeah, just Google ketone metabolic therapy framework for glioblastoma and its open access. So that has stimulated research at different places. But I’m excited about research that we’re doing with Moffitt Cancer Center, which is the largest cancer center.
We’re one of the largest in Florida, a tier one cancer center where we’ve got various projects, glioblastoma, maybe a breast cancer, but also lung cancer. So was specifically using ketone metabolic therapy to augment immune therapy, specifically the checkpoint inhibitors. And that has to do with what I described about ketone metabolic therapy, specifically beta hydroxybutyrate activating the adaptive immune system and making checkpoint inhibitors, which is a class of drug that’s, and CAR T therapy.
So now they actually have a study with CAR T therapy and checkpoint inhibitors. So ketones tend to expand the T-cells that are associated with CAR T therapy. So just kind of enhancing that therapy. And with the checkpoint inhibitors, it tends to just enhance cancer specific immunity that is augmented by PD1 inhibitors. So they’re specifically studying that.
So I’m excited about that. So that’s on the cancer front. And then we can jump, if you have no questions, I could jump to other, the Alzheimer’s, the metabolic psychiatry.
Tim Ferriss: Let’s talk, yeah, let’s talk about those. Let’s hop to the Alzheimer’s and metabolic psychiatry. Would love to dive into that because it’s in front of mind for me. And just as a, I’m not sure if I made this clear, doing the couple weeks of strict ketosis, segueing to a sort of 16/8 ketogenic diet and then moving to kind of a paleo-ish diet has produced some of the best labs I’ve ever had and also the best oral glucose tolerance test that I’ve ever logged.
And from a mood stability standpoint, and I am also for at least the last few weeks, supplementing with the monoester and a diester, the sort of Q-I-T-O-N-E. But all of those things combined, I’ve got to say, psychologically from the standpoint of sustained focus and mood, has been just kind of mind-blowing, to be honest. So I’d love to hear any and all thoughts on Alzheimer’s metabolic psychiatry front.
Dr. Dominic D’Agostino: Yeah. So metabolic psychiatry, I would encourage people to listen to Chris Palmer who you, I kind of put on your radar. I don’t know if you remember. I sent you the link to the metabolic —
Tim Ferriss: Yeah. Yeah. Yeah. Appreciate that.
Dr. Dominic D’Agostino: So I was like, “You’ve got to watch this, Tim. It’s going to change sort of the landscape of psychiatry.”
Tim Ferriss: Yeah. I remember that was a recording from a conference, I believe, where he was interviewing one of his patients on stage. Yeah.. I remember that.
Dr. Dominic D’Agostino: The Metabolic Health Summit, which is part of Metabolic Health Institute, which is you can get educational credits through that. So yeah. We brought Chris in and it was such a compelling story and he treated Matt Baszucki. So Matt Baszucki is the son of Jan and David Baszucki, because he quickly went into durable remission.
Tim Ferriss: Who are well-known from Roblox.
Dr. Dominic D’Agostino: Well-known from Roblox. Yeah. Sort of billionaire philanthropists that are changing, actually, ultimately maybe the standard of care for psychiatry. And I think they single-handedly are funding metabolic psychiatry with Shebani Sethi, she’s at Stanford, Chris Palmer at Harvard, and I work with them closely as an advisor. There’s at least a dozen other institutes that are doing metabolic psychiatry research for schizophrenia, bipolar, major depression, anorexia nervosa, which is a psychiatric disorder that kills more people than any other disorder and a range of different things and anxiety disorders and alcohol use disorders, alcohol withdrawal syndrome. So they’re doing research on that.
So with metabolic psychiatry, there’s a lot of pilot studies, mostly bipolar, looking at a range of different things, ADHD too. And then there’s apps that are emerging like MetPsy, metpsy.com. That’s a collaboration with Dr. Ally Houston, he’s at Oxford and Georgia Ede who might be good to have on the show. She’s from Harvard psychiatrist. So that app is more of a comprehensive app that incorporates ketogenic therapy, but also lifestyle stuff and then coaching. So metabolic therapy coaching for mental health.
Tim Ferriss: How do you spell the name of the app?
Dr. Dominic D’Agostino: MetPsy is M-E-T-P-S-Y, right? M-E-T-P — I’m trying to think.
Tim Ferriss: Yeah. Better at the science than the branding, I guess.
Dr. Dominic D’Agostino: Yeah. M-E-T-P-S-Y.com, MetPsy. So I think they have their website up. So they’re basically in their onboarding phase. So they should go live pretty soon. But I’d like to add that the Baszuckis, I remember that they’re funding a big study at Oxford right now and the Baszuckis will match dollar for dollar any donation and spearheading sort of that. Using the app and using ketogenic therapies in combination with lifestyle therapies too.
So metabolic psychiatry is rapidly emerging in a number, and this ties into work we did. I guess my wife did. I was on the paper but she ran the study. We were doing seizure studies with exogenous ketones, and the most efficacious one for this application was the racemic ketone salts in the MCT. We were gavaging them and she was —
Tim Ferriss: What does gavage mean?
Dr. Dominic D’Agostino: Oh, so it’s basically like tube feeding the animal. So instead of mixing the ketones in with the rat chow, they eat it. And so it’s taking a syringe and based on the weight of the animal, you pull in the amount of ketone ester or this case, it was MCT and ketone salts. We did the esters too, and it did have an anxiolytic effect, anxiety reducing effect.
And then you administer that to the animal and what we are doing is we do seizure studies, put them inside a hyperbaric chamber and we go two to three times more normal and it induces a seizure. But what we observed when we put the animals in ketosis is that instead of them trying to bite us and kill us and not wanting to be held, they were very chill and calm.
So it was just, “Well, this is great. We can handle the animals easier and get them into the chamber without them trying to bite us.” And my wife’s a behavioral neuroscientist and she was like, “Well, we should do some behavioral studies because I think there’s something here.” So we did elevated plus maze. So in this case, the animals can go inside a closed little cave or it can come out into the open arm in the elevated plus maze, which is exploratory behavior. They’re more extroverted if they come out and more introverted and kind of like their fear response if they go into the cave.
So we got results that we published. The title is like “Anxiolytic Effect of Ketone Supplementation.” We published I think three papers and showed the mechanisms and stuff too. So that was an early paper over 10 years ago, just basically showing that inducing acute ketosis with this formulation and doing the elevated plus maze produces an effect that was analogous to a dose of benzodiazepine.
Like if you look at, I don’t know, Xanax or other things in elevated plus maze, it was like, yeah, 20 or 30 percent more time in the open arm. So they’re less fearful to be in environment and making them more like a social lubricant, maybe like Benzo or something. So it had that effect in the animals.
And when we look at the blood work and even take out the hippocampus in the brain, the levels of GABA to glutamate are higher. And then in another study we did with Angelman syndrome, we looked at the mechanism of that and there’s an enzyme called glutamic acid decarboxylase, and a lot of anti-seizure drugs kind of target that.
So the protein levels were higher, essentially showing that your brain converts more glutamate, which is anxiety evoking, like wakefulness enzyme. It’s converting more glutamate, which is excitatory to GABA, which is brain stabilizing. That’s like your chill, like alcohol.
Tim Ferriss: It’s what you take before bed. Yeah.
Dr. Dominic D’Agostino: Yeah. Yeah. So that was, and a variety of different studies, we also looked at adenosine receptor signaling. That’s a little bit more complicated to describe, but there’s a number of different effects contributing to that. So there’s a clear rationale, I think, for depression. If you do an FTG PET scan on someone that’s depressed, it shows glucose type of metabolism.
One thing to mention, I think an important thing to mention in the context of bipolar, you can have a hyper glycolytic effect. And Dr. Iain Campbell from Edinburgh University has published some elegant reviews and is doing some work on that front in describing the research there. But I think it’s important because some of the feedback coming out, and I think you even mentioned too, when ketones get really high, what we observed, if ketones get too high, that can cause an anxiogenic effect.
Tim Ferriss: Yeah. Get more anxious.
Dr. Dominic D’Agostino: A sweet spot, maybe one to two. I wouldn’t go above three, probably 1.5 to 2 millimolar range. That seems to be a level of ketones that safely does not produce a metabolic acidosis. So what we do see that when you get above three, it starts to change blood pH.
So it seems to maybe overwhelm the respiratory and renal compensation and your kidneys put out by carb and then there’s respiratory and renal compensation that regulates your blood pH. But the animals that succumb to ketoacidosis and died from the ketone esters that we gave them in early studies had to do with that acidification of the blood.
So it was just an overwhelming, so ketones are acidic and when you deliver it into an ester form, there’s nothing to buffer that. When you give a ketone salt, the electrolytes are kind of like a buffer for that.
So you have the metabolic effect, you have the changing of the brain neuropharmacology, and in bipolar, you throw anti-epileptic drugs at bipolar patients, and it’s largely ineffective. So it makes sense that a ketogenic therapy would work for that.
And the neuroinflammation too. So things that trigger neuroinflammation, and that could be an infectious agent, that could be a virus, that could be T. Gandhi. I mean, it could be like a bacteria. There’s various things that could cause psychiatric disorders. Various infectious agents create that neuroinflammation. So I think neuroinflammation, and then when someone has a seizure too, the inflammatory state of the brain gets much higher.
So I think ketogenic therapies are working through multiple mechanisms, more or less in synergy to produce that. It’s not one mechanism. When we published the NLRP3, I got requests from Genentech and various pharmaceutical companies to go there and give a talk on the mechanism so they could drugify. And I would throw up a big flow chart of all these mechanisms, and I think they would get frustrated. And it was like, “Well, tell us the mechanism so we can make a drug out of this.”
But I think the beauty of ketogenic therapies is that it’s pleiotropic, right? Which means it’s many mechanisms working in synergy. You could say Metformin, GLP1 drugs are working through metabolism, and they’re kind of pleiotropic also.
Tim Ferriss: Do you use either of those?
Dr. Dominic D’Agostino: I’ve experimented with metformin, and that is a way for some patients to increase their ketone levels. So we’ve published on metformin from the context of that it increases mitochondrial oxidative stress, so it’s a weak toxin to deliver. Most people didn’t know that when we were studying that. And I think metformin can enhance, increase AMP kinase, maybe increase insulin sensitivity and has a very weak effect at reducing blood glucose if you have a normal glucose. But it does tend to increase ketones a little bit.
And I think there’s about 150 studies on clinicaltrials.gov right now on metformin, as a means to augment cancer therapy. So I think that could be a tool in the toolbox for some people. When I take it, and I do really intense — if I do an intense workout, I felt sick. An issue with metformin is it could produce lactic acidosis. It’s producing lactic acidosis because it’s a weak — it is a toxin to the liver, so it’s de-energizing the liver. But also when I took it up to two grams per day, I had a photosensitivity. So when I went outside, the sun gave me a rash.
Tim Ferriss: You mentioned on your wrists.
Dr. Dominic D’Agostino: Yeah.
Tim Ferriss: Am I making that up? Yeah.
Dr. Dominic D’Agostino: Yeah, it tended to correlate with that. And then I got off of it. Then I experimented with it again and it tended to be — at the begin — I’m in Florida and it was May. It’s like when the sun’s really starting to crank. Then I just go outside all day and it’s like, “Where is this rash coming from?” So it’s a photosensitivity reaction that I got and that concerns me. So I have it, but I don’t use it.
Tim Ferriss: May I ask you a quick question just related to metformin for a second?
Dr. Dominic D’Agostino: Mm-hmm.
Tim Ferriss: Is I was looking back on notes on prior conversations, and I think you mentioned Dale Bredesen on an episode of STEM-Talk. But specifically, for folks with the APOE4 genotype, like yours truly, do you think metformin may be more interesting? But let’s assume in my case, let’s call me metabolically healthy. So maybe yes, maybe no. I remember a long time ago having a chat with Nav Chandel, I want to say, I might be getting the name slightly wrong, from Northwestern. He was like, “Ah, if you’re doing a bunch of exercise and getting your diet straight,” he’s like, :I don’t think that you’re going to see a lot of benefit.” But he didn’t have the APOE4 information on me. And then berberine I have written down for some reason. I’m just wondering if there’s anything to either of those for APOE4 specifically?
Dr. Dominic D’Agostino: Yeah, berberine is pretty similar to metformin’s glucose lowering effect. So that’s something that you can consider if you don’t want to take metformin. I’m of the opinion that for the general population, eating a standard American diet that is averse to working out and just trying to really modify their diet, metformin I think is a very potentially effective drug for longevity. It’s going to reduce blood glucose, since most people are pre-diabetic, or have type 2 diabetes that are in their 40s, 50s, and 60s. And it will reduce your incidence of cancer, specific kinds of cancers like pancreatic cancer. I think the data’s good on that, and I think it’ll shift metabolic biomarkers that we have historically good data on in the right direction.
Tim Ferriss: Does metformin do anything that taking a GLP-1 like tirzepatide or something doesn’t do? I’m just wondering if it’s an additive effect.
Dr. Dominic D’Agostino: Well, they’re totally different drugs. But people who take metformin and one gram to two gram dose, two grams is high. But when they do that, they tend to eat less calories. So it does create —
Tim Ferriss: I see.
Dr. Dominic D’Agostino: A little bit of, for me, GI issues. Maybe a little bit of loose stools in the beginning, and that could be factoring in there. So it does tend to improve metabolic biomarkers across the board if you’re trending towards metabolic dysregulation or metabolic syndrome. A GLP-1 works essentially through caloric restriction and just increasing appetite through in part, a mild gastroparesis and decreasing gastric emptying time. But also works on the brain, and I think has a wide range of beneficial effects. I think it’s a game-changing drug that’s going to change the whole landscape of metabolic therapies. And I think —
Tim Ferriss: Yeah, seems to have a — from what I’ve read, and maybe I don’t want to over interpret here, but potential neuroprotective effects, right?
Dr. Dominic D’Agostino: Yeah.
Tim Ferriss: So that’s the main reason I would be looking at potentially low-dose GLP-1.
Dr. Dominic D’Agostino: Yeah, I like the low dose. I like that you preface it with low-dose because I think higher doses are not studied enough long-term to avert potential side effects that we don’t know about.
Tim Ferriss: Yeah. And do you take berberine or is it superfluous because of the diet, you don’t really need anything to lower glucose?
Dr. Dominic D’Agostino: Yeah, I’ve experimented with it and it did decrease my glucose in response to a meal. I did dihydroberberine, which is a more potent version of berberine. But interestingly, after about a week, I started to get a headache. And then I got off — I don’t know if it has a vasodilate or maybe it impacts liver metabolism in a way that was — who knows? Maybe decreasing my caffeine metabolism. These are things that come to mind. I am a fast metabolizer of caffeine.
Tim Ferriss: Yeah, you still consume quite a bit of coffee. Yeah?
Dr. Dominic D’Agostino: I do. I fill this up. So this is Metabolic Mind. Actually, Metabolic Mind is part of the Baszucki’s Group metabolic psychiatry. So I have —
Tim Ferriss: All right. So you’re holding up —
Dr. Dominic D’Agostino: I do one of these per day. Yeah.
Tim Ferriss: What is that? That’s like 16 to 20 ounces, something?
Dr. Dominic D’Agostino: 24. I think about 24 ounces.
Tim Ferriss: 24 ounces.
Dr. Dominic D’Agostino: Yeah.
Tim Ferriss: Yeah. Okay. It’s metal. It looks like a thermos, basically.
Dr. Dominic D’Agostino: Yeah.
Tim Ferriss: Okay, got it.
Dr. Dominic D’Agostino: Relatively strong coffee. I do that and pour one cup, and I usually finish it about now and no caffeine. Yeah, caffeine at four or 5:00 p.m. is probably going to disrupt sleep latency and sleep timing. But yeah, GLP-1, amazing class of drug. We’re covering that now at med school in our nutrition courses we’re teaching.
And then the SGLT-2 inhibitors are also a pretty interesting class of drug that I think has a lot of potential. So if someone trying to bring their glucose levels down, for example, trying to get that — these are prescription drugs. So of course, go to your doctor. But that’s a pretty good lever to pull, especially if someone’s resistant to dropping their carbs, if they’re eating some carbs.
Tim Ferriss: Well, yeah.
Dr. Dominic D’Agostino: Yeah, GLP-1 and SGLT-2 are great.
Tim Ferriss: Well, this is also a tool in the toolkit with, let’s just say elderly patients who are — even if they wanted to comply, may not have the mental faculty to comply with ongoing. And you can’t have, necessarily, 24/7 supervision to prevent them from eating bagels. Which maybe you can do. Just all the meds in the morning and then one injection a week or whatever it might be. Do you take any supplements or medications with the explicit goal of mitochondrial health or maybe just the side effect of mitochondrial health?
Dr. Dominic D’Agostino: Yeah. Well, I think ketones shine there. The D, both the D and the L, beta-hydroxybutyrate. So that’s first and foremost. And we are doing research with NAD.
Tim Ferriss: These injectables?
Dr. Dominic D’Agostino: I can’t talk about the research that we’re doing in depth. But we’re working with Metro International Biotech. So they have phase two and phase three trials for Alzheimer’s. So there’s NR, nicotinamide riboside, nicotinamide mononucleotide. So the problem with those is that the liver is pretty greedy and takes a lot of that. And then the muscles are — so a lot of it’s maybe not getting to the brain.
But if people just Google MIB-626, so that’s one of their drug forms of NAD, that’s a stabilized form of NAD. And then they have a whole suite of NAD molecules that most people don’t know about, but are in experimental trials. And we’re doing some of those preclinical animal model work in our labs. So I do think — for certain applications, we didn’t see an effect. But at the same time, they are — for applications like non-alcoholic fatty liver disease, maybe Alzheimer’s, maybe inflammatory disorders, improving. If used for a long period of time, markers of mitochondrial health I think improve. So NAD, people may know NAD is basically a substrate for the sirtuins and various enzymes. There’s 500 different enzymes. So a class of proteins that are called sirtuins rely heavily on NAD. So this is an important thing to consider.
Tim Ferriss: And this sirtuin is just for folks who are like, “Have I heard that before?” I want to say back in the day when resveratrol was everywhere in the news and super mouse and all you have to do is drink wine, but maybe 20 cases of wine. All of that stuff with trans-resveratrol, that’s where the sirtuins popped up?
Dr. Dominic D’Agostino: Yeah.
Tim Ferriss: Yeah.
Dr. Dominic D’Agostino: The sirtuins are really heavily reliant on NAD. And NAD is involved in everything that we study. So five to 600 metabolic enzymes need NAD for fuel. So that’s important to consider. And DNA repair is exclusively tied to NAD levels. So remember I mentioned reductive stress with D-beta-hydroxybutyrate?
Tim Ferriss: Yeah.
Dr. Dominic D’Agostino: Reductive stress means that the NAD to NADH ratio would drop. So you get more NADH relative to NAD. That could be problematic because the availability for NAD may not be there for sirtuins and other — so a redox balance formulation.
Tim Ferriss: I see.
Dr. Dominic D’Agostino: So that feeds back. I don’t want to get too far into that, but I think it’s impacting the redox balance, which is getting us to revisit the various ketogenic formulations and to study this, in cell-based systems, animal models. It’s hard to do in humans. You could do a 31-phosphorus MRS if you have a four or 7-Tesla system like Harvard has. So this is one way to look at like phosphocreatine, ATP, pH, and also NAD to NADH ratios. So this is one way. Actually, we do have that at our Alzheimer’s center, and that’s on the list of to-dos, to look at this reductive kind of stress thing.
So NAD, I’m just throwing that out there. I think there’s a lot of criticism towards NAD now. That happens from time to time. Because moving science from cell-based systems to animal models to humans, there’s a massive learning curve there. We’re learning that with some of the ketogenic agents. We’re just at the cusp of really understanding the dosage, timing, scheduling and form of exogenous ketones that’s optimal. And it’s going to vary dependent upon the situation that you’re trying to treat. And also individually, I think people are going to have. So that opens up this whole personalized precision ketogenic metabolic therapy, or the NIH is throwing a lot of money on personalized medicine based on genetic markers, and based on biomarkers that some of them that you can measure in real time. Like continuous ketone monitoring, continuous glucose, and maybe lactate monitoring.
Tim Ferriss: That’s cool. Yeah, that’s very cool. One last supplement question because I’m looking back at past notes. And I’m probably going to mispronounce this. But idebenone, more observable version of CoQ10. Maybe that’s a fair description. Maybe it isn’t. Do you still take that or no longer?
Dr. Dominic D’Agostino: Yeah, I think CoQ10 is on the short list of five supplements that I would recommend to people. Although I don’t take it, I do get quite a bit from the foods that I eat. I eat a lot of heart, liver, animal products that have CoQ10 in it. But if you’re on a statin, if you’re on metformin and other drugs, they could potentially deplete you. And then CoQ10 has a solid track record for cardiovascular health. So idebenone is a drug stabilized form of that. And then when I discussed that on your podcast, that was in the context of something called the Deanna Protocol. The Deanna Protocol is after Deanna Tedone. She has ALS, she was diagnosed well over a decade ago, was given two or three years to live. She’s alive and well today, we’re just emailing me yesterday. So Deanna Tedone had advanced ALS and then has been stabilized using the Deanna Protocol, which is included at the time, idebenone. But I think it became a drug.
So idebenone became the standard of care for Friedrich’s ataxia, and then you couldn’t get it on Amazon. But I think ubiquinol, or CoQ10, it would be a good substitute for that. And I don’t use it myself. But I think that’s if you’re older in age and you have cardiovascular heart problems in your family. However, with that said, we actually ubiquinol, we did high doses in our animal models, and we saw some kidney toxicity. We had some animals die. And —
Tim Ferriss: Oh, Jesus. It’s like —
Dr. Dominic D’Agostino: But that was rodent models we used. Again, we use really high dose for oxygen toxicity. We’ve looked at everything under the sun. But it was this unexpected side effect. Then I went to the literature and showed that it’s such a powerful antioxidant in some ways, and it maybe was concentrating in the kidneys. So there was a couple of papers came up, and then we think that that’s why the animals may have died. We were using a MitoQ, like various forms that are more mitochondrial specific. We’re using more potent forms of the CoQ10. So it may not be similar to the commercially available forms.
Tim Ferriss: What are the other supplements on that short list? You said four or five supplements. What are the other ones?
Dr. Dominic D’Agostino: That I take. Yeah, so creatine monohydrate would be the staple thing that I’ve used since I was a teenager. First and foremost, exogenous ketones, and the data is emerging on that, I think that’s going to be the next creatine for that. But creatine, for Alzheimer’s disease, we didn’t talk about it. But a dosage of 10 to, even if you’re larger, 20 grams. And that’s not a misspeak there, 20 grams of creatine. Spread out maybe five grams, three to four times a day for advanced Alzheimer’s, if you can tolerate it. [inaudible 02:20:12]
Tim Ferriss: I’m taking 20 grams today just because I didn’t get very good sleep last night. I just find it to help with recovering from, let’s call it sleep deprivation. But yeah, got to watch the split dosing.
Dr. Dominic D’Agostino: Yeah. Vitamin D, but you have to measure that in your lab. So you want that to be — you don’t want it over a hundred, right? So you want vitamin D levels that are probably like 60 to 80, would be a good level of vitamin D and getting that checked. But I think you should check it first. It’s weird. I live in Florida, I get tons of sun. But if I’m not supplementing vitamin D, I trend to be low 30s. It could be trend — but so when I supplement it, I basically stay in the mid-60s to 70s. So vitamin D and melatonin, I think is a great neuroprotective antioxidant supplement to take at nighttime. And I don’t take omega-3 supplements, but just because I did — Rhonda Patrick connected me with the omega-3 guy and I tried the OmegaQuant. My DHA levels and EPA levels were off the charts.
Out of curiosity, I got off of fish for a month or so and it went down to normal ranges. And then I tried Nordic Naturals, which — it was a company that reached out to me and I was like, “Okay, well, I’ll remove omega-3s from my diet and then add it back in with a dose.” And it popped me back up to a level similar to if I’m eating tons of sardines per day. So if you don’t like sardines and you don’t like eating a lot of fish, I think Nordic Naturals is probably one of the go-to brands. I’m not paid to say that or anything, but they’re legit. But you could do the OmegaQuant test. I think there’s so much data on EPA and DHA that I think ultimately, the omega-3 levels will be part of standard blood work. There’s so much data emerging on that, that I think probably within the next 10 years, when you get comprehensive metabolic panel, CBC, DHA, and EPA will probably be added to that.
Tim Ferriss: All right, Dom. Well, we could go for many more hours, I am sure. But let’s start to land the plane for this round. And I do want to ask, of course, if there’s anything else that you’d like to mention or point people to. Anything you’d like to recommend, formal complaints you’d like to lodge? People you’d like to secure in front of a large audience? No, I’m kidding. But anything that you’d like to say or point people to? Any resources, anything that you’re up to, where they can find you? Anything at all?
Dr. Dominic D’Agostino: Yeah, I just want to mention KetoNutrition. That’s our informational website, ketonutrition.org. And we’ve hosted a conference where many people, Dr. Valter Longo, Rhonda Patrick, who’s been the keynote speakers, that’s the Metabolic Health Summit. That’s been the conference, and that is run by Metabolic Health Initiative. So I direct people to Metabolic Health Initiative, and it’s run by three of us. My colleagues, Dr. Angela Poff and Victoria Field run that show. I tag on for the ride.
But that’s an ACCME, accredited medical education platform. So everything that we’re talking about here, we have speakers and we create a medical education platform, so people can learn about metabolic psychiatry. People can learn about metabolic based therapies and metabolic drugs, like GLP-1 drugs and hormone optimization and things like that. So I would mention that. The brand of ketones that I use that I often get asked is Audacious Nutrition KetoStart. So that evolved out of our work with cancer, neurodegeneration and seizures. We’re doing work at Byrd Alzheimer Center on probably 20 or more ketogenic compounds in development that are mostly alcohol-free. So I think all of them are actually. We have some really interesting studies on Alzheimer’s and a lot of other — so hopefully in the next year be able to share some of that preclinical animal model work. Hyperbaric oxygen, so we have a 28 million study —
Tim Ferriss: That’s huge.
Dr. Dominic D’Agostino: At the University of South Florida. I am just peripherally involved in that or just know the people running that. And it’s essentially evolved out of the DOD work that looked at the muddy waters of hyperbaric oxygen therapy for that. But I —
Tim Ferriss: It’s a good way to put it. The muddy waters.
Dr. Dominic D’Agostino: Yeah, I’ve been part of reviewing grants and also manuscripts, and I think there’s a lot of interesting studies that’s going to emerge. By the time this airs, I think they will be on PubMed. Essentially, showing that hyperbaric oxygen therapy protocols, more mild hyperbaric oxygen at 40 to 60 sessions, and people that had traumatic brain injury a decade ago, can enhance cognitive function, reaction time, and a wide variety of metrics associated with brain function. So I think this work coming out of Israel, I would like to see it replicated. I would like to see — the work that’s different at the University of South Florida is that it’s very innovative and that it’s using a sham.
Instead of using hyperbaric air as the control, they’re using — they basically pulse pressure in the beginning to make people think they’re being pressurized and at the end, so their ears pop a little bit. And I don’t know every — it’s blinded. People don’t know even what they’re getting. If you question them, they don’t know if they’re getting hyperbaric oxygen. But I do think that oxygen is a powerful drug, and I am excited about that research, if you ask me. I’m excited if it proves it or disproves it. I think we’re going to get an unambiguous answer to this question about hyperbaric oxygen for a traumatic brain injury, and people with and without post-traumatic stress syndrome. So my thing is that if they put patients on ketone metabolic therapy, that would augment and enhance hyperbaric oxygen therapy, and decrease the potential for risk of an oxygen toxicity seizure, which goes up. If you’ve had a traumatic brain injury, your risk of oxygen toxicity seizure would increase because —
Tim Ferriss: Now, this is pretty specific to military? Or what are we talking about?
Dr. Dominic D’Agostino: Yeah, they’re all vets. And if they do find out that they get a beneficial effect from that, then after the experiment, they’ll be able to get that for free service. So there’s six — like quarter to half a million dollar hyperbaric chambers. So the hard shell chambers, there’s six of them in this facility. And it’s the most elaborate hyperbaric oxygen therapy study that has ever been done. And it’ll answer the question about the efficacy. So that’s ongoing now, and I’m excited about that. I’m also excited about potentially using that facility, because it’s next to the Moffitt Cancer Center for patients that are undergoing various cancer treatments that could be enhanced with hyperbaric oxygen therapy. Because it augments the immune system and it’s actually an FDA approved application for radiation necrosis. So if you’ve had radiation, then your insurance would actually cover it. But it can enhance certain therapies that we’re working on now. Yeah.
Tim Ferriss: Yeah. Amazing.
Dr. Dominic D’Agostino: Yeah.
Tim Ferriss: All right. Well, we will link to all of those things in the show notes as always. And I encourage people to check all of those out. I’m going to check all of them out. And Dom, thanks so much for the time, as always.
Dr. Dominic D’Agostino: Nice to see you.
Tim Ferriss: I took a ton of notes. I have maybe even more questions on top of that for more text messages. Sorry in advance. And so nice to see you again.
Dr. Dominic D’Agostino: Yeah. You too, Tim. Yeah, thank you for having me on. I appreciate it.
Tim Ferriss: Yeah. Absolutely. And folks, show notes can be found at tim.blog/podcast. Just search Dom or Dominic and a lot of them will pop up. Just look for the most recent. And until next time, be a bit kinder than is necessary. It matters, it helps, to others and to yourself. And as always, thanks for tuning in.
The post The Tim Ferriss Show Transcripts: Dr. Dominic D’Agostino — All Things Ketones, How to Protect the Brain and Boost Cognition, Sardine Fasting, Diet Rules, Revisiting Metformin and Melatonin, and More (#825) appeared first on The Blog of Author Tim Ferriss.
2025-09-03 23:10:04
Dr. Dominic D’Agostino (@DominicDAgosti2) is a tenured associate professor in the Department of Molecular Pharmacology and Physiology at the University of South Florida Morsani College of Medicine and a Visiting Senior Research Scientist at the Institute for Human and Machine Cognition.
He teaches medical neuroscience, physiology, nutrition, and neuropharmacology, and his research focuses on the development and testing of nutritional strategies and metabolic-based therapies for neurological disorders, cancer, and human performance optimization. His work spans both basic science and human clinical trials.
He has a strong personal interest in environmental medicine and enhancing the safety and resilience of military personnel and astronauts. In this capacity, he served as a research investigator and crew member on NASA’s Extreme Environment Mission Operations. His research has been supported by the Office of Naval Research, the Department of Defense, the National Institutes of Health, private organizations, and nonprofit foundations.
He earned his B.S. in Nutritional Science and Biological Sciences from Rutgers University in 1998, followed by a predoctoral fellowship in Neuroscience and Physiology at Rutgers and the University of Medicine and Dentistry of New Jersey. He then completed postdoctoral training in Neuroscience at Wright State University’s Boonshoft School of Medicine in 2004 and at University of South Florida Morsani College of Medicine in 2006.
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KetoNutrition.org | Facebook | Twitter | University of South Florida
The transcript of this episode can be found here. Transcripts of all episodes can be found here.
“I think the beauty of ketogenic [therapy] is that it’s pleiotropic, right? Which means it’s many mechanisms working in synergy.”
— Dr. Dominic D’Agostino
“I think the best way to measure to suggest you’re in autophagy is a glucose ketone index after a period of fasting.”
— Dr. Dominic D’Agostino
“About 30 percent of the population hyperabsorbs cholesterol.”
— Dr. Dominic D’Agostino
“HSCRP is a better indicator of cardiovascular disease than LDL cholesterol. We know that now. [No one would believe it] If someone said that 10 years ago.”
— Dr. Dominic D’Agostino
“I wouldn’t go above three. Probably 1.5 to 2 millimolar range. That seems to be a level of ketones that safely does not produce a metabolic acidosis.”
— Dr. Dominic D’Agostino
“When we published the NLRP3, I got requests from Genentech and various pharmaceutical companies to go there and give a talk on the mechanism so they could drugify. And I would throw up a big flow chart of all these mechanisms, and I think they would get frustrated. And it was like, ‘Well, tell us the mechanism so we can make a drug out of this.'”
— Dr. Dominic D’Agostino
“I went on a vacation where I forgot melatonin and I slept like a baby probably because I was up every morning. The sun is the ultimate circadian synchronizer. I got off of melatonin to check my endogenous melatonin, and there was no suppression.”
— Dr. Dominic D’Agostino
“So we went to these blue zones and they just, at night after their dinner, the males will do a shot of alcohol, usually wine, but sometimes ouzo and they’re all in their nineties and hundreds, they’re in the blue zone. So it’s a universal characteristic.”
— Dr. Dominic D’Agostino
Want to hear the last time Dom was on the show? Listen to our previous conversation in which we discussed disease prevention, longevity, cancer, ketogenic diet mastery, the detoxifying effects of ketosis on pre-cancerous cells, how to jumpstart daily ketogenic cycles, “cheat” meals, and much more.
The post Dr. Dominic D’Agostino — All Things Ketones, How to Protect the Brain and Boost Cognition, Sardine Fasting, Diet Rules, Revisiting Metformin and Melatonin, and More (#825) appeared first on The Blog of Author Tim Ferriss.
