Y Combinator Startup Podcast - #99 - Laura Deming

Episode Date: October 23, 2018

Laura Deming is a partner at The Longevity Fund. They invest in companies that will allow us to live longer and healthier lives.You can learn more about them at Longevity.vc.Laura’s on Twitter @LauraDeming.The YC podcast is hosted by Craig Cannon.***Topics00:22 - Why focus on longevity now?2:12 - How did Laura get started in longevity?3:22 - Why raise a fund?5:52 - What does Laura do personally for longevity?9:07 - Worm and mouse studies10:44 - Craig's personal habits12:37 - Human studies15:22 - Mica asks - Do you think immortality is going to be achieved by: 1. Curing all disease and stop aging so we could live with our own bodies forever 2. OR is going to be something like porting our brain, "mind" to a computer/robot?17:37 - Most likely strategies to increase lifespan19:47 - Ryan Hoover asks - Ask about the ethics of longevity. Jack J. Fernandes asks - Do people actually want to live longer?21:44 - Mica asks - How would immortality change society? Wouldn't we become more complacent? Since we have "forever" to do things wouldn't that diminish our rate of innovation? And since less new individuals are being created we would have access to less new ideas. We would just stop creating new Newtons, Einsteins, Mozarts…24:52 - Cognitive enhancement25:52 - Daily habits34:12 - Tech environment changes in the past 5-10 years39:22 - What percentage of people in labs want to start companies?41:37 - Pioneer43:57 - Confidence45:52 - Podcasting49:12 - Choosing media to consume52:17 - Sam Betesh asks - The last thing that led to a step function change in average life span was germ theory. What new areas of research might provide the next step function change?55:07 - Extending fertility windows57:22 - Jason Choi asks - What % of longevity is attributable to lifestyle choices vs genetics and the progress of technology in influencing both.58:37 - Fatih asks - is blood transfusion a thing or just a hoax1:00:42 - Rapamycin1:02:27 - Testosterone1:04:37 - Chris asks - Aubrey De Grey, IIRC, mentioned a number of times that we might, in the future, replace organs and tissues with new organic ones before they fail. Is this actually a reasonable idea, or is it more likely that we'll replace them with synthetic ones, if we replace them at all?1:06:07 - Mica asks - Laura did a "cookie diet" for one month. Why did you do it? How did you feel? Doesn't it go against all the research on longevity? ;-)1:08:07 - Is Laura actually not doing anything strange in her diet?

Hey, how's it going? This is Craig Cannon, and you're listening to Y Combinators podcast. Today's episode is with Laura Deming. Laura's a partner at the longevity fund. They invest in companies that will allow us to live longer and healthier lives. You can learn more about them at longevity.vc. And Laura's on Twitter at Laura Deming. All right, here we go. So, Laura, why now, in terms of longevity? What's happened to make you raise a fund and start investing in research and companies?

Yeah. So we think this is an insanely important part of the story because if you were Aristotle and you were like trying to start longevity fund, you would have a terrible time. It'd be like the worst idea. And so timing is super important. Like why now for the first time in like 2000, 3,000 years is at the correct time to work on longevity. To us, a lot of that comes back to tooling and what's available for us to use. You know, prior to the 1900s, if you wanted to impact biology, you know, maybe you should have been a physicist. You know, worked on optics, helped make the first microscope. And like Robert Hook, a physicist, you know, discovers the cell. So, you know, there's so much that comes from physics and other disciplines into biology to push it forward. But then I think in the 1900, something kind of fascinating happens, which is that for the first time, there's kind of this acceleration of tooling, right? X-rays, NMR, all these things, you know, the Catholic. very tube discovered mass spectrometry, but, you know, by this guy trying to find the mass of the electron, which is so cool. And so all these physics tools are coming online, but then also more biology-driven tools. And so really, I think, you know, and we can get into this more specifically, maybe a later time, but kind of what's excited at us is just seeing the tools available to characterize, like, life become available for the first time ever, right? You know, for all millennia, you had Darwin and, like, Mendel talk about genetics. And, like, there was no knowledge of what was actually going on at the ground.

level. And in 1953, for the first time, you have, like, the link between molecular biology and, like, we're looking at with microscopes and, like, genetics and, like, this, you know, sort of concept of ferretity, which is just super exciting. And what caused you to jump in? Well, I mean, A, I think it was born in, like, a very lucky time, right? Which I think you always have to be, you know, sort of cautious or, like, I guess, like, a little bit concerned if you believe that about yourself, right? Like, why now? Like, you know, should it really be the lucky time. But then I think also, you know, as a kid, or A, just, like, had a lot of relatives that were, you know, sort of aging, and that was very striking, but also, you know, really wanted to solve cancer.

And I remember talking to my dad about this, and I was like, oh, like, I want to solve cancer. And it's like, well, you know, cancer is a subset of aging. So if you want to solve cancer, you're just like, you know, solve aging and like to secure all these other things as well. And that just, you know, that coupled with kind of like hanging off my grandma, you're like, that's just going to make sense to me as a kid. I was like, okay, well, like, you know, guess I'll go solve aging then. Like, that's the biggest problem.

Because cancer is not the number one cause of death in the U.S., right? It's heart disease, something like that. Right. But, you know, just really, if you look at all the age-related diseases, you know, past this year-un point are driving kind of like the majority of sort of natural deaths, so to speak. So, you know, like, once we got rid of infectious disease, like, it really became the case of, like, aging, which wasn't previously, like, necessarily the biggest issue, sort of, like, rose to the forefront. Yeah. And so that, that kind of, I mean, it sort of just, I think, made sense to, like, a small trial that that was important. Huh.

And so why raise a fund rather than, you know, just go, go for curing cancer? So the thinking at the time was, you know, possibly in a good way, like, Emperor has no clothes, like, extremely simplistic. Like, you have to understand. So I was at MIT and I was like a sophomore. And I was also 16. And I had like maybe $1,000 in my bank account. And so like, you know, knowledge about like the financial industry, like, rollsably low. My dad had been in public investors. So I kind of knew a lot about like the idea of investing in things like that. That was a generally good thing to do. And I'd worked in like aging labs for maybe four years. And I think the striking thing was just like there was just like no money to like make. drugs. And it's kind of hard, you know, like, when you're in a lab, you just have, like, no idea what's going on in the outside world. And so I would, like, ask venture capitalists, like, I would, you know, call up a few in the phone book and, like, you know, a few responded. And so, like, have these, like, random conversations. And just be like, you know, I'm just, I'm curious. I'm a student. Can you, like, tell me more about, like, how this industry works. Like, you know, are you funding aging therapeutics? And, like, none of them had heard of, like,

aging therapeutics. They were kind of, like, Asian therapeutics. Like, what did you say? And so that was just very striking that, like, something that I personally, believed, like, on the technology, like, not just like from a mission perspective, like, on the technology side was like super exciting, was kind of generally not really, like, looked at a lot by these folks who were supposedly like the great translators of technology. And then I think also it kind of made sense, like, you know, the first ever mutation found to really extend where my spend was in 1983. The next was like 1993. And so really the field started about like 20, 30 years ago. It's like kind of made sense. Like, if you think about like how long it takes for fuels like get traction, like become known, like, okay, there may be like less than 100 good labs in this space. Maybe like people just. Like, like, people just. just haven't had enough time on like the venture or like investment side to understand that this is like really cool and important. And so like then it kind of made sense that like you might want to start a fund if that were the case to like help more drugs going to get started out of the space. So in other words, like the big pharmaceutical companies are not investing in these pilot ideas. They weren't at the time. So this was like five years ago or something. Seven years ago,

yeah. So things have really changed. You know, seven years ago there were like maybe like three companies have been started or so that had like the aging brand on them. Yeah. There was like zero people and like arch ventures was one of the few that were like taking risks. There's like maybe 10 million invested like that year in total into like the space. Right. And like in the past four years, we've had like 10 billion plus. We now see like 300 companies per year. So it's just really changed.

Like it's very, very striking to have watched to go from like zero to like what it is today. Yeah. Now it's totally a trend. Yeah. Hopefully it sticks around. So you have not a million, but many questions for you. I think like the top of the list for me is what you do personally. Ah, yes.

This is probably the. most common question. And I think all my friends will always say that I answer this terribly because I, you know, I'm kind of like, you know, I come from a semi-scientific background. And so, like, we like to get like to the ground truth of things. And it's just really hard. Like, there's just like a million. Like, if you start reading mouse studies and longevity, like you will find mouse studies that say, like, if you decrease, like, they've done this, like, really cool experiment where you take fat and sugar and protein and you decrease the level of each of them, but keep a total calorie intake the same, you can kind of test, like, which

component of diet is like contributing to longevity. And they did this and they like did kind of like a full matrix. And they like life spend studies for each of like the different proportions. And what they found from that study in mice was that like decreasing protein was the number one kind of thing that increased longevity. And so from that you might infer that like maybe less protein is good. But at the same time, it doesn't seem like, you know, maybe if you work out a lot, that would be different. And so I've come to the conclusion that kind of like, you know, I have some thesis about like what is good and what is not good. But it just as a scientist, it's really hard to say that there's kind of like a good kind of like real kind of like hypothesis there.

Okay. And so. So which are like not a lot of like not just despite like reading probably more papers on this than like most people in the world. Yeah. It really is something where I don't see things that I think are extremely clear kind of like movers for longevity. On like the diet level, obviously that like aren't confounded by other things. So what's your diet? Well, I've tried a variety of things. I think right now it's just kind of like. like the sort of like bare minimal like try to eat low sugar. Um,

personally trying low protein, um, just because I think that is somewhat supported by kind of like literature. Yeah. Um, and, uh, low protein is like a gram per kilogram gram per day.

Um, I think just sort of like, uh, not, it's, it's a good question. Like what, what is the correct per person?

And also if you exercise. Yeah. Um, I actually once tried to calculate out if you exercise, like how much protein would be required to like a pleasure and just like, like, replenish and actin protein. Yeah.

And it's kind of fascinating. I think that there might actually be like, you know, up to 100-fold increase in power, like, in your muscles where, like, if they all fired at the same time, you get, like, you know, sort of a lot of power. But any, but I mean, I, you know, I just, I don't have any strong recommendations on diet. Like, I really, like, I read basically all the studies. Yeah. And I think maybe low protein, low sugar are both, like, intermittent fasting seems to be, like, somewhat supported. Are you doing that? I've tried it.

I think it's kind of hard to maintain if you, like, you know, have a graduating sleep cycle. but yeah I wish I had better recommendations for that for that area okay and in terms of supplements you're doing anything um there's a variety people recommend everything from nad plus all the way through to like metformin um for the kind of the more adventurous um I think that so we actually have a secret list at the fund of like on market drugs and things that we think based on like our like body of evidence might be having an impact on life spent and we're monitoring them some of them I personally think it would be like intriguing to take we don't release that list just because we were afraid that if we did and kind of like somebody acted on it and kind of like didn't work out well for

them that just like a terrible thing to do to like them. But we have a secret list of things that we think are like interesting. Okay. And I think for the Nd Plus though, there's some evidence of like positive effect there. But we haven't seen great lifespan studies showing like a large increase in lifespan. So like that'd be like my one concern there. Okay. Cool. Because yeah, in the the worm and mouse studies, there have been like, you know, a hundred percent increase in lifespan, right? With certain. So worm studies, we've gotten up to 10 fold report. reported, you know, possibly more. That's by decreasing a gene product, though. So that's kind of like, if you want to go and take a gene therapy or we had such a thing, you know, from birth, possibly like that would work. But probably the effect would be a lot smaller. In mice, we've got about it up to a twofold increase. And that was a combination of a mutation and restricting the total caloric intake of the mouse. Okay. Down to what relative? I don't remember for that study. On average, I think people will do CR to about 30 percent of normal caloric intake.

But it really varies. So if you take 40 different, and this is where it gets complicated, you take 40 different genetically different strains of mice and you change their diet in the same way. Half will live shorter and half will live longer. And so, you know, I used to, as a kid, I was always like, oh, you're like, there's a simple answer. And I think that there is. But I think it is a lot more sort of reliant on genetics and other things than we'd like to think. How long of your family members lived? How long of my family members lived?

Your grandparents, great grandbrans. Well, my grandma is still going. She's in her mid-90s. It's a good sign. Yes, exactly. They've all lived, you know, about age 80 or above. So, you know, hopefully. How about yourself?

How long is your family? Not 90. So, yeah, we'll see how it goes. I need it more than you. Right. Yeah. What would you say the number one health hack that you'd recommend to your audience would be? I mean, well, I mean, I've done a little bit of blood work.

So everything is kind of anecdotal and based on feel. But I was vegetarian for eight years. Oh, interesting. For environmental reasons. And then I realized that I had like developed this entire vocabulary around cheating. So for example, if I was traveling, it was like cultural meat. And it was allowed. And then, you know, if I was like, you know, over your house and like you made chicken or something, I'd be like,

whatever, I'll have it. I see. And at the point it was like twice a month, I was like, I'm not vegetarian anymore. So then I started eating more. protein, but really just more eggs. Yeah. And then I felt a lot better. But really, the main thing is sleep.

Yeah. No, that makes sense. I will say, actually, one thing that's interesting on the health spend front, I think people have this like intuition that when they feel better, that's a metric, that's a metric for something that's good for them. Yeah. I think it's actually not true. So if you look like a lot, to some extent, like, you know, maybe you want to optimize,

like, robust, very cheerful lifespan, in which case, like, taught logically it is. Yeah. But most of the time, or a lot of the time, when you, you. you see R mice or you do other things like make them live longer. So a total number of years increases, they're not kind of like as happy on a day to day to day basis, like a little bit thinner, a little bit more than thoracic in some cases. So I think it's kind of like, you know, whenever someone says like, I really feel better because I'm doing X.

I'm always like, oh gosh, like I wonder if that's like the correct thing. Like maybe, maybe not hard to say. Well, when people talk about health span in my mind, it's very correlated to how I feel. Right. If I was going to do caloric restriction and every day would suck for 90 years, I would opt out. I mean, I don't know if there's a drug. For instance, like, I know a lot of people who have experimented with, like, keto and other random diets, and they're just caffeinated to the gills. Like, there's low energy.

That's so funny. That's one thing you can do. Oh, my gosh. Yeah, it's hilarious. Yeah. So I don't know. But one thing I've been curious about, like, there seems to be relatively limited data on actual humans. Yes.

So how might someone set up a study? Is it even possible now, or is everything still regulated? There is this fellow near Barzolite who's working on what's called the Tame trial, and the point of that is to assay the effects of this drug bed form, which is a very old diabetes drug, on sort of markers or biomarkers of aging of aging that he has kind of put forward. And the cost for that will be about $60 million. And if people do it, the idea would be, okay, well, here's our first pass at testing, aging in humans. And so finally we have some more data. The way that trial was sort of motivated was there was these kind of large finding that in hundreds of thousands of patients, or I think about actually 70,000 in that population, from kind of like a UK study,

if you look retrospectively, people who had been taking metformin for decades, they had apparently like a little bit better kind of health span. So they had less age-related disease, the diabetics did on this drug, even then they're kind of like non-diabetic counterparts who were not taking metformin. And so I think that, you know, hard to say that studies like kind of like definitive evidence, but that kind of motivated all this sort of question asking of, you know, could we really nail down in humans at trial to like test, you know, metform in particular? particular. That said, you know, I think that, you know, a lot of biologists will really kind of, you know, say, oh, it's very important to test things in humans. And of course it is. If we could do that, we would be doing it kind of all over the place. But I think increasingly over the years, and maybe just like I started out in worm biology, I'm kind of like more and more excited about like the animal kingdom. Like, you know, the animal kingdom is just like absolutely awesome. Like we have one company in our, you know, current sort of, you know, sort of portfolio that's working on this and they're amazing, you know, fauna. But kind of like it's like, there's such diversity of phenotypes, right? and like how can we learn from other animals

opposed to just like our lowly selves? Because like, you know, for example, there's naked mole rats and rats, right? Like, naked mole rats are pushing 30 on lifespan. Like, we have no idea how long they live. Like, their mortality rate at 30 is not going up. So we're just like watching these guys, like waiting for them to start dying. And then like rats, which have like very similar physiology live maybe like three to four years.

And so what on earth is different between these two animals, right? Like, like, that's just absolutely fascinating. I think it's also important because like, you know, a lot of like, you know, physicists or mathematicians, and I used to be this way, like, we're always worried what there's, like, inherent, like, limitation on, like, a complexity level? Like, what if, given a certain complex system, a certain rate of metabolism, like, you have to die because there's some kind of, like, you know, sort of theory about, like, entropy increasing over time and that, like, you know, must drive and just, like, too complex to, like, really intervene.

But then, like, you know, these animals are basically the same size, like, have so, like, so many other similarities, like, it would just be very hard to maintain, like, that theory and also accept this kind of, like, large differential and longevity. Yeah, absolutely. So someone has to, question that I thought was kind of funny. Yeah, here we go. So Micah asks, basically, do you think immortality is going to be achieved by curing all diseases?

So in other words, like living forever? Or like, what's going to happen first? That or are we going to just upload our consciousness to a computer and live forever that way? I think that. So that is a question that I used to get very interested in sort of like, well, you know, if you care about this, like, you'd be working on kind of like the bell. Yeah, where do you work? Yeah, exactly.

I think so the way I kind of think about it, which is not a good answer, but it's kind of like a framework we're thinking about this question is I think about biology like a set of tools, right? So you can you can kind of see this in like the kind of like things that had become available recently for us to use to affect human health. What I mean by that is like, you know, prior to like the 1900s or like even like just the 1980s or maybe like the 1930s, like the first time you really put this marker. If you wanted to make a drug, it was like a small molecule, right? It was like you got a plant, you found something from a plant that was useful. Or you put some solve in a wound. We realized that's a bad idea. Don't do that.

Not very good for sterility. There are always things you would do. But then, like, you know, in the 20th century, for the first time, we use, like, proteins, you know, insulin or antibodies created by, like, our own bodies or, you know, the bodies of, like, the bodies of, like, the mice that, like, we kind of, you know, quote them in, to treat disease. And so we actually use something that came from life to treat, you know, kind of like a living organism. We now, just in the past kind of three years have, like, landmark approvals. and viruses being used to, like, blow up cancer, literally, like, these are called oncolitic viruses. There's new drugs using genetically engineered cells. You've probably heard of, you know, Cartian, kind of like this whole kind of, you know,

oncology phenomenon. Also stem cells being used. And so I think kind of like the final frontier of all of that, like, use of kind of like biology's own system to do cool stuff is the brain understanding kind of like that system. But I think to lead up to that, you kind of will do so many things that it may be the case that, like, we kind of get there at the same time. So, you know, like, that's like the final frontier. And we solve it, but kind of like along the way, we've also kind of like done enough work on the other tooling kind of fronts that we get to kind of like to a kind of, you know, maybe we don't solve kind of like lifespan itself, but like long jemnity is definitely impacted but kind of like the work up to that up to that time.

Right. Exactly. And do you sense that there's like a strong signal at this point as to what might be the way that we, you know, a bunch of people ask these questions, but like increasing lifespan like 20%. Like right. Yeah. If you had to put money on it, obviously you literally put money on it. What would be the most likely thing to take off? The most likely thing to take off? In the next, I don't know, 50 years. So here's how we think about it. We have extremely strong confidence that it's possible to impact lifespan between like, you know, three months to maybe 10 years. Yeah. And, you know, obviously like, you know, different probabilities with what we have to, in fact,

we're pretty certain that there are some things in the clinic already or on the market that with some probability are impacting life span. Like, lifespan seems to be very malleable, you know, to a small degree. I think the larger question is like, well, you know, A, how many of those can you like put together to like get kind of the max will impact from like that first wave? And then B, our thesis is that none of those things will be sufficient on their own to result in like an engineered lifespan. So you have this first way of things like kind of work, but like they're kind of limited. Like they have kind of like a maybe like 60 percent and that's like the max. So then the question is like how can you like go above that? And we think that really all comes back to tooling.

And so that's where I don't know if I'm, you know, we're Aristotle or kind of like we're like Newton or like maybe like in the best case scenario. We're like Einstein or like, you know, of someone today in the realm of physics in terms like going to the moon. And we've tried to go to the moon kind of like 600s would be a little bit hard. More recently maybe a little bit easier. But like I think that's where we have we have some hope and optimism, but we're not as confident that there are things today that we'd point to to to say that's going to result in kind of like unbounded engineered ability to kind of like impact longevity. And that's why we also really care about about tools when we think about. about like investing in the space, not just kind of the first wave of like awesome therapies that will be available sooner, but like maybe aren't just kind of like engineerable.

Right. So you're kind of hedging if this is still a foundational stage. Right, exactly. I think we'd love to think that it is. Yeah, of course. Yeah, yeah. Like, like, my argument for foundational stages would be like, this is the first time ever in history that we have the link between genetics and molecular biology. Like that happened in 1953. That happened in 1953. Maybe it's been 70 years. So you're like, well, what happened and so, you know, couldn't just have happened like right after 1953. But I think that'd be the argument for like, that's why today makes sense from like engineering perspective. Okay.

Hmm. And then ethically, you know, Ryan Hoover asked like about the ethics of longevity. Another, uh, Jack Fernandez asked like, people want to actually want to live longer. Right. Do you have strong opinions on this? Or are you kind of, you know, stepping back? So we get, we get asked about this all the time. And it was funny because when I started the fun, I never thought that people would like ask those questions. Yeah. Because to me the reason. You thought it was a. assumed. Well, because the reason we started the fun was to cure, like, things like cancer and Alzheimer's. And so, like, from our perspective, like, well, you know, like, you

would never ask, like, is it good to cure cancer? Like, no one would ever ask that question that I've heard it, or maybe some people would. But then we realize that, like, when people think longevity, they think about it as different than those things. And so I think, like, you know, from our perspective, like, I just, you know, I think it makes sense to cure, like, these disease if we can. And so we definitely wanted to do that. And so, like, you know, we would never deviate from kind of our mission. I think, you know, from a broader scale, it's kind of like two camps of like, do you want to be like Malthusian and you're thinking a kind of like, you know, the world is like a bounded place. Like, you know, it's really like limited resources. Like, you know, it's really like limited resources. Like, you know, it's really like, you know, the world's like, you know, it's like, like, philosophical standpoint. I'm more on the kind of the latter sort of camp. I like that kind of viewpoint a little bit better. But yeah, I think to us, like just the like the rationale for longevity really was, let's cure HLA diseases. How do you do that? You work on.

aging. Hmm. And yeah, and maybe there are multiple universes where we the... Right. I'm trying to get David on the podcast. That would be so... I met him one time when he talked about it.

Really? Yeah, yeah, yeah. Would you have to, like, go to him and his house? That's what I did when I met him. That would be the best interview ever. Yeah, he did run with Sam Harris. It was kind of cool.

Oh, my gosh. But really, like, in terms of having an actual opinion on this, so there was a cool one on the ethics. Mike asked, how would it, mortality changed society, wouldn't we become more complacent since we have to quote, forever to do things? Wouldn't that diminish our rate of innovation? And since less new individuals are being created, we would have less access to new ideas. In other words, like, there are fewer newtons, fewer Einstein's. And sort of this is like why the basic income argument or one of the

basic income arguments, right? Right. We allow for these people to succeed. Well, so I think there are two implicit assumptions there. One is that we understand how people are motivated and that their motivation stems from this feeling that, like, they will die. Yeah. And I think number two is this idea that, like, people have an innate kind of rate of loss of new ideas of age, kind of innate, like, loss of openness. And so I think, you know, addressing both of those. On the first point, I don't, I just, I don't think that that's true personally.

Like, I don't think that, like, I'm motivated to do things because, like, I know that I'm going to die. Like, I think that, you know, perhaps everyone else is, and this is just kind of like a personal thing, but, you know, I think I'm motivated by many things, like, curiosity. competition, sort of like, you know, personal growth, kind of like wanting to be like better next year than like, you know, was today, kind of like a sense of mission and importance kind of like, you know, it's important to go do certain things. And, you know, I think if you ask most people, you know, maybe they'd have different answers, but I just, you know, I'm curious

of like death really is like the core kind of like motivator to do things, you know, for everyone in the world. It's like that. That's one thing. It might result in a few people wanting to go to war, which might be problematic if you kind of like want more war and more soldiers or Or not if you would like less war. That would be an interesting thing. But I think for that question, I just, I don't, I don't agree that we really understand, like, the core motivation of everyone on this planet and that that is, by its sort of definition, the fear of death. I think the other thing that's interesting is sort of to the second point, the question of like loss of ideas with age, you know, there is a lot of like just cognitive, like, change with age, which is very fascinating, right? And sort of like, you know, biologically, you do change.

And, like, you know, part of what we, like, really want to do, you know, is impact aging. But, like, a large part of it, like, we could just make a cognitive enhancer. So you were, like, sharp until you're nine and then you, you know, dropped. Like, that would be equally, like, that would also be, like, an awesome product in of itself. Like, just cognitive enhancement, like, alone would be great. And so I think, I think actually people kind of, like, undercounting the value potentially, you know, if you're a Newton, absolutely brilliant. And you help develop a field and maintain your 20-year-old openness and kind of, like, fluidity for 100 years. All through to age 90.

Yeah. Like, what insane kind of ideas would be able to be. Newton be coming up with at age 90. Yeah. Like with that kind of openness. The counter argument there was like, well, he would just go and do alchemy. And so then you have like, you know, young Newton being great and then like old Newton like doing alchemy.

The counter argument is like, well, maybe alchemy like caused a decline in thinking because like he was sniffing too much mercury. So I want counter. Yeah. Yeah. Yeah. You almost won an argument for like outsider scientists who don't get discovered until they die.

And then they have like a hundred years of portfolio. Right. And they're also just, I mean, like so many people like, you know, some incredible at Stanford who are still. amazing and coming up with extremely novel ideas and like, you know, Hawking publishing on like Black holes in entropy, right? Like this final paper, like on this completely novel, fascinating field. And like, was that, like, you know, was he declining? Would we like Hawking to kind of like step aside for like the younger generation? Like, can't we have both, I guess, would be a question.

Interesting. So would you be a proponent of like, you know, giving the entire, like, somewhat like florid in the water, putting like provigil in the water? I think that I'm never a fan of things that don't involve individual choice. So anything that, like, would be sort of coercive or kind of, like, enforcement, then, like, no. But I mean, so, like, if everyone would sign up for it, then, like, I do think that, you know, there's, like, all this fascinating work on, like, cognitive enhancement, like, just starting to come out today. And, and that's a, I mean, we've seen a lot of companies that we're super excited about that have to do with kind of, like, you know, making your neurons kind of, like, make more science. It's, like, increasing with

their, like, rate of division or, you know, hypothetically, I think that erasible contentious, but, you know, like, that to us is kind of, like, that's part of longevity. If we just had a pill for like cognitive enhancement, you know, that in itself would be like absolutely wonderful. Yeah. I mean, everything I've tried, it's, yeah, it works. There are sometimes where you get this feeling that you're, you know, you're really good at like you're crushing email, but you're not like them at the most like creative and you're just like sweating the whole day. Not coming up with the deep thoughts. Yeah.

Yeah. It's actually fast. And remember this book, um, daily habits. No. I would actually reckon, I think you might like it. It's, um, the daily habits of, um, mostly writers. and artists. Okay.

But it's super fascinating because the details kind of like how they live their life. And it's just extremely variable. But the most common thing is that they all wake up and go to sleep. They have a very set routine.

When they wake up, do work and go to sleep. I'm already on that cycle. Yeah. I mean, what, a thing I have found is that my, my mornings are just much more valuable

than my evenings. Yeah. Especially in the middle of the day. Like, I'm just kind of useless. So I just work out at like two in the afternoon. I'm curious why that is. Like,

it's either biological or, or psychological, right? Sort of like, you know, you get like too much loaded into your brain and you don't want to think. Or it'd be really fascinating if sleep played a key role there. It would sort of like sleep does something biologically and perhaps psychologically that like somehow induces like an optimal state like right when you wake up. But yeah. Have you tried it like sleeping in the middle of day and then just getting back to work? I haven't, but that's an interesting idea.

Yeah. I'm curious what that would do. Possible. Interest. Yeah, I'm so curious about cognitive enhancement. We did a podcast with Rosalind Watts who is at Imperial. about psychedelics. Oh, that's awesome.

It was awesome. I mean, it's very similar. Actually, her research with Robin Carhart Harris at Imperial is in Michael Pollan's book. Oh, interesting. No, I did. I've heard so much about it, though. Yeah. It's really great.

But, I mean, it's kind of like cognitive enhancement in a very broad sense in terms of like trying to break you out of your old habits and like have more confidence. Increase openness. Yeah, exactly. And so are you, are you taking anything? like any in the eutropic sense consistently um no i think i don't even do caffeine because the general thought it's like try to win yourself off of everything kind of like if you can perform great there then like perhaps someday like there'll be a safe driver that comes on market that's that's worth

worth trying but um yeah i also like i like i like marcus realist like stosis like they do have kind of like you know none of the necessary things but like maybe that's just application of that philosophy now i think about it yeah some part of that just makes me angry like i just like i want Well, it's like it all, you know, kind of like the caloric, I'm, I don't know. I'm a, I'm a dichotomy. Like, it's all stretched apart because I'm very much a creature of habit. Okay. That being said, like, caloric restriction, not having like a beer with my friends.

Like, all of this stuff, I just like, don't. I'm not doing it. I'd rather, I'd rather work out an extra time. But then, but then some people say, like, that's bad for your heart, right? You know, like, you can't win. You can't win. Yeah. So I don't know. I feel like in some ways it's like the devil I know and I just avoid other vices like texting while driving and smoking. That's interesting.

What is like the thing that you do that you're the most proud of? Like the habit that is like the harsh for you to maintain that you nevertheless are kind of like quite happy to like be able to do. I mean exercise is no problem because I go great. I go crazy without doing it. Right. I think what's consistently the hardest to maintain is giving energy to the side projects that are creatively demanding. Oh, that's interesting. Because I, this is what I didn't expect.

I used to work for myself and I work at YC. And obviously, and there are obviously, like you have so much energy in the day. And obviously you can like push harder and get work done and like be more disciplined. But I found that like there are certain side project ideas that are just kind of like too much to even think about. Oh, interesting. And so I'm yeah. Like when I when I make progress on that, I'm very happy with myself because the side projects that are like, you know, I've like made like little SaaS tools and stuff. And that's cool.

But it's definitely not the hardest thing. And what, like, allows you to make progress on those projects? Just internal motivation, like, wanting to do it. I think the, uh, what's always helpful is just imagine, imagine yourself in 10 years and, like, look back. Oh, interesting. And then just use that as a metric for like what you want to, would you be proud of yourself for having done that? That seems like someone like the Bezos framework of like, you know, when you're 60 and you kind of look back on your life. Yeah.

That's interesting. But then. But then. But it's dude, it's like, who's to say what's going to lead to the next thing? That's great. So, like, you know, all right. So before we did the podcast, like I was talking about working at the onion, right? Right.

And now I'm here. Yeah. And you're like, that's not a standard trajectory. Right. So you can't really say authoritatively, like, the best way to spend your time is X. But when I, when I was a kid, someone said to me, like, before you start working on something, think about what winning looks like. And that's kind of a framework for projects for me.

Oh, that's interesting. But I don't know. That's just a personal thing. What other like hacks and motivations like do you have in your arsenal? I just don't spend time with people that annoy me or like stress me out. Okay. Yeah, that seems like it was a positive thing. I am never busy, but I'm fine using that excuse.

Oh, you're never busy. I always have time for my friends and like the things I really want to do. And I just cut everything else out. So I don't know. How about you? That makes, um, hacks and motivations. I think it's like always trying to keep the baseline pretty, pretty low, like kind of, you know, like. Yeah.

Like, I think like, you know, like, I think like, like, you. You can control, like, your output, but you can't really control, like, how the world responds to it. So it's kind of like, if you're just like, all right, if I do good output, then like, that's great. And then like, however the role responds, like, can control it. But like, like, being really happy when you do stuff that you can control is I think probably the biggest, like, mental hack for, because I mean, you, usually like you just can't control. It's so hard. Because you're, you're still pretty young. How old are you?

24. Yeah, yeah. So I remember when I just moved out here, I am. How old were you then? Uh, 20. three oh interesting and you just come out of college or yeah so what happened was um i was in new york for college and then i lived there for like a couple years afterwards and uh my girlfriend and i split up and i was like i'd always wanted to live in california and new york was just like grr i just like grinding at me

and so i i just moved out here oh interesting wow which has been cool and so when i like did you have a job or something we just like moved out. So the onion moved from New York to Chicago and almost everyone left. And so I started a company with my friends. Huh. And we were doing these hackathons where developers and comedians made stuff together. And it's like it was a total not startup, total small business. Super fun.

Yeah. And we did one with Twitter. And so I moved out here for that thinking I would be out here for like months. Right. And now it's like whatever six years later. But what about California? was like so different for you that you had to stay here. Well,

I love doing the outdoor stuff, uh, for sure. Okay. Uh, but it's a trade. I don't know. Everyone wants to talk shit both ways.

And it's totally a trade. Um, culturally, it's not the same thing as New York. But then if you're working in like, tech, this is where, or entertainment stuff. I mean,

New York's kind of a mix, uh, but there's L.A. Um, it just seems so much, so much more professional. Not in like the polished sense. Yeah.

Like everyone is or like, Most people are here. And that's cool. That was cool to me. Like going to these like, you know, coffee shops and seeing, you know, this person that I only seen on the internet before. And I was like, man, all this shit's happening here. That's interesting. But I don't know.

How do you think these have changed? And also, sorry, I don't want to like to. But how do you think these have changed like in the past seven years? Or I guess, has it been seven years for you? Or something like that. Yeah. What has been the biggest thing that's changed? Like, I got they're both positive or negatively or neutrally.

in myself or in like the environment that you've seen from like oh yeah that's easy oh that's super easy tech is uh completely vilified that's been the biggest shift oh interesting yeah yeah i mean it's like if it's not this next election it's the one afterwards like tech is the evil thing interesting um and what did you see what drove that or kind of um hmm well in some ways it's like an incredible amount of wealth being accrued to a small amount of people. They're young and I think their amount of power is just off-putting to so many folks. Oh, I see. It's kind of like, Girard, like you have like the person to vilify and...

It just feels like the new banker to me. And that's the... That's been the shift. Not a great precedent in general. Yeah, I don't know. Because have you noticed anything? honestly I think it's kind of head like in bio is just you know no one ever face attention to bio we're just all the way over here kind of like you know working on things that take a really long time

and are very like hard and expensive and some people are like oh yeah they're still over there like still working on drugs and so I don't think as much and they're like very few weirdly there are very few billionaires in biotech I think this is something that was very striking to me when I first came out of sort of like I was looking for people who were amazing and also I made like a lot of capital and biotech because like those are the people who like would be successful and like know how to build business as well at least was my thought. And there were very few of them. A lot of them were in VC who had invested in these companies. So I was like, where are the founders not getting the capital that like, how does that equation work?

And then I think one of them was like a former salesman. It's like the most informative meeting I ever had about sales. He was just like, because I was trying to understand like how do you sell a business or an idea. And like, you know, from MIT's like, you know, complicated. Like we had a textbook about it and like, right. And he was like, you just sit the person down and tell them what to do. I was like, okay. Now I think I understand how this whole area of life, you know, how to communicate a little bit better than I did previously.

That's so funny. Yeah, I really hope more of these companies. I mean, they are popping up already. Like you've seen longevity, biotech. And if there is any kind of lull in the ecosystem, it's just going to be like fertile ground. Well, I think there was like there's been historically a lack of like founder-driven companies. And like obviously the fun environment has changed to make it more likely to happen like the next couple of years. Yeah.

But it's just so striking. Like it really is different when you have like, because you like, I think if you look at like the wealth created in tech and in biotech, it's like, you really see the distribution, you know, going so much more to venture capital, I think than to founders. And that was just, that's been like really, there's a really weird thing to kind of like observe on like first coming here. So like, like, why is that the case? Do you have different terms than normal BC funds? Well, I mean, I for for our funds. Yeah. I mean, if that's like a like a strong opinion you have, like, what are your terms?

Yeah. Yeah. Well, my definition, like, you know, we have age one. So, you know, what you folks are working on. Like, you know, that's founder driven. That's like, you know, sort of trying to give people, you know, sort of leg up and promote kind of like gradsunes and postdocs as the founders drives the company and, like, not try to replace them. Yeah. I guess like kind of like some other firms, which I think is a, you know, a fair strategy.

If like that's, you know, sort of, you know, something that that's been your bulwark for like decades. But, I mean, I think marketing would say it's similar to what's happened in software, right? Like, you know, you had this first wave of kind of like professional managers. You had kind of like a swing back to technologists. You kind of like a swing back to the middle. Kind of like, now we'd like some more managers, please. but like, you know, still technologists are kind of driving the show. And I think in Bywood might be kind of like midway through that.

We're kind of like we've had like the managers period for a long time. We might have more technologists. And then like maybe kind of like swing back to the middle. That's like a pretty simple pattern match. Like, you know, who knows what really happened in the future. Hmm. Yeah, because the, that's interesting. If it's a trailing thing from software, because you probably knows.

Yeah. Yeah. So what's happened now is like maybe 10 years ago or when YC started. It was incredibly rare for you to be able to just like pitch an idea. Exactly. Exactly. Now, you can easily do that. But more importantly, you can, I mean, I hear crazy numbers from people leaving college and going to work at Facebook or big companies. And I think that's like overall probably bad for the ecosystem because it like it encourages this like extreme risk aversion.

Right. And I think the likelihood of lifestyle inflation and never starting something is high. But think about so what enabled YC right? AW. Yeah. I mean, AWS, from the outside, a huge part of it, right? Like, the first ever ability, driven by tooling to kind of spend something up really cheaply. And I think in bio, and it's like what everyone talks about, it's really like, you know, there really was this point where like, you know, drop in cost of sequencing has been occurring over the past, like, you know, 18 years.

But really up until like the past two or four years, you could not get a thousand dollar genome, right? Like, that is a recent phenomenon. And so, like, what argument would be like, you know, look at like luminous revenues, you know, like today, it's absolutely crazy how someone they are to like, Intel's revenues, like, right in the 1970s. Or, like, the parallel there is, like, extremely, and this is, like, you know, our friend of mine, um, made to, like, notice this, but kind of like, there's just like, this really striking parallel between, like,

the enabling technology that we kind of see, you know, in kind of like one, one segment and they kind of like, what's happening about today. Um, and who knows what will happen in the future, but there is an interesting parallel there. Hmm. Huh. Do you think there are people in labs?

Well, actually, like, what percentage of people working in labs do you think want to start companies? So this is the fascinating thing. So we were, we were, we were, curious about this because if you look at the amount of funding that's available on the venture side to go into biotech in the past couple years, it's insanely, I mean, it's double-tripled in the past couple years alone, but the number of companies funded has stayed fairly constant. And so we're just looking at this, like, what the heck is happening here, right?

And what's happened is, like, the number on the top end of, like, the median hasn't even changed. It's like the top end of, like, the corporate, like, the corporate companies are getting more capital per company. So it's like all capital has come from LPs because you've seen, like, you know, the NASDAIC Bioting index, you know, go from like, stagnant, up until 2011, like monotonically increasing, or it's different of a small dip. And then, like, where do you put all this capital? There were no more companies to invest in. And so we were like, well, why are more people not starting companies? We went and talked like 100 grad students and postdocs. And the answer they gave us was like absolutely striking. It was like most of them,

so it may be like, you know, 10% were worried about reputation risk, like they didn't want to leave, fail and then go back. 80% had never thought about the idea of starting company. Like, they just were not aware that there was, you know, a possibility. And so you could argue, okay, maybe that's like they're not entrepreneurial. But, you know, if you think about, like, you know, in the 80s or in the 90s, like, would you have gone as a CS student at Stanford, like, started like started like started to like start something? I think that process easier. And so I think really what it's since it's a lack of education, you know, and kind of like just availability of options to these people, which is like makes you so angry, right? Like, you know, like you should never be forced or kind of like convince you something that you don't want to or that's not good for you. But you should be aware of your options. Like, how are all these smart people? not aware of like all the possibilities that are out there for them. I mean, it's, I think the saddest slash funniest one I've heard is when someone often in like a hard science, like lab or background, they learn about YC and then think that we're just giving them loans.

And they're like, oh, no, I can never do that. Yeah, which is like, I mean, I don't know. If you had had no exposure to this, like, why wouldn't you think that? I mean, like, and all of these myths exist. But I think the education thing is a good point. For the most part, people don't even know. That's absolutely crazy. Yeah.

So you should talk about your, I mean, dude, you have so many questions. But you should also maybe mention your project, Daniel, because that's relevant. Yes. Yes. Yeah. So super excited. So my friend, Daniel Gross, started this really, really awesome sort of project called Pioneer. And what pioneer is, is trying to find like the lost Einstein's of the world.

I think it's like an awesome tagline. And, you know, I think Danny has a fascinating background in that, like, he, you know, was kind of on track to join, like, the Israeli army and then, you know, uploaded a kind of application to YC. And, you know, like, basically, like, his whole life changed after, like, one flight out here and a meeting with, like, you know, Paul Graham and co. Sort of like this, you know, he's not an incredibly successful person, but kind of like, you know, would he have had the same chance if not for, like, a lucky, you know, I think his dad forged him, like an article about YC, like, that was how I found out about it, right? Really? I don't know. Yeah. That's great.

I think that's one thing you mentioned. And so there's this coincidence that kind of drove his journey. And so the question is, like, you know, how many people are there out there that, like, with a small intervention could, like, you know, drastically have, like, a different life course. And so Pioneer, sort of Pioneer. Is it a pioneer dot app is this place where if you're anybody in the world and you have a project you want to work on, you can apply. It can be anything, anywhere from kind of like, I want to have more of my high school friends do, like, science stuff all the way through to, like, I'm 80 and I finally want to write my novel.

And, you know, there's a thing called the Pioneer Tournament where people work for about 30 days, kind of, you know, do their project. and kind of like the community votes like on their kind of like most kind of, you know, favorite people. And they kind of based on that, at the end, you know, a set of people are selected to like be flown to San Francisco. You received about like a $5,000 grant. And they kind of like join the pie in community, which is kind of like this, you know, set of really ambitious outsiders trying to change the world. And so I raise it is because like, you know, my personal story was coming from New Zealand at age 12, you know, based on like a random email I sent to like a professor here. And it was the first thing I'd ever sent to like someone who was on a family member and she responded. But if she. hadn't responded and like that luck hadn't occurred and like you know where would I be I have no idea yeah um and so that's why I think it's just like pioneering was so exciting because it might help a lot and everyone who's listening to like you should definitely definitely apply pilot your own app um because you know I think it unlocked so much potential of like everyone in the world who like could be doing awesome things I think it's so cool yeah just enabling people to like have the the confidence thing has been the biggest surprise for me at YC oh interesting I think a huge unspoken part of YC's

successful is that it gives people the confidence to do their thing. Right. And they're often like, I mean, sometimes it's insider, you know, like tracked. Like I went to Stanford, whatever. But sometimes it's like total outsider people and it works out. And I think that like, yeah, man, without systems that give people that that little extra push, a lot of people will never do it. Ah, interesting.

It is counterintuitive, yeah. I mean, it's crazy. Like, because I do these office hours occasionally with people who are interested in applying, right? And they're awesome. They're great. And all it takes is like that one meeting where you're just like you're good enough. You can do it. And that's it.

That's so fascinating. Huh. It's crazy. Interesting. Yeah. I mean, I think one of the fascinating things that the dynamic is going to run into is sort of like, how do you give that to like, how do you scale that feeling of like transmitting confidence? It was like, you know, yeah, it's non-trivial. Well, you asked me about podcast before we started, right?

And so this is like a crazy side effect of podcasting because it makes you feel and the thing, it makes you feel like you know someone really well. But the reality is you kind of do. And so that like that relationship of someone as like whatever, just like friend or mentor or whatever is enough to be like, oh, like I kind of get this. I can be myself with them and I can kind of just like express whatever I want to do. But then there are totally like weird elements for me. Like I'll be like in the bathroom at demo day. Literally.

I'll be in the bathroom at demo day and like someone will like tap me on the back and be like, oh man, I like the podcast like, cool, not now. That's so funny. Do people feel like they know you from hearing so many of your conversations with others and kind of like how you think about the world? I guess like because you said that one thing that you find fascinating is like how other people think about the world. Yeah. But I guess like the way that you ask questions must give so information about how you build models or view systems.

Or how stupid I am. Yeah. No. I mean, I don't talk a ton about myself. I mean, I do. But yeah, people get the sense. And I was actually thinking about talking to my friend about this this morning of like, what is it about the, how am I different on the podcast versus in real life? Oh, interesting.

There's like some dissonance for both of us, right? There's like going to be some dissonance there. Right. And I'm curious about like how to best merge the two. And I haven't figured it out yet because I actually don't know what the, what the gap is. So you don't know what your podcast. I was, I was about to text him and I didn't. Huh.

Yeah. Because I mean, you seem pretty kind of like on the surface similar. But yeah, I guess it would be hard to know without one period of observation. Oh, have you listened to it before? No, just the content of like our 15-minute conversation before we started and then kind of like... Oh, right. Yeah. Basically, it's the same thing.

Yeah, maybe. Huh. Interesting. Yeah, I don't know. It'd be better if you were more like the person that you... Like, yeah, like, what authenticity do you think would bring like that? Like, you don't have kind of now. I'm curious.

So in some ways, I'm just selfishly interested in like making it something. something that feels more like me. And it's my thing. Right. You're always curious about like gains, you know, what can make the show better. Right. And when I think about the podcast that I like, you know, things like Rogan, stuff like that. I mean, obviously, like, that's not fringe.

But I imagine, and this is again, like projecting because I've never hung out with him. Huh. I imagine that it's like very close to what hanging out with the person is like. And then when I watch the podcast with me sometimes, I can tell that I'm nervous or not as like, I don't know, natural as normal. Do you think it's the environment? Like if you made this like feel like you're living room, that it would be slightly different? Um, yeah, it's possible. Yeah, it's totally.

I mean, I think one thing that would be benefited. show it's like hang I mean you're this is you know you're great so it's like very chilled it's very easy yeah but sometimes like uh hanging out with someone beforehand oh I see so it feels like you have a conversation and then it just continues into yeah and in the uh my desire to keep it like on topic right can make it less natural than it could be right that makes sense yeah you know what I mean yeah because you always come back to like one thing But then maybe that's not actually the organic way that it would have gone. Right.

Because, I mean, like, well, actually, this would be a good test. Because I'll put this one out and people are like, dude, what the fuck are you doing? Stay on topic with longevity stuff. Yeah. I don't know. Yeah. That's interesting. I don't know.

It's tough. Because are you a podcast person? I actually am not. Like, I really only do books and papers. Because podcasts are kind of annoying. Like, you can't fast forward through things. easily and kind of like use your eyes like figure out if like they were transcribed then I might read them but yeah which you can some do we do but not everyone but then I also feel like I don't

I think there's like something about deep being decroyid you know because if everyone is listening to the same podcasts and you go and like spend the same amount of time reading like people and like the Greeks kind of like you know like what these cities was thinking you might have like very outdated information that's like not very informed you know about today but you also might like I guess get a similar feel for how somebody was, but have it be like more decorrelated and therefore ideally kind of like more sort of like maybe like a better viewpoint than the normal. I think you should. I think it's like, I mean, dude, the amount of times I've heard people reference sapiens

or Charlie Munger is like, I just can't deal. I mean, they're great. They're awesome ideas, whatever. Right. But like everyone's consuming the same media. Yeah. And I think it's interesting. because if you if you don't and you try to understand it from first principles, which I think

is like, first principles itself being like kind of like, I think that is often cited is like the good thing, but maybe not fully understood. It can be like quite different. I think one thing most people don't realize, like, you know, math and science often are like more artistic than they are kind of like logical, but like everyone's trying to like frame things as like a logical process. Yeah. Well, because it's, I think a counterintuitive thing is that you, well, I mean, it's obvious

when you say it out loud to pursue an idea. in math or science, you have to be inspired to pursue it because you don't know if it's true beforehand. Exactly. No, it's so crazy. Like, I think it's fascinating, you look at Newton, right? Like, Newton spent, he had this amazing year when he was 21. He, like, discovers all these things.

And then he goes into, like, alchemy in the Bible. And you're like, what? Like, where does that come from? But I think part of it is, like, the kind of, I mean, obviously, it's something logical and analytical, like, is these, like, books where he's so curious. But I think also, like, he has some kind of, like, a little bit, like, a mysticism. Like, this is kind of these weird aspect of it's like a little bit artistic. And we kind of like, we forget that. We're like, oh, yeah, like scientists are kind of like robots.

But they're really, yeah, they're really not. Definitely not. Definitely not. All right. So let's actually get some of these questions. Okay. Grace. All right, man. So which ones appealed to you? Because we have so many. I think the ones that are like factual or good. So just like the research questions probably. All right. Let's do that. So maybe we should rip. because I'm genuinely interested in a lot of these.

And I read your longevity FAQ, which is awesome. It's very like Tim Urban, wait but why style. Maybe it's the drawings that got me. Yeah. But that was cool. Well, yeah. Yeah, that must have taken a lot of work. Yeah, it was like, you know, just drawing the kind of like axes and then like three lines.

Yeah. It was hard. So Sam Batesh asked. Do you think there's going to be another step function change in human lifespan since, you know, germ theory? What's the next one? I think this is a super fascinating question and time to be alive because, like, you know, you know, it's fascinating. You know, you look back and kind of like, you know, germ theory is just like such a huge breakthrough. I think, but one thing I think is lost also is like there's another breakthrough that's similar related,

which is that like life comes from life. Yeah. Because like for all history, we think that like there's spontaneous generation of life, like literally up until like, you know, right about that time. And then the stirers like, nope, nope, nope. Like, you know, these germs are coming in like through like the neck of the pipe. It's, it's not. And so, you know, that and that was huge breakthrough. And then, you know, obviously Darwin kind of like, you know, also very important. I think the thing that, um, we kind of have an intuition will be important in longevity that most people are kind of not paying attention to is like what it, it's going to sound way

too philosophical. But really when you get into it, I think it's the important thing. What does it in to be alive. And at what point are you kind of differentiating between the germline, which is kind of like your reproductive cells and the stone, which is kind of like your kind of skin and tissue, because there is a immortal line of kind of like living kind of things that has been replicating since like our first ancestor, right, transmitted through our germ line. When I have a kid, that kid does not come out and like have the same amount of aging that I do when I have it. It is kind of like brand new, right? And like how the heck does that happen? And how do you fit that? And how do you fit that kind of paradigm. And if you take, for example, a bacterium, now there's some bacterium

that do asymmetrically divide and, like, possibly have some form of aging, but kind of like, you know, do you look at a bacterium and think like that that thing like that thing is aging? Maybe, maybe not. And so what is it about multilarity and kind of like are germline and a certain and the differentiation between the two that's caused us to kind of evolve or start this kind of like aging phenomenon? And, you know, given that, is it natural? Or can we think about how our desire to kind of like live longer ourselves fits into kind of like that differentiation? because, you know, nature has already solved for kind of like living forever on some level, right, on the cell level. And so kind of what is it about, yeah, our stoma that, like, is so different.

And are there any things that we can repurpose and use, you know, for that. And so I think that that area is going to be super, super fascinating. And then I'm also just broadly in love with the question, like, what is life, right? Kind of like, that's so interesting. Like, you know, Schrodinger in like the 1930s kind of writing this fascinating tracks, like bringing like Maxwellbrook and others in. And so that, you know, that and kind of the people thinking about like, you know, sort of German England, at MIT are just absolutely incredible in their work. That's probably a longer answer.

Like, you know, we just think like, I love this question because sort of like, you know, we spend so much time thinking about like the practicalities, but kind of like the higher level order of like, what would be the actual breakthrough? I think that like that, that are just like really interesting. Sort of tangent. You mentioned, yeah, giving birth. Is someone working, or I mean, I assume someone, but like are people working on extending fertility windows if you extend health.

in because that seems like, you know, if you could live forever, right? As a dude, like, I can just opt out, right? Like, I'm just, all right, I'm not going to have kids or I'm not going to like, in my mind, that's the real issue, right? It's like allocating time. Yeah. You know, so if, say you work aggressively until you're 30. Yeah.

Or 35 or whenever. And then you have kids. Like, all of a sudden, you have to take care of this thing or it will die. Right. So being able to push that until you're 60. Yep. Seems like really valuable. Yep.

Well, so we think that's, that is, and so I don't want to say fascinating too many times. It really is a fascinating area because, you know, there are some animals, many, in fact, where, like, you know, you have some octopi that lay their eggs and then their mouth disappears. And they're, like, sitting on their eggs and, like, literally commit suicide. And if you reverse, like, glandular action, like, gives rise to that, they just keep on living. And so it's like you have programs in essence all over the animal kingdom. And, like, we're, you know, anthropocentric humans. And so we say, oh, that doesn't happen to us. But if you think about menopause, right, like, women, like, what is that?

That is a clocked, acute onset of kind of loss of health, right? Not as fertility, like many other things, you get fat distribution, you know, bone loss acutely at the time of menopause. So many of the things get, like a lot worse in a clocked fashion. And you kind of look at other animals. You're like, oh, we're all like that. You know, but really are we that different. And so that area is just, and there are even some hormones that we're looking into right now that are involved in that process that we think we're super fasting for longevity. And so I think like that area is just, yeah, it's really, really interesting.

So, yeah, I mean, is it more, I imagine it's more likely for it to be an artificial womb than reengineering humans. But maybe that's inaccurate. I think the artificial womb is not one that we naturally look at it because it's sort of like not, you know, if you solve that problem when it's just like solved longevity problem. Right. But I think there's actually, you know, that would be cool. But like even just thinking about like what is venipause? Yeah. Right?

Because like, you know, why is it so timed? Like what is the clock that like turns on? And if we like turned off that clock, like would it push backward? Is there some kind of natural? And there's some like obvious answers for that. But I, you know, it just, it really is. And you think about like, how did evolution decide like that was a correct time? So that I think that it was just like, yeah, really interesting.

That's awesome. All right. Jason Choi asks, what's the percentage of longevity attributable to lifestyle choices versus genetics and the progress of technology and influencing both? Oh, interesting. So there's a recent paper that actually came out super fascinating with guy Yanit Erlich in science. And what it did was they have a public. database of heredity. So basically, like, a family tree, unfortunately doesn't have actual

genomic data for each person, but you have a lot of lifespan data. So age, birth, and, sort of death dates, many generations back. And so you can ask, what is the kind of like heritability of longevity? You know, if your parents lived longer or you're also likely live longer. And I think prior to that we'd had about a 25% heritability kind of figure. I think that dropped to, like, about 11%. I could be off on this figure, but I think that paper was about 11%. Could be wrong. And so, That, I think that's kind of the current statement from the field is that like that's, you know, are prior on like percentage of longevity tripled genetics. I think that underestimates the potential impact of genetics on longevity because sort of like, you know, do you have kind of like mutants that are like long lived in the population?

And so maybe, you know, I think it doesn't tell you like how much genes could be changed influence longevity. But yeah, about 11% would be like the current estimate from the field. Hmm. Okay. There you. Fati asks, is blood transfusion? So this is parabiosis. Right.

Yeah. Is it a thing or just a hoax? Oh, gosh. No, the blood boy question. Yeah, I know. The blood boys are like, they false around. Everywhere we go, we're asked about the blood boys. So one thing that's fascinating, right, is like, sorry, it's fascinating all the time.

If you go back and ask, what are the first ever things discovered to impact longevity? You know, the tools that we had prior to 1950 did not. allow us to do genetics, they did not allow us to do like any of the things that we now kind of focus on longevity. The one thing that, you know, Alex Correll in 1912 gets the double prize for sewing blood vessels together. And so what is one of the things that has tried in the early half of like the 20th century? Because like that's the only thing that we have the tools to do, it's like literally, you know, you're sewing blood vessels together between a young and an old mouse. Yeah. And that does appear to have positive impact. You know, there are three or four nature and

science papers that have come out recently showing, you know, there's some positive impact on kind of like the function in the brain. some positive impact on function on the heart, some on muscle. So we do see positive impacts. I haven't seen to date a really good longevity study. So I think we've seen a lot of evidence of like age-related kind of phenotypes getting better. But I personally have not seen a study that like really, you know, makes me super excited about kind of like the number of extra years. Lots of stuff to like indicate that might be the case if done correctly. But just I actually haven't seen that study, you know, like sort of done. Yes. There's been some studies published like in the

mid-1900s about paribiosis that I think I might have cited that kind of indicated an exception, but they're kind of like really replicated properly to really believe that. And so I think there's probably some impact on lifespan. Like I don't think we have that well characterized yet. Hmm. Okay. So true. Like not a hoax. Not a hoax. But I think people really overfocus on that because it's such an easy story to tell all right. Like, oh, vampires. Vampires. Oh, it's all just vampire. Yeah. Like, yeah, no, no. There are like, you know, 60 different things that make, you know, X live longer and like you have to look at you know but people don't want to hear about like daftoans and receptor like you want to hear about like vampires yeah no I mean it's just like

like kind of what I was saying before about like tech being seen as black and white like sort of like everything people just want the pill oh actually I wanted to talk about rapamycin ah right yeah so my friend Nicola wrote a New York article about it oh awesome I'm like I'm slightly terrified but can you can you just break it down um so so rapamycin is this this is this really, really interesting drug, discovered on Rapa Nui, the aisle in a soil sample as many, many drugs were. And, you know, kind of what it does is many things. But I think one thing that's been focused on is an impact on what's called mTOR, which is a protein that's part of kind of two different complexes of proteins. And so, you know, the problem with repomycin

is it has a lot of kind of like side effects, right? It's originally developed like, you know, maybe immune suppressant in one use. And so do you really want to be taking that, like, you know, continuously? Probably not. There's a lot of doctors, you know, if you ask kind of like a subset of kind of like people who specialize in crazy things that might actually work in longevity, if you then will say like pulse rapamycin, so taking rapamycin and very kind of, you know, huge doses, but then like on a schedule not continuously is a good thing. Yeah. And I think that like we don't see that like being disproven or like implausible. It is, I think, a risky endeavor on some level. One thing I would say is, you know, there are several companies trying to develop much safer versions that do the same things.

to have the positive benefit, like, don't have, like, all the other kind of, like, sort of negative effects. And so I personally just kind of like wait until those, like, get a little bit farther along. But, I mean, rapid mycin is kind of reported. I think the other fascinating thing is, like, I don't think we have a great feeling for what the max is on the lifespan X percent that's possible with hapamicin. Yeah. Like, the question is, like, if you dose it up, like, what's the maximum dose and how much,

at what point you start to get, like, decreasing returns and longevity? It's not clear that we've actually hit that barrier quite well. That's the other fascinating, like, sort of thing. Interesting. What about, I've heard people taking testosterone and like that is debated over like, you know, maybe it increases health span, but it actually makes short in lifespan. No, we get a lot of, and there's a lot of people, like, we're in a low T society. There's also, I think a lot of people taking growth hormone, you know, for longevity. Yeah.

And when I first, when I first saw that and kind of like an airplane magazine, I was furious because, like, in worms, if you, if you, like, knock out the analog of growth hormone receptor, they live longer. And, you know, mice, like, dork mice are the long-lived mice. And within a species, not between species, but within a species, you know, being smaller is actually a correlate with kind of longevity. But I think, you know, one thing there is like maybe taking growth hormone makes an 80-year-old feel a lot better. So it's kind of like a health span optimization. So back to that kind of like, you know, do you feel better like that results in a long life span? But I don't think that's a great thing obviously to do for kind of like actual lifespan in general. Because to clarify, it can increase or encourage like cancer cell growth?

I mean, there's this possibly a minor thing there. I think for the most part, there's a not fully defined complex signaling pathway that seems to kind of be quite related to longevity. That was first discovered in worms and then kind of like also characterized in humans. Like there's a subset of Dorffs, for example, who appear to compare to their relatives, suffer much less cancer and metabolic disease. And that correlates with what you expect from mice. Like if you mutate mice to be Dorffs, they live about 60% longer than normal. Like 60%. Pretty non-trivial.

Pretty solid. Right. How much shorter would you be if you can live 60% longer? How much shorter? I'm not quantitatively. I don't know. Not like 10% obviously, but like, you know, between a 50 and 70. But, but, but I are 80.

I'm not actually sure for those mice how much more they were quantitatively. But I think the interesting thing is you can actually possibly decorrelate like the being smaller with the effect. So it's like not just like a size. It's like a single thing as well. Would you make that trade if you're like one foot tall? The trade is positive. So the idea is like you can decouple like the being small of like longevity benefits. Oh, I know, but I'm asking you a would you rather?

What do you think that's true? Yeah, probably. Probably. Probably. Yeah, yeah. That's awesome. So Aubrey de Grey, another like kind of famous longevity person. Someone asked about them. So Chris asks, he's mentioned several times about replacing organs with new organic ones before they fail.

Is that a reasonable idea or would they more likely be replaced with synthetic ones? Oh, interesting. I think so this is. is an area that we're still building are, it's like maybe too late to be like seven years and still thesis building. Yeah. But it, you know, I think there, there's so many things that have to go right for that to become like the obvious thing to do.

You know, in some ways it's like the oldest version of aging, right? And that like, you know, back to our friend Alex Carrell and his Nobel Prize, but like, you know, he is doing the first ever kind of like sewing up kind of like the organs and kind of like, let's get a, you know, little if you read his paper that's like, let's just grab this like dog kidney and like, we'll take this one for this other dog and like, you know, plug it in. And you're like, well, okay, that's the early 1900s. So in a sense what Aubrey's proposing is the oldest most kind of like worked on idea.

But then, you know, I think we also, we just haven't seen that done well on the rejuvenation front a lot recently. And I think I don't, I think we're still fully understanding. You know, there's some things where like if you get an organ for somebody who's had cancer, for example, there's like a small rest of like 10 years later, you might also incur like some kind of negative event. And just things like that, I think we're still understanding kind of how to how to weigh those. those risks. But I think it's fascinating. It's a surprising fact that it sounds the most most, you know, sounds the most kind of like old method of kind of like considering working in the space. Right. Well, you're just like take the part out, put it in another right to go. Yeah.

Yeah. All right. So I have a very important question. So Micah said you did a cookie diet. Is that true? Yes. Yeah. How did that go? I think it was pretty informative in that, you know, again, I wouldn't recommend any way to like go eat just cookies, but... Were these, like, fancy health food cookies? No, no. So the reason I did it was my friend had claimed that he had only eaten whipped cream

and bacon for a month. And that this was possible. Of course, it's impossible. Yeah, all right. But then he was like, but I actually feel pretty good too. And I thought that it was total BS. And that he probably, I mean, he's a very smart and like, you know, congenious person. So I was like, well, like, either he's like very different than I really thought he was or that's possible to do. And so I wanted to test it.

And so I tried that and was like, well, you actually kind of can. And you kind of feel fine. So then I was just like curious, like if you took any random thing, like any random food object, like just ate that for a month, like what would happen? And the cookie diet, like, worked very well. But I just, for the long term, it seemed like probably not a good idea. So switching off of that to like a lower sugar diet, it's probably a good idea. Did you, were you doing blood tests or resolved by feel?

No. No, I should have done blood tests. That's funny. Yeah, there was this well-known long-distance hiker, Andrew Skirka. He's written up a bunch of blogs and stuff. And he's pretty well known for having kind of extreme. He just has a diet that can take anything, it seems like.

So he was like, I think for a while it was just like Snickers and Pringles, something like that. That sounds great. Yeah, which I mean, I guess if you have enough toothpaste like on the Pacific Crest Trail, you're fine. Yeah. You have to kind of wonder, though, like how much worse that would be than like one example is, right? I think that, like, a lot of, for example, eating meat, maybe the worst part of me is, like, if your animal is stressed, like, had, like, a lot of the incorrect type of hormone directly before, like, being killed. But actually, like, a more important thing, like, whether you're eating meat or not. And sort of, like, what the kind of, like, minor things are that we don't think about, like, the axes that aren't, like, what those are.

But, yeah, hard to say. Hard to say. Cool. All right. My last question is, are you seriously not doing anything really weird? There's, like, no pills. There's no weird food. There's no crazy fasting.

Um, I mean, I think that, like, apart from true. trying to eat the cookie diet. So one thing that I was trying to do for a while was like I was trying to quite understand, you know, because we're just like black boxes and like you intake some number of calories. And like you should be able to calculate like where they all go, kind of like how many are necessary to like eat each day, kind of like from first principles, like figure out kind of like what optimal diet would be. I tried to do that for muscle. So it was like like how many proteins should want to eat 30 minutes after working out? The first problem was it's really hard. Like why three minutes after working out is the correct amount of time? No idea because sort of like,

you know, our cells are expanding to that period of time. like, it's hard to, you know, figure out. Also just got really down in the weeds of, like, how many amino acids would be required to, like, replace certain things. And, and I think I came out of that just kind of, like, very convinced, like, a lot of the things that, like, people talk about at the high level, like, wrong and, like, perfectly theoretically. So, like, a lower level. And that, like, I shouldn't have the time to kind of, like, really think about doing that for, like, a full diet. And so I think at this point, until I have, like, you know, maybe a full year to kind of, like, go back and understand that whole area better, it's kind of, like, just, you know, the obvious things, because history is probably. like a good teacher for like you know baseline health nice all right if someone wants to learn

more about you where should they go yes um so we run longevity fund uh and i'm just uh laura at longevity dc and anyone can reach out and we love to talk to you cool thanks for coming in awesome thank you for having me all right thanks for listening so as always you can find the transcript and the video at blog dot ycombinator dot com and if you have a second it would be awesome to give us a rating and review wherever you find your podcast see you next time.