¶ Introduction
Hey everybody, welcome back to another episode of First Principles. We're today here with Brian Johnson, the man who is trying to live forever. We're going to talk a lot about a bunch of different things in this conversation, both the science of what he's actually doing with Blueprint, this protocol that he's put together, but then also his philosophy towards life and basically where he thinks humanity is headed and why he's doing this in the first place. So Brian, thank you so much for being
¶ Zeroth Principles Thinking: Going Beyond First Principles
on. Yeah, happy to be here. Awesome. Well, I think that maybe that's an easy place to start. Well, not easy, but it's a fun place to start is about kind of like the broader thing that led you here. I mean, I think it's interesting that, you know, you have this principle or you have this idea of zeroth principles thinking, and yet this is the first principles podcast. So maybe let's try to just, you know, address the
I mean, I guess there were a few beats. After selling Braintree of MO, this had been a goal my entire life, try to do something meaningful for the future of humanity. And that's such a challenging question. If you read history and you learn about various people in various places, sometimes discoveries or behaviors were accidental, and sometimes they were thought through carefully. And if you try to actually pose a question, like right now, like if you
were trying to influence the future of the human race, what do you do? And so I did two things to try to sort that out in my mind. One is I gathered all of my smartest friends, and I did 12 dinners around the country. And I would pose the thought experiment to them and say, now let's imagine we're in 2050. What did we do in 2016 that allowed this world to
be remarkable? Then I listened intently to everyone's ideas. Basically, you could imagine whatever the zeitgeist was in 2016, I wrote down all those ideas and I drew a box around the ideas and then I challenged myself that I couldn't do anything inside that box because inside that box was basically a collection of first principle thinking It was the things that people were identifying were the next step
in the iteration of various technologies. And so I challenged myself to zero. But then when I started looking outside the box, I realized that it was a very challenging thing to do. And so I confronted this, when my mind was searching for in the unknown space, I was struggling to think coherently. Like, how do you construct thoughts in zero space? And so one night I went to bed and feeling deeply the limitations of my own intelligence, I thought, I need to find
a framework that allows me to punch through. And that night I had a dream about zero-wealth principle thinking. And the idea just dropped in my mind. I jumped up and I wrote it all down. I thought, I can't forget this. But yeah, it was one of the most exciting moments of my entire life. where I felt like it gave me like a new appendage where I could maybe feel
more, see more, intuit more. And so, yeah, so I've been working on this concept of zero principle thinking and how, um, I think going forward, we may need to transition from first to maybe a higher ratio Totally. And the basic idea being that, you know, first principles is great about working in a system, right? Like you can get down to the nitty gritty,
¶ The Journey to "Don't Die": Bryan's Thought Experiments and Realizations
like the bare, like fundamentals of the, of the system you're in. But zeroth principle thinking is that throw the system away. Like what is the new system we need to be doing? Like, uh, totally disregard all that first principle stuff and where should we be Exactly. Like examples, germ theory. So in 1870, you're trying to identify what it
is that is causing people to die. especially around maybe births and surgeries and other things, then this idea that there are microscopic objects that the eyes can't see would be insane to contemplate in the 1870s. And most people rejected the idea that there were these invisible things called germs. And so that's an example, you know, special theory of relativity is also, you can't take Newtonian physics and first principle think your way into the next iteration
of physics. Because yeah, these things, they don't just change the graph, you know, they change the x-y axes. Like, they Totally. Have you ever heard of the book After Virtue by Alastair MacIntyre? No. Oh, actually, I have heard of it. I haven't read it, though. It's a really good book. I actually found it back when I was like a high school debater because I was like looking at it for arguments or something. But there's a really good thought experiment in
it that's super zeroth principally. So, Uh, there are two guys that are sitting around a campfire. It's like prehistoric times. Um, one guy turns to the other and says like, you know, have you ever heard of this thing called like the wheel? Have you ever thought of this? And the guy's like, no, what are you talking about? And so the first guy goes, well, it's like, it's like the circle and like how it can like rule things. And like, it has this thing, uh, but it hasn't been invented yet. And
the other guy turns up, he's like, I think you just invented it. Like the process of describing this new thing is the act of invention. And so his argument is, if you can describe something, if you actually have words for it, then you've already done the act of invention. So it's like sort of what you're trying to do is do that, like invent, truly invent in a way that is, you know, goes beyond the words that we have today. I think it's pretty cool. Exactly. Totally. Um, Heck yeah. So I'm
curious. So that was the thought experiment. That was the theoretical framework that you were operating within. Were there a lot of ideas that be kind of like came to you within zeroth principle thinking and you had to sort of whittle it down to don't die? Or was it did Yeah, once 0th principle thinking became a framework I could play with, then I was set off on the task of how could you find a 0th principle endeavor. And then, that was basically don't die. So,
death is inevitable. And we've talked about life being everlasting in religious settings, but never in IRL. And so we've kind of jumped from, yeah, we made that leap. And so don't die in IRL is a different thought process. And then I needed to develop the philosophical structure that supports what that means. And specifically, what does that mean when you're on the eve of creating super intelligence? And so I was trying to stitch together how to understand reality in this moment from the
vantage point of the wisdom of the 25th century. That's like a thought experiment where you're in the 15th century and you're trying to deduce reality in some coherent fashion with the wisdom of the 21st
¶ Is "Don't Die" a Religion? Examining the Parallels
Yeah, absolutely. I mean, I think the, it is definitely like one of those thoughts of like, you know, that is beyond the current, the thing that is definitely not the current thing or it wasn't at the time of, you know, we did have, we sort of had like measured self and
we had sort of longevity stuff. And there were, there were some, you know, like the, whatever the Peter Atiyah's of the world, the Tim Ferriss of the world, we had those kinds of folks that were, that had been talking about longevity for sure, but definitely not with the frame of don't die. and definitely not to
the kind of same extent of the experimentation that you've been doing. So, I mean, how did you see yourself as sort of, you know, either working with and like on top of some of the other research that people have been doing versus Yeah, it's definitely a yes and situation. I'm a yes and kind of person. with friends and trolls and everyone else. I'll quickly, I've been doing these dinners at my house. Actually, Christian,
it'd be great to have you attend one. But I'll, maybe I'll just quickly walk you through like what I do to arrive at this don't die thing. So there's five turns in the conversation. It takes us about two and a half hours. And so I opened with the thought experiment of if you had access to an algorithm, actually, let me just do it with you. Sure. Yeah, let's
go for it. Christian, if you had access to an algorithm that could give you the best physical, mental and spiritual health of your life, Because in exchange for that, you did what the algorithm said. You went to bed when it said, you ate what it said, you exercised in the ways that it suggested. Would Without knowing more, I don't know. I'd be afraid of what else I would give up. Are there experiences that I don't get to have anymore? Am I deciding to forego pleasure to have this thing? If all
else equal, 100% obviously yes. But I would wonder about that. So you basically want to think with first principles and Kind of, yeah. That's my brand, man. No, So it's like a no, but a
cautious maybe. Yeah, it's a cautious maybe no. Okay. Now let's imagine that the 25th century is observing our conversation, and they see me pose this question to you, and they're simply observing, what are the characteristics of intelligence and morals and ethics and norms and assumptions of a homo sapien that I actually think about this all the time, and I would love to get your answer to it, too, of what will future generations basically judge us for? I think
there's so many things. They're going to judge us for eating animals that were birthed naturally, for sure, 100%. Because they're going to have the ability to create matter however they want, basically. They're going to judge us for I don't know, treating homes as assets, like there's a there's a big long list of these
things. But I think there are plenty of things are going to judge us for and I'm sure I'm sure there are things that we haven't discovered that related to health And so when they observe your answer, where they they hear you say, No, because I want to learn more. And like, I see a trade off space of sensorial pleasure. And you know, and like you, you so how would they assess your
¶ Bryan's Roles in "Don't Die": Philosopher, Embodiment, Message Bearer
intelligence? What are you revealing with Maybe this is just too easy because I think I know where you're headed with it, is that my brain is in control, that I'm thinking through it, and that I myself have this limited understanding of what will be best for my I think it is true. So yeah, the first turn of the thought experiment is meant to provoke our beliefs that remain invisible to us. So we all blurt out an answer, and it's kind of our knee-jerk reaction to a somewhat provocative question,
and it kind of shows our cards. The second turn, it shows a mirror to us, and we become much more self-reflective, just like you've done. So now you've seen this from both angles. Okay, so what could possibly happen in the future that might change our responses and how the 21st century would view our evolution. So I'm going to make three statements right now. So if we contemplate what's happening with AI, I think there's one specific thing that is
important. One is I think that AI is going to know more than any one of us individually and all of us collectively, and it will discover better than any one of us individually and all of us collectively. So And whether someone says that's impossible, AI is in a nascent state, I'm talking about from the perspective of the 25th century. So give it some time, 20 years, 50 years, 100 years, whatever.
Over some duration of time, AI is going to be better at both knowledge acquisition and knowledge management and discovery. And so that's going to create a situation where we are transitioning as a species from one of knowing to not knowing. and our entire existence is based upon knowing many things. And so when that happens, what do we do as a species? AI is probably going to be better at being you than you are you. It's gonna be
better at being you than you are. And so we know this, we say yes to an algorithm that helps us navigate in our car. We say yes to an algorithm to entertain us on our phones. We say yes to an algorithm, so on and so forth. Soon we'll have algorithms that help us with our reasoning processes. We do this in text-based form now, right? But you can see it naturally that algorithms just do things better over time. And
¶ Sponsor Break
we say yes in all these incremental ways. And eventually we'll just say like, legit, this algorithm is better. Like I'm actually more productive. I'm happier. I'm more stable. You can, you can imagine a world where it just generally gets better. Now I'm going to avoid dystopic outcomes for the moment, but generally speaking,
that's what we see is like algorithms generally improve our lives when we say yes. So if we take those two principles of where we're going, then the most important question in this part of the galaxy surfaces. What do we do as the most intelligent species we know in this part of the galaxy? What do we do when we're giving birth to superintelligence? When we don't, or we're not the
knowing party anymore, we're not the discovery party anymore. When it's not clear what our control is going to be on how this thing evolves, what do we do? So I have an answer. I have a proposal, but I'd I think that the fact that it is more intelligent than us means that what we think about it might not really matter that much. Like, I think that because it is so much better at reasoning, any answer
¶ Quantifying Death: Introducing "Die Scores" for Behaviors and Choices
that I come up with for what it should do is going to be very, I actually think we might actually be seeing this in the way that we're training AI, like right now in 2024, like we're hitting, you're seeing a little bit of an asymptote. And I think a lot of that is due to the fact that humans are rating the answers, the AI, and we're just like saying what we would have said. So it's, it's sort of a paradox. It's like, you know, AGI or whatever is this infinitely smarter thing, like better
than us. And so it'd be the equivalence of me like going up to my like pet rabbit and saying like, what do you think is the best way to care for you pet rabbit? It It has no idea. So this is when I went through this thought process, I arrived that we really can only say one thing with confidence. And that is Don't Die. Don't Die is the most played game by everybody on planet Earth every second of every day. We play it more than religion,
we play it more than capitalism, we play it more than anything. Like right now, if something were to threaten your life or my life, we would stop the podcast and we would take care of not dying. As a species, it is the only thing we agree upon. And it's not that we even disagree, like, don't die in 20 years. People will smoke and people will take risks. So it's not even that we agree on don't die in 20 years. We agree we don't want to
die right now. And so if we have to really figure out what alignment means, that's the singular thing we align on as a species. And so don't die individually, don't kill each other, don't kill the planet, and align AI with don't die. And so then, whatever happens after Don't Die, like what games we play, how we evolve, that's all a secondary consideration to securing Don't Die as the zeroth order operating system of
this planet. And so that's what my entire endeavor was about, is I wanted to demonstrate me as the embodiment of Don't Die. Like, how do you actually be that? And so it's a system where you measure every single way my body dies every day. You try to find therapies to slow down that speed of aging and then compensate for aging damage. And then you measure to see how you did and you repeat again and again
and again. trying to drive the you know death to zero not you can't stop entropy so you can just slow it down a certain degree and then repair and then it's the same protocol that would apply to earth you take the earth you measure everything you know billions of data points a second you look at the science of how do you maintain a coral reef that's healthy you know like a biosphere that's healthy you implement the protocol again and again and again And so you do that for all
verticals in society. And so as a species, I guess my proposal is, we currently live in this luxurious world where we can say many things about existence, and we're quickly narrowing that aperture to be able to only say one thing, which is lock in on don't die. And then we can, of course, we can join hands and play games and Bob don't die. But we can't do that until we first secure don't die as the singular operating system
¶ What is Death and What is Aging? A First Principles Perspective
I love that. I think that is really interesting, too, because and I wanted to ask you this question of like, what do you see your role as in the system? Like you just said, it's sort of the embodiment of don't die. I also hear though, there's a lot of like, you're like the chief philosopher of don't die. And that you've sort of done the thought experiments that lead you to
conclude that we shouldn't die. Like, there's like a lot of I think therefore I am sort of parallels of like, just shed all this other stuff that we can't be certain about what can we be certain about not dying? Like, let's let's be certain about our existence first. Yes. So there's philosopher, there's embodiment. What are the other roles that you play within Don't Die, and which of them do you I mean, there's five levels of ambition that I would
categorize. It's start a company, start a country, start Because in any other generation of time, you really all in the past couple thousand years, you can only aspire to one through three. You could never aspire to four or five. It just was out of technical reach. And so now like just in the past few years, a reasonable person could aspire to four and five. And that's insane. Like it levels up ambition of the species to a never before contemplated goal. And
so yes, I think that is, it's not just my goal. I think it's our Got it. So if there's this shared goal as a species, which is don't die, and you're trying to bring it about, obviously, like that's, you know, you've had the original idea, you think it's powerful, you've seen its impact on your life, you want to bring it to as many people as possible. I mean, it does, I
mean, it feels a little bit religious, though, doesn't it? I mean, in the same sense that religion is a set of shared ideals that people get behind that change their lives, that that make them do rituals that, uh, you know, have them believe in things that are larger than themselves, especially with the whole kind of like, um, I wouldn't call it ascetic, but I would call it like you're sort of surrendering self-control, like your own self-control to
a certain extent. It is, it is fairly religious in that sense. I mean, as I know that, um, you know, there was a, there was a period of your life where you were more religious and then sort of, you weren't like, do you see that parallel or do you, do you feel that parallel and how you're kind Religion is used in a pejorative term, right? So it's like, if you're going to pull out the R word, you're basically going to level an insult. It's not like someone starts a company and you admire the
ambition, you admire the galvanization, you admire the idea. You talk about a religion and it's like, you know, all of a sudden everyone's apprehensive and they want to cast shame. But religions are, you
¶ Measuring Biological Age: Organ by Organ Analysis of Bryan's Body
know, like the most durable form of human organization. ever created. And so it's a really weird cultural thing to just jump on the bandwagon and say, you know, religion's bad. And so, you know, the people, of course, use the pejorative word like cult. Yeah, I guess what I'm saying is I want to call to our attention, to our zeitgeist, that we are presuming we're better than religion, that we ourselves are You are post-religion, but everyone is religious. Everyone
follows rituals. Everyone follows shared community practices. It's a really silly debate. And so like, I just embrace it. Like if people want to call Don't Die a cult, like, yes, we are. And our evil design is to get you to go to bed on time and eat well. Like we are pernicious and like we're coming after But like, there's
no better way to deal with it than just say yes and. But yeah, I mean, if you're ambitious, then you should never deride the most durable form of human change ever Using Strata makes all of your identity tools stronger, connecting any app with any service that you want to use. Strata's Identity Orchestration platform separates the identity logic from your applications, so you can optimize existing IAM tools and manage them from
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strata.io slash firstprinciples. Let's get back to the show. If Blueprint or Don't Die is sort of like religion, and you are, you know, its greatest follower, but also sort of its like, you know, message bearer. Do you think a lot about, you know, to bring it back to sort of first principles, do you think about like the building blocks of getting a meme into the world?
Like, what are those? And you have so many different tactics that you've used on social media from, you know, posting, like, semi-nude photos to, like, picking fights to, you know, like, being inspirational. Like, all the whole gamut. Like, have you thought a lot about bringing a meme into the world and how you do that from Yeah, it's kind of like a... I do play with old mediums. I play with seriousness and troll and, you know, and fights because it's like an instrument where You
want to play as many notes as you can. You want your range to be, you want a big dynamic range. And if you're serious or sincere is your primary currency, you could only play so many songs. As I'm always looking for the broadest dynamic range just for the music creation in all the different factors. So yeah, I mean right now I'm trying to formalize and create action behind Don't Die. So I've done it with help, right? That translates to
basic things we know about. But if you take it to an adjacency like school lunch. So for example, when you smoke two cigarettes, it shortens your life by 30 minutes. So let's just say you can actually quantify certain behaviors and what they have for a cost of life. So let's say we're trying to quantify the cost of the school lunch we give in America to kids. So let's say it's a piece of pizza, it's chocolate milk, and it's canned vegetables. And let's just say together we
assign a die score of 7 minutes. So we're feeding our kids die. Now that's helpful because if you tell somebody about die individually, they're going to put up all these blocks like, but I prefer a life of stimulation. I want my alcohol and my benders with my friends. Like they're going to defend all their vices. They're going to defend all their behaviors. They're going to tell me that life, that death is beautiful because
it replenishes the earth and death is wonderful because it gives life to me. Like they're going to have all these elegant arguments defending death and their own vices. If you frame it like, hey, we're feeding kids die. You can't defend that. Nobody wants kids to eat dye. And so that's a good example of, okay, if you want to eliminate
¶ The Penis as a Marker of Overall Health and Vitality
dye from school lunch, what do you do? And that is the same process I went through, right? You have to quantify death. You have to figure out what the science is of not dye. Then you have to go through the protocol again and again. So we get zero don't dye for kids. And if you get to a positive side of your extending life, even better. So you take that format and you then say, okay, now it is don't dye coral
reef. what is don't die, international relations, what is don't die, biosecurity, I take any domain in society, how do you quantify death in all its forms? And you basically say, alright, as a species, this is our game. Like before, it was like how to make the most amount of money or how do you the most, you know, social media followers, like we're gonna play a brand new game and see who can rack up the biggest don't die score. Very
I love that. Okay, so this is a perfect time to dive in more deeply into what the don't die kind of program is, how you think about it, and the therapies you chose and how you chose them and all that sort of stuff. I mean, I think just to start it at the true like, ground floor And how do you think about those things from the first principles, like super, super basic level in a conversation last week at this group I was with this gentleman's response was, I'm okay to die.
Like, I, you know, I'm fine. Like, I'm just going to go on to my next version." And it's like, my response to him is like, you can say that because you're not dead, right? It's like, can we just be honest? Every time your mind chirps with any kind of understanding about reality, you're only given that privilege because you're not dead. And so to realize, and this, it takes people time to go through this loop. They don't understand that don't die is what gives them breath. And so that is a
basic level. Like once you take that as a starting point, then you can walk into the other pillars of the Don't Die Oh, no, it's okay. So basically, I would love for us to take like a kind of like a big step back and say like, what is death Yeah, yeah. Okay, cool. So what we did that was unique is we said, you know, when the heart stops pumping, how would you, how would you go
about doing this? So like, if you're in health and wellness, and you're with a group of friends and the topic comes up, you may hear questions like, you know, I'm doing one nostril breathing, you know, to activate my, you know, my, my parasympathetic nervous system where people will be like, I've got a cold plunge practice or like I do yoga or I do Pilates, like everyone's got their thing, right? And so if you hang out in health or wellness, you have a near infinite number of things that people
are going to do. Eastern medicine and spiritual practices and like community with it, different dimensions via psychedelics, like everyone's got a gem. But what we did is we said, okay, so there's an infinite search space. How do you find the power laws? Like you have to basically say,
¶ Epigenetic Clocks and the Pace of Aging Calculated Tests
like, we can actually only do like 20 things and we can only do those 20 things really well. So what we did as a team, I hired 30 medical professionals. We combed through all the scientific literature on health span and lifespan. And then we found the effect size of what actually worked the best. And then we ranked the biostatistical data to say, what do we actually believe? And then we rank ordered those. We said, all right, we have the power laws. Let's start with number one. And
so number one was too risky. It was a gene therapy that basically you can't turn off. So we said, OK, too risky. We can't answer number one. What's number two? And then we went down the list. And so we've gone down, I think we're up to like 200 something now, but we've implemented all the power laws. And then we recorded all of this and we shared all my data publicly. And as far as we know, I have the best biomarkers of anyone in the world. Now, this is not to say
people don't have better biomarkers than me. They maybe do. We just don't know about it. So of people who are measured across the areas of cardiovascular ability and inflammation and total bone marrow density and speed of aging, et cetera, this whole long list of stuff, I have the best biomarkers in the whole world. And so it demonstrates it actually works. Like we took me as a 43 year old who had beat himself up his entire life, like bad sleep,
chronically depressed, terrible diet. And we took me from a terrible place to like among the best in the world in three years time. And so I wanted to show like basically the four minute mile for longevity. Like so people would be like, I didn't think that was possible. And now I'm Someone's done it. There's a guy who's done it. So it's possible. Is there literally an Excel spreadsheet somewhere, which is like that, like 300, 500 rows of all this, this research. That's so crazy. I love that. And
is very, very hard. Because yeah, most as you would expect, most people are trained in a specific discipline in a certain religion. Like, you know, it is a religion is once you get in that world, it's almost impossible to block to change their frame. And so it's really a bunch of misfits who like they, they're either in a system or outside of
it, and they just feel uncomfortable. They don't formally enter systems. And so Yeah, they're like, like refugees almost like and we just kind of pick we just kind of pick them up and they find a home with us where we we play fast and we're robust. But Do you have your body divided among people like is are there like so I work at a satellite company like we have different responsible engineers for different parts of the satellite, like the solar arrays or
the, you know, the flight computer or something. So do you have the equivalent of like responsible engineers for like, do you have like an ear guy and Yeah, we do it on an organ by organ basis because redefined if I can say I'm chronologically 46, but that's not really helpful. I need to talk about my heart age. And when I speak about my heart's age, I need to speak about it from its anatomical, uh, a function, anatomical and then functional capacity.
So I need to measure my heart age by like, you know, 10, 15 measurements. And then you've got a true estimate on biological age. And that's true for every organ. And so I'm, I'm chronologically 46. But Yeah, that's so interesting. I love that. So that like, that is such a rethink of what age is obviously, like, mostly I, I'm 33, because I've been alive, I was born 33 years ago, and a couple months or whatever. But
so for can we dig into that a little bit? Like, I don't know if there are specific examples of organs that you would like, highlight is interesting in the way that you're calibrating the age of it. But is it like a functional thing?
¶ Bryan's Experience with Follistatin Gene Therapy
Or is it like, are there are there like, I'm sure there's a lot of function, but then also deeper data of like, I'm curious if a couple examples. Cardiovascular ability through VO2max. So it's how well your body can utilize oxygen. That is a well, that data set is solid. Like you, it's an age graph. So at age 18, you peak and then you decline from there. That doesn't mean that you're highest at age 18. You can get higher over time as you build, but generally speaking, age
18 is when you peak. And so yeah, my cardiovascular ability, my VO2 max is 58.7, which is the top 1.5% of 18 year olds. And then if you look at my total bone mineral density, It's important. I'm in the top 0.02% of 30 year olds, which is age minimum for that test. And if you look at my nighttime erections, you know, it's like, it always makes people laugh, but it's a really important marker for psychological, cardiovascular and sexual health. I'm better than the average 18-year-old by
a significant margin. Because the younger you are, the more erections you have, and then they start tapering down over time until you have none. And so yeah, if you take any one of my few dozen markers that are big ones, there's very clear age graphs on where something should be at a certain age. And so we've tried to take every single one, kidney, liver, heart, pancreas, thymus, brain, ears, eyes, everything,
Is there a particular one that you feel like more people should know about that don't? Like thymus is one you've mentioned, I've heard you talk about before, I think that most people don't know what that is. Are there other ones that are, maybe is that one that you would highlight as more people should know I mean, this is why I did the penis. Because like, you know, I was I was talking about my heart. We had just done this. I think one of the coolest things we did is we reduced my
thymus age by seven years. Thymus is like this gland right behind your sternum. It's responsible for your immune system. It's really important. Like you don't want to, you know, an aged thymus. And so through
¶ Kernel: Building a Mass Market Brain Interface with Time-Domain FNIRS
this protocol, we reduced my thymus age by seven years. We published it. We did three MRIs. We coded brand new software. We put so much effort into it, and we shared it publicly, and no one cared. So we did that several times with these different organs. And so one day I was talking to my team. We're like, you guys, we're doing this really cool process of we do rigorous biological age measurement. We look at the science and the therapies. We measure again. It didn't
work. We did the scientific method. what if we did sexual health? And so I posed the question to the team, what would it take for me to have the most quantified penis in the world? What would you do? What measurements do you do of penis function? And then I went and did all of them. I did all the penis measurements. And then we said, okay, so now we have a baseline on this. What are the therapies that have clinical evidence
as efficacious? And then we gave a score. We said, okay, so this kind of all collapses into like, what are your nighttime boners? And like, no one, no one knew what, you know, like, no one knew nighttime boners were relevant. No one knew it was a marker of biological age. No one knew, but it showed the process of measurement, intervention, you
know, protocol. So like, that was really helpful, because it really got the point across that you can actually approach each function, each biological organ of the body, and approach it with scientific That's so so I think it's there's two examples that you talked about that I think are interesting to kind of compare against each other. VO two max, most people hope of like, I think I've heard about it, you know, that you see the athletes with
a mask and they're on the treadmill. And, you know, they're, it's like, you know, people know that one. And I'm sure there's tons of data for it. nighttime erections, I'm sure, I don't know, but I would assume that there's not a lot of data already. And probably the comparison that you had to do to like, was, was probably harder. Like, where did you actually, could you find other studies like, like existing studies that you compare yourself to? Or was it curious to kind of
compare those? Cause it's like super, super extremely studied. Everybody less studied i'm sure you guys had to really dig probably to go find stuff but um you did you you ultimately did find studies one study that had done nighttime erections and then we found a company out of the uk adam help they had built a a device that does erection measurements there's a little cube it sits at the base of the penis and you put it on before you go to bed, you just
forget about it. You put it on, you think it's going to be annoying, it's actually just fine. It seems distracting. Yeah, exactly. You're fine, just fine. And then it measures the number of nighttime tumescence at the boner, and so it measures the quality. So it's looking at engorgement of the penis, and it happens during REM sleep. And so I had so many of my friends, when I posted this, they messaged me with great concern. They're like, I'm getting no boners. I'm never erect. And
most of the time, their sleep quality was atrocious. So when your sleep quality goes down, boners just evaporate. And so that's why it's a good evidence. Like, if you are not convinced that sleep is really important, just look at all the critical functions that just go away immediately, including... So it's a really good learning experience of people creating these intuitions that, you know, going to bed on time really matters. And your
last meal of the day matters a lot because it determines how you sleep. And just to draw this domino effect, it's like, okay, I can see how these pieces fit together, that a person's vitality really is in this chain reaction of events. So it helps people understand that you go back into this primary thing of like, does it make sense to become a martyr for... You're basically paying with double or triple time life points by doing My memory or my creativity is most
robust in my dreams. I have more ideas in my sleep than I do when I'm awake. The quality of my days are That's when the other dimension is reaching out to you to tell you your principal ideas. Yeah. I'm curious, can we talk a little bit about the PAC, Pace of Aging Calculated Tests? I'm curious to hear about those. So there's, I don't know if I'm saying it right, doon-doon-doon, doon-doon-doon,
that one. That's the main one, right, for DNA methylation, is that, that's When we first started, so there's these new clocks they use, they look at DNA methylation patterns, like chemical signatures in the body, and these chemical signatures have information encoded that are patterns about your age. And so they change with age. And so when the clocks first came out a couple years ago, when I first started Blueprint, we were like, hey, cool, clocks. But
¶ The Power Law Interventions: Identifying the Most Effective Longevity Levers
the clocks are trained with, each clock is trained for a certain objective. So the clocks are different. So when you hear people complain, like, I did this clock and it said I was this age, and this clock said it was that age, it's because the clocks are trained differently. So it's not like the clocks are bad. It just means they're trained for different objectives. And so what we did when we started, We said, okay, we're
just going to test all clocks. So we tested me with six clocks, and then I think we waited six months or eight months, and we tested me on eight clocks again, and I had reversed my epigenetic age by 5.1 years. And that was one of the first viral hits we had. We're just playing around. We're just trying to figure out, what is the clock? And what do they say? And how do we compare them? But we were not really thinking I'd reverse my
age by 5.1 years. We were like, hey, the clock shows something. But then over the years, we've really focused on this true diagnostic denuded pace. So it's based upon one of the most robust longitudinal studies out of New Zealand. I think it's one of the longest running ever. It's a third-gen clock now, and initially we would say it's a silver standard marker, because blood, cholesterol, and triglycerides, those things are gold standard in terms of predicting all-cause mortality.
But these, we'd say, are silver standard because they haven't yet crossed that threshold of predictability for all-cause mortality. It's getting very close now where they can predict this. So it's now getting the respect of more and more people of like, okay, this was like an emergent thing. We were skeptical of this. Now we're taking it much more seriously because it's now predicting the phenotypic markers
much more accurately. So I started with over so if you're if you score a one on the test if I'm 46 I score one that means I'm aging at a normal rate of a 46 year old. If I'm aging at 1.01 or more and faster than normal and 0.99 or less I'm aging slower then. And so we've worked my speed of aging down to 0.64, which is my most recent measurement. It's lower than 99 plus percent of 20 year olds. So it's one of the lowest scores in the world for men. And we're very proud
of this because we've worked so hard. It doesn't matter if we do it, but like a rough summary of it is for every 12 months that pass, I age for seven months and I get free So I know that there's a, I don't know very much about this. I know that at the end of your DNA, there's like these things that are repeating maybe, and we don't, I don't know what they do. Maybe somebody else does their, uh,
¶ Assembling a Team of Scientific Misfits to Tackle Aging
but they have something to do with aging. Have you, is that something that you measure as Yeah, we measure it. We have measured it for years. It's something we routinely do. We have been unsuccessful to change my telomere length with almost everything. Like there have been small changes, but nothing really important. But the telomeres, I think is the number one performing. It was a combination of telomere. I think if I remember right, it was a study of telomeres, plotho
and folstatin gene therapy. And so we haven't done telomere telomerase gene therapy yet because it's not yet safe like you can do it but once you do it you can't turn it off and so there's only one person who's done it and it's it's just a risk like you if you if something goes wrong like cancer you can't turn it off and so i did do my first gene therapy in october i did so in the world of gene therapies you need a delivery vehicle to get the gene therapy in the body and
what most people use is called an AAV And so that's the one that can't be turned off, and it has other complications with antibodies. I used a plasmid, and so it's a friendly vehicle. It delivers a protein inside the nucleus, and then it just produces more of a protein. Like for example, what I did is full of statin. So this gene therapy is producing higher levels of full of statin that
I would otherwise have in my body. And this has been typically seen with bodybuilders where you've seen like the big cows or dogs that are just very large and muscled out. Have you seen those? Yeah, yeah, yeah. Yeah, they're terrifying. And so that's what folic acid has been associated with. But we've been looking at it for its rejuvenation effects across whole bodies. We've been doing looking at my muscle mass
¶ Dreaming Up Ideas: Bryan's Nocturnal Creativity
and my bone mineral density and a whole bunch of markers. Like we're trying to see like what whole body effect because As the most measured person in history, we get this really interesting view of everything that goes on when we do these therapies. And so the thing that the gene therapy did, which was interesting, is it lowered my speed of aging to this 0.64. Before, it was hovering at like a 0.69, 0.7. And this is the only one we did that could be responsible for it. So
in that regard, it's efficacious. We've been very happy So most of most of my listeners will know this is mostly a, like a deep tech hardware-y kind of podcast where we talk to a lot of folks that have built, you know, these devices or have built, you know, new machines. You've actually done this. You, you, you helped with Kernel, which is I think an FNIRS project. Is
that right? Do you mind telling us about like what that was and how Yeah, so after selling Braintree Venmo, it was this question of what to do. And so in that time duration I spoke to you about of trying to figure out, I did two things to kind of just fill the time. One is I started a venture fund. I invested $100 million into deep tech. So I invested in synthetic biology, genomics, computational therapeutics. For example, I was the first money behind Ginkgo Bioworks, which
¶ Telomeres and the Risks of Telomerase Gene Therapy
is now the world leader in synthetic biology. And so I did that, it was cool because I got to work in the trenches with scientists, entrepreneurs, like how do you commercialize deep tech? And then the second thing I did is I built Kernel. And so my contemplation was We are currently the intelligence building AI, and it may be interesting if we built our intelligence alongside of AI. Currently, integrating the brain and AI is very hard. We have all these things in between us. We have fingers,
we have to type, and visual systems. I wanted to build the world's first mass market brain interface that could make reading the brain output easy to integrate with AI. And so we, we started with the team and we had this question that we were going to look at it from a first principles perspective. Like, how can you figure out what is happening inside the brain? So we spent two years looking at every possible way, electrical, magnetic, acoustic, and
electrical. And then we mapped out each path and we said, okay, what can the technology do? What are the challenges for commercialization? We spun up systems internally, we acquired data, we pressure tested the various paths, but it was such a cool thing. We were just this group of people at the edge of physics and science trying to figure out these new modalities. And so we ended up deciding on building a time-domain functional near-infrared spectroscopy
system. And so it's basically, think of it like wearable fMRI. You put a bike helmet on your head, and you've got images of the brain in minutes. And it's low cost versus being in a big claustrophobic system. We were successful. We built an ASIC. That took like four years to build out. I personally invested $64 million in the company. I kept it alive through the financial crisis. I kept it alive through COVID. It was just like this, like deep tech is hard enough,
but then to ride through multiple crises. So that was brutal. But yes, the tech is built, it's working. We're now in clinical trial, clinical studies for mild cognitive impairment and depression. So I'm very proud that we actually built something that had never been built before. It works. We just showed gold standard equivalent with fMRI. So we succeeded. Like we built a mass market
¶ Reflections on the Challenges of Commercializing Deep Tech
brain interface. So I'm very proud of it. It was a really fun endeavor to do. And so I hope that we succeed at these things and we can go off to much bigger things of getting these in Yeah, those things that the more I've learned about the the near infrared
spectroscopy stuff is so cool. It's like somewhere between like brain radar, where you're like kind of pinging these like infrared systems off, but then also it's kind of like this little, um, well, I don't know what you call them, like the little the little blood finger clip things. Exactly, right. It's the same idea. It's the same idea. But it's just looking into your brain and seeing what's happening. I think exactly right. Well, awesome. Thank you so much for doing this. I mean, any any
kind of final thoughts to people other than don't die? How Yeah, I would say if anyone listening is interested in building Don't Die With Me, I'm putting together a group of people. And we're going to get together and we're going to talk about the various verticals, like bring your idea, bring your specialty. And then we'll work through the thought process of like, how do you actually quite so take an abstract concept like international relations. How
do you think about nation-states working on Don't Die? What does that even mean? So I try to break apart complicated topics into actionable things. And yeah, I'm really trying to build it out, number one. And number two, yeah, I would just encourage people that to really think about, like, we really may be at, you know, on the eve of the most spectacular existence in this part of the galaxy. And I know our lives are full and the day is demanding and there's all kinds of things that demand our
attention. But really, if we can get our shit together as a species and realize the preciousness of this moment, it may be spectacular, far beyond our imagination. So I hope that we can band together and do this. I think it'd just be an amazing journey to