[00:00] So Laura, why now in terms of longevity? What's happened to make you raise a fund and start [00:06] investing in research and companies? Yeah, so we think this is an insanely important [00:13] part of the story because if you were Aristotle and you were like trying to start a longevity fund, [00:18] you would have a terrible time and be like, you know, the worst idea. And so timing is super [00:25] important. Like why now for the first time in like 2000, 3000 years is it the correct time to [00:31] work on longevity? To us, a lot of that comes back to tooling and what's available for us to use. [00:39] Prior to the 1900s, if you wanted to impact biology, maybe you should have been a physicist, [00:46] worked on optics, helped make the first microscope. And like Robert Hooke, a physicist, [00:50] you know, discovers the cell. So, you know, there's so much that comes from physics and other [00:55] disciplines into biology to push it forward. But then I think in the 1900s, something kind of [01:00] fascinating happens, which is that for the first time, there's kind of this acceleration of tooling, [01:04] right? X-rays, NMR, all these things, you know, the cathode ray tube discovered, mass spectrometry, [01:09] but, you know, by this guy trying to find the mass of the electron, which is so cool. And so all these [01:15] physics tools are, you know, coming online, but then also more biology-driven tools. And so really [01:20] I think, you know, and we can get into this more specifically maybe later time, but kind of what's [01:24] excited us is just seeing the tools available to characterize life become available for the first [01:30] time ever, right? You know, for all millennia, you had Darwin and Mendel talk about genetics, [01:35] and there was no knowledge of what was actually going on at the ground truth level. And in 1953, [01:39] for the first time, you have the link between molecular biology and what we're looking at with [01:44] microscopes and genetics and this sort of concept of freddy, which is just super exciting. [01:50] And what caused you to jump in? [01:52] Well, I mean, A, I think I was born in like a very lucky time, right? I think you always have to be [01:57] sort of cautious or like, I guess, like a little bit concerned if you believe that about yourself, [02:00] right? Like, why now? Like, you know, should it really be the lucky time? But then I think also, [02:04] you know, as a kid, or A, just like had a lot of relatives that were, you know, sort of aging, [02:08] and that was very striking, but also, you know, really wanted to solve cancer. And I was, I [02:13] remember talking to my dad about this, and I was like, oh, like, I want to solve cancer. And he's [02:16] like, well, you know, cancer is a subset of aging. So if you want to solve cancer, you just like, [02:19] you know, solve aging and like, takes care of all these other things as well. And that just, you [02:23] know, that coupled with kind of like hanging off my grandma's were like, that just kind of made [02:26] sense to me as a kid. I was like, okay, well, like, you know, guess I'll go solve aging then. [02:29] Like, that's the biggest problem. Because cancer is not the number one cause of death in the US, [02:33] right? It's heart disease, something like that. Right. Well, you know, just like, if you look at [02:36] all the HLA diseases, you know, past this certain point are driving kind of like the majority of [02:41] sort of natural deaths, so to speak. So, you know, like, once we got rid of infectious disease, [02:45] like it really became the case like aging, which wasn't previously like necessarily the biggest [02:49] issue, sort of like rose to the forefront. Yeah. And so that kind of, I mean, it sort of just, [02:54] I think made sense to like a small trials that that was important. Huh. And so why raise a fund [02:59] rather than, you know, just go for curing cancer? So the thinking at the time was, you know, [03:05] possibly in a good way, like Emperor has no clothes, like extremely simplistic. Like, [03:08] you have to understand, so I was at MIT and I was like a sophomore. Yeah. And I was also 16. [03:13] And I had like maybe a thousand dollars in my bank account. And so like, you know, knowledge [03:17] about like the financial industry, like relatively low. My dad had been a public investor, so I kind [03:20] of knew a lot about like the idea of investing in things like that. That was a generally good [03:23] thing to do. And I'd worked in like aging labs for maybe four years. And I think the striking [03:28] thing was just like there was just like no money to like make drugs. And it's kind of hard, you [03:33] know, like when you're in a lab, you just have like no idea what's going on in the outside world. [03:37] And so I would like ask venture capitalists, like I would, you know, call up a few in the phone book [03:40] and like, you know, a few responded. And so like have these like random conversations and just be [03:44] like, you know, I'm just curious. I'm a student. Can you like tell me more about like how this [03:48] industry works? Like, you know, are you funding aging therapeutics? And like none of them had heard [03:52] of like aging therapeutics. They were kind of like Asian therapeutics. Like what did you say? [03:58] And so that was just very striking that like something that I personally believe, like on the [04:02] technology, like not just like from a mission perspective, like on the technology side was like [04:06] super exciting was kind of generally not really like looked at a lot by these folks who are [04:10] supposedly like the great translators of technology. And then I think also it kind of made sense, [04:15] like, you know, the first ever mutation found to really extend the lifespan was 1983. The next was [04:20] like 1993. And so really the field started about like 20, 30 years ago. It's like kind of made sense [04:24] like if you think about like how long it takes for a field to like get traction and like become known, [04:28] like, okay, there may be like less than a hundred good labs in this space. Maybe like people just [04:32] haven't had enough time on like the venture or like investment side to understand that this is [04:36] like really cool and important. And so like then it kind of made sense that like you might want to [04:40] start a fund if that were the case, like help more drugs going to get started out of the space. [04:44] Hmm. So in other words, like the big pharmaceutical companies are not investing in these pilot ideas. [04:49] They weren't at the time. So things are really- [04:51] So this was like five years ago or something? Yeah. [04:52] Seven years ago. Yeah. So things have really changed. You know, seven years ago, there were [04:55] like maybe like three companies have been started or so that had like the aging brand on them. [04:59] There was like zero people interested like Arch Ventures was one of the few that were like taking [05:03] risks. There's like maybe 10 million invested like that year in total of like the space, [05:07] right? And like in the past four years, we've had like 10 billion plus. We now see like 300 [05:11] companies per year. So it's just really changed. Like it's very, very striking to have watch it go [05:15] from like zero to like what it is today. Yeah. Now it's totally a trend. Hopefully it sticks [05:20] around. So you have not a million, but many questions for you. I think like on top of the [05:26] list for me is what you do personally. Yes. This is probably the most common question. [05:32] And I think all my friends will always say that I answer this terribly because I, you know, [05:36] I'm kind of like, you know, I come from a semi-scientific background and so like we like to [05:40] get like to the ground truth of things and it's just really hard. Like there's just like a million, [05:45] if you start reading mouse size and longevity, like you will find mouse size that say like if [05:48] you decrease like they've done this like really cool experiment where you take fat and sugar and [05:54] protein and you decrease the level of each of them and keep a total calorie intake the same, [05:58] you can kind of test like which component of diet is like contributing to longevity. [06:02] And they did this and they like did kind of like a full matrix and they'd like life span studies [06:05] for each of like the different proportions. And what they found from that study in mice was that [06:09] like decreasing protein was the number one kind of thing that increased longevity. And so from [06:14] that you might infer like maybe less protein is good, but at the same time, it doesn't seem like, [06:18] you know, maybe if you work out a lot, that would be different. And so I've come to the conclusion [06:22] that kind of like, you know, I have some theses about like what is good and what is not good. [06:26] But it just as a scientist, it's really hard to say that there's kind of like a good kind of like [06:30] real kind of like hypothesis there. Okay. And so I'm sure like not a lot of like, [06:35] despite like reading probably more papers on this than like most people in the world, [06:40] it really is something where I don't see things that I think are extremely clear kind of like [06:47] movers for longevity on like the diet level, obviously that like aren't confounded by other [06:51] things. So what's your diet? Well, I've tried a variety of things. I think right now it's just [06:57] kind of like the sort of like bare minimal, like try to eat low sugar. Personally, trying low protein [07:04] just because I think that is somewhat supported by kind of like literature. Yeah. And low protein [07:09] is like a gram per kilogram per day. I think just sort of like not it's a good question. It's like, [07:18] what is the correct per person? Also, if you exercise. I actually once tried to calculate out [07:23] if you exercise like how much protein would be required to like replenish like all of your [07:27] myosin and actin proteins. Yeah. And it's kind of fascinating. I think that there might actually be [07:30] like up to a hundredfold increase in power like in your muscles where like if they all fired at the [07:35] same time, you get like sort of a lot of power. But I mean, I don't have any strong recommendations [07:42] on diet. Like I really like I read basically all the studies and I think maybe low protein, low sugar, [07:48] are both good. Like intermittent fasting seems to be like somewhat supported. Are you doing that? [07:53] I've tried it. I think it's kind of hard to maintain if you like, you know, have a [07:56] graduating sleep cycle. But yeah, I wish I had better recommendations for that area. [08:03] Okay. And in terms of supplements, you doing anything? [08:06] There's a variety of people who recommend everything from NAD plus all the way through [08:09] to like Metformin for the kind of the more adventurous. I think that so we actually have [08:14] a secret list at the fund of like on market drugs and things that we think based on like our [08:19] like body of evidence might be having an impact on lifespan and we're monitoring them. Some of them, [08:24] I personally think would be like intriguing to take. We don't release that list just because [08:27] we were afraid that if we did and kind of like somebody acted on it and kind of like didn't work [08:31] out well for them, that should be like a terrible thing to do to like them. But we have a secret [08:35] list of things that we think are like interesting. Okay. And I think for the NAD plus though, [08:39] there's some evidence of like positive effect there, but we haven't seen great [08:42] lifespan studies showing like a large increase in lifespan. So that'd be like my one concern [08:45] there. Okay, cool. Because yeah, in the worm and mouse studies, there have been like, you know, [08:51] a hundred percent increase in lifespan, right? So worm studies, we've gotten up to tenfold reported, [08:58] you know, possibly more. That's by decreasing a gene product though. So that's kind of like, [09:03] if you want to go and take a gene therapy or we had such a thing, you know, from birth, [09:08] possibly like that would work. But probably the effect would be a lot smaller. In mice, [09:12] we've got about up to a twofold increase and that was a combination of a mutation and restricting [09:17] the total clork intake of the mouse. Okay. Down to what? I don't remember for that study. On [09:23] average, I think people will do CR to about 30% of normal clork intake, but it really varies. So [09:28] if you take 40 different, and this is where it gets complicated. You take 40 different, genetically [09:33] different strains of mice and you change their diet in the same way, half will live shorter [09:38] and half will live longer. And so, you know, I used to, as a kid, I was always like, oh, you know, [09:42] like there's a simple answer. And I think that there is, but I think it is a lot more sort of [09:47] reliant on genetics and other things than we'd like to think. How long have your family members [09:55] lived? How long have my family members lived? Your grandparents, great grandparents. Well, [10:00] my grandma is still going. She's in her mid nineties. It's a good sign. Yes, exactly. So [10:05] they've all lived, you know, about age 80 or above. So, you know, hopefully, [10:09] how about yourself? How long is your family? Not 90. So yeah, we'll see how it goes. I need [10:14] it more than you. Right. What would you say the number one health hack that you'd recommend to [10:20] your audience would be? I mean, well, I mean, I've done a little bit of blood work, so everything's [10:25] kind of anecdotal and based on feel. Yeah. But I was vegetarian for eight years. Oh, interesting. [10:33] For environmental reasons. And then I realized that I had like developed this entire vocabulary [10:39] around cheating. So, for example, if I was traveling, it was like cultural meat and it was [10:45] allowed. And then, you know, if I was like, you know, over your house and like you made chicken [10:50] or something, I'd be like, whatever, I'll have it. I see. And at the point it was like twice a [10:54] month. I was like, I'm not vegetarian anymore. So I started eating more protein, but really just [10:59] more eggs. And then I felt a lot better. But really the main thing is sleep. Like, yeah, [11:04] prioritizing that. That makes sense. I will say that actually one thing that's interesting on the [11:08] health plan front, I think people have this like intuition that when they feel better, that's a [11:12] metric for something that's good for them. Yeah. I think it's actually not true. So if you look [11:17] like a lot to some extent, like, you know, maybe you want to optimize like robust, very cheerful [11:22] lifespan, in which case, like, like tautologically it is. Yeah. But most of the time or a lot of the [11:27] time when you see our mice or you do other things like make them live longer, so total number of [11:31] years increases, they're not kind of like as happy on a day to day basis, like a little bit thinner, [11:35] a little bit more lethargic in some cases. So I think it's kind of like, you know, whenever someone [11:38] says like, I really feel better because I'm doing X, I'm always like, oh gosh, like, I wonder if [11:41] that's like the correct thing. Like maybe, maybe not. Hard to say. When people talk about health [11:45] span in my mind, it's very correlated to how I feel. Right. If I was going to do caloric [11:50] restriction and every day would suck for 90 years, I would opt out. I mean, I don't know [11:56] if there's a drug. I, for instance, like, I know a lot of people who have experimented with like [12:00] keto and other random diets and they're just caffeinated to the gills. Like, there's low energy. [12:07] That's so funny. That's one thing you can do. Oh my gosh. Yeah, that's hilarious. Yeah. So I don't [12:12] know. But one thing I've been curious about, like, there seems to be relatively limited data on actual [12:18] humans. Yes. So how, how might someone set up a study? Is it even possible now or is everything [12:25] so regulated? There is this fellow in your bar's light who's working on what's called the TAME [12:28] trial. And the point of that is to assay the effects of this drug, but form, which is a very [12:33] old diabetes drug on sort of markers or biomarkers of aging that he has kind of like put forward. [12:40] And the cost for that will be about $61 million. And if people do it, the idea would be, okay, [12:44] well, here's our first pass at testing aging in humans. And so finally we have some more data. [12:49] The way that trial was sort of motivated was there was this kind of large finding that in [12:55] hundreds of thousands of patients, or I think about actually 70,000 in that population from kind of [12:59] like a UK study. If you look retrospectively, people who had been taking med 4-1 for decades, [13:03] they had apparently like a little bit better kind of health span. So they had less HLA disease. [13:09] The diabetics did on this drug, even then they're kind of like non-diabetic counterparts who were [13:13] not taking that form in. And so I think that hard to say that studies like definitive evidence, [13:18] but that kind of motivated all this sort of question asking of, could we really nail down [13:23] in humans a trial to like test, you know, met form in particular. That said, you know, I think that [13:29] a lot of biologists will really kind of say, oh, it's very important to test things in humans. And [13:32] of course it is, if we could do that, we would be doing it kind of all over the place. [13:36] But I think increasingly over the years, and maybe it's just like I started out in worm biology, [13:40] I'm kind of like more and more excited about like the animal kingdom. Like, you know, the animal [13:44] kingdom is just like absolutely awesome. Like we have one company in our current sort of, you know, [13:48] sort of portfolio that's working on this and they're amazing, you know, fauna. But kind of like, [13:54] there's such diversity of phenotypes, right? And like, how can we learn from other animals [13:58] as opposed to just like our lowly selves? Because like, you know, for example, there's naked mole [14:02] rats and rats, right? Like naked mole rats are pushing 30 on lifespan. Like we have no idea how [14:06] long they live. Like their mortality rate at 30 is not going up. So we're just like watching these [14:10] guys like waiting for them to start dying. And then like rats, which have like very similar [14:13] physiology, live maybe like three to four years. And so what on earth is different between these [14:18] two animals, right? Like that's just absolutely fascinating. I think it's also important because [14:23] like, you know, a lot of like, you know, physicists and mathematicians that I used to be this way, [14:27] like we're always worried, what are those like inherent like limitation on like the complexity [14:31] level? Like what if given a certain complex system, a certain rate of metabolism, like [14:35] you have to die because there's some kind of like, you know, sort of theory about like entropy [14:39] increasing over time and that like, you know, must drive and just like too complex like really [14:42] intervene. But then like, you know, these animals are basically the same size, like have so like [14:47] so many other similarities. Like it would just be very hard to maintain like that theory and also [14:51] accept this kind of like large differential longevity. Yeah, absolutely. So someone asked [14:55] a question that I thought was kind of funny. Yeah, here we go. So Micah asks, basically, [15:00] do you think immortality is going to be achieved by curing all diseases? So in other words, like [15:05] living forever or like what's going to happen first that or are we going to just upload our [15:10] consciousness to a computer and live forever that way? I think that so that that was a question that [15:17] I used to get very interested in sort of like, well, you know, if you really care about this, [15:21] like you're working on kind of like the biology. Yeah, where do you work? Yeah, exactly. I think [15:24] so the way the way I kind of think about it, which is not a good answer, but it's kind of [15:27] a framework for thinking about this question is I think about biology like a set of tools, right? [15:32] So you can kind of see this in like the kind of like things that have become available recently [15:38] for us to use to affect human health. What I mean by that is like, you know, prior to like, [15:44] you know, the 1900s or like even like just the 1980s or maybe like the 1930s, [15:49] like the first time you look at this marker, if you wanted to make a drug, it was like a small [15:52] molecule, right? It was like you got a plant, you found something from a plant that was useful. [15:55] Or you like put some salt on a wound, which we realized that's a bad idea. Don't do that. [15:59] Not very good for sterility. There are things you would do. But then like, you know, in the [16:04] 20th century, for the first time, we use like proteins, you know, insulin or antibodies created [16:10] by like our own bodies or the bodies of like the mice that like we kind of cloned them in [16:14] to treat disease. And so we actually use something that came from life to treat, [16:18] you know, kind of like a living organism. We now just in the past kind of three years have like [16:22] landmark approvals and viruses being used to like blow up cancer, literally, like these are called [16:26] oncolytic viruses. There's new drugs using genetically engineered cells. You've probably [16:32] heard of, you know, CAR-T and kind of like this whole kind of, you know, oncology phenomenon, [16:35] also stem cells being used. And so I think kind of like the final frontier of all of that, [16:39] like use of kind of like biology's own system to do cool stuff is the brain understanding kind of [16:43] like that system. But I think to lead up to that, you kind of will do so many things that it may be [16:47] the case that like we kind of get there at the same time, right? So, you know, like that's like [16:50] the final frontier and we solve it, but kind of like along the way, we've also kind of like done [16:53] enough work on the other tooling kind of fronts that we get to kind of like to a kind of, you know, [16:58] maybe we don't solve kind of like lifespan itself, but like longevity is definitely impacted by kind [17:02] of like the work up to that time. Right, exactly. And do you sense that there's like a strong signal [17:07] at this point as to what might be the way that we, you know, a bunch of people ask these questions, [17:12] but like, you know, increasing lifespan, like 20%. Like, if you had to put money on it, obviously, [17:18] you literally put money on it. Yes. What would be the most likely thing to take off? [17:24] The most likely thing to take off in the next 50 years. So here's how we think about it. Like, [17:30] we have extremely strong confidence that it's possible to impact lifespan between like, you [17:35] know, three months to maybe 10 years. Yeah. And, you know, obviously like, you know, different [17:39] probabilities with what we have to in fact, we're pretty certain that there are some things in the [17:44] clinic already or on the market that with some probability are impacting lifespan. Like lifespan [17:50] seems to be very malleable, you know, to a small degree. I think the larger question is like, well, [17:55] you know, A, how many of those can you like put together to like get kind of the maximum impact [18:00] from like that first wave? And then B, our thesis is that none of those things will be sufficient [18:06] on their own to result in like an engineered lifespan. So you have this first wave of things [18:09] that like kind of work, but like they're kind of limited. Like they have kind of like a maybe like [18:13] 60%. And that's like the max. So then the question is like, how can you like go above that? [18:18] And we think that really all comes back to tooling. And so that's where I don't know if I'm, [18:21] you know, we're Aristotle or kind of like we're like Newton or like maybe like in the best case [18:25] scenario, we're like Einstein or like, you know, of someone today in the realm of physics in terms [18:29] like going to the moon, like you've tried to go to the moon and kind of like 1600s would be a [18:32] little bit hard. More recently, maybe a little bit easier. But like, I think that's where we have [18:37] some hope and optimism, but we're not as confident that there are things today that we'd point you [18:40] to say that's going to result in kind of like unbounded engineered ability to kind of like [18:44] impact longevity. And that's why we also really care about tools when we think about like investing [18:48] in the space, not just kind of the first wave of like awesome therapies that will be available [18:51] sooner, but like maybe aren't as kind of like engineerable. Right. So you're kind of hedging [18:55] if this is still foundational stage. Right. Exactly. I think we'd love to think that it is. [19:00] And like, yeah, like 1953, my argument for foundational stage would be like, this is the [19:04] first time ever in history that we have the link between genetics and microbiology. Like that happened [19:08] in 1953. That's pretty landmark. Maybe it's been 70 years. You're like, well, what happened in 70? [19:12] Couldn't it just have happened like right after 1953? But I think that'd be the argument for like, [19:15] that's why today makes sense from like engineering perspective. Okay. [19:20] And then ethically, you know, Ryan Hoover asked like about the ethics of longevity. Another, [19:26] Jack Fernandez asked like, people want to actually want to live longer. [19:31] Do you have strong opinions on this or are you kind of stepping back? [19:34] So we get asked about this all the time. And it was funny because when I started the [19:38] fund, I never thought that people would ask those questions. Yeah. Because to me, the reason- [19:42] You thought it was assumed. Well, because the reason we started the fund was to cure like [19:45] things like cancer and Alzheimer's. And so like from our perspective, it was like, well, you know, [19:49] like you would never ask like, is it good to cure cancer? Like no one would ever ask that question [19:52] that I've heard of, or maybe some people would. But then we realized that like when people think [19:56] longevity, they think about it as different than those things. And so I think like, you know, [19:59] from our perspective, like I just, you know, I think it makes sense to cure like these diseases [20:04] if we can. And so we definitely wanted to do that. And so like, you know, we would never deviate from [20:10] kind of our mission. I think, you know, from a broader scale, it's kind of like two camps. So [20:13] like, do you want to be like Malthusian? And you're thinking of kind of like, you know, the world is [20:16] like a bounded place. Like, you know, it's really like limited resources or like kind of like David [20:20] Deutchian, like, you know, like, you know, we're on, you know, spaceship Earth, but like, no, [20:23] we're not to actually like, let's go and like explore the cosmos and kind of like unlimited [20:26] resources and energies like in all matter. I think like just like kind of like from a [20:31] like philosophical standpoint, I'm more on the kind of the latter sort of camp. I like that kind [20:35] of viewpoint a little bit better. But yeah, I think to us, like just the like the rationale for [20:40] longevity really was let's cure age-related diseases. How do you do that? You work on aging. [20:43] Hmm. And yeah, maybe there are multiple universes where we live. I'm trying to get David on the [20:49] podcast. I met him one time when we talked about it. Really? Yeah. Would you have to like go to him [20:55] and his house? That's what I did when I met him. That would be the best interview ever. Yeah, [21:01] he did one with Sam Harris. That was kind of cool. Oh, my gosh. But but really, like in terms of [21:07] having an actual opinion on this. So there was a cool one on the ethics. Mike asked, how would [21:12] immortality change society? Wouldn't we become more complacent since we have to quote forever to do [21:18] things? Wouldn't that diminish our rate of innovation? And since less new individuals [21:23] are being created, we would have less access to new ideas. In other words, like there are fewer [21:28] Newtons, fewer Einsteins. And sort of this is like why the basic income argument or one of the basic [21:33] income arguments, right? Right. We allow for these people to succeed. Well, so I think there are two [21:38] implicit assumptions there. One is that we understand how people are motivated and that [21:42] their motivation stems from this feeling that like they will die. Yeah. And I think number two is [21:46] this idea that like people have an innate kind of rate of loss of new ideas of age, kind of innate [21:52] loss of openness. And so I think addressing both of those on the first point, I think they're kind [21:58] of all questions. I don't think that that's true personally. I don't think that I'm motivated to [22:05] do things because I know that I'm going to die. I think that perhaps everyone else is, and this is [22:10] just kind of a personal thing, but I think I'm motivated by many things like curiosity, competition, [22:14] sort of like personal growth, kind of like wanting to be better next year than like was today, kind [22:20] of like a sense of mission and importance, kind of like it's important to go do certain things. [22:25] I think if you ask most people, maybe they'd have different answers, but I'm curious if death [22:31] really is like the core kind of like motivator to do things for everyone in the world. That's one [22:36] thing. And my result is a few people wanting to go to war, which might be problematic if you kind [22:40] of like want more war and more soldiers, or not if you would like less war. That would be an [22:45] interesting thing. But I think for that question, I don't agree that we really understand like the [22:49] core motivation of everyone on this planet and that that is by definition the fear of death. [22:55] I think the other thing that's interesting is sort of to the second point, [23:00] the question of like loss of ideas with age. There is a lot of like just cognitive like [23:05] change with age, which is very fascinating, right? And sort of like biologically you do change. [23:10] And like part of what we really want to do is impact aging, but like a large part of it, [23:15] we can just make a cognitive enhancer. So you were like sharp until you're nine and then you [23:18] dropped. That would be equally like that would also be like an awesome product in and of itself. [23:22] Just cognitive enhancement alone would be great. And so I think actually people kind of like [23:27] undercounting the value of potentially if you're a Newton, absolutely brilliant. And you help [23:32] develop a field and maintain your 20 year old openness and kind of like fluidity for 100 years, [23:36] all the way through to age 90. Like what insane kind of ideas with Newton becoming up with at [23:40] age 90, like with that kind of openness. The counter argument there was like, well, he would [23:44] just go into alchemy and something you have like, you know, young Newton being great and then like [23:47] older Newton like doing alchemy. The counter argument is like, well, maybe alchemy like caused [23:50] a decline in thinking because like he was sniffing too much mercury. So I don't want to counter. [23:54] Yeah, you almost won an argument for like outsider scientists who don't get discovered until they die [24:00] and then they have like 100 years of portfolio. Right. And they're also just, I mean, like so many [24:06] people, like, you know, some incredible physicists at Stanford who are still amazing and coming with [24:10] extremely novel ideas and like, you know, Hawking publishing on like black holes and entropy, [24:14] right? Like this final paper, like on this completely novel, fascinating field. [24:18] And like, was that like, you know, was he declining? Would we like Hawking to kind of like step aside [24:22] for like the younger generation? Like, can't we have both? I guess would be a question. [24:26] Interesting. So would you be a proponent of like, you know, giving the entire or like [24:31] somewhat like fluoride in the water, putting like provigil in the water? [24:35] I think that I'm never a fan of things that don't involve individual choice. [24:38] So anything that like would be sort of coercive or kind of like enforcement, then like, no. [24:42] But I mean, so if everyone would sign up for it, then like, I do think that, you know, there's [24:46] like all this fascinating work on cognitive enhancement, like just starting to come out today. [24:50] And that's a, we've seen a lot of companies that we're super excited about that have to do with [24:53] kind of like, you know, making your neurons kind of like make more sign-ins, increasing the like [24:57] rate of division or, you know, hypothetically, I think that aerosol is a bit contentious, but, [25:01] you know, like that to us is kind of like, that's part of longevity. If we just had a [25:05] pill for like cognitive enhancement, you know, that in itself would be like absolutely wonderful. [25:10] Like limitless. [25:11] Yeah. I mean, everything I've tried, I think it's, yeah, it works. There are some times where you [25:18] get this feeling that you're, you know, you're really good at like your crush and email, but [25:21] you're not the most creative and you're just like sweating the whole day. [25:25] Not coming up with the deep thoughts. Yeah. It's actually fascinating. I remember this book, [25:29] Daily Habits. I would actually, I think you might like it. It's the daily habits of mostly writers [25:34] and artists, but it's super fascinating because the details kind of like how they live their life. [25:38] And it's just extremely variable. But the most common thing is that they all wake up and go to [25:42] sleep. They have a very set routine. And when they wake up, do work and go to sleep. [25:45] I'm already on that cycle. Yeah. I mean, what a thing I have found is that my [25:53] mornings are just much more valuable than my evenings. Especially in the middle of the day, [25:57] like I'm just kind of useless. So I just work out at like two in the afternoon. [26:01] I'm curious why that is. Like it's either biological or psychological, right? Sort of like, [26:05] you know, you get like too much loaded into your brain and you don't want to think. [26:08] Or it'd be really fascinating if sleep played a key role there. I would sort of like sleep does [26:12] something biologically and perhaps psychologically that like somehow induces like an optimal state, [26:16] like right when you wake up. But yeah. Have you tried it? Like sleeping in the middle of the day [26:21] and then just getting back to work? I haven't, but that's an interesting idea. I'm curious what that [26:25] would do. Possible. Interesting. Yeah. I'm so curious about cognitive enhancement. We did a [26:31] podcast with Rosalind Watts, who is at Imperial about psychedelics. Oh, that's awesome. [26:36] Where it's awesome. I mean, it's, it's very similar. Actually her research with Robin Carhart [26:43] Harris at Imperial is in Michael Pollan's book. Oh, interesting. No, I did. I've heard so much [26:47] about it though. It's really great. But I mean, it's kind of like cognitive enhancement in a very [26:52] broad sense in terms of like trying to break you out of your old habits and like have more confidence. [26:58] Increase openness and yeah, exactly. And so are you, are you taking anything to like any in the [27:04] nootropic sense? No, I think I don't even do caffeine because the general thought is like try [27:11] to wean yourself off of everything kind of like if you can perform great there, then like perhaps [27:15] someday like there'll be a safe stuff that comes on market. That's, that's worth, worth trying. But [27:20] yeah, I also like, I like Marcus Surrealist like Stoicism is like the idea of kind of like, [27:23] you know, none of the necessary things, but like maybe there's some application of that philosophy [27:26] that I think about it. Yeah, some part of that just makes me angry. Like I just really want to. [27:31] Well, it's like at all, you know, kind of like the caloric, I'm, I don't know, I'm a dichotomy. [27:37] Like it's, it's all stretched apart because I'm very much a creature of habit. Okay. That being [27:43] said, I like caloric restriction, not having like a beer with my friends, like all of this stuff. [27:49] I just like, don't, I'm not doing it. I'd rather, I'd rather work out an extra time, but then, [27:56] but then some people say like, that's bad for your heart. Right. You know, like you can't win. [28:01] Yeah. So I don't know. I feel like in some ways it's like the devil I know. And I just avoid [28:08] other vices like texting while driving and smoking. That's interesting. [28:18] Hmm. What is like the thing that you do that you're the most proud of, like the habit that [28:21] is like the hardest for you to maintain that you never the less are kind of like quite happy to [28:25] like be able to do? [28:29] I mean, exercise is no problem because I go crazy. I go crazy without doing it. Right. [28:37] I think what's consistently the hardest to maintain is giving energy to the side projects that [28:45] are creatively demanding. Oh, that's interesting. Because I, this is what I didn't expect. I used [28:52] to work for myself and now I work at YC and obviously, and there are obviously like you [29:00] have so much energy in a day and obviously you can like push harder and get work done and like be [29:05] more disciplined. But I found that like there are certain side project ideas that are just kind of [29:14] like too much to even think about. Oh, interesting. And so I'm, yeah, like when I, when I make progress [29:20] on that, I'm very happy with myself because the side projects that are like, you know, [29:24] I've like made like little SaaS tools and stuff and that's cool, but it's definitely not the [29:30] hardest thing. And what like allows you to make progress on those projects? [29:36] Just internal motivation, like wanting to do it. I think the, what's always helpful is just imagine [29:43] yourself in 10 years and like look back. Oh, interesting. And then just use that as a metric [29:49] for like what you want to, would you be proud of yourself for having done that? [29:53] That seems like something like the, the business framework of like, you know, when you're 60 and [29:56] you kind of look back on your life. Yeah. That's interesting. But then, but it's dude, it's like, [30:02] who's to say what's going to lead to the next thing? That's great. So like, you know, all right. So [30:08] before we did the podcast, like I was talking about working at the onion, right? Right. And now I'm [30:12] here. Yeah. And you're like, that's not a standard trajectory. Right. So you can't really say [30:20] authoritatively, like the best way to spend your time is X. But when I, when I was a kid, [30:29] someone said to me, like, before you start working on something, think about what winning looks like. [30:34] And that's kind of a framework for projects for me. Oh, that's interesting. But I don't know. [30:41] That's a personal thing. What other like hacks and motivations like do you have in your arsenal? [30:52] I just don't spend time with people that annoy me or like stress me out. [30:56] Okay. Yeah, that's a positive thing. I am never busy, but I am fine using that excuse. [31:06] Oh, you're never busy. I always have time for my friends and like the things I really want to do. [31:12] And I just cut everything else out. So I don't know. How about you? [31:17] That makes hacks and motivations. I think it's like always trying to keep the baseline pretty, [31:24] pretty low, like kind of, you know, like, yeah, like I think like you can, you can control like [31:29] your output, but you can't really control like how the world responds. So it's kind of like, [31:32] if you're just like, all right, if I do good output, then like, that's great. And then like, [31:35] how are the world responds? Like can't control it. But like, like being really happy when you [31:39] do stuff that you can control is, I think, probably the biggest like mental hack for [31:43] because I mean, you just can't control. It's so hard because you're, you're still pretty young. [31:48] How old are you? 24. Yeah. So I remember when I just moved out here, I am. How old were you then? [31:56] 23, 23. Oh, interesting. You just come out of college or? Yeah. So what happened was, [32:03] I was in New York for college and then I lived there for like a couple years afterwards. [32:08] And my girlfriend and I split up and I was like, I'd always wanted to live in California and New [32:13] York was just like grinding at me. And so I just moved out here. Oh, interesting. Wow. [32:20] Which has been cool. And so when I. Did you have a job or something or just like moved out? [32:25] So the onion moved from New York to Chicago and almost everyone left. And so I started a company [32:31] with my friends and we were doing these hackathons where developers and comedians made stuff together. [32:37] And it's like it was a total not startup, total small business. Super fun. Yeah. And we did one [32:45] with Twitter. And so I moved out here for that thinking I would be out here for like months. [32:50] And now it's like whatever, six years later. But what about California was like so different [32:54] for you that you had to stay here? Well, I love doing outdoor stuff for sure. Okay. [33:00] But it's a trade. I don't know. Everyone wants to talk shit both ways. And it's totally a trade. [33:06] Culturally, it's not the same thing as New York. But then if you're working in like [33:09] tech, this is where or entertainment stuff. I mean, New York's kind of mix, but there's L.A. [33:16] It just seems so much so much more professional, not in like the Polish sense. Yeah. Like everyone [33:22] is like most people are here. And that's cool. That was cool to me. Like going to these like, [33:28] you know, coffee shops and seeing, you know, this person that I only seen on the Internet before. [33:33] And I was like, man, all this shit's happening here. That's interesting. But I don't know. [33:39] How do you think these have changed? And also, sorry, I don't want to like to, [33:41] but how do you think they've changed in the past seven years? Or I guess, [33:44] has it been seven years for you or something like that? Yeah. What has been the biggest thing [33:48] that's changed? Like I either both positive or negatively or neutrally in myself or in the [33:55] in like the environment that you've seen from like, oh, yeah, that's super easy. Tech is [34:00] completely vilified. That's been the biggest. Oh, interesting. Yeah. Yeah. I mean, it's like if [34:05] it's not this next election, it's the one afterwards. Like tech is the evil thing. Interesting. [34:11] And what did you see? What drove that or kind of. Well, in some ways, it's like an incredible amount [34:20] of wealth being accrued to a small amount of people. They're young. And I think their [34:27] amount of power is just off putting to so many folks, obviously with the Facebook thing and like [34:34] Gerard, like you have like the person to vilify and it just feels like the new banker to me. [34:40] And that's the that's been the shift. Not a great precedence. [34:45] And I don't know, because have you noticed anything? [34:50] Honestly, I think it's kind of like in bio is just, you know, no one pays attention to bio. [34:53] Like we're just all the way over here kind of like, you know, working on things that take [34:57] a really long time and are very like hard and expensive. And some people are like, oh, you know, [34:59] they're still over there, like still working on drugs. And I don't think as much. And they're [35:03] like very few. Weirdly, there are very few billionaires in biotech. I think this is something [35:07] that was very striking to me when I first came out of sort of like I was looking for people who were [35:10] amazing and also made like a lot of capital and biotech, like those are the people who like would [35:14] be successful and like know how to build business as well. This was my thought. [35:18] And there are very few of them. A lot of them were in VC who had invested in these companies. [35:22] I was like, where are the founders not getting the capital that like, how does that equation work? [35:27] And then I think one of them was like a former salesman. It's like the most [35:31] informative meeting I ever had about sales. He was just like, because I was trying to understand, [35:34] like, how do you sell a business or an idea? And like, you know, from MIT, it's like, you know, [35:38] complicated, like read a textbook about it and like write. And he was like, you just sit the [35:41] person down and tell them what to do. I was like, okay, now I think I understand how this like whole [35:48] area of like life, you know, what, how to communicate a little bit better than I did previously. [35:53] That's so funny. Yeah, I really hope more of these companies, I mean, they are popping up [35:58] already. Like you've seen longevity biotech. And if there is any kind of lull in the ecosystem, [36:04] it's just going to be like fertile ground. I think there's been historically a lack of like [36:09] founder different companies. And like, obviously, the funding environment has changed to make it [36:13] more likely to happen like the next couple of years. But it's just so strikingly, it really is [36:17] different when you have like, because I think if you look at like the wealth created in tech and [36:20] in biotech, it's like, you really see the distribution, you know, going so much more to venture capital, [36:24] I think, than to founders. And that was just, that's been like really, that was a really weird [36:28] thing to kind of like observe on like first coming here. So like, why is that the case? [36:32] Do you have different terms than normal VC funds? [36:34] Well, I mean, for our funds? [36:37] Yeah, I mean, if that's a like a strong opinion you have, like, what are your terms? [36:41] Yeah, well, by definition, like, you know, we have H1, so you know, so much what you folks are [36:44] working on, like, you know, that's founder driven, that's, you know, sort of trying to get people, [36:49] you know, sort of leg up and promote kind of like grad students, postdocs as the founders of the [36:53] company and like not try to replace them. Yeah, I guess like, like kind of some other firms, [36:56] which I think is a fair strategy if like that's, you know, sort of, you know, something that's been [37:01] your bulwark for like decades. But I mean, I think marketers would say it's similar to what's [37:06] happened in software, like, you know, you had this first wave of kind of like professional managers, [37:10] you kind of like a swing back to technologists, you kind of like a swing back to the middle of [37:12] kind of like, now we'd like some more managers, please, but like, you know, still technologists [37:15] are kind of driving the show. I think in bio, we might be kind of like midway through that, [37:18] we're kind of like, we've had like the managers period for a long time, we might have more [37:22] technologists. And then like, maybe kind of like swing back to the middle. That's like a pretty [37:26] simple pattern match. Like, you know, who knows what will happen in the future? [37:28] Hmm. Yeah, because the that's interesting if it's a trailing thing from software, [37:34] because you probably know. Yeah. So what's happened now is like maybe 10 years ago, [37:38] or when YC started, it was incredibly rare for you to be able to just like pitch an idea. [37:43] Exactly. Now you can easily do that. But more importantly, you can I mean, I hear crazy numbers [37:50] from people leaving college and going to work at Facebook or big companies. And I think that's like [37:54] overall probably bad for the ecosystem, because like it encourages this like extreme risk aversion. [38:00] Right. And I think the likelihood of lifestyle inflation and never starting something is high. [38:06] But think about so what enabled YC, right? AWS, from the outside, a huge part of it, right? Like [38:15] the first ever ability driven by tooling to kind of spin something up really cheaply. [38:20] And I think in bio, and it's like what everyone talks about, sort of like, you know, there really [38:23] was this point where like, you know, dropping cost of sequencing has been occurring over the past, [38:27] like, you know, 18 years. But really up until like the past two or four years, you could not [38:31] get a thousand dollar genome, right? Like that is a recent phenomenon. And so what argument would be [38:35] like, you know, look at like Illumina's revenues, you know, like today, it's absolutely crazy how [38:40] some of the art like Intel's revenues, like right in the 1970s, or like the parallel there is like [38:44] extremely. And this is like, you know, our friend of mine may to like notice this, but kind of like [38:48] there's just like this really striking parallel between like the enabler technology that we kind [38:52] of see, you know, in kind of like one segment and then kind of like what's happening about today. [38:56] And who knows what will happen in the future, but there is an interesting parallel there. [38:59] Hmm. Huh. Would you think there are people in labs? Well, actually, like what percentage [39:05] of people working in labs do you think want to start companies? So this is the fascinating thing. [39:09] So we were we were curious about this because if you look at the amount of funding that's available [39:13] on the venture side to go into biotech in the past couple of years, it's insanely, I mean, [39:17] it's double tripled in the past couple of years alone, but the number of companies funded has [39:22] stayed fairly constant. And so we're just looking at this like, what the heck is happening here? [39:26] Right. And what's happened is like the number on the top end of like the median hasn't even [39:30] changed. It's like the top end of court, like the top court of companies are getting more capital [39:33] per company. So it's like all capital has come from LPs because you've seen like, you know, [39:38] the nasdaq biotech index, you know, go from like stagnant, you know, up until 2011 to like [39:42] monotonically increasing or with a small dip. And then it's like, where do you put all this capital? [39:48] There are no more companies to invest in. And so we were like, well, why are more people [39:51] not starting companies? We went and talked to like a hundred grad students and postdocs [39:55] and the answer they gave us was like absolutely striking. It was like most of them. So it may be [39:59] like, you know, 10% were worried about reputation risk. Like they didn't want to leave, fail and [40:02] then go back. 80% had never thought about the idea of starting a company. They just were not aware [40:07] that it was a possibility. And so you could argue, okay, maybe that's like they're not [40:11] entrepreneurial. But, you know, if you think about like, you know, in the eighties or the nineties, [40:14] like would you have gone as a CS student at Stanford, like started something? Maybe. [40:18] But like maybe you'd have a lot higher of a barrier or bar to doing that. I think that's [40:21] part of why she started something, that process easier. And so I think really what it's like, [40:25] it's just a lack of education and kind of like just availability of options to these people, [40:30] which is like, makes you so angry, right? Like, you know, like you should never be forced or kind [40:34] of like convince you something that you don't want to, or that's not good for you. [40:36] But you should be aware of your options. Like how are all these smart people [40:40] not aware of like all the possibilities that are out there for them? [40:43] I mean, I think the saddest slash funniest one I've heard is when someone often in like a hard [40:50] science, like lab or background, they learn about YC and then think that we're just giving them [40:55] loans. And they're like, oh, no, I can never do that. Yeah. Which is like, I mean, I don't know, [41:02] if you had no exposure to this, like, why wouldn't you think that? I mean, like, [41:07] and all of these myths exist, but I think the education thing is a good point. For the most [41:11] part, people don't even know. That's absolutely crazy. Yeah. So you should talk about your, [41:16] I mean, do you have, dude, you have so many questions, but you should also maybe mention [41:20] your project, Daniel, if, because that's relevant. Yes. Yes. Yeah. So I'm super excited. So my friend, [41:26] Daniel Gross started this really, really awesome sort of project called Pioneer. [41:32] And what Pioneer is, is it's trying to find like the lost Einstein's of the world, [41:36] which I think is like an awesome tagline. And I think Danny has a fascinating background in that. [41:41] He was kind of on track to join the Israeli army and then uploaded applications to YC. [41:47] And basically his whole life changed after like one flight out here and a meeting with [41:53] Paul Graham and sort of like this, you know, he's not this incredibly successful person, [41:57] but kind of like, you know, would he have had the same chance if not for like a lucky, [42:00] you know, I think his dad forwarded him like an article about YC, like that was how he found out [42:03] about it. Right. Really? I don't know. I think that's one thing you mentioned. So it's like, [42:07] this coincidence that kind of drove his journey. And so the question is like, you know, how many [42:10] people are there out there that like with a small intervention could like, you know, drastically [42:14] have like a different life course. And so Pioneer, sort of Pioneer.app is this place where if you're [42:20] anybody in the world and you have a project you want to work on, you can apply. It can be anything [42:24] anywhere from kind of like, I want to have more of my high school friends do like science stuff all [42:28] the way through to like, I'm 80 and I finally want to write my novel. And, you know, there's [42:33] a thing called the Pioneer Tournament where people work for about 30 days, kind of, you know, do [42:36] their projects and kind of like the community votes like on their kind of like most kind of, [42:40] you know, favorite people. And they kind of based on that at the end, you know, a set of people [42:44] are selected to like be flown to San Francisco, you receive about like a $5,000 grant and they [42:48] kind of like join the Pioneer community, which is kind of like this, you know, set of really [42:51] ambitious outsiders trying to change the world. And so I resonate this because like, you know, [42:56] my personal story was coming from New Zealand at age 12, you know, based on like a random email [43:01] I sent to like a professor here and it was the first time I ever sent to like someone who was [43:05] on a family member and she responded. But if she hadn't responded and like that luck hadn't occurred [43:09] and like, you know, where would I be? I have no idea. And so that's why I think it's just like [43:13] Pioneer is so exciting because it might help a lot and everyone who's listening, like you should [43:17] definitely, definitely apply. Pioneer.app. I think it unlocks so much potential of like everyone in [43:22] the world who like could be doing awesome things. I think it's so cool. Yeah, just enabling people [43:26] to like have the confidence thing has been the biggest surprise for me at YC. Oh, interesting. [43:32] I think a huge unspoken part of why YC is successful is that it gives people the confidence [43:39] to do their thing. Right. And they're often like, I mean, sometimes it's insider, you know, like [43:43] tracked, like I went to Stanford, whatever. But sometimes it's like total outsider people [43:48] and it works out. And I think that like, yeah, man, without systems that give people that [43:54] little extra push, a lot of people will never do it. Ah, interesting. It is counterintuitive. Yeah. [44:01] I mean, it's crazy, like, because I do these office hours occasionally with people who are [44:05] interested in applying, right? And they're awesome. They're great. And all it takes is like that one [44:11] meeting where you're just like, you're good enough. You can do it. And that's it. That's so [44:15] fascinating. And then they apply. Huh. It's crazy. Interesting. Yeah. [44:23] I mean, I think one of the fascinating things that Danny's going to run into is sort of like, how do you [44:28] give that to like, how do you scale that feeling of like transmitting confidence? [44:35] It was like, you know, yeah, it's non-trivial. Well, you asked me about podcasts before we started, [44:40] right? And so this is like a crazy side effect of podcasting because it makes you feel and the [44:50] thing it makes you feel like you know someone really well. But the reality is you kind of do. [44:56] And so that like that relationship of someone as like, whatever, just like friend or mentor or [45:04] whatever, is enough to be like, oh, like, I kind of get this. I can be myself with them and I can [45:12] kind of just like express whatever I want to do. But then there are totally like weird elements for [45:16] me. Like I'll be like in the bathroom at demo day, literally, I'll be in the bathroom at demo day. [45:21] And like someone will like tap me on the back and be like, oh man, I like the podcast. Like, cool. [45:24] Not now. That's so funny. Do people feel like they know you from hearing so many of your [45:30] conversations with others and kind of like how you think about the world? I guess like, because [45:33] you said that one thing that you find fascinating is like how other people think about the world. [45:36] Yeah. I guess like the way that you ask questions must give so much information about how you [45:40] build models or view systems or how stupid I am. Yeah, no, I mean, I don't talk a ton [45:51] about myself. I mean, I do. But yeah, people get the sense. And I was actually thinking about [45:56] talking to my friend about this this morning of like, what is it about the how am I different on [46:02] the podcast versus in real life? Because there's like some distance for both of us, right? There's [46:07] like going to be some dissonance there. Right. And I'm curious about like how to best merge the two. [46:14] And I haven't figured it out yet because I actually don't know what the gap is. [46:18] So you don't know what your podcast is? I was about to text him and I didn't. [46:22] And yeah. Because I mean, you seem pretty kind of like on the surface similar. But yeah, I guess [46:30] it would be hard to know without one period of observation. Have you listened to it before? [46:34] No, just the conflict like our 50 minute conversation before we started and kind of like. [46:38] Oh, right. But I guess basically it's the same thing. Yeah, maybe. Huh. Interesting. Yeah, I [46:42] don't know. It'd be better if you were more like the person that you like. Yeah, like what what [46:49] authenticity do you think would would bring like that? Like you don't have kind of now curious. [46:58] So in some ways, I'm just selfishly interested in like making it something that feels more like [47:06] me. And it's it's my thing. Right. You're always curious about like [47:13] gains, you know, what can make the show better. Right. And when I think about the podcast that I [47:20] like, you know, things like Rogan, stuff like that. I mean, I mean, like that's not fringe, [47:26] but I imagine and this is again like projecting because I've never hung out with him. [47:32] I imagine that it's like very close to what hanging out with the person is like. [47:38] And then when I watch the podcast and me sometimes I can tell that I'm nervous [47:43] or not as like, I don't know, natural as normal. Do you think it's the environment? Like if you [47:49] if you made this like feel like you're living in that it would be slightly different or? [47:54] Um, yeah, it's possible. Yeah, it's totally. I mean, I think one thing that would be beneficial [48:01] is like hang. I mean, you're this is, you know, you're great. So it's like very chilled. It's [48:04] very easy. Yeah. But sometimes like hanging out with someone beforehand. Oh, I see. So [48:10] it feels like you have a conversation and then it just continues into. Yeah. And the [48:16] the my desire to keep it like on topic can make it less natural than it could be. [48:24] Right. That makes sense. Yeah. You know what I mean? Yeah. Because you always come back to like [48:30] one thing, but then maybe like that's not actually the organic way that it would have gone. [48:35] Right. Because I mean, like, well, actually, this would be a good test because I'll put this one [48:38] out and people like, dude, what the fuck are you doing? Stay on topic with longevity stuff. Yeah. [48:43] Yeah. I don't know. Yeah. [48:46] Totally interesting. I don't know. It's tough because you are you a podcast person? [48:50] I actually am not. Like, I really only do books and papers [48:58] because podcasts are kind of annoying. Like, you can't fast forward to them easily and kind [49:01] of like use your eyes like figure out if like they were transcribed, then I might read them. [49:05] But yeah, which you can. Some do. We do. But not everyone. But then I also feel like I don't. I [49:11] think there's like something about being decorated, you know, because if everyone's [49:15] listening to the same podcasts and you go and like spend the same amount of time reading like [49:19] people like the Greeks kind of, you know, like what the cities was thinking, you might have like [49:24] very outdated information that's like not very informed, you know, about today. But you also [49:28] might like, I guess, get a similar feel for how somebody was, but have it be like more [49:32] decorrelated and therefore ideally kind of like more sort of like maybe give you like a better [49:38] viewpoint than the normal. I think you should. I think it's like, I mean, dude, the amount of [49:43] times I've heard people reference Sapiens or Charlie Munger is like, I just can't deal. I mean, [49:48] they're great. They're awesome ideas, whatever. Right. But like everyone's consuming the same [49:53] media. Yeah. And I think it's interesting because like if you if you don't and you try to understand [49:58] it from first principles, which I think is like for first principles itself, I think like kind of [50:02] like I think that is often cited as like the good thing, but maybe not fully understood. [50:06] It can be quite different. I think one thing most people don't realize like, you know, math and [50:10] science often are like more artistic than they are kind of like logical. But like everyone's trying [50:13] to like frame things like a logical process. So yeah, well, because it's I think a counter [50:17] intuitive thing is that you well, I mean, it's obvious when you say it out loud to pursue an idea [50:25] in math or science, you have to be inspired to pursue it because you don't know if it's true [50:29] beforehand. Exactly. No, it's so crazy. Like, I think it's fascinating. You look at Noon, [50:36] right? Like Noon spent he had like this amazing year when he was 21. He like discovers all these [50:40] things. And then he goes into like alchemy in the Bible. And you're like, what? Like, where does [50:44] that come from? But I think part of it is like, the kind I mean, obviously, it's illogical and [50:49] analytical, like is he's like, books, we're so curious. But I think also like he has some kind [50:54] of like, a little bit like a mysticism, like this kind of this weird aspect of it's like a little [50:57] bit artistic. And we kind of like we forget that we're like, oh, yeah, like scientists are kind of [51:01] like robots. But they're they're really Yeah, they're they're really not. Definitely not. [51:07] Definitely not. All right. So let's actually get some of these questions. [51:12] All right, man. So which ones appeal to you? Because we have so many. [51:17] I think the ones that are like factual are good. So just like the the research questions, [51:21] probably do that. So maybe we should rip through because I'm genuinely interested in a lot of [51:29] these. And I read I read your longevity FAQ, which is awesome. It's very like Tim Urban, [51:36] wait, but why style? Maybe it's the drawings that got me. Yeah. But that was cool. Yeah. Yeah. That [51:44] must have taken a lot of work. It's like, you know, just drawing the kind of like axes and then like [51:49] three lines is. Yeah, it was hard. So Sanbatesh asks, do you think there's going to be another [51:58] step function change in human lifespan since, you know, germ theory? What's the next one? I think [52:04] this is a super fascinating question and time to be alive because like, you know, you know, it really [52:10] it's fascinating. You look back and kind of like, you know, germ theory is just like such a huge [52:14] breakthrough. I think the one thing I think is lost also is like there's another breakthrough [52:18] that's similar related, which is that like life comes from life. Yeah. Because like for all history, [52:23] we think that like there's spontaneous generation of life, like literally up until like, you know, [52:27] right about that time. And then the steers like, nope, nope, nope. Like, you know, these germs [52:31] are coming in like through like the neck of the pipe. It's not. And so, you know, that and that [52:35] was a huge breakthrough. And then, you know, obviously Darwin kind of like, you know, also [52:39] very important. I think the thing that we kind of have an intuition will be important in longevity [52:44] that most people are kind of not paying attention to is like what it's going to sound way too [52:49] philosophical, but really when you get into it, I think it's the important thing. What does it mean [52:52] to be alive? And at what point are you kind of differentiating between like the germ line, [52:59] which is kind of like your reproductive cells and the so much kind of like your kind of, you know, [53:03] skin and tissue, because there is a immortal line of kind of like living kind of things that has [53:08] been replicating since like our first ancestor, right? Transmitted through our germ line. When I [53:13] have a kid, that kid does not come out and like have the same amount of aging that I do when I [53:17] have it. It is kind of like brand new, right? And like, how the heck does that happen? And how do [53:22] you fit that kind of paradigm? And if you take, for example, a bacterium, now there's some [53:25] bacteria that do asymmetrically divide and like possibly have some form of aging, but kind of like [53:29] you, you know, do you look at a bacterium and think like that, that thing is aging? Maybe, maybe not. [53:34] And so what is it about multilayered and kind of like our germ line and the differentiation between [53:38] the two that's caused us to kind of evolve or start this kind of like aging phenomenon? [53:43] And, you know, given that, is it natural? Can we think about how our desire to kind of like [53:47] live longer ourselves fits into kind of like that differentiation? Because, you know, nature has [53:51] already solved for kind of like living forever on some level, right? On the cell level. And so kind [53:55] of what is it about, yeah, our soma that like is so different and are there any things that we can [54:00] repurpose and use, you know, for that? And so I think that that area is going to be super, [54:05] super fascinating. And then I'm also just broadly in love with the question, like, what is life, [54:08] right? Kind of like that's so interesting. Like, you know, Schrödinger in like the 1930s, [54:11] kind of like writing these fascinating tracks, like bringing like Maxwell book and others in. [54:14] And so that, you know, that and kind of the people thinking about it, like, you know, sort of [54:18] Jermaine Lind at MIT are just absolutely incredible in their work. That that's probably [54:23] sort of a longer answer, like, you know, we just think like, I love these questions, [54:27] sort of like, you know, we spend so much time thinking about like the practicalities, [54:29] but kind of like the higher level order of like, what would be the actual breakthrough? I think [54:32] that like that that are just like really interesting. [54:36] Sort of tangent. You mentioned, yeah, giving birth is someone working. I mean, I assume someone, [54:43] but like, are people working on extending fertility windows if you extend health spend? [54:48] Because that seems like, you know, if you could live forever, right. As a dude, like I can just [54:53] opt out. Right. Like, all right, I'm not going to have kids or I'm not going to like in my mind, [54:59] that's the real issue. Right. It's like allocating time. Yeah. You know, so if, [55:03] say you work aggressively until you're 30 or 35 or whatever, and then you have kids, [55:09] like all of a sudden you have to take care of this thing or it will die. Right. So being able [55:13] to push that till you're 60 seems like really valuable. Yeah. Well, so we think that's that's [55:20] that is sort of I don't want to say fascinating too many times, but it's a fascinating area [55:25] because there are some animals, many in fact, where like, you know, you have some octopi that [55:30] lay their eggs and then their mouth disappears and they're like sitting on their eggs and like [55:34] literally commit suicide. And if you reverse like glandular action, like gives rise to that, [55:38] they just keep on living. And so it's like you have programs in essence all over the animal kingdom [55:42] and like we're, you know, anthropocentric humans and so we say, oh, that doesn't happen to us. But [55:46] if you think about menopause, right, like in women, like what is that? That is a clocked acute onset [55:52] of kind of loss of health, right? Not as fertility, like many other things you get, [55:55] your distribution, you like bone loss acutely at the time of menopause. So many other things get [56:00] like a lot worse in a clocked fashion. You kind of look at other animals like, oh, we're all like [56:04] that. But really, are we that different? And so that area is just there are even some hormones [56:09] that we're looking into right now that are involved in that process that we think are super fasting [56:12] for longevity. And so I think like that area is just, yeah, it's really, really interesting. [56:16] So yeah, I mean, is it more, I imagine it's more likely for it to be an artificial womb [56:21] than re-engineering humans, but maybe that's inaccurate. [56:23] I think the artificial womb is not one that we necessarily look at because it's sort of like not, [56:27] you know, if you solve that problem when it's just like solve longevity problem. [56:31] But I think there's actually, you know, that would be cool, but like even just thinking about like, [56:35] what is menopause? Right? Because like, you know, why is it so timed? Like what is the clock that [56:41] like turns on? And if we like turned off that clock, like would it push backward? Is there some [56:45] kind of natural? And there's some like obvious answers for that. But I, you know, it just, [56:50] it really is. And you think about how did evolution decide like that was the correct time? [56:54] So that I think that it was just like, yeah, really, really interesting. [56:56] That's awesome. All right. Jason Choi asks, what's the percentage of longevity attributable [57:02] to lifestyle choices versus genetics and the progress of technology and influencing both? [57:07] Oh, interesting. So there's a recent paper that actually came out, a super fascinating [57:12] with guy, Yaniv Ehrlich in science. And what it did was they have a public database of heredity. [57:16] So basically like a family tree, unfortunately doesn't have actual genomic data for each person, [57:21] but you have a lot of lifespan data. So age, birth and sort of death dates, many generations back. [57:27] And so you can ask, what is the kind of like hereditability of longevity? You know, [57:32] if your parents lived longer, are you also likely to live longer? And I think prior to that, [57:36] we'd had about a 25% hereditability kind of figure. I think that dropped to like about 11%. [57:40] I could be off on this figure, but I think that paper was about 11%. Could be wrong. And so that, [57:45] I think that's kind of the current statement from the field is that like that's, you know, [57:50] our prior like percentage of longevity attributable to genetics. I think that [57:54] underestimates the potential impact of genetics on longevity because sort of like, you know, [57:57] do you have kind of like, you know, mutants that are like long lived in the population? No. [58:02] And so maybe, you know, I think it doesn't tell you like how much genes could be changed influence [58:06] longevity. But yeah, about 11% would be like the current estimate from the field. [58:10] Okay. Thank you. Fatih asks, is blood transfusion, so this is parabiosis. [58:17] Is it a thing or just a hoax? Oh gosh, no, the blood boy question. Oh, [58:21] wait, the blood boys are like, they fall surround everywhere we go, we were asked about the blood [58:26] boys. So one thing that's fascinating, right, is like, sorry, it's fascinating all the time. [58:30] If you go back and ask, what are the first ever things discovered to impact longevity? [58:37] You know, the tools that we had prior to 1950 did not allow us to do genetics, they did not allow [58:43] on the molecular level, they did not allow us to do like any of the things that we now kind of [58:47] focus on longevity. The one thing that Alex Carell in 1912 gets the Nobel Prize for sewing blood [58:52] vessels together. And so what is one of the things that is tried in the early half of like the 20th [58:56] century, because like that's the only thing that we have the tools to do. It's like literally, [59:00] you know, like you're sewing blood vessels together between a young and old mouse. And that does [59:03] appear to have positive impacts. There are three or four nature and science papers that [59:07] have come out recently showing, you know, there's some positive impact on kind of like the function [59:11] of the brain, some positive impact on function of the heart, some on muscle. So we do see positive [59:16] impacts. I haven't seen to date a really good longevity study. So I think we've seen a lot [59:22] of evidence of like age related kind of phenotypes getting better. But I personally have not seen a [59:26] study that like really, you know, makes me super excited about kind of like the number of extra [59:30] years. Lots of stuff to like indicate that might be the case if done correctly, but just I actually [59:34] haven't seen that study, you know, like sort of done yet. There's been some studies published like [59:39] in the mid 1900s about parabiosis that I think I might have cited that kind of indicated an [59:44] exception, but they're kind of like really replicated properly to really believe that. [59:48] And so I think, you know, there's probably some impact on lifespan. Like I don't think we have [59:50] that well characterized yet. Okay. So true, like not a hoax, not a hoax, but I think people really [59:59] over-focused on that because it's such an easy story to tell. Right. Like vampires, vampires, [60:02] I get that. And you're like, no, no, no, no, no, like, you know, 60 different things that make, [60:07] you know, acts live longer and like you have to look at, you know, but people don't want to hear [60:10] about like daft humans and receptor. They want to hear about like vampires. Yeah. No, I mean, [60:13] it's just like, like kind of what I was saying before about like tech being seen as black and [60:17] white, like sort of like everything people just want the pill. Oh, actually I wanted to talk about [60:21] rapamycin. Yeah. So my friend, Nicola wrote a New York article about it. Oh, awesome. I'm like, I'm [60:31] slightly terrified. But can you, can you just break it down? So, so rapamycin is this, is this [60:38] really, really interesting drug discovered on Rapa Nui, the aisle in a soil sample, as many, [60:42] many drugs were. And, you know, kind of what it does is many things, but, but I think one thing [60:48] that's been focused on is an impact on what's called mTOR, which is a protein that's part of [60:52] kind of two different complexes of proteins. And so, you know, the problem with rapamycin is it has [60:57] a lot of kind of like side effects, right? It's originally developed as like, you know, maybe [61:01] immune suppressant in one use. And so do you really want to be taking that like, you know, [61:04] continuously? Probably not. There's a lot of doctors, you know, if you ask kind of like a [61:09] subset of kind of the people who specialize in crazy things that might actually work in longevity, [61:14] if you then will say like pulse rapamycin, so taking rapamycin and very kind of, you know, [61:18] cute doses, but then like on a schedule, not continuously is a good thing. And I think that [61:23] like we don't see that like being disproven or like implausible, just kind of like, it is, [61:27] I think a risky endeavor on some level. One thing I would say is, you know, there are several [61:31] companies trying to develop much safer versions that do the same thing. So like have the positive [61:35] benefit, like don't have like all the other kind of like sort of negative, negative effects. [61:39] And so I personally just kind of like wait until those like get a little bit farther along. [61:43] But I mean, rapamycin is kind of reported. I think the other fascinating thing is like, [61:47] I don't think we have a great feeling for what the max is on the life expectancy that's possible [61:51] with rapamycin. Like the question is like, if you dose it up, like what's the maximum dose and how [61:56] at what point you start to get like decreasing returns of longevity. It's not clear that we've [62:00] actually hit that barrier quite well. That's the other fascinating like sort of thing. [62:03] Interesting. What about, I've heard people taking testosterone and like that is debated over like, [62:09] maybe it increases health span, but it actually might shorten lifespan. [62:12] No, we get a lot of, you know, there's a lot of people who are like, we're in a low T society. [62:16] There's also, I think a lot of people taking growth hormone, you know, for longevity. [62:20] And when I first saw that in kind of like an airplane magazine, I was furious because like [62:24] in worms, if you like knock out the analog of growth hormone receptor, they live longer. [62:30] And mice like dwarf mice are the long lived mice and like within a species, not, you know, [62:34] between species, but within a species, you know, being smaller is actually a correlate with kind [62:38] of like longevity. But I think, you know, one thing there is like maybe taking growth hormone [62:42] makes an 80 year old feel a lot better. So it's kind of like a health span optimization. So back [62:47] to that kind of like, you know, do you feel better like that results in longer lifespan? [62:49] But I don't think that's a great thing, obviously do for kind of like actual lifespan. [62:54] Yeah. Because to clarify, it can increase or encourage like cancer cell growth? [63:01] I mean, there's this possible minor thing there, but I think for the most part, [63:04] there's a not fully defined complex signaling pathway that seems to kind of be quite related [63:10] to longevity that was first discovered in worms and then kind of like also characterized in humans. [63:15] Like there's a subset of dwarfs, for example, who appear to compare to their relatives suffer much [63:20] less cancer and metabolic disease. And that correlates with what you'd expect from mice. [63:25] Like if you mutate mice to be dwarfs, they live about 60% longer than normal, like 60%. [63:30] It's pretty nontrivial. [63:31] Pretty solid. [63:32] Right. [63:33] How much shorter would you be if you could live 60% longer? [63:35] How much shorter? I'm not quantitative. I don't know. I'm not like 10%, obviously, [63:41] but like, you know, between a 50 and 70. But I'm not actually sure for those mice how much more [63:48] they were quantitatively. But I think the interesting thing is you can actually possibly [63:51] de-correlate like the being smaller with the effect. So it's like not just like a size, [63:55] it's like a signaling thing as well. [63:56] Would you make that trade if you're like one foot tall? [64:00] The trade is positive. So the idea is like you can decouple like the being small with [64:04] like longevity benefits. [64:05] Oh, I know. But I'm asking you would you rather? [64:07] Oh, would I make that trade? Yeah, probably. [64:10] Probably. Yeah. Yeah. That's awesome. [64:12] So Aubrey de Grey, another like kind of famous longevity person, someone asked about them. [64:18] So Chris asks, he's mentioned several times about replacing organs with new organic ones [64:23] before they fail. Is that a reasonable idea or would they more likely be replaced with synthetic [64:29] ones? [64:29] Oh, interesting. I think so this is an area that we're still building our, it's like maybe [64:34] too late to be like seven years and still thesis building. But I think there are so [64:40] many things that have to go right for that to become like the obvious thing to do. [64:45] In some ways it's like the oldest version of aging, right? And that like back to our [64:49] friend Alex Carell and his Nobel Prize, he is doing the first ever kind of like sewing [64:53] of kind of like the organs and kind of like, let's get a little few readers papers like, [64:57] let's just grab this like dog kidney and like, we'll take this one from this other dog and [64:59] like, you know, plug it in. And he's just, and you're like, wow, that's the early 1900s. [65:03] So in a sense, what Aubrey's proposing is the oldest most kind of like worked on [65:08] idea. But then, you know, I think we also, we just haven't seen that done well on the [65:14] rejuvenation front a lot recently. And I think I don't, I think we're still following, you know, [65:19] there's some things where like, if you get an organ from somebody who's had cancer, for example, [65:22] there's like a small risk like 10 years later, you might also incur like some kind of negative [65:26] event. It's just things like that. I think we're still understanding kind of how to weigh those [65:31] risks. But I think it's fascinating. It's a surprising fact that it is, you know, sounds the [65:35] most futuristic, but it's actually the most kind of like old method of kind of like considering [65:39] working in the space. Right. Well, you're just like, take the part out, put it in another, [65:43] right, to go. Yeah. Yeah. All right. So I have a very important question. So Micah said you did a [65:49] cookie diet. Is that true? Yes. Yeah. How did that go? I think it was pretty informative in that, [65:58] you know, again, I wouldn't recommend any way to like go just cookies, but- Were these like fancy [66:02] health food cookies? No, no. So the reason I did it was my friend had claimed that he had only eaten [66:09] whipped cream and bacon for a month and that this was possible. Of course it's possible. Yeah. [66:15] Right. But then he was like, but I actually feel pretty good too. And I thought that it was total [66:18] BS and that he probably, I mean, he's a very smart and like, you know, conscientious person. So I was [66:23] like, well, like either he's like very different than I really thought he was or that's possible [66:27] to do. And so I wanted to test it. And so I tried that and I was like, well, you actually kind of can [66:33] and you kind of feel fine. And so then I was just like curious, like if you took any random thing, [66:37] like any random food object, like just ate that for a month, like what would happen? And the cookie [66:43] diet like worked very well, but I just, for the long term, it seemed like probably not a good idea. [66:47] So switching off of that to like a lower sugar diet is probably a good idea. Did you, were you [66:50] doing blood tests or was all by feel? No, no, I should have done blood tests. That's funny. Yeah. [66:55] There was this well-known long distance hiker named Andrew Skurka. He's written up a bunch of [67:00] blogs and stuff and he's pretty well known for having kind of extreme, like he just has a diet [67:06] that can take anything it seems like. So he was like, I think for a while it was just like snickers [67:12] and Pringles, something like that. That sounds great. Yeah. I mean, I guess if you have enough [67:17] toothpaste like on the Pacific Crest Trail, you're fine. Yeah. You have to kind of wonder though, [67:24] like how much worse that would be then. Like one of the examples, right? I think that like a lot of, [67:27] for example, eating meat, maybe the worst part of it is like if your animal is stressed, like had like [67:31] a lot of the incorrect type of hormone directly before like being killed, but actually like a more [67:35] important thing, like whether you're eating meat or not, just sort of like what the kind of like [67:38] minor things are that we don't think about, like the axes that aren't like explicit, [67:41] like what those are. But yeah, hard to say. Hard to say. Cool. All right. My last question is, [67:46] are you seriously not doing anything really weird? There's like no pills, there's no weird food, [67:52] there's no crazy fasting. I mean, I think that like apart from trying to do the cookie diet, [67:58] so one thing that I was trying to do for a while was like, I was trying to like [68:02] quantitatively understand, you know, because we're just like black boxes and like you intake some [68:06] number of calories and like you should be able to calculate like where they all go, kind of like [68:10] how many are necessary to like eat each day, kind of like from first principles, like figure out kind [68:14] of like what optimal diet would be. I tried to do that for muscle. So I was like, like how many [68:18] proteins should we eat 30 minutes after working out? The first problem was it's really hard, [68:22] like why 30 minutes after working out is the correct amount of time? No idea because sort [68:24] of like, you know, our cells are expanding at a period of time, but like it's hard to, you know, [68:28] figure out. Also just got really down in the weeds of like how many amino acids would be required to [68:33] like replace certain things. And I think I came out of that just kind of like very convinced, [68:37] like a lot of the things that like people talk about at a high level are like wrong and like [68:40] provably theoretically still like a lower level and that like I shouldn't have the time to kind [68:44] of like really think about doing that for like a full diet. And so I think at this point until I [68:49] have like, you know, maybe a full year to kind of like go back and understand that whole area [68:52] better, it's kind of like just, you know, the obvious things because history is probably like [68:57] a good teacher for like, you know, baseline health. Nice. All right. If someone wants to learn more [69:02] about you, where should they go? Yes. So we run longevity fund and I'm just laura at longevity.vc [69:08] and anyone can reach out and we love to talk to you. Cool. Thanks for coming in. Awesome. Thank [69:13] you for having me.