Luke Martin (host) with Alex Colville (age1). Descript transcription of "Alex Colville-FINAL GO LIVE.mp3", timecodes at each speaker change, Oct 21 2026.

[00:00:00] Alex Colville: I don't think a lot of people realize this, but semaglutide and tirzepatide have more revenue than OpenAI and Anthropic combined. When we look back, you know, 100 years from now at this point in history, it's gonna be one of the most impactful flips that happened this decade, without a doubt. No one's proven these interventions can work in humans to slow the rate of aging, and that is going to happen in the next 10 years.

[00:00:23] Luke Martin: You have tech billionaires, you have AI labs, NVIDIA teaming up with Eli Lilly, Brian Armstrong with CZI. Why is all this exploding at the same time? 

[00:00:30] Alex Colville: And it's so obvious it's gonna be one of the biggest markets of any industry ever. 

[00:00:34] Luke Martin: Do you think someone alive today will live forever? 

[00:00:37] Alex Colville: I, I think everyone loves...

Everyone's, like, so when they hear the, like, immortality word get in headlines, they love it. They're just like, people get so excited about the live forever immortality line. But I think everybody forgets is, like, the world is inherently dangerous. Uh, like you know, j- just, like, just yesterday somebody in my hometown died, uh, you know, driving back from McDonald's in, like, the main route in the town- Gosh, yeah

which is so sad. Uh, a- and I think, you know, will someone live forever? E- even if you solve the biological aging component, you still have all these other things, and if you're gonna live for tens of thousands of years, something could very easily take you out that's really stupid or really dumb. Uh, and so, like, this whole immortality thing, like, will we solve biological age to give somebody that potential in our lifetime?

I probably, like, five or 10 years ago would have said no. Um, but now I'm, I'm probably more 50/50 on it, and in part just literally feeling the singularity. Like, feeling- Right, right ... the acceleration of the intersection of AI and bio. It's, it's hard to extrapolate once you hit a really, really steep exponential.

[00:01:45] Luke Martin: I think that is the tough part. It's, uh, we're getting closer. It's like robotics, is it all happening very soon? Is it a ChatGPT moment? Same with AI. What's the next step up? And now with longevity, we were just talking about with peptides, all my friends are talking about it. There's another weird aspect where I think our lives, like noticeably change each year with technology.

If I go back to my grandparents, I'm sure, you know, we have newer medicines, our life's way different, but they weren't taking anything too different than what I take. I don't take any crazy medications every day. I take some caffeine, I have food, I drink my water. It's like it's, it really hasn't advanced that much.

Is that because our system is kind of designed backwards? We just help you once you're sick, or? 

[00:02:22] Alex Colville: Yeah. The, the day-to-day is, is the part that, you know, I'm personally absolutely obsessed with, and I am entirely convinced that in the next 10 to 15 years, this is gonna be a step change in terms of what is, you know, available in our day-to-day interventions to finally enable preventative med- uh, medicine.

I think that's what drives me crazy, is you're exactly right. Like, our, like what we take f- as preventative medicine today is still this like maybe, you know, trillion dollar wellness industry of things that don't really work. It's like so many peptides. Everybody's doing their multivitamin- Mm ... uh, sort of stack or aspirin or these sorts of things, and they just like point blank aren't working in the way that you would want a preventative medicine to work.

[00:03:06] Luke Martin: Right. 

[00:03:07] Alex Colville: Uh, and you know, maybe an example here is like my, my grandfather was one of the first US soldiers to be treated with penicillin. Um, was like in basic training in, uh, late 1930s, uh, early 1940s, got pneumonia- S- very close to dying, treated with penicillin, lived like normal rest of life, right? And which is insane.

Yeah. Like, you know, literally died in his 90s. Yep. Uh, and I- I'm like waiting for that penicillin moment for the aging field, and I really do think it's in the next 10 to 15 years. Um, and we're starting to see it with, with kind of like preventives for cardiovascular disease. So everyone's, uh, very familiar and uses statins, uh, once you hit a certain age, and I think that's just like we're, we're waiting for our statins, but beyond just cardiovascular disease.

[00:03:57] Luke Martin: You have tech billionaires, you have AI labs, you have NVIDIA teaming up with Eli Lilly here in SF, crypto founders, Brian Armstrong, with a, with a massive new company making a dent, uh, and some exciting, uh, experiments on the way. CZ of Binance even is kind of funding a big research effort. It's all converging on longevity and, and this field at the same time.

Culturally too, Bryan Johnson becoming the most tested human being- ... and all my friends all about peptides. And- Yeah ... yeah, I was k- I was like, why is all this exploding at the same time? So that's not just a feeling, like you, you do think there is a step change coming. That's, that's not all just like I'm looking at Twitter more, 'cause I am doing that.

But I was, I was wondering if it's just me. It's actually happening. 

[00:04:36] Alex Colville: Yeah, it is actually happening, but it, it's really funny. I, I was so wrong in the order that I, like the order of operations. I was so convinced that we were gonna get the interventions first, and that was when we were gonna see the ChatGPT moment of the aging field, of this explosion of interest and excitement.

It was like totally the opposite order of operations, where it was really Andrew Huberman, Peter Attia, Bryan Johnson brought this field, this concept to the masses. I remember I 

[00:05:04] Luke Martin: was like- The eyeball is the capital. Yeah. 

[00:05:05] Alex Colville: Yeah. I remember I was in Istanbul, uh, probably like two and a half years ago. My Uber driver, he like asked me what I did there, and, and I was like: Oh, I work on longevity.

Uh, and he was like: Do you know this guy, Bryan Johnson? Uh, and, and yeah, it's like literally been the past three years that it's flipped a switch in terms of becoming more widespread. Uh, but it, it's still not the root... Like I- we're still like, I think five to 10 years away from the magical step function of the field, from all this excitement, all these podcasts to day-to-day- Really making a dramatic im-im-improvement in terms of how we age.

[00:05:43] Luke Martin: Why now though? So do you think it's AI is, is gonna accelerate us there? The, the singularity pull as you describe it? Is it because we have all the, the Hubermans talking about it every single week? Is it just the capital influx? 'Cause there's a lot of that too. Like, what is the... I'm sure it's all three, but like, what, what do you think it is?

[00:05:58] Alex Colville: I think we're, you know, a couple of years away, call it like three to four years away from the first products. Okay. Okay. And I think that even was on track to happen without the podcasts, without AI. Like, I think we were, we were only a couple years away from the field showing its first proof of concept, and I think that is going to be very magical.

Like, like, um, n-not quite the same experience as when we first experienced like an LLM, when we all tried out our first version of ChatGPT- ChatGPT ... or something- Yeah. Yep. Yep ... and created a poem for the first time. It's not gonna be quite that like instantaneous rate of feedback. Uh, but, uh, for example, next year, a company called Loyal, uh, that we've had a lot of involvement with, is going to be...

I should say, knock on wood, they're on track to launch the world's first, uh, FDA-approved therapy to increase lifespan, uh, in dogs. Yeah. And I think this is going to be a very real product moment for people in everyone's homes, a daily oral treat, uh, that has been shown to, uh, positively impact biology of aging.

And for the human version, I think, you know, we're only a few more years- I see. I see ... after that away, and, and I think this has all been actually in motion and in progress for, for like a decade now. 

[00:07:14] Luke Martin: Humans can't eat that though, right? Like if it starts working for my dog, I can't- I can't have one here and there 'cause they're, people will try it.

As we've both seen, people are willing to be pioneers and try. It's not recommended. 

[00:07:25] Alex Colville: I, I cannot recommend- Okay ... anybody to take the dog treats, but- It's not gonna 

[00:07:29] Luke Martin: stop them. 

[00:07:30] Alex Colville: I agree with you. It probably will not stop them. 

[00:07:33] Luke Martin: It's just not gonna stop 'em. Yeah, I've been trying to understand, like, the investable biotech versus the narrative, 'cause you- Yeah

you see a lot of that, you see a lot of people on the, on the podcast. Hubrin I'll bring up just because he has the read/write kind of thesis. He kind of talked about, uh, and just what I saw as well in my own personal life, we had a period where it was all about Fitbit, tracking your health, these wearables.

We're, we're just kind of trying to figure out how healthy we are. Now we're at the stage of writing to your biology, so we're intervening, we're taking peptides, you're taking things for hair loss or fat loss, whatever else. You have a framework which kind of lays out where it goes after that, and I think it, it was really helpful for me when, when I was reading that of saying, "Okay, this is where we are now.

This is where it can go," not only in terms of interest, but investable opportunities. Can you walk through that? The, the four, there's delay, replace, pause, and, uh, reverse, and we'll get to kind of why that's the holy grail. But what is that framework? I think it'll give people watching, especially if they're new or they're in the peptide world, that are trying to figure out where the hell does this go, can you just walk through that framework?

[00:08:32] Alex Colville: Yeah. And, and I think you're exactly right. We've seen really the rise over the past two years of this measurement read phenomenon- Yeah ... uh, almost to the point where there's getting a little bit of a backlash where people are like, "I don't wanna be told that I slept horribly- Right ... last night." Like- Yeah

it's not helping. Uh, or, you know, the, I, I think people are really craving the intervention. 'Cause you can measure all you want, but it's a lot more fun if you have actually something to dial the needle in- Sure ... in one direction or another. And so that's, that's kind of been a, a core part of my own thesis in terms of how I view a lot of these measurement companies, and I really do think that this write wave- Yeah

is, is going to be s- yeah, just really, really fun to dip our toes into. And it's gonna take time. It's not gonna be like an overnight complete flip trajectory phenomenon. Um, but I do think it's, like, when we look back, you know, 100 years from now at this point in history, it's gonna be one of the most impactful flips that happened this decade, without a doubt.

Uh, and so in terms of our framework- Yeah ... uh, yeah, really, we, we've tried to break down, uh, what the potential buckets at a very, very high level, uh, could look like in terms of how we could write our own biology of aging. Yeah. And, uh, the way we kind of think about it is there's really kind of this first generation of interventions where really the goal is to simply slow, uh, or, or prevent many aspects of biology of aging.

Um, and these are not gonna look- Uh, like some, you know, crazy fancy new technology, but there's gonna be the first proof point, right? Like, no one's proven these interventions can work in humans to slow the rate of aging, and that is going to happen in the next 10 years. Um, so that's kind of this, like, uh, prevent category.

Um, we, we have this, uh, category of replace. Uh, when we think about kind of second gen interventions of much, much bigger effect sizes, these- this is where AI is going to play- Okay ... a, a very big role as we push these categories of interventions forward. But when we think about the second gen or next gen interventions, we really think of, like, r- replace, where one of our goals is to be able to replace every single cell in the human body over the next 50 years.

Uh, an- another, uh, category, uh, and I should add tissue in there as well, cell and tissue, uh, over the next 50 years. So that's replace. Uh, and the kinda theory there is just that it's so many things are going wrong in aging in terms of how cells age or how tissues age, but if you simply take a fresh young cell or a fresh young tissue, swapping out one with a ton of damage is sometime easier than trying to repair the, you know, hundreds of thousands of different forms of macular molecular damage that happen at a cellular level.

[00:11:09] Luke Martin: I wanna keep going. Where are we getting the fresh ones? 

[00:11:14] Alex Colville: You're donating, right? 

[00:11:16] Luke Martin: So that is- that's where it comes from? Is it fresh donation? Are we creating them in a lab? I mean, we're 3D printing metal now. It's like there's... I don't know. Can we 3D print them, or do I 

[00:11:24] Alex Colville: have to donate? So, uh, the, the- I'd say currently we don't know.

Okay. Okay. Uh, it, it- but there are many approaches in parallel in terms of how to derive new tissue for a transplant, uh, or new cell types. Um, so one of the revolutions of, of the past 30 years in medicine has been Dr. Shinya Yamanaka, a Nobel Prize winner. He showed for the first time that you can take a differentiated scale, uh, cell, like a skin cell, and go back up the scale of pluripotency to a pluripotent stem cell.

And so this technology is, is known as induced pluripotent stem cells, iPSCs. This has been completely revolutionary in terms of we always thought you could only go from stem cell to a differentiated cell. And this has unlocked a whole new category of medicines that everyone was very convinced was gonna have really quick translation to humans.

Well, it turned out it took us like 20 years to figure out a lot of the kinks and a lot of the optimizations and a lot of the ways to kind of massage these induced pluripotent stem cells into usable functional cells that can engraft into humans. And just in the past year and a half, we now have human clinical trial data that we can take these, uh, human pluripotent stem cells, derive neural cell types, implant them in humans, and have them survive and engraft and function for over a year and a half.

Only in the past year and a half after, you know, 20 years after this key discovery have we been able to do this. So one source is just gonna be our own cells and- Oh my God ... and the ability to take them and turn them into stem cells. Uh, there's another phenomenon that was one of the Science Magazine breakthroughs, uh, I wanna say five, five years ago or so now, uh, which is called synthetic embryos, uh, where you're actually able to, from, uh, your embryonic stem cells, uh, create, uh, something that is akin to...

S- so I'd say like an- they call them like integrated stem cell models. But something akin to a model that could actually grow out with clone of your own cells to potentially be able to, to have tissues and cells to engraft back into yourself. 

[00:13:28] Luke Martin: I see. I see. 

[00:13:29] Alex Colville: Uh, 

[00:13:29] Luke Martin: so this is- So it's a build, a building block for the rest of what comes after, tissue and everything else.

Okay. 

[00:13:33] Alex Colville: Exactly. And so scientists have only been able to push it to very, uh, limited amount of timescales both in mice and humans so far and, you know, on the order of like small amount of weeks or, or many amount of days. Uh, but there's a race going on in many labs around the world as to who can push these synthetic embryos or integrated stem cell models out as far as possible until they've grown organs and cells that could be usable for transplant.

[00:13:58] Luke Martin: Correct me if I'm wrong, this might be a super simplified version, but the, the previous thing you talked about that we learned 20 years ago and is now being implemented in humans, taking a cell, so let's say it's a 60-year-old's skin cell or a hair cell, bringing it back to its stem cell, and then this model you just talked about where we're kind of fast-forwarding weeks and, and having it build the tissue, this is like time travel.

I mean, we're taking a cell and bringing it back. We're having something in two or three weeks it, it can build a system. Like what? Is that what's going on here or is that a, a, am I kinda- mixing two different concepts. 

[00:14:29] Alex Colville: Yeah, and, and, uh, uh, scientists think some, a part of the fundamental basis here is one of the most repeated experiments in biology, uh, which is reproduction, uh, sex, having kids.

Uh, every time we have kids, um, it, we don't pass along age to our offspring. And so you can have people in their, you know, 40s, 50s, 60s. Yes, you're at higher risk for genetic diseases, and there is a reason that fertility declines and all these sorts of things, but fundamentally, like, you can accumulate a lot of age in your body, but when you reproduce, that age is not passed on to your offspring.

Otherwise, your offspring would live a lot shorter- Wow ... with each generation. Um, and so Nature has discovered some sort of technique to either rejuvenate cells entirely or select cells, uh, that are somehow protected from age in that process. So some people call this the immortal germline, some people call it germline rejuvenation.

Uh, it's one of the least studied, in my opinion, phenomenon in biology, but also the most impactful. Yeah, that's 

[00:15:32] Luke Martin: wild. 

[00:15:32] Alex Colville: So this fact caused Yuri Milner, Jeff Bezos, uh, also rumored to be Bill Gates, to invest, uh, $3 billion into the company Altos Labs, was really formed around this principle. Uh, and Shinya Yamanaka, until very recently, was an advisor associated with the company.

Oh my gosh, 

[00:15:49] Luke Martin: yeah. 

[00:15:50] Alex Colville: Um, so this is really- when you're describing this, like, ability to really turn the clock back- That's what 

[00:15:54] Luke Martin: it sounds like, yeah ... 

[00:15:55] Alex Colville: it is at least thought from all the experiments that we have to date that when you take an aged cell, turn it back to an induced pluripotent stem cell, you're reversing most aspects of biology of aging.

[00:16:07] Luke Martin: So age, yeah, time, I guess, I'm substituting those two words, but in a lot of ways they're the same, right? I mean, that's the full framework, right? That's the fourth stage. That's the holy grail, as you would describe it, is that epigenetic reprogramming? 

[00:16:18] Alex Colville: Yeah, so, uh, you know, we're taking it from replace, which is kind of our, you know, maybe, uh, first of these second gen categories.

A second of these second gen categories would be to restore age inside a cell. And so this is this whole category that you're describing of epigenetic reprogramming, uh, where instead of what I just described, where you go all the way back to a pluripotent stem cell, uh, you're not messing with the, uh, differentiation state of a cell, but instead you're only turning back the clock on the age of a cell.

On age. And so we have a, a couple different experiments that have served as proof of principle for this. This is actually what I studied in the first half of my PhD at Stanford. Uh, specifically joined the lab to study this phenomenon, and I'd say the evidence is still to this day very early, uh, but now there are a number of companies, including Altos Labs, including RetroBio, funded by Sam Altman, and including, uh, NewLimit that you alluded to earlier with Brian Armstrong.

Uh, NewLimit, I would say, is really, uh, probably the leader of those three, uh, in terms of translating this phenomenon to humans, and so far their data looks very promising on the journey to do that. 

[00:17:28] Luke Martin: How does it feel? I mean, so you, you studied this, and you were in Sinclair's lab in undergrad, got a PhD under Tom Rando at Stanford.

This has kind of been your whole life, and for 20 years you're kind of, this is what you literally studied. Now you build a company and, uh, also, uh, running a fund, deploying all this money into, and now it's all happened. Just last year you have a, a human trial and- Some of this stuff works. How does that feel?

I was talking to roboticist for 40 years, now he's at, uh, RoboStrategy, and he was describing to me, he's like, "For 40 years, I felt like, man, the next five or 10 years is gonna take off," and he just couldn't see it. And now they figured out the brain and the hand, and he's like, "Oh my gosh." It's like, it's, it's what he's been waiting for his whole life.

Is there a little bit of that for you? You're like, "It's, it's finally happening." Like how does that feel, man? It's crazy. 

[00:18:13] Alex Colville: Uh, it, it feels so electrifying, um, because, and, and, you know, uh, the, the category we didn't talk about there was, uh, pausing, fully pausing the clock as kind of the second gen intervention.

Yeah. And in that, uh, we could describe cryopreservation, this notion of like fully pausing the clock. Yeah. Uh, and, and there's definitely a story there in terms of a co-founder at the fund, uh, Age1, Laura Deming, uh, in terms of her journey, and she's been pioneering a lot of work in the cryopreservation space.

Uh, but I remember distinctly when she kind of started on that journey, uh, a part, you know, uh, I think a lot of people speculated about this, but a, a part of the journey into cryopreservation, you're really thinking about how the aging field hasn't made, you know, dramatic leaps or significant progress. It has been in more of the slower path.

Yeah. And I think that's been one of my favorite transitions, is in the past three years, she's just gotten this whole reinvigoration of being so amped and excited about the space. Um, but for us here a- at the team, it's, it's kind of this notion of lock in. Yeah. I think everyone's feeling this with vibe coding right now.

You've just entered this whole new era where you see people just completely vibe code an entire weekend and not even come out of their apartment. Uh, we're getting towards the point o- of entering that for the aging field, and even just yesterday, Anthropic Life Sciences, uh, they had this huge announcement with their new model, uh, specific to the life science industry, uh, but they also highlighted that they were working on preclinical programs for aging and rare and neglected diseases.

So when you have Anthropic, uh, publicly stating that this is going to be one of their big focus areas Game on. 

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[00:20:45] Alex Colville: usually this costs 20 bucks. For listeners of this show, if you're tuned in right now, you get to do it for free. Keep 80% of the profits.

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[00:20:56] Luke Martin: Was there a moment, if it didn't happen like this, if it all wasn't converging, were you thinking, "You know what? I'm just gonna... Hopefully cryo works out and, and they can bring me back in 50 years"?

Was th- is that a thought of some people in, in your field, in your industry? I'm sure it is. 

[00:21:08] Alex Colville: Yeah, so I'll, I'll say, like, uh, th- uh, cryonics, uh, L- Laura likes to dis- distinguish, and I totally get it, the cryonics is really freezing, uh, tissues and, and humans without solving ice crystal damage. Uh, and so she likes to make the distinction that this next gen of the cryo field is working on reversible cryopreservation.

So instead of just freezing people with all this ice crystal damage and hoping we have the technology, you know, a million years from now to solve cell membranes that have been ruptured and information that's been lost, seem really hard to do. Uh, simply start from the beginning, do the process in a way to not have ice crystals form either upon freezing or thawing.

[00:21:46] Luke Martin: Oh, I see. 

[00:21:47] Alex Colville: Uh, and so that's a cool nature of it. Uh, but in terms of was that, uh, you know, pe- people's thinking? I mean, th- th- the beauty- That's a backup plan. The beauty of cryopreservation is that it's really, um It, it's really much more towards an engineering problem than a biology problem, and aging is very distinctly- Bi- yep

on this biology axis. There's so many different thousands of types of damages, and, and we really don't understand it well at all. Uh, and, and cryo, we know, you know, ice crystals are one of the biggest problems. There's several other problems, but it's a pretty short list. Yeah. And you kind of know via engineering principles and physics how to minimize a lot of the risks and- Mm-hmm

and negative things associated with it. Um, and so yeah, it feels like an inherently very tractable str- like, a tractable problem relative between the two. And so that, you know, I'm, I'm sure played a role with Laura in terms of Until Labs and what she's been building in that space, and is a part of the reason why we at, at the fund are super excited about, about cryo and where it's at.

Um, but yeah, luckily, AI Yeah, it's caught up. All these other things are helping out with the aging- Yeah ... part of the field, too. 

[00:22:56] Luke Martin: Oh, that's funny. Uh, I wanna talk a little bit about Brian Armstrong. You, you hinted at it there, the NewLimit. There was a three, $3.1 billion raise for his new company, NewLimit.

They're running the human trials, uh, next year, I believe. Are you excited for those trials? Because that is, I think doing what you described, is kind of the holy grail. Is that... Are they doing the same thing, where we'll finally get to, like, actually test of not just working in mice, also working in humans, or is it slightly different?

[00:23:21] Alex Colville: Yeah, so I, I think New, NewLimit is one of the most talented teams in the field. Uh, Jacob Kimmel, who's the president, has long been somebody that myself, Laura, uh, most of my colleagues have regarded as one of the top five smartest people you'll find in the field. I could spend all day listening to Jacob.

He's just... Yeah, he's, he's phenomenal. I'll end my rant about him. But I- it's, it's n- yeah, not a secret how I feel about Jacob and that team. Yeah. Um, but, but yeah, New, NewLimit, um, you mentioned 3.1 billion raise. I think it's 3.1 billion valuation. Valuation. But y- like, uh- I 

[00:23:56] Luke Martin: saw the big number, I got excited.

[00:23:57] Alex Colville: Yeah. They now have over, like, 600 million in cash. Yeah, yep, yep. It was a, a very large raise, uh, that they just closed by all the top funds in Silicon Valley. Uh, and, and what will they do with 600 million in cash? This is the big question, right? Yeah. Uh, so what they've publicly announced, they're working on first liver And so they have this very interesting, uh, data showing that when you treat old mice with alcohol, they don't do well.

Yeah. Not so different than us. Some analogies there to humans. Relatable. Uh, a- and you know, when you treat the young mice with alcohol, they're, like, totally fine, they run around, no big deal. Uh, and, and so they've created this, uh, reprogramming therapy, uh, based on lipid nanoparticles and mRNA technology, uh, that can...

When, when these older mice are treated with it, um, they're able to thrive like young mice under the exposure to alcohol. Uh, and, and so this, this first therapy, they're pursuing alcohol liver disease and other forms of, of liver disease with the hopes of expanding to a much broader patient population. Uh, in parallel to that, they're targeting immune cell aging and kidney aging.

[00:25:07] Luke Martin: Best case scenario, liver disease, they solve. Worst case scenario, we cure hangovers. Yeah. I mean, that seem- The old mice are doing well. I mean, there's gotta be, there's gotta be some kind of middle ground there. 

[00:25:18] Alex Colville: Um- Well, we'll see. But w- that's the cool part. With the $600 million in cash, they're well-funded to get through, uh, potentially testing, you know, their first three or four therapies in humans.

Um, and I think that's gonna be really exciting to, to watch, uh, o- over the next five years or so, their position. And what I love about them, too, is they're so open about it, right? They have this public blog. They're constantly updating in terms of the exact state, uh, of the new science that they've developed.

[00:25:43] Luke Martin: Is that different? Is this an industry where everyone's kind of guarded, or is it more open source, right? I come from crypto, and open source is kind of in the ethos. And you look at a lot of other places, AI's kind of going through that battle, too, of open weights, open source, this model is just for us, then you have the Chinese open source models.

Is this... Is that unique, them being open about it? 

[00:26:02] Alex Colville: Uh, I would say it is very unique. Part of this modern longevity biotech movement, um, was really created by my co-founder, Laura, i- in part. She drove so much of, of this expansion of the space we saw today. Uh, but in, in parallel to her, one of the other huge forces that drove it was actually Google.

Google, uh, made a massive investment in a daughter company at Alphabet called Calico. They went and they poached, uh, an absolute legend from the biotech field, Art Levinson. Uh, b- uh, was previously, uh, CEO of Genentech, you know, one of the biggest biotechs in the Bay Area, most well-respected, amazing track record.

He's also, I believe, the chairman of the board of Apple. Uh, and, and, you know, they brought him in as CEO of this super secretive aging-focused company. They took a lot of the legends of the aging field and also brought them in this company and, and they gave it billions of dollars in funding. They brought in a collaboration with AbbVie, one of the biggest pharma companies in the world, that then matched a lot of the money that they were putting into this.

And, you know, combined, it must have been well over $4 billion committed to, to Calico over the, over the past, uh, now 13 years or so. And I remember for me, uh, I was an undergrad, and there was this Time magazine cover, uh, that was like, "Can Google solve death?" And I literally, like, printed it out, had it on my desk- Yep.

Yep ... for probably, like, five years after that, and I was like, wow, like, if Google is ambitious enough to take this on, like, this is gonna be a whole movement. This is gonna be a huge movement of people doing this. Uh, but Calico was notoriously one of the most tight-lipped, secretive organizations- Oh, wow ... uh, that, you know, I've really seen in any field.

They just would not talk with anybody about what they did. And finally, in the past two years, they've flipped a bit on that and become more open. Mm. But I would say they really started a precedent, at least in the aging field, of high secrecy- Yep ... not a lot of collaboration. Um, you know, whether that was intentional or not, I'm, I'm not sure.

Uh, pr- probably in the early days- Sure ... definitely. Um, but there's also, you know, the Sam Altman company, Retro. Uh, they've also been, I'd say, a lot more on the stealthier side of things relative to NewLimit. Yep. Now, what's the right around strategy? There's a strategy. Who knows? Uh, but it'll be fun to watch play out.

[00:28:15] Luke Martin: With NewLimit's experiment, I know right now they're focused on a few of... There's a long way to go until we solve everything with aging. But in terms of thinking about that framework again, is there a chance even if we solve it, if the experiments go well, that isn't what solves aging? Is there a chance that we have a fifth thing we have to add to the framework, and we say, "Look, that's still really good at solving liver disease and it solves this, but we don't have this holistic How do you think about that?

Or, or are you saying, is it your view that if the, some of these experiments go well and we can apply it more broadly to everywhere else in the body, we solve it? 

[00:28:48] Alex Colville: Yeah, I th- I think it's gonna take such a coordinated effort across a ton of different approaches. Like one, even, even just right now, I think it's way too early to say if it's going to be, uh, restoring and, and reversing cell age- I see, yeah

or tissue age, or replacing that's ultimately going to be the winning phenomenon. Yeah. There's also in this like prevent delay, you could, uh, theorize how it might be possible to identify the primary drivers of aging if they did really exist. Yeah. Like it could turn out that genome instability and DNA damage was just this, the most upstream driver, and if you could just stop, uh, the genome from becoming unstable over time, you could totally stop the rate of aging and, and create a species with like- Or, 

[00:29:31] Luke Martin: yeah

[00:29:31] Alex Colville: negligible senescence or something. Right, right. That may be possible. Do I think it's likely? No, but it might be possible. Uh, with, with new limit, even if you can reprogram the age of cells, there are still a variety of other problems potentially. One of those being extracellular damage. So most of the cells, our body have extracellular matrices.

These accumulate damage. If you're only altering the age inside of cells, that may benefit the ECM, but it might not fully solve a lot of the things that accumulate or go wrong with age. And so I think it's gonna have to be a very multi-pronged, uh, approach. I don't think there's just gonna be one shining thing that can, can solve everything, sadly.

[00:30:10] Luke Martin: I wanna ask about this. We touched on it at the beginning, but just because so many of my friends do think peptides could even be that. They look, they're like, "All right, I take this, I'm skinny for the rest of my life." It's like that's, maybe that's all some people need. Um, but yeah, I'm just so curious. You know, people taking it for weight loss, for getting their hair back.

It's this cocktail of drugs. Everyone's kind of, my guy has the best peptides. I get this, this one's safe. Mm-hmm. How do you know what's real in that world versus what's kind of just narrative and hyped? Or is it, are you reading papers? I know you, you're not like a peptide specialist, but when you look at some of this stuff, like how do you just decide and you say, "Guys, you shouldn't be doing this," or, "Guys, you should be"?

Not even if you necessarily tell them, but like for your own self, like how do you make that, uh- How do you decide? 

[00:30:51] Alex Colville: Yeah, th- and I, I'm, I'm like the probably the boring answer, which I don't take any peptides. I'm with 

[00:30:56] Luke Martin: you, yeah. 

[00:30:57] Alex Colville: I, I think there, you know, there are the interventions that I find, uh, probably, like, the, the most likely that I would take in the next 10 years.

But in terms of, of how I sort through things, it's really hard 'cause there's just so- It's so tough ... limited data. And, and that's why in some sense I do love that people are being pioneers in terms of doing more exploration. Mm. Because in some sense, like, if we only rely upon data, uh, it's, it's just really hard to make fast progress.

Data that already exists, excuse me. Right. So we should be actively trying to generate a lot new data in a, in, in many different ways. Yep. Now, my problems with the space are when people make huge claims about things based off of data that clearly isn't robust or isn't real effect sizes, right? Like, it- N of 1 s- most of the time cannot tell you enough evidence to know for sure that something works, unless it's a really, really dramatic effect size, which a lot of these peptides probably aren't having.

Um, but there are some interesting, like, tidbits of, like, aging h- field lore- Yeah ... with some of these peptides. Like, one of them, uh, the most common that people talk about, BPC 157. Yep. Uh, people like to talk about its mechanism in terms of affecting VEGF, uh, increasing angiogenesis of our blood vessels. And some people Probably rightfully so, they get a little nervous or cautious around that because, uh, cancer, oncology, a lot of cancers are driven in part by increased angiogenesis.

So it's a little bit of a sketchy relationship there. Uh, but there's actually, uh, older s- papers, probably like five-year-old papers now in the aging field in, in science that show if you increase VEGF in mice, they actually live, uh, 20 to 25% longer, very robustly. This is one of, like, the, the most well-powered recent lifespan experiments I've seen in, in mice.

So, you know, there is a chance that BPC-157 has some sort of relation to that mechanism, but I will refuse to tell a single soul to take it- Yeah ... until I see it proven. 

[00:32:53] Luke Martin: Or even, yeah, you don't even know if what you're taking is BPC-157. That's part of the problem, too. 

[00:32:57] Alex Colville: That's a huge part of the problem.

Supply is nuts. In the studies, when people actually have really looked at what is in these peptides and, and things sold from sketchy sources, I think most people are very disappointed in, in terms of seeing how much is actually the thing that's on the label. 

[00:33:13] Luke Martin: Yeah, I was trying to figure out if it's just as hard for you.

I mean, I look at Twitter sometimes. It's Martin Shkreli arguing with the founder of this peptide thing. It's my friend telling me, "I promise this, this stuff's good." It's like, I don't know who the hell to trust. I mean, I'm sure it is. It l- it seems like it's working. You look good, man. I don't know. Um, and then I saw this news.

So the FDA dropped these docs recommending zero of the seven big peptides get added to the 503A list. I don't even know what that means. Does that mean peptides are gonna become more prominent? Does that mean the FDA is regula- like even the news about this space, I'm like, I don't... Is that, does that mean we're all gonna be able to buy peptides at CVS?

Or does that mean we have to keep buying them on, you know, with Bitcoin on some website? Like w- what is the news about peptides? Are they becoming easier to get, harder to get? What's kind of y- your, your view on where the industry goes? Not necessarily to take them, but, like, are they accelerating or, or what's happening there?

[00:33:59] Alex Colville: Yeah. Uh, f- uh, I'll be honest, uh, not my domain. Okay, okay. I have not followed the latest. Okay. Like, I've just- Yeah, it's just, it's- All I know is that, uh, you know, Big Podcast wanted this to be a thing. I swear. And those are the power of podcasts. I know. Big Podcast wanted it to be a thing, and now it is somehow- They told me ask-

becoming a thing with you guys They told me to ask you this. That's why. 

[00:34:17] Luke Martin: Yeah. 

[00:34:18] Alex Colville: So should it be a thing? That's where I think I'm much more skeptical, uh, based on the level of evidence we have, but everything I'm seeing does seem like the FDA is becoming way more lenient, uh, in terms of peptides. 

[00:34:30] Luke Martin: Big peptide, yeah.

Big Podcast asked me to include it. That was, that was for the, the sponsorship there. Um, all right, I wanna move on. So AI and, and what that's unlocking here in this field, I'm trying to figure out is it a compute problem? Is it a data problem? Is it... Like what, what is AI actually accelerating with all, all of this?

When I look at NVIDIA making their big investment with Eli Lilly here, when I see Anthropic is now a biotech company, like how are they using AI? And everyone's doing something a little bit different, so I'm, I'm sure the answer is a little bit different there, but, like, what is AI actually unlocking here?

[00:34:59] Alex Colville: Yeah. So I'd say that the two most dramatic shifts I've seen so far, uh, which have been- Really unbelievable in, in terms of just, like, the step function changeability with it. Um, one has been on the molecule generation side of things. Uh, so now for certain modalities of medicine, it is remarkably easier, uh, and, and faster and cheaper to generate the molecules.

Again, not like full leap, no humans, no wet lab in the loop, but a lot closer to that. Uh, and I'll get into that in a little more in a det- in, in a second. The, the second category is just, I think, what most people are experiencing in, in most industries, which is you can just do so much of the day-to-day, like 30 to 95% faster.

Yeah. Uh, you know, whether it's a regulatory filing or looking into your com- competition or looking for new business development, partnering opportunities, getting up to speed on a new target. Mm-hmm. Uh, all of these have just been made so much easier. And so I think we are really feeling that on a day-to-day basis in therapeutics, where it's now become almost democratized to, to run a therapeutics company in a way that it wasn't like a year and a half or two years ago.

Uh, and I think that's really cool. Um, but on the molecule side of things, we're seeing, like, uh, companies like, uh, Nabla Bio, for example, or, uh, China Discovery is more in this realm. Uh, we're, we're seeing a lot more efforts that enable you to, to generate almost, like, zero-shot molecules, and that's happening both for antibodies and, and small molecules.

Now, we have a very, very long ways to go, and today the, like, the, the extent is usually they're just, like, making newer versions of existing medicines against those targets, and they're able to do it really fast. But the next step, which I think is inevitable, is being able to do kind of these zero-shot molecule generation, even against new targets.

[00:36:54] Luke Martin: I was reading this, uh, there was this blog, this girl, Nicole Fitzgerald, I think the company's called Tacit Labs, and she was talking about soon we're gonna have a million zero-person biotech companies. Almost in the sense of you can vibe code a SaaS product or vibe code some prediction market or whatever people are building this, this week.

But with enough Claude tokens, you can just one shot. You can do the research, you can do everything. You were kind of saying there's still some steps you can't do. We don't have the wet lab capability and we don't have robots that can walk around yet and do all those. What's your ta- Are we still, like, really far away from that?

Is that a little bit, uh, too ambitious when you hear that, that like, you know, I could spin up a biotech company? Like can I really... You know, I, I know AI's gonna help us. We can one shot a molecule, but that's still very far. Like, what's your take on... It still seems like a lot of resources and, and a lot of smart people you have to get in a room to actually make this work.

[00:37:41] Alex Colville: Yeah. So, so the bottleneck and the moat, uh, where AI is not making nearly as big of an impact yet is on taking that molecule and then getting it approved and proven- I see ... for safety and efficacy for a disease. Uh, like the molecule generation part It's hard, it's expensive, it's, it's, it's long, but relative to the rest of the whole process- Yeah

of taking that then optimized molecule and getting to an approval, like that is where A ridiculous proportion of the cost and time is in drug development. A- and so, like, that has become almost, like, the final frontier in, in some sort of a sense, uh, is choosing the right things that are most likely to work going into that stack, uh, and then funding and running that stack as cheaply and most economic as possible.

And everyone was so buzzy about AI revolutionizing medicine. Yeah. Uh, what has made a way bigger impact in terms of our ability to, to produce medicines over the past, uh, six years has just been China biotech. Like, biotechs in China have made, in my opinion, a way bigger impact to the drug development landscape and to our ability to make medicines, and it was...

It, you know, had nothing to do with AI technology. It was simply, uh, an extremely highly skilled cheap labor force- Okay ... uh, a crazy work ethic and an ability of regulatory environment, an ability to test things in humans for, uh, you know, on dramatically shorter timescales and at a fraction of the cost of, of what you can in the US.

And so to, to get to that future of, like, uh, a million people running zero-person biotech companies- Yeah ... I think they would still need millions of dollars each- Yeah ... to, to run it. Yeah. And that's... Like, this is the part that I think AI is still really struggling with, is how do you, how do you solve that gap of, of just the long, expensive, difficult part of drug development?

[00:39:31] Luke Martin: I was not expecting China biotech, but not the AI. That's a, that's wild. 

[00:39:35] Alex Colville: Like, we, we went... Like, I think five or six years ago, uh, I, I think it was about 3 to 5% of drugs licensed by big pharma companies came from China. Mm-hmm. And last year, I believe that rose to about half of drugs, uh, were licensed from China for, for big pharma.

[00:39:52] Luke Martin: Is that still the case now? Is AI closing that gap? 'Cause we sometimes have the best models. I know that not everyone can access them and... Or is it still, that's still kind of the trend? Is China still this powerhouse now and advancing? 

[00:40:03] Alex Colville: That's, that's the trend. Yeah. Like, we won't, we won't see AI in the US closing that gap for probably another three years or so, where we actually might to start see the data.

Uh, it'll probably even be way longer than that, that we'll see AI start to reverse that trend. Um, but that, that's been one of the, like, craziest things to me, is there's just so much hype, so much money around AI, and then it was just, like, China- Clearly, yeah ... with, with not new technology, but just very cheap, highly skilled labor and, and crazy 996 work ethic making it happen.

[00:40:35] Luke Martin: That's insane. What about, uh... What's your take on some of these AI companies now becoming biotech companies, right? You have NVIDIA and Eli Lilly, their partnership, billion-dollar SF lab. You have, uh, the spin out of Google DeepMind and Google's contributions you were talking about for a long time ago. But even now, them creating isomorphic labs.

You have Sam Altman personally funding Retro. Yeah. You have, uh, Anthropic now. They have a... Every single week, it feels like they have a new announcement of, "They're a biotech company, we're investing in this." What's your take on why they're doing that as opposed to just investing in companies that are do- It, it feels like...

I don't know. It's- I understand AI is gonna advance a lot of industries and coding and all these other, but it feels like there's a very specific focus on them becoming biotech companies themselves. Like, why do you think that's happening? 

[00:41:19] Alex Colville: You know, with the caveat, we've got plenty of friends across those.

Sure, yeah. Several of our investors- Yeah ... our very early employees at all those that you named. Yeah. Uh, but m- my impression and what I've seen, like publicly, for example, from Anthropic- Right ... like they put out this great market map, uh, where they were like areas, uh, where AI could make the biggest impact, how much impact AI has made.

If you look at this market map, life science is one of their highest areas. Um, they've publicly talked about on their life science team that life science might be the second biggest focus at Anthropic in terms of market. 

[00:41:53] Luke Martin: Wow. 

[00:41:53] Alex Colville: Uh, it's, it's, it seems like it's certainly in their top five of what they're really, like sinking their teeth into or, or looking at very seriously.

Um, and I think the, the reason for that is biotech, uh, therapeutics It's a v-- It, it just has a very strong patent-protected moat. It's huge revenues. I don't think a lot of people realize this, but semaglutide and tirzepatide have more revenue, uh, than OpenAI and, and Anthropic combined. Um, and if you even look at, like, rates of revenue growth, it's...

Y-you know, you would assume that the tech companies are, are dominating the GLP-1s. No, like the GLP-1s are cur- growing at crazy rates in terms of that very high revenue amount. Um, and, and so I think An-Anthropic, uh, and, and OpenAI and, and Google, they're looking around and they're saying, "Okay, we've got crazy high valuations.

We need crazy amounts of revenue. Where can that revenue growth come from? Well, if only one product can command more revenue than my entire company has in, in this biotech world, that could be a potentially very smart place to grow revenue." And inherently, I think what i-is very exciting about, uh, biotech world right now as a place to invest is it's just in...

It's, it's very AI resilient compared to most industries. You're just not gonna have Anthropic wipe out your fields in, in a day or a year. It's just not gonna happen. 

[00:43:11] Luke Martin: Yeah. Like, why? Just there's still too many hard problems to solve. Even we throw all the intelligence at it, it's still just gonna take that long.

[00:43:19] Alex Colville: Exactly. A-and it's, it's just a highly regulated industry. Uh, I think, like, Marc Andreessen loves tweeting about how the price of regulated industries goes up and up and up over time, and the price of non-regulated industries goes down and, and pushes towards commoditization. Like most tech over time goes to commoditization.

Yep. Biotech therapeutic world does not. 

[00:43:40] Luke Martin: I see. Yeah. 

[00:43:41] Alex Colville: I mean, it does in some sense in that every drug- Right ... becomes generic after patent life ex- uh, expires, and it's like this almost indefinite benefit to humanity that we have these cures that are available for, like, pennies or dollars, uh, after a certain extent.

But it's a regulated industry. Like it's, it's just not going to get completely wiped out by AI. And I think that, and its massive revenues, in some sense way bigger than the AI world's, that's pretty appealing to these frontier labs. 

[00:44:06] Luke Martin: 100%. Yeah, th- I was looking at when Fable c- when they kinda took Fable away, I don't know, I think I saw news it's coming back depending on when this goes live.

Someone's probably asking Fable, you know, "When?" Who knows? But- ... there's gonna be a new model that's banned. Uh, it's happening so fast. 

[00:44:20] Alex Colville: Yep. 

[00:44:21] Luke Martin: One of the only things they blocked was biotech, right? They, they also blocked some of the security audit stuff for code, and they blocked different, uh... Trying to keep us all safe, but I thought that was so curious.

When I think about AI's application here, this feels like one of the, the only fields where AI's kinda, like, returning the favor of as machine intelligence expands this field, accelerates things, it keeps humans alive longer versus a lot of the other things that we can apply AI to. It's like, is that helping us if we have a million robots around?

Like, is that replacing us? Biotech, it feels like AI's keeping us here, and they're kinda keeping us away from using it. Like, what's your take on why- biotech is dangerous for us to use with these models? Like, what- 

[00:44:58] Alex Colville: Yeah. I, I, I'm certainly not an expert on this and, and not the most up to date on it, but my, my take is I definitely, um, one, appreciate that the founders of pretty much all the frontier labs deeply care about biosecurity and about the threat that pandemics and, and bioterrorism have.

I think that is inherently, like, we are very blessed that that's the case. I think if you threw most Fortune 500 CEOs and put them in charge of the frontier labs- Yeah. Let 

[00:45:25] Luke Martin: them do it ... 

[00:45:26] Alex Colville: they, like, would not give a shit about this, and they would just be like, "Whatever, plow forward. Like, doesn't matter." And I at least, like, uh, uh, feel very grateful, uh, that our, our leaders, uh, of these frontier labs, like, deeply care about existential threats to humanity Does that mean I think they, like, take things as seriously as they should or do as much as they should?

No, and I think, like, they get it wrong a lot of the time, and I think it's really hard, uh, in their job to get it right all the time. Um, but, but so, I mean, my main takeaway is I'm just very grateful that they do care about this. Uh, with the most recent release, do I think it was fully necessary to shut off access?

Probably not, but, like, I'm, I'm okay with a more precautionary approach at first, and, you know, they were pretty quick to, to, to reverse things in, in this case, which I, which I think bode well. 

[00:46:10] Luke Martin: You can't have one without the other. If we have a big advancement, the AI helps us understand something new about biology, it's...

someone can use that against us too. 

[00:46:16] Alex Colville: Yeah, ab- absolutely. Um, but to kind of your earlier point there, I am, I'm also very excited that the leaders of these frontier labs do see the potential of AI doing good, 'cause I agree with you. You look at all the applications of AI and you're like, it's, it... some, it's not- People 

[00:46:32] Luke Martin: are worried, man.

It's, 

[00:46:33] Alex Colville: it's not black and white. I know. I know. You know, how good a lot of these applications are. Like, I'm optimistic about a lot of them, but it's, it's not, like, black and white, and you can't be like, "For sure this is good." Yeah. At least in the biology worlds, besides for bioterrorism, it's pretty easy to be like, "Yes, this is just, like, is a great thing for humanity- Right.

Yeah ... and, like, is something we should do," and there's certainly some aspect to that that I think, um, these frontier labs really wanna be associated with, uh, great PR from doing good in this space. Uh, they definitely know that if, you know, the frontier lab is seen as curing cancer, they're not going to get shut down or restricted or regulated.

So yeah, is it a little scary to hide behind that veil? Maybe. But, like, I, I do think it's, it's... yeah, it's, like, obviously a huge net good for humanity that they care a lot about this. 

[00:47:18] Luke Martin: The other thing that's been cool, I mean, even in our own industry, where I came from, crypto, you have Brian Armstrong, we've already talked about, but, um, people like CZ and Vitalik.

I mean, Vitalik Buterin, founder of Ethereum, open source biotech fund. I guess I already asked you this, of whether or not that's relatively new, of all these different walks of life saying, "All right, we have to converge on biotech, longevity. This is a focus." Have you been seeing that the whole time, and it's just because I'm focused on it now, so I notice it of, "Oh, wow, I know these people.

They're, they're from another industry. They think it's important"? Have you just constantly been seeing this of, like, if you have a lot of money, you wanna focus on longevity because you wanna live a long time? 

[00:47:50] Alex Colville: Yeah, what, what's interesting is I th- I think there's this notion, and I see headlines all the time, of how many people c- care about this field and put big funding in this field.

The amount of funding that's been put in this field is- Tiny- Still 

[00:48:03] Luke Martin: tiny, 

[00:48:04] Alex Colville: yeah ... compared to other fields. Like, absolutely minuscule. If you look, like, the amount of investment in this field compared to AI, it's like n- it's like, there, j- you wouldn't even see it on a bar chart. And, and so when I hear about it, I'm all like, oh yeah.

That's great. It looks great as a tiny start- Yeah ... to what we're gonna see. We are just in the earliest innings of people caring and putting resources in the space. Uh, y- you mentioned Vitalik Buterin. Yeah. Um, someone who, you know, I really appreciate how much of a futurist he is. He really cares deeply about humanity and, and thinking through next best steps for humanity.

Um, he was actually, uh, a part of, kind of like three and a half years ago, we had a great whiteboarding session with him when we were outlining what the next generation of our fund could look like. 

[00:48:45] Luke Martin: Nice. 

[00:48:46] Alex Colville: Um, and he really wanted us actually to name it FSL, like faster than the speed of light, which I thought was an amazing name.

Yeah. I thought it was really cool. That is a good name. Uh, we ended up going with a name Laura had previously, uh, used for one of the, the old accelerator funds she ran, which was AgeOne. Um, but Vitalik, just talking with him about it, it's just, it, it was really cool to see how much he saw that this was an integral part of the future.

Yeah. And I, at first, when I encountered Network States, like, I do not come from the crypto space. Mm-hmm. I did help run a family office of, of an Ethereum, uh, investor, uh, James Fickling. He's a fantastic human. Uh, but I did not come from the crypto world. And so when I came in, you know, there's so many things going on.

It's really entertaining. But- Some good, 

[00:49:28] Luke Martin: some bad. 

[00:49:28] Alex Colville: Yeah. Yeah, but like, I'm a scientist, I'm a nerd. Yeah. I'm like mostly just blinders on, focused on the field of aging. Uh, but w- with Network States, I, like, didn't get it until I heard Vitalik talk about, like, okay, you live on a block. Most of the food around you is unhealthy.

So much of the environment is unhealthy. Like, imagine just, like, having the choice to live in a network state, a community, where, like, health wasn't just, like, something you had to seek out, it was the default. You could just, like, choose to live in a community that was healthy by default and, like, with people who are aligned to that philosophy versus just, like, the neighbors you happen to be born next door or, or move next door, next to.

And yeah, I thought that was, like, such a cool framing. 

[00:50:05] Luke Martin: He's like a, I don't know. I mean, there's an Elon Musk, there's Vitalik. There's, like, certain people, you just... I feel like he sees the future on everything. He's an impressive human being. I wanna get into how you invest and also just kind of the history of AgeOne.

I speed ran it, but can you give me more of a history of where you studied and then, uh, Laura, her longevity fund, which I believe was the first ever longevity fund, and now this has been the successor. Can you just give, like, a little bit of history on that? 'Cause I don't wanna just speed through it. Like, I'm trying to also understand it.

[00:50:32] Alex Colville: Yeah. So I owe Pretty much, uh, all of my career to Laura, uh, in, in, in terms of her mentorship. Uh, but she is one of the coolest, most fascinating humans you'll ever meet in your life. Um, she grew up, uh, homeschooled in New Zealand, like totally off the grid, out of left field is, is kind of how I think about it.

Uh, and she met this, uh, well, got connected to this professor at UCSF. She cold emailed Dr. Cynthia Kenyon. She was one of the absolute pioneers of the aging field. Found this, uh, mutation in worms called DAF-2 that significantly extended the lifespan in worms, and this was the second-ever gene shown when you mutate it, you can dramatically increase the lifespan of worms.

[00:51:16] Luke Martin: Okay. 

[00:51:17] Alex Colville: The first one was Age 1. Oh, I see, I see, I see. So that's where our name comes from. We are- we're named for worms. Uh, y- when you do a full mutation in the Age 1 gene in worms, you can actually increase their lifespan 10X. How long- Which is crazy- How long do- ... 'cause I don't think a lot of people think in humans like, "Oh, wow, we can like 10X the lifespan of an animal.

Like, could we do that in humans?" Yeah, it's, it's interesting proof of concept. 

[00:51:37] Luke Martin: How long do worms live? Sorry, I don't wanna go too much on a tangent, but like how- 

[00:51:41] Alex Colville: The next half hour of this podcast will be dedicated- Just straight into worms ... to worms. I would love that. That'd be awesome. What is it, 

[00:51:45] Luke Martin: like 10 days to 100 days, or there's like a year?

Where 

[00:51:48] Alex Colville: worms out there? Um, it, it's, it's like, uh, three weeks to four weeks, so like in, in the range of like 20 to 30 days, yeah. 

[00:51:54] Luke Martin: That's insane. 

[00:51:55] Alex Colville: Um, but now like, uh, most recently, one of our founders, she ran like a philanthropy program, Impetus Grants, fast grants for aging, and they have a professor that was able to take out the lifespan of worms to pushing towards like a year, uh, which is so cool.

Um, but anyways- Wow. 

[00:52:11] Luke Martin: Yeah. Sorry. 

[00:52:12] Alex Colville: Enough on the worms. On a tangent. Yeah. Worm episode- It, it would be the follow-on- I- ... 

[00:52:15] Luke Martin: episode. Yeah. We will do that. 

[00:52:17] Alex Colville: Uh, but Laura grew up in New Zealand, cold emailed Cynthia Kenyon as a 10-year-old, and was like, "Hey, can I come work in your lab?" Uh, Cynthia was like, "Hey, read this book, 'Molecular, uh, Biology of a Cell.'"

Uh, Laura did. Then heard out about it. Um, Cynthia invited her to come work in a lab. Laura moved her family to here in San Francisco to work in Cynthia's lab, started working on extending the lifespan of worms. Uh, she went to MIT when she was 14 years old, uh, to study in part physics. Uh, dropped out at 16 years old as a part of the first cohort of the Thiel Fellowship, uh, to build our fund.

Uh, and so she, uh, you know, originally under the name the Longevity Fund. She built it in 2011. Her dad had to sign all the paperwork for it 'cause she legally was not an adult. Oh my gosh. And, uh, her first fund made five major investments. Four of them went on to IPO. Uh, I met her in 2017, uh, which is when she raised the second fund, and she kinda took me under her wing at that point.

I was in the first year of my PhD. Like her, since very young age, have just been absolutely obsessed with this notion of why we have constraints when we age. Makes no sense. Like, I think, like, one of the ultimate forms of freedom is biological freedom, and it drives me nuts that as humans we don't have that.

Uh, and so when we met, it was like we got introduced by alumni of my program at Stanford, his partner at ABC, Francisco, and he was like, "Alex, meet Laura." "You both are obsessed with trying to, like, completely solve aging." Yep. Uh, and it was just, like, such a natural pairing, and was really grateful to her for taking me under her wing.

And so, uh, when it came time for, uh, about three and a half years ago when she launched this company, Until Labs, working on reversible cryopreservation, she brought me in from the family office she had put me at to build the next generation of the fund with her. 

[00:54:01] Luke Martin: That is so cool. That's wild. 

[00:54:03] Alex Colville: And, and it's, but it is cra- it's very surreal for me because she has been the, the biggest mentor in my life, and she's younger than me.

[00:54:11] Luke Martin: But it really wa- it was the first ever longevity fund. Like, that's, that wasn't... The AI didn't feed me that wrong? 

[00:54:15] Alex Colville: Oh, yeah, yeah. Uh, so first longevity fund, when she built the fund, there were probably, like, you know, a handful, maybe, like, seven companies or something like that that had ever been built on this thesis of targeting biology of aging.

And so when she ra- raised the fund, everyone was like, "Why are you raising a fund for a field that doesn't exist?" Like- ... there's no companies here. There's only been six or seven. And Laura, you know, one of the many, many, many reasons I, I love and admire her is, like, she's just obsessed with counterfactual impact.

And she was like, "That's exactly why there needs to be a fund, is because there's no companies in this space. If you're willing to fund it, it will exist, and it's so obvious it's gonna be one of the biggest markets of any industry ever." Uh, so yeah, we're, we're the first, uh, longevity-focused VC fund. I'll tell you, it's a lot more fun to invest in the space now than it was for her- Yeah

back then. Yeah. Uh- Yeah ... and one of the coolest transition moments has even been in the past three years, like, we never had an acquirer. Like, there was nobody willing to buy an aging company- Right ... until the past two years, and now finally we have, um, a series of pharma companies that are building out their internal theses, and now they have full-time employees at some of them that have longevity in their title, like Eli Lilly.

Oh 

[00:55:24] Luke Martin: my gosh, yeah. 

[00:55:25] Alex Colville: It's a really cool new era. It's a little bit more fun now that things are, are boiling up more rapidly. 

[00:55:30] Luke Martin: I can imagine. I wanna get into some of your, your thought process, uh, the founder-led thesis as example, as an example of what lets you kind of evaluate, uh, what you're gonna invest in, what ideas you s- you see as exciting.

Hearing that story now, it kinda makes sense. I think you've said moonshots are actually de-risked. Like, you're kinda looking maybe for founders that haven't had success yet. You want someone with insane ambition of, is this possible? Can you explain that, how moonshots are, are kind of de-risked, something that who knows if it's feasible?

'Cause if you say that to an average person, they're like, "Hold on, I want the su- the sure thing." For you, it's, it's a slightly different approach. 

[00:56:05] Alex Colville: Yeah, this is something I would not have believed myself 10 years ago. Uh, I was, like, much more conservative, was much more incrementalist, I would say. Uh, and then just watched Laura at work in Silicon Valley, watched these amazing founders like Celine Halioua with Loyal in terms of building this, uh, company that at the time everyone thought was absolutely insane of a company working to extend the lifespan of dogs.

Yeah. And now it's like no one blinks an eye at it. It's commonplace. But when you, when you build a company, you know, call it a moonshot or a very ambitious deep tech company, when you do this, it, it's a superpower because when you go and you talk to somebody, they are so much more likely to want to work for you as, like, absolute top talent in the field than, you know, the 10th other thing that is super boring and incremental.

Yeah. Like, people wanna work on things that matter. Uh, and, and so I really do think that it... like, from a fundraising standpoint, from a recruiting talent standpoint, sometimes the most de-risk thing is doing something that other people think is insane. 

[00:57:06] Luke Martin: How do you determine the difference between someone who's bold like that, who has that vision, versus someone who's just gonna burn through $30 million?

I mean, there's like a, there's a fine line of, like, this person is very ambitious, but they might be headed the wrong direction. What is that determination? Is it just this person's an outlier, I believe in it, and, and you're making kind of a subjective judgment there? Like- 

[00:57:25] Alex Colville: Yep ... 

[00:57:26] Luke Martin: how do you do that? I know it's, there's an art to it.

It's not a science. You can't, you can't write it down and say, "Look, this is how you do it." But I'm trying to figure it out 'cause it applies across industries. 

[00:57:33] Alex Colville: Yeah. And, and, uh, you know, there's, there's so much element of chance and luck along the way too that, like, y- yeah, ultimately it's a probabilities game.

Ult- ultimately, like, you will have a lot of these failure, total burnout, wasted bun- much of money moments. But inherently in venture, that is a great outcome. It's the 

[00:57:53] Luke Martin: game. 

[00:57:54] Alex Colville: Yeah. Uh, li- like, if everything is succeeding, you're almost, like, not swinging big enough. Uh, but in terms of how you try to optimize for founders that are more likely to actually be the ones who can pull it off versus those who totally fizzle out but maybe make it on the cover of Forbes and get 30 Under 30 or something- Yeah

one is just this, like, uh, maniacal ability to have both a really solid five-year plan and a really solid 15-year plan. Uh, and, and so when we think about these really grand ambitious moonshots, you need the pragmatic markets along the way that can get you there. Um, and so, uh, you know, an example, uh, with Laura, with Until Labs, like she wants to solve reversible cryopreservation for entire humans.

So to give anybody with an incurable illness, say a child with a terminal cancer, the ability to come back in two to three years when a cure may be in phase three trials and may be available for them, uh, when they are, you know, kind of reversibly cryo-pre- uh, uh, unfrozen, let's say. Yeah. But Laura was very smart, and she knew that this would take, you know, 10 to 15 years- Yeah

or, you know, something on a longer timescale. Uh, however, using the exact very similar technology tree roadmap, she could unlock a market of, uh, reversibly cryopreserving organs for transplant. And this, it turns out, is a many, many billion dollar market in its own right. Um, if you look at another one of our founders, science, uh, company science, Max Hodak, one of the co-founders of Neuralink, one of the smartest future-forward founders you'll meet.

He has this m- maniacal obsession with what are the five to 10-year markets that unlock the 20-year, uh, or 30-year goal of uploading your mind into a, a hive mind or, uh, having a bio hybrid be able to integrate into your brain to have a BCI that has a zillion more channels than you would otherwise. Um, and so I'd say that is the phenotype that just like sends us through the roof when we find and meet them.

Somebody who's able to build the five-year plan and the 15-year plan, and they both make a lot of sense, and they're super ambitious doing it. 

[00:59:59] Luke Martin: That's fascinating. I was, uh, I was sitting in on a podcast, this was two weeks ago, this guy Sandy Corey, very, very impressive, uh, investors at Horizon. Early investor in Palantir, one of the first believers in the company, billion to one.

And one of the things that just struck me, uh, stuck with me from the conversation is he meets with these founders, and sometimes he doesn't even ask for the pitch deck. He's like, "No, I just want to know if this person is an outlier. Like, do they have it or not?" Yeah. And, you know, "Show me the pitch deck after.

If it's a good meeting, I'll-- Show me the company you're building after." And I was like, I couldn't-- At first I was like, "Is he serious?" He was definitely serious. Yeah. And a track record to prove it, but I was like, man, that, you know, as you said, it's like there's, there's little elements there that you're, you're, you're getting from someone that tell you.

Uh, I want to get into some of those, some of the investments as well that you've made. Loyal, uh, saving the dogs. I made the joke that hopefully the humans aren't taking it, but that's gonna be live for dogs when? Like, when is that happening? Someone with a dog probably saw that moment earlier. They're skimming through, they're skimming through the interview.

They're like, "When can I buy this?" When is that happening? 

[01:00:55] Alex Colville: Yeah, that's been one of the most surreal experiences for me, and back to this point about sometimes building really ambitious deep tech, you know, quote unquote moonshots as a superpower. Like Loyal will go viral maybe like every other week, uh, without them trying.

Like no new news. They don't 

[01:01:09] Luke Martin: need 

[01:01:09] Alex Colville: to. Like sometimes I'll just open up Twitter, and it'll be Loyal news from two years ago going viral. And I'm like, what? Like what? How is this happening? And like people just love it, and, and, you know, I think it's the, the power and then, yeah, building things that people really want.

Um, but in terms of when they'll be live, uh, there is no definitive timetable. Uh, they are, you know, they've, uh, they needed three things to get an, uh, the equivalent in the veterinary world of an accelerated approval. So in the dog world, this is called, uh, the RXE pathway, a reasonable expectation of eff- uh, effectiveness They have gotten two of the three components.

So they need an efficacy approval, a safety approval, and, uh, their, uh, manufacturing package cleared, and they have had their efficacy and safety packages approved, and now they need the manufacturing package. Last step, yep. So they are on track to do that, uh, likely by the end of next year. Um, but still some error bars in that.

But hopefully by the end of next year, uh, we'll be able to have, you know, uh, so many different Americans be able to have their dog take the first Loyal treatment. 

[01:02:14] Luke Martin: That's so incredible. And on the cryo side, you, you talked about some of the early bets that Laura made and the five to 15 year, two of your first seven investments were also in, in cryopreservation.

Have you signed up? Have you... Like, or is it something that you would do? 

[01:02:27] Alex Colville: Well, that's what I really admire and respect about Laura is, you know, there's some companies out there that will charge you and take your money right now, but they haven't solved the problem, and they're not close or on track to solving the problem of- Interesting

ice crystal formation and damage. Yeah. Like, Laura's not going to market that until- 

[01:02:43] Luke Martin: Until it's solved ... 

[01:02:44] Alex Colville: until, yeah, at le- at least there's, like, a path to solve it, right? Right. Well, we know how 

[01:02:47] Luke Martin: to... Yeah. 

[01:02:48] Alex Colville: At least it's, like, very close to solving. Um, and, uh, so would, would I sign up if I had the ability for something that would work?

Yes. Uh, but in the meantime, just investing heavily in the space in, in terms of people who are willing to solve the tech tree component to it. Uh, yeah, no, I think it makes so much sense, and it, uh, you know, if you've ever known somebody with, uh, an incurable illness or a terminal illness, um, I think it's, like, one of the most devastating experiences that you can possibly go through of, like, seeing someone you love completely run out of options.

You know, you go down your, your set of therapies, your first line, your second line, your third line, um, and at some point there's, like, nothing left. 

[01:03:29] Luke Martin: There's no more time, yeah. 

[01:03:29] Alex Colville: Um, exactly. 

[01:03:31] Luke Martin: Before we wrap, I just wanna hit on a couple of these big ideas I've seen you talk about. You've called for a Manhattan Project for aging Can you describe what that would look like?

Who would run it? Who funds it? And, and why we need that? 

[01:03:43] Alex Colville: Yeah. So, um, there have been, to the credit of, of some of the frontier pioneers in, in Silicon Valley, a number of these well-funded companies as we've described. But, but I, I, I still just, like, given the activity, the progress that we have made, uh, when I describe things like, you know, uh, iPSC technology, induced, induced pluripotent stem cells that went 20 years ago, Nobel Prize, now, now data in humans, like we're just such on this precipice of being able to translate so much more of the basic biology in the space, uh, that I, I feel like once you get that taste of what's possible, that is the time to slam on the gas, put a bunch of investment in the space in terms of really flipping that corridor.

Uh, and, and to me, aging is one of the ultimate challenges of the therapeutic space, the ultimate challenge of, of human health to some extent. Um, and the, the dividends, the economic dividends for the US in making a huge investment in the space would be enormous. Uh, I've got a friend, Rani Rahmani, you can check out her analyses online about this, but it's literally like trillions of dollars that the US can save by making huge investments in the field now.

And, and to me, we're being extremely short-term thinkers by not doing that. 

[01:05:03] Luke Martin: What about the size of... You talked about the fundraising a little bit on how much money's actually going in here. The, the announcements make it seem insane. It looks so big, but you compare it to the fundraisers in the AI world, it's very small.

When I was talking to Andrew Kang and the team over at Urbo Strategy, it was wild to me when he was talking about the, the total market cap of all robotics is still like $200 billion. And it's like, there's a meme coin I saw yesterday it's worth $8 billion. It's like, okay, there's a big bit of a gap here if robotics works at all.

If you had to describe, like, what do you think the, the total... Even a lot of these companies are private, so it's hard to, but like, where is it on a scale like that? Is it in the trillions yet if you combined a lot of the longevity companies kind of focusing on this, or is it not even there yet? Still hundreds of billions.

[01:05:42] Alex Colville: No, not, not even hundreds of billions. Like they- like if you added up all of the longevity market cap of longevity aging-focused companies right now, I, I, I think you'd be probably like 15 billion Something in that range. 20 billion? Yeah. Like, like it's, it's not what you think it is, uh, in, in terms of the scale.

Like, there's still, like, you know, like 1/50 the amount of companies and investment of, like, the cancer space, for example. Like, that's changing. Still, it- it's, it's tiny, it's minuscule, and these big companies, um, you know, not all of them were set up the most efficiently too, in terms of I think a lot of people would want a do-over how, how some of these billions of dollars have been invested.

Um, and so yeah, everyone sees that and they're like, "Oh my gosh, we've already poured so much in. Where's the promise? Where's the progress?" And I'm like- 

[01:06:29] Luke Martin: It's still early. 

[01:06:30] Alex Colville: No. Yeah. It's so early. And, and, like, money in this space is extraordinarily high leverage now, I would say. 

[01:06:38] Luke Martin: Fascinating. The only, I, I have two more.

What's the, the dumbest thing the longevity industry currently believes right now? Maybe not the people in it, but but that you see talked about. Well, it's one of the things. I mean, there's, like, you know, in my industry with crypto, it's like there's one coin. It's like, guys, no one should buy that, and that's the guy you're playing golf with.

He's like, "I own so much of this coin." It's like, I don't know how to tell you this. Are you, are you talking- Is there anything like- ... 

[01:06:57] Alex Colville: me and my fart coin? It's gonna go to zero. 

[01:06:58] Luke Martin: Uh, not fart, fart coin I like. That's a good coin. If you would've said something else, I don't know. Not financial advice. 

[01:07:04] Alex Colville: Yeah, no, there, there's so many of, of these things right now in the aging field that, that drive me nuts.

I mean, again, like all the noise, excitement about, about all the peptides that are not GLP-1s or therapeutic peptides, I'm just like, ah. It's like, it's fine, it's entertaining, but it's not moving the needle. Yeah. Like this isn't gonna get you 10 extra healthy years, uh, of life or 30 extra years of healthy life.

Like let's try to focus on those things. Yep. Um, in the aging field, I think there's just like a lot of classic memes that people will fall into, and this is something I think outside of the science world people don't really realize. But, uh, it's very easy for an early publication not based maybe on the most strong science to explode into almost like 1,000 publications mimicking various forms of that original publication.

Uh, and, and so one, uh, area that I could describe here is a, a field called cellular senescence. Okay. Uh, which, like the pop culture v- version of it, people will say that some of your cells as you age become zombie cells. Yeah. Where they stop dividing. They start spewing out these pro-inflammatory cytokines, and this whole niche field has been built around this phenomenon.

And in vitro in a dish, if you just like study cells in a dish, this is like absolutely a very real phenomenon, very studiable. In vivo, uh, in, in mice or in humans, it's the Wild West because we do not have good markers to measure these cells. Even after like 15, 20 years of studying this phenomenon, we still can barely identify them in vivo.

Um, and, and so there's many case examples in aging where there's things that are just so frustrating because biology is hard. It's really hard to get to the bottom of a lot of this. But what drives me nuts is sometimes people aren't really even trying to get to the bottom of it. They're just trying to get another grant or push things along, and it leads to this like hardly of inflated space.

Another example, like NAD supplementation could be very useful, important for energy levels, something like this. But in terms of the link to longevity in humans, really doesn't exist. There's a ton of companies profiting from this narrative, a ton of longevity companies profiting, uh, longevity clinics profiting from this narrative.

Strong data does not exist. 

[01:09:07] Luke Martin: All right. Good to know. For people watching, careful on the peptides. I'm just gonna, I'm gonna keep repeating that. We already, I already got my, my big, uh, big podcast ad. Last thing, if you could only invest in one of the four categories, whether it's delay, replace, pause, reverse- You had to bet the fund on it in the next 10 years.

Age one is not gonna do that. But if you had to, which do you pick and why? 'Cause as you know, people are gonna look at this, they hear that 15 billion number, they say, "Man, I need to start focusing on this. I need to start learning about it. I wanna invest." If you had to pick one of those categories, which would it be?

[01:09:35] Alex Colville: Impossibly hard question. Uh, but I, I would say the... It would probably be the first generation of just prevent or slow aging. And the, and the answer is, like, I'm convinced that the next 10 years is going to be a really magical transition to commercial mode, uh, for the space. Like we-- The aging field still doesn't have a single commercial product demonstrating like real proof of benefit in humans, and that is gonna be huge.

Like, we need that ChatGPT moment for the aging field, and that's gonna happen in the next ten years. Um, and, and we're working on, uh, a couple incubations internally that I think can deliver this in the next ten years. Um, and I think that to me, of just this like enabling the aging field to have a first product that is a meme in a sense, people love it.

Like it's a product people love. It makes their life way better. They can, you know, hang out with their grandkids with more energy, move around more. Like, I think this is gonna happen in the next ten years, so I would invest in that. But if you ask me the same question for like, you know, five years down the line, I would say probably replacing or restoring, but I would be really torn between the two.

[01:10:41] Luke Martin: That's tough. Impossibly hard question. You still did well. Alex Colville, thank you very much for doing this.