Hey, how's it going? This is Craig Cannon, and you're listening to Why 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're trying to start a longevity fund, you would have a terrible time. You'd have the worst idea.
And so timing is super important. Why now for the first time in 2,000, 3,000 years is the correct time to work on longevity? To us, a lot of that comes back to tooling, what's available for us to use. Prior to the 1900s, if you wanted to impact biology, maybe you should have been a physicist.
It worked on optics, helped make the first microscope, and like Robert Hooke, a physicist, discovers the cell. So there's so much that comes from physics and other disciplines into biology to push it forward. But then I think in the 1900s, 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.
The catheter ray tube discovered mass spectrometry, but by this guy trying to find a massive electron, which is so cool. And so all these tools are coming online, but also more biology-driven tools. And so really, I think, and we can get into this more specifically, what's exciting is just seeing the tools available to characterize life become available for the first time ever. For all millennia, Darwin and Mendel talk about genetics, and there was no knowledge of what was actually going on at the ground truth level.
And in 1953, for the first time, you have the link between molecular biology and looking at microscopes and genetics and this concept of heredity, which is just super exciting. And what caused you to jump in? Well, A, I think I was born in a very lucky time, right? I think it was sort of cautious or a little bit concerned if you believe that about yourself.
Like, why now? It should be a lucky time. But I think also, as a kid, A, I just had a lot of relatives that were aging, and that was very striking, but also really wanted to solve cancer. And I remember talking to my dad about this, and I was like, oh, I want to solve cancer.
He's like, well, you know, cancer is a set of aging. So if you want to solve cancer, you just can solve aging and take care of all these other things as well. And that just made sense to me as a kid. I was like, okay, well, let's all go solve aging, then.
That's the biggest problem. Because cancer is not the number one cause of death in the U.S., right? It's heart disease. Right.
Well, if you look, all the age-wise diseases, you know, past a certain point are driving kind of like the majority of sort of natural deaths, so to speak. So, you know, once we got rid of infectious disease, it really became a case of aging, which wasn't previously necessarily the biggest issue, sort of like rose to the forefront. And so that kind of, I mean, it just made sense to like a small trial that that was important. Huh.
And so why raise a fund rather than, you know, just go for a caring answer? So the thinking at the time was, you know, possibly in a good way, like Emperor has no closing, excuse me, like, you have to understand, so I was at MIT, I was like a sophomore. Yeah. And I was also 16, and I had like maybe $1,000 in my bank account.
And so, like, you know, knowledge about the financial industry, like, relatively low. My dad had been a public investor, so I kind of knew a lot about, like, the idea of investing in things like that as a good thing to do. And I had 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, you know, call up a few in the phone book, like, you know, a few respondents, like, having some kind of conversations. And just be like, you know, I'm just curious, my student, can you tell me more about, like, how this industry works? Like, you know, are you finding 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, like, something that I personally believe, like, on the technology side, like, super exciting, was kind of generally not really, like, looked at a lot by these folks who are supposedly the great translators of technology.
And I think also, it kind of made sense, like, the first ever mutation found to really send real medicine was in 1983. The next was, like, 1993. And so really it started about, like, 20, 30 years ago. So it kind of made sense, like, if you think of, like, how long it feels, like, yet traction will become known.
Like, okay, maybe, like, there's not 100 good labs in this space. Maybe, like, people just, like, haven't had enough time on, like, the adventure or, like, the 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 sort of find out that case to, like, help more drugs and get started out of the space. So, in other words, like, the big pharmaceutical companies are not investing in these piloting.
They worked 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 that have been started or so that have, like, the aging brand on them. There was, like, zero people in such, like, Arch Ventures. We wanted a few that were, like, taking risks. There was, like, maybe 10 million invested that year in total in the space, right?
Like, in the past four years, we've had, like, 10 billion plus. We now have, like, 300 companies per year. So it's just really strange. Like, it's very striking to watch you go from, like, zero to, like, what it is today.
Yeah, now it's totally a trend. 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 come from a semi-scientific background so, like, we like to get, like, to ground truth of things. And it's just really hard.
Like, there's just a million. If you start reading mouse studies and longevity, like, you'll 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 and keep the total calorie intake the same. You can kind of test, like, which component of diet is, like, increasing longevity. And they did this and they, like, did kind of the full matrix.
And they, like, spent each of the different proportions. And what they found from that study in life was that, like, decreasing protein was the number one kind of thing that increased longevity. And so from that you might infer, 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 come to the conclusion that, kind of, like, you know, I have some theses about, like, what is good and what is not good. But as a scientist, it's really hard to say there's kind of, like, a good, kind of, like, real kind of, like, hypothesis there. Okay, and so... So I'm sure, like, not a lot of, like, just despite, like, reading probably more papers on this than, like, most people in the world, 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, they're a lot of 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, the sort of, like, bare minimal, like, try to eat low sugar.
I'm personally trying low protein, just because I think that is somewhat supported by kind of, like, literature. But low protein is, like, a gram per kilogram per day? I think it's sort of, like, not... It's a good question, like, what is the correct per person also if you exercise?
I actually once tried to calculate out if you exercise, like, how much protein would be required to be required to be much more of all of your mouse and action proteins. And it's kind of fascinating. I think that there might actually be, like, up to 100-fold increase in power, like, in your muscles, where, like, if they all fired at the same time, you know, sort of a lot of power. But, I mean, I just 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 intimate fasting seems to be, like, so much 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. Yeah. But, yeah, I wish I had better recommendations for that area.
Okay. And in terms of supplements, are you doing anything? There's a variety of people working on everything from AD+, all the way through to, like, Metformin, for the kind of more adventurous. I think that...
So we actually have a secret list that's kind of, like, on-market drugs and things that we think, based on, like, our, like, body of evidence might be having an impact on lifespan, and we're monitoring them. Some of them, I personally think, would be, like, intriguing to take. We don't release that list 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's, like, a terrible thing to do, like them. But we have a secret list of things that we think are, like, interesting.
Okay. And I think we're going to be positive. There's some evidence positive back there. But we haven't seen a large increase in lifespan.
So that'd be, like, my one concern there. Okay, cool. Because, yeah, in the worm and mouse studies, there have been, like, you know, 100% increase in lifespan, right? With certain...
So worm studies, we've gotten up to 10-fold reported, you know, possibly more. That's by decreasing a gene product, though. So that's kind of, like, if you want to go into gene therapy or we had such a thing, you know, from birth, possibly, like, that would work. But it would probably have to be a lot smaller.
In mice, we've got about it up to a two-fold increase, and that was a combination of amutation and restricting the total caloric intake of the mouse. Okay, down to what? I don't remember for that study. On average, I think people do see about 30% of normal caloric intake.
But it really varies. If you take 40 different... And this is where it gets complicated. If you take 40 different genetically different rates 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... I was like, oh, you know, 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 have your family members lived? How long have my family members lived? Your great-grandma is. Well, my grandma is still going.
She's in her mid-90s. That's a good sign. Yes, exactly. They've all lived, you know, about age 80 or above.
So, you know, hopefully... 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 recommend to your audience would be? Well, I mean, I've done a little bit of blood work, so everything's 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, I was, like, over your house and, like, you made chicken or something. I was 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, I started eating more protein, but really just more eggs.
And then I felt a lot better. But really, the main thing is sleep. Yeah, no, that makes sense. And also, actually, one thing that's interesting on the health plan front, I think people have this, like, intuition that when they feel better, that's a metric for something that's good for them.
And it's actually not true. So, if you look, to some extent, you know, maybe you want to optimize, like, robust, very cheerful lifespan, in which case, like, tautologically it is. But most of the time, or a lot of the time, when you see our mice or you do other things like make them live longer, so a whole number of years increases, they're not kind of, like, as happy on a day-to-day basis. They're a little bit thinner, a little bit more large in some cases.
But I think it's not like, you know, whenever someone's like, I really feel better, I'm always like, oh, gosh, I wonder if that's, like, the correct thing. Like, maybe, maybe not. Well, when people talk about health span, in my mind, it's very correlated to how I feel. Right, yeah.
If I was going to do a 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, I know a lot of people who have experimented with 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 so regulated? There's this fellow nearby who's working on what's called the TAME trial. And the point of that is to assay the effects of this drug, on markers or biomarkers 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, OK, well, here's the first pass at testing aging humans and so finally comes from our data. The way that trial was sort of motivated was there was this kind of large finding that in hundreds of thousands of patients or I think about actually 70,000 in that population from kind of a UK study, if you look retrospectively, people who hadn't taken metformin for decades, they had apparently like a little bit better kind of health span. So they had less age-wide disease.
The diabetics did on this drug, even in their kind of non-diabetic counterparts so we're not taking metformin. And so I think, you know, hard to say that is definitive evidence but that kind of motivated all this sort of question asking of could we really nail down in humans the trials like test metformin in particular. That said, I think that a lot of biologists will really kind of say oh, it's very important testing to humans and of course it is. We could do that.
We would be doing it all over the place. But I think increasingly over the years I'm kind of like more and more excited about the animal kingdom. Like the animal kingdom is just like absolutely awesome. We have one company in our current portfolio that's working on this and they're amazing in fauna.
But there's such a diversity of phenotypes, right? And like how can we learn from other animals as opposed to just like our lily cells? Because like, you know, for example, there's naked mole rats and rats. 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 waiting for them to start dying and then like rats which have like very similar physiology living like three to four years. And so what on earth is different between these two animals, right?
Like that's just absolutely fascinating. I think it's also important because like you know, a lot of like your physicians and I used to be were always worried what is an inherent limitation on like a complexity level. Like what if given a certain complex system and a certain metabolism like you have to die because there's some kind of like sort of theory of entropy increasing over time that like you know must thrive just like two complex like will intervene. But like these animals are basically the same size like have 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 longevity. Yeah, absolutely. So someone asked a question that I thought was kind of funny. Yeah, here we go.
So Micah asked, basically do you think immortality is going to be achieved by curing all diseases? So in other words, like whatever. 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 was a question that I used to get very interested in sort of like, well, you know, if you care about this, if you're working on biology. 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 a frame for thinking about this question is I think about biology like a set of tools, right?
So you can kind of see the kind of like things that have become available recently for us to use to affect human health. What I mean by that is like, you know, prior to like, you know, the 1900s or like even like just the 1980s if you wanted to make a drug, it was like a small molecule, you got a plant, you found something from a plant that's useful, or you like put some salt in a wood, which was too bad, not very, not very good sterility. There are things we would do, but then like, in the 20th century, for the first time, we use like proteins, you know, insulin or antibodies created by like our own bodies, you know, the bodies like the mice that we kind of quote them in to treat disease. And so we actually use something that came from life to treat, you know, like an organism.
We now, just in the past three years, have like landmark approvals and viruses being used to like blow up cancer, 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 if you had to put money on it, obviously you literally put money on it, like what would be the most likely thing to take off in the next 50 years? So here's how we think about it. Like we have extremely strong confidence that it's possible to impact lifespan between like, you know, three months to maybe 10 years and you know, obviously like different probabilities with what we have to, in fact, we're pretty certain that there's some things in the clinic already or on the market that some probability are impacting lifespan.
Lifespan seems to be very malleable to a small degree. I think the larger question is like, well, A, how many of those can be put together to get the maximum impact from that first wave? And then B, our thesis is that none of those things will be sufficient on their own to result in engineered lifespan. So you have this first wave of things that kind of work, like they're kind of limited, like they have kind of like maybe like 6%, and that's like the max.
So then the question is how can you go above that? And we can get all things back to tooling. But that's where I don't know if I'm, you know, we're Aristotle or kind of like, we're Newton or maybe like about tools and we think about investing in this case. 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 foundational stage. Right, exactly. I think we'd love to think that it is. of course.
1953, my argument for foundational stage would be like, this is the first time ever in history that we have a liquid genetics in microbiology. That happened in 1953, that's pretty landmark. Maybe it's been seven years ago. What happened in seven years?
Couldn't it just happen right after 1953? I think that's why today makes sense from an engineering perspective. And then ethically, Ryan Hoover asked about the ethics of longevity. Another, Jack Fernandez asked, people actually want to live longer.
Do you have some opinions on this or are you kind of stepping back? So we get asked about this all the time. And it's funny, when I started the fun, I never thought that people would ask those questions. Yeah, you thought it was assumed.
Well, because the reason I started the fun was to cure things like cancer and Alzheimer's. And so, from our perspective, you would never ask, is it good to cure cancer? No one would ever ask that question that I've heard of, or maybe some people would. But then we realized that when people think about it, they think about it as different than those things.
And so I think, from our perspective, I just, you know, I think it makes sense to cure these issues if we can. And so we definitely wanted to do that, and so we would never deviate from our mission. I think, you know, from a broader scale, it's kind of like two camps, like, do you want to be like Malthusian, and you're thinking of kind of like, you know, the world's bound in place, like, you know, it's really limited resources, kind of like David Deutschian, like, you know, we're on, you know, spaceship earth, but no, we're not actually, like, let's go, like, it's for the cosmos, kind of limited resources, like, energy is, like, all that or, I think it's just, like, kind of like, from a, I think it's just kind of like, well, it's kind of like, more on the kind of ladder, sort of camp, so I like that kind of viewpoint a little bit better. But yeah, I think to us, like, the rationale of the one that really was, let's cure these diseases, how do you do that you work on aging?
Hmm, yeah, maybe there are multiple universes, where we look at it. I'm trying to get there on the podcast. I met him one time when we talked about it. It's about, 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 new ones, fewer nonsense. And sort of this is, like, why the basic income, or one of the basic income arguments, 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 loss of openness.
And I think, you know, it's actually both of those. On the first point, I don't think that that's true personally. I don't think that, like, I'm motivated to do things because I know that I'm going to die. Like, I think that, you know, perhaps everyone else is just kind of, like, I think I'm motivated by many things, like curiosity, competition, sort of, like, you know, personal growth, kind of, like, wanting to, like, eat better next year than, like, you know, what's today?
Kind of, like, it's a 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 have different answers, but I just, you know, I'm curious if, like, death really is, like, the core kind of, like, motor to do things for everyone in the world. Like, that's one thing. It might result in people wanting to go to war, which might be problematic if you kind of, like, want more soldiers, or not if you want, like, less war.
That's a very interesting thing. But I think for that question, I don't agree that we really understand, like, the core motivation of everyone's planet, and that that is, by 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 age, there is a lot of, like, just cognitive, like, change of age, which is very fascinating, right? So, like, you know, biologically, you do change.
And, like, you know, part of what we, like, really want to do, you know, is a packaging. But, like, a large part of it, like, we just take a cognitive enhancer, if you were, like, sharp until you're 90, then you, you know, dropped. Like, that would be, like, that would also be, like, an awesome product in itself. Just cognitive enhancement, like, alone would be great.
And so I think actually people kind of, like, undercounting the value of potential, if you're a Newton, absolutely brilliant, and you help with all the field, and maintain your 20-year-old openness and kind of, like, fluidity, all the way to age 90. Like, what insane kind of ideas would be coming up with at age 90? Like, with that kind of openness. The counter-argument there is, like, well, he'll just go do alchemy.
So then you have, like, you know, young Newton being great, and then, like, well, he'll do alchemy. The counter-argument is, like, well, maybe I'll be, like, positive inclined in thinking because, like, he's taking much mercury. Yeah, you almost won an argument for, like, outsider scientists who don't get discovered until they die, and then they have, like, 100 years of portfolio. Right.
I mean, and there are also just, I mean, like, so many people, like, you know, some incredible offices at Stanford who are still amazing, coming with, like, extremely novel, like, you know, Hawking publishing on, like, Blackpool's entropy, right? Like, this final paper, like, on this completely novel, fascinating field. I'm like, was that, like, you know, was he declining? Would he, like, Hawking kind of, like, step aside for, like, the younger generation?
Like, can't we have both, I guess, would be a question. Yeah, I mean, everything I've tried, it's, yeah, it works. There are some times where you get this feeling that you're, you know, you're really going to, like, you're crushing email, but you're not, and you're just, like, sweating the whole day. Not having deep thoughts, yeah.
It's actually fascinating. I remember this book on Daily Habits. No. I would actually, I think about, like, it's the Daily Habits of mostly writers and artists, but it's super fascinating because it feels like how they live their life, and it's just extremely variable.
The most common thing is they all wake up and go to sleep. They have a very certain routine. I'm already on that cycle. So, yeah, I mean, what, a thing I have found is that my mornings are just much more valuable than my evenings, especially in the middle of the day.
Like, I'm just kind of useless. I just work at it, like, two in the afternoon. I'm curious why that is. Like, it's either biological or psychological, right?
Sort of, like, you know, you get, like, too much loaded into your brain and you don't want a thing. Or if you feel like that, if sleep played a key role there, it was, like, sleep does something biologically and perhaps psychologically to, like, somehow induce an optimal state, like, right when you wake up. But, yeah. Have you tried it?
Like, sleeping in the middle of the day and then just getting back to work? I have, but that's an interesting idea. I'm curious what that would do. Possible.
Interesting. Yeah, I'm so curious about cognitive enhancement. We did a podcast with Rosalind Watts, who is at Imperial, about Psychedelics. Oh.
That 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'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. It's just, like, trying to break you out of your old habits and, like, have more confidence.
Increase openness. Yeah, exactly. And so are you taking anything, like, in the nootropic sense? Is there something?
No, I think I don't even do caffeine, because general plot is, like, try to win yourself off of everything, kind of. If you can perform great there, then, like, perhaps someday, like, there'll be a safe type of market that's worth trying. But, yeah. I also, like, I like Marcus Realist, so this is a good idea of, like, you know, none of the necessary things.
But maybe that's an application of that philosophy, you know what I think about it. Yeah, some part of that just makes me angry. Really? Well, it's, like, it all, you know, kind of, like, the color.
I don't know. I'm a dichotomy. Like, it's all stretched apart, because I'm very much a creature of habit. Okay.
That being said, I like color 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. Hmm.
Hmm. What is, like, a thing that you do that you're the most proud of, like, the habit that's, like, hard for you to maintain that you nevertheless are kind of quite happy to, like, I mean, exercise is no problem. Because I go crazy without doing it. Right.
I think what's consistently 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 now I work at YC.
And, obviously. And there are, obviously, like, you have so much energy in a 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 make progress on that, I'm very happy with myself. Because of the side projects that are, like, you know, 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, 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's usually something like the piece of paper, like, you know, when you're 60 and you can look back on your life. Yeah. That's interesting. 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, 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 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 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's a good point. It's 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... Hacks and motivations. I think it's, like, always trying to keep the baseline pretty low.
Like, kind of, you know, like... Yeah. I think, like, you can control, like, your output, but you can't really control, like, how the world responds. So, it's kind of, like, if you're just, like, all right, how you get output, then, like, that's great.
And then, like, how the world responds, like, can't control it. But, like, being really happy when you do stuff that you can't control is, I think, probably the biggest, like, mental hack for... I mean, you just can't control. It's so hard.
Because you're still pretty young. How old are you? I'm 24. Yeah, yeah.
So, I remember when I just moved out here. How old were you then? 23. Oh, interesting.
You just came out of college, or...? Yeah. So, what happened was, I was in New York for college, and then I lived there for, like, a couple years afterwards. And my girlfriend and I split up, and I was, like, I always wanted to live in California, and New York was just like...
And so, I just moved out here. Oh, interesting. Wow. Which was cool.
And so, when I... Did you have a job or something, or you 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.
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, never six years later.
But what about California? It was, like, so different for you that you had to stay here. Well, I love doing outdoor stuff, for sure. But it's a trade.
I don't know. It's, like, a polished sense. But, 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'd 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? I also don't want to, but how do you think these have changed, like, in the past seven years? Has it been seven years for you?
Something like that, yeah. What has been the biggest thing that's changed, like, either both positively or negatively or mutually? In myself? In, like, the environment that you've seen from, like...
Oh, yeah. Tech is completely vilified. The whole 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. With the Facebook thing. It's like, Gerard, like, you have, like, the person to build by.
It just feels like the new banker to me. And that's the... Yes. That's been the shift.
So not a great precedent. Yeah, I don't know. Because have you noticed anything? Honestly, I think it's kind of like in bio.
It's just, you know, we're just all the way over here, kind of, like, you know, working on things that take a really long time and very, like, hard and expensive. People are like, oh, they're still over there, like, still working on drugs. And so I don't think it's as much. And there are, like, very few...
Weirdly, there are very few players in biotech. I think this is something I was very interesting to me when I first came out. I was looking for people who were amazing and also made a lot of capital. And I was like, those people who would be successful and know how to build business as well.
That's what I thought. And there were very few of them. A lot of them were in BC who had invested in these companies. I was like, where are the founders not getting the capital?
Like, how does that equation work? And I think one of them was a former salesman. I think the most important thing I ever had about sales was just like, because I was trying to tell you how do you sell a business or an idea. I was like, okay, now I think I understand how this whole area of life, 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 of biotech.
And if there is any kind of lull in the ecosystem, it's just going to be fertile ground. Well, I think there's historically a lack of founder-driven companies. And obviously, the funding government has changed to be more likely to happen in the next couple of years. But it's just so striking.
It really is different. Because I think the wealth-created and biotech, it's like, you really see the distribution going so much more into capital, I think, with the founders. And that's a really weird thing to observe on first coming years. So, like, why is that the case?
Do you have different terms than normal VC funds? Well, I mean, for our funds? Yeah, I mean, if that's a strong opinion you have, what are your terms? Yeah, well, we have H1.
So, you know, that's founder-driven. That's, like, you know, sort of trying to get people, you know, sort of leg up and promote kind of the grassroots as a founder as a company and not trying to replace them. I guess, like, kind of on some other firms. Which, I think, you know, a fair strategy.
Like, that's, you know, sort of something that's been your bulwark for, like, decades. But, I mean, I think, Mark, you said that some of what's happened in software. Like, you know, you have this first wave of, kind of, like, professional managers. You can swing back to technologists.
You can swing back to the middle. Like, now we'd like some more managers, please. Like, you know, still technologists are kind of driving the show. And I think about it, kind of, like, midway through that.
We've had, like, a manager's 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, who knows what will happen in the future? Yeah, because the... That's interesting if it's a trailing thing from software. Because you probably know.
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. 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. Right, yeah. And I think that's, like, overall probably bad for the ecosystem. Yeah.
Because, 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 what enabled YC, right?
Yeah. AWS, from the outside, a huge part of it, right? The first ever ability driven by tooling to kind of spin something up really cheaply. And I think in bio, it's like what we were talking about, you know, there really was this point where, like, you know, dropping cost of sequencing has recurred over the past, like, you know, 18 years.
But really, up until, like, the past two or four years, you could not get $1,000 genome, right? Like, that is a recent phenomenon. And so, like, what argument would be, like, you know, look at Luminous revenues, you know, like, today. It's absolutely crazy how some of the art of, like, Intel's revenues, right, in the 1970s.
Or, like, the parallel there is, like, it's true. And this is, like, a friend of mine who made to, like, notice this. But, like, there's just, like, this really incredible, like, the naval technology that we kind of see, you know, in kind of, like, what's happening about today. And who's all happening in the future?
So there is an interesting parallel there. Hmm. Do you think that 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 curious about this. 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 been fairly constant.
And so we're just looking at this, like, what the heck is happening here, right? And we're talking about the number on the top end, like, the median hasn't even changed. It's, like, the top end of, like, the companies are getting more capital per company. So it's, like, all capital has come from LPs.
seen like, you know, the NASDAQ index, you know, it was like stagnant until 2011, like monotonically increasing. And then like, where do you put all this capital? There are no more companies invested. And so we were like, why do people want to start companies?
We went and talked to like a hundred grad students and postdocs. And the answer they gave us was like absolutely striking. It was like most of them. So maybe like, you know, 10% were at reputation risk.
Like they didn't want to leave, fail and go back. 80% had never thought about the idea of starting companies. They just were not aware there was, you know, a possibility. And so you argue, okay, maybe that's like, they're not entrepreneurial.
But you know, if you think about like, you know, in the 80s or the 90s, like would you have gone as a CS student and started something, maybe, but maybe you have a lot higher of a barrier or bar to doing that, right? I think that's part of why that process easier. And so I think really looks at the lack of education and kind of like just availability of options to these people, which makes you so angry, right? Like, you know, like you should never be forced to kind of convince you something you don't want to, but that's not good for you.
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, 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 Yeah.
Which is like, I mean, I don't know if you had no exposure to this, like, why wouldn't you think that? I mean, like, and all 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, you have so many questions, but you should also maybe mention your project, Daniel. Yes. Yes.
Yeah. So I'm super excited. So my friend Daniel started this really, really awesome sort of project called Pioneer. And what Pioneer is, is it's trying to find the lost signs of the world.
So he's like an awesome tagline. And, you know, I think Danny has a fascinating background that like he, you know, was on track to join like the Israeli army and then, you know, uploaded it up to YC. And he like basically his whole life changed after like one flight out here and a meeting with like, you know, Paul Graham and he was sort of like this, you know, he's an incredible person, but kind of like, you know, would he have had the same chance if not like a lucky, you know, and his dad forged in like an article about what I see like that. So I found out of that, right?
Really? I don't know. That's great. I mean, this is coincidence that kind of drove history.
And so the question is, you know, how many people are there out there? Like this small intervention could like, you know, drastically have a different life course. And so Pioneer as a Pioneer.app is this place where if you're anybody in the world, you have a project you want to work on, you can apply 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 18 and I'm going to write my novel. And, you know, you have this thing called the Pioneer Tournament where people work for about 30 days, you know, either projects and kind of like the community votes like on their kind of like most favorite people.
And based on that, at the end, you know, a set of people in San Francisco, you received about like $5,000 grant and they kind of like joined the Pioneer community, which kind of said really ambitious outsiders trying to change the world. And so I was saying this because, you know, my personal story was coming from New Zealand at age 12, you know, based on like a random license, like a professor here. And it was the first time I ever sent someone who was on the phone number and she responded. But she had responded and like that luck hadn't occurred.
Like, you know, I have no idea. And so that's why I think it's just like so exciting because it might help a lot. And everyone's like, you should definitely apply to your app. I'm just, you know, unlocks potential.
Like everyone in the world who like can be doing awesome things. I think it's so cool. Yeah. Just enabling people to like have the confidence thing has been the biggest surprise for me at YC.
I think a huge unspoken part of YC is successful is that it gives people the confidence to do their thing. 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, without systems that give people that little extra push, a lot of people will never do it.
Ah, interesting. It is counterintuitive. Yeah. I mean, it's crazy.
Like, cause 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. And then they apply. Huh.
It's crazy. Interesting. Yeah. I mean, I think one of the fascinating things that the daddies are going into is like, how do you give that to, like, how do you scale that feeling of like transmitting confidence?
It was like, you know, it's not trivial. Well, you asked me about podcasts before we started, right? And so this is like a crazy side effects 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 and literally, I'll be in the bathroom and someone will tap me on the back and be like, oh man, I like the podcast. Like, cool. Not that. 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? Because you said that one thing that you find fascinating is how people think about the world. But I guess the way that you ask questions was give so much information about how you build models or these 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 podcasts versus in real life?
Because there's like some dissonance for both of us, right? There's like going to be some dissonance there. And I'm curious about like how to best merge the two. And I haven't figured it out because I actually don't know what the gap is.
So you don't know what you're, I mean, I was about to text and I didn't. And yeah. I mean, you seem pretty kind of like on the surface similar, but yeah, I guess it'd be better if you were more like the person that you, yeah. What, what office do you think would, would bring like that?
Like you don't have kind of now. So in some ways I'm just selfishly interested in like making it something that feels more like me and it's my thing. Right. Um, you're always curious about like gains, you know, what can make the show better.
Right. And, uh, when I think about the podcast that I like, you know, things like Rogan, stuff like that, I mean, like that's not fringe, but I imagine, and this is again, like, because I've never hung out with him. Um, I imagine that it's like very close to what hanging out with a 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 in the room, it would be slightly different or? Um, yeah, it's possible. Yeah, it's totally. I mean, I think one thing that would be beneficial is like, I mean, you're, this is, you know, you're great.
So it's like great chills. It's very easy. But sometimes like, uh, hanging out with someone beforehand. Oh, I see.
And then it just continues into. Yeah. And the, uh, my desire to keep it like on topic can make it less natural than it could be. Right.
That makes sense. Yeah. You know what I mean? Yeah.
Cause you always come back to like one thing, but then maybe like, that's not actually the organic way that it would run. Right. Because I mean like, well, actually this would be a good test because I'll put this one out and be like, dude, what the fuck are you doing? Staying on topic with longevity stuff.
Yeah. I don't know. Yeah. That's totally interesting.
I don't know. It's tough. Uh, cause are you a podcast person? I actually am not.
It's like, I really only do books and papers. Cause podcasts are kind of annoying. You can't fast forward easily and kind of like use your eyes. Like if you're transcribed, then I might read them.
Yeah. Which you can, some do, we do, but not everyone. Then I also feel like, I don't, I think it's like something about being de-correlated. Everyone's into the same podcasts and you go and like spend the same amount of time reading like, well, I'm like the Greeks kind of, you know, what the students are thinking, you might have like very outdated information that's like not very informed, you know, but you also might like, I guess, get a similar feel for how somebody was, but have to be like more de-correlated and therefore, um, ideally kind of like more, um, sort of like giving you a better viewpoint than normal.
I think you should. I think 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, but like everyone's consuming the same media. Yeah.
And I think it's like, if you, if you don't, and you try to understand it from first principles, which I think like, first principles itself, I think it's like, I think it's often science is like the good thing, but you're not fully interested. It's quite different. I think one thing people don't realize like, you know, math and science often are like more artistic than they are kind of logical, but like everyone's trying to like frame things like a logical process. Yeah.
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, uh, I think it's logical and analytical, like, it's like, so curious.
I think also like, yes, kind of like, a little bit of mysticism, like this kind of weird aspect that's a little bit artistic. And we kind of, we forget that. Oh yeah, science are kind of like robots. Um, but they're, they're really, yeah, they're, they're really not.
Definitely not. Definitely not. All right. So let's actually get some of these questions.
Uh, all right. So which ones appeal to you? Cause we have so many. Um, I think the ones are like factual or good.
So just like the research questions probably. Um, so maybe we should rip through because I'm genuinely interested in a lot of these and I read, I read your longevity FAQ, which is awesome. It's very like, um, Tim Urban way, but why style? I mean, it's the drawings that got me.
Yeah. But that's cool. Yeah. Yeah.
That must've taken a lot of work. Uh, it's like, you know, just drawing kind of like axes and then like three lines is, yeah, it was hard. Um, so Sam Patesh 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. Um, because like, you know, you know, it really, it's fascinating. You look back and kind of like, you know, germ theory is just a huge breakthrough. I think one thing I think is lost also is like, there's another breakthrough that's similar related, which is like, life comes from life.
Yeah. For all history, we think that like there's spontaneous generation of life, like literally like, you know, right about that time. And this year's like, nope, nope, nope. Like, you know, these girls are coming in like the neck of the pipe.
It's not. And so, you know, that, and that's huge breakthrough. And then, you know, obviously Darwin kind of like, you know, also 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, excuse me, it's not a way philosophical, but really when you get into it, I think it's the important thing.