The Realest Longevity Guru - EP 85 Alex Colville

0:00Alex Colville: There's a dude in the longevity and aging field who is, he's not super well known outside of those worlds. He's not a Brian Johnson. He's not a Andrew Huberman, but I would say he's actually maybe one of, if not the most influential. He's very quietly been investing money in this field for a long time. And he's a major player. His name is Alex Colville. He is the co-founder and general partner of Age One, a venture capital firm. He's been investing even before he started running this firm. He's the guy that I kind of go to when there's a new startup or a new branch of science and I'm trying to reality check it.

0:45Alex Colville: Alex has a PhD in genetics from Stanford, so he's got the cred, but he's also, he's just very even keeled. He's not religious about this stuff. He digs in incredibly deep. I just use him to ground myself and to try to figure out what to really spend my time on and care about. I think you will find him fascinating. We get into his life, his career, obviously the science that he thinks is real and that you should be paying attention to. if you were going to trust anyone, I would put my reputation behind Alex. I think he's the real deal here and that you should listen to what he says. He's also, he's nice.

1:30Alex Colville: He's enthusiastic. He's just a good dude. I will confess that we are friends and you can do with that what you will. Come listen. We're going to get into longevity land. I am Ashley Vance. This is Core Memory. Here we go.

2:01Alex Colville: Welcome to the Core Memory Podcast. This is Ashley Vance. We are joined today by Alex Colville. Alex, hello. Hey, Ashley. How are you? I am doing fantastic. Good. You're always cheerful, I think. yeah well it's like curling is on right now like this is the best this is the best time of the year you're oh god because you're from like Maine or New Hampshire or something right which one is it yeah from Maine yes so you did you actually do curling no but I'm not the super anything with ice I'm like this is the best thing ever it's the most exciting sport I don't know if you ever played like broomball or anything like that no I grew up warm places I did not snow or ice no you did yeah i mean it's it's it's how you survive mentally through the season yeah yeah i do what you gotta do do you did you hockey um all my friends did but i was a big skier okay struggle rope ski racing competitive ski racing um was was really into it uh you know which is particularly crazy when it's like minus five degrees and you're wearing a skin tight race suit yeah and flying down literally a sheet of ice uh it's a good time yeah yeah i never did any of that I've never, I've never skied.

3:10Alex Colville: It's terrible. And we have ski week in California and all the kids go off and I feel like a terrible parent because I, I was never taught this. And so I could not teach my children. I've just abandoned them. I've abandoned my child. Um, okay. Alex, dude, we, I feel like we've known each other three years, four years, something like that. I consider you my, I mean, I'm always bioteching and longevity reporting, but I consider you my source of truth, my kind of level setter for all these things that I encounter. And so I want people to know, I find you very rational in a field that is not always specializing in rationality.

3:59Alex Colville: and and i appreciate that you go deep on the science and um yeah i'll just be like what do you think this that that and i i feel like you're always you know just really um even keeled and knowledgeable on on all things longevity aging related and so you're you're kind of my um my oracle on some of this stuff i've been called the switzerland of aging okay which i think i want to branch beyond that, but I'm happy with that as a base. Well, throw some hot takes out here. Totally undermine what I said and, and this, this moniker. And, uh, but you're also, you're the, um, you run age one, which is a longevity aging related venture capital firm.

4:44You used, you were young, are young.

4:48Alex Colville: You used to manage a very large fund before that, um, for, I don't, I don't know if we're supposed to name him or not. James Fickle, who's invested super deep in science, brain, aging, all that. And you, like at a very young age, in your 20s, were managing some ridiculous amount of money for him and where it was going to be directed. And you got a PhD at Stanford, I believe, in genetics? Genetics. Genetics. Yes. So you kind of, you know, I hear Stanford's good. I think you probably know what you're talking about. on some of this stuff. And so, so, but these days are kind of a venture capitalist.

5:29Yeah, exactly. I mean, it's, it's a common theme, like from, you know, you're describing like growing up on ice and in Maine and Maine's actually the oldest state in the country. Uh, it's like by, by median age of the population. Oh, this is news.

5:44Alex Colville: Okay. I have to fact check this on Chappie WC lifetime. Uh, yeah. So oldest state by median age of the population. Um, and I think that surprised a lot of people because they're like oh everyone thinks of florida uh no it's actually maine and so you just grow up and you're surrounded by people that have their quality of life reduced by aging uh and you know that that was just pretty shocking to me uh because i was like wow that seems suboptimal um and and then everyone's kind of like oh yeah that's that's life like this is natural part of life um and and so i was kind of like growing up being like wow like the villain is the vibes of uh like most people just being like oh yeah decline with age is natural uh and then when they actually experience that decline with age everyone's like oh my gosh this is like the worst thing ever yeah uh and and that like premise has been like my whole life with all the stops that you described is like trying to shift that vibe why is that do the young people just flee Maine or are people retiring there I mean that seems like a crazy place I mean it's very pretty I'm sure.

6:47But yeah.

6:48Alex Colville: Yeah. It's both. It's, it's the, it's like, it's both of those are combining to, to cause it to be the oldest by median age, because most of the employers, like, you know, there was Fairchild Semiconductor that's had a couple of acquisitions and Texas Instruments, but then the money jewelry industries are like lobstering and logging paper mills, you know, blueberries and potatoes. There's not a lot of young, exciting industries. It's changing uh and pretty rapidly like portland has become a really cool place uh but yeah just by and large there hasn't been the industry just keep young people around and then like older people love it because it's beautiful it's serene you don't have to to deal with noise and pollution and yeah it's just beautiful nature but okay but you were legit um noticing this as like a teenager and and just got interested in aging as a result yeah yeah i mean like in part the thing i think that happens to everybody at some point.

7:41I was like, had grandparents get cancer and started asking one why it happened, like how we get cancer, what it comes to be. And then just was really kind of mad at the answers. I'm like, well, that seems silly. We just like accept this as status quo. And then from there, there was a really pivotal journalist that I am forever grateful for that wrote The Challenge of Our Age. So it was like a 10-part series in the Portland Press Herald about the challenge of aging and the demographic shifts and the burden on caregivers.

8:11Alex Colville: So this is a local journalist. Local journalist. Yes. There we go. Okay. Yeah. Love to see it. And this like, I don't know, it was just like perfectly hit my brain. At that point, actually, I was kind of in undergrad. So it was kind of like came out like at the end of high school and in undergrad. And it just like hit me like a ton of bricks. And I was like, wow, okay, I need to go back to this. Like, cause I, at the time I was really interested in cancer because the perfect personal connection, that's what I was grappling around. And then the aging thing really hit. And then I was like, wow, okay.

8:44There's like so many other things being caused by aging that are problem. Like how can we get to that root cause? Started just Googling endlessly. Like what is aging? What causes it? What drives it? How did it evolve? All these sorts of things. And that pretty much led me down the path of on now.

8:59Alex Colville: But like, instead of, I would think maybe become a doctor, but no, you were, you're more root causing. Yeah, it was more root causing. And during undergrad, I worked with David Sinclair, Harvard Medical School. So he's famous for his New York Times bestseller, Lifespan. Slightly controversial figure. Yes. Absolutely. Too crazy, but a little, yeah. Yeah, yeah. Yeah, he's one of these pioneers that has like totally, you know, I think he probably can say that more people are in the field because of him than anybody else. You know, maybe Brian Johnson can compete with him now for that claim. But he was, you know, a real pioneer in terms of putting this on the map and getting everybody excited about what's possible.

9:43And I think naturally in that role, you can sometimes get a little bit too excited about what's possible or the timelines. And that, you know, may have happened along the way at various points. but yeah I certainly brought more people in the field than anybody

9:55Alex Colville: I've always wondered if he kind of hates me just because he was doing this and then I showed the spotlight on Brian and then I feel like he overtook David a bit on all this stuff yeah I've never talked to David for some reason he's like one of the few people yeah I've been curious about that okay well this all makes sense you've got an axolotl on your shirt because yeah it's i mean i'll say it's a pretty regular basis that i have axolotl attire on this was a little bit special in that not only it's the shirt but i actually brought socks uh which which i'm quite i'm quite proud of i'm gonna like rip out the the headset here but it must be demoed oh geez you're not joking around wait let me see if we could yes we can see this on on the camera yeah both okay that's great wow so for people who are just listening these are not Not, I mean, I guess all socks are three-dimensional, but these are very three-dimensional socks.

10:57Alex Colville: They have an actual axolotl growing out of the edge. Yeah, they're little crocheted axolotls that are hugging your legs. My mom got me them for Christmas. Okay. I was like, these are the best. But why the axolotl? Why the axolotl? You know, in this frustration with everyone's kind of complacency about aging and, you know, I think a big part of the problem is showing that something can be done. I think the world is going to continue to be very complacent until you're able to show people like, oh, the aging field has had like one win. Like we can modify aging. We could delay aging, prevent aging, could reverse aspects of aging.

11:33If we can do that like credibly, I think everyone's going to pile in and it's going to be one of the biggest, best transitions ever. But until that happens, we're going to struggle to do that. So, I mean, Y-axolotls, like a lot of the coolest stories ever in medicine have been catalyzed by discoveries from animals. So famously with GLP-1s came in part from the Gila monster and X-xanded-4 and kind of GLP-1 analogs in the Gila monster. And there's many examples of this through the history of medicine, because it turns out that millions and millions of years of evolution can do things biologically that it would take PhD students a little bit longer.

12:14Yeah. I don't know. Yeah, a little bit longer.

12:16Alex Colville: But I've known this and I've forgotten it. What's the axolotl famous for in this field? Regeneration. That's right. So it can regenerate almost every organ in its body, can regenerate parts of its spinal cord, which I find particularly really crazy. Uh, there's like the lampre eel can regenerate a whole centimeter of a spinal cord, like complete transection. Axolotl can't quite do that, but they're, they're really cool and they can regenerate parts of their brain, parts of their heart. Uh, remarkable entire limbs is like the most famous one. And do they live really long? Let me put on my Switzerland of aging hat.

12:54It's, it's one of these that people will like refer to them as like, oh, they're really resistant to aging and these sorts of things. And I think that is true. They have some varieties of what we call negligible senescence, where they don't seem to accelerate in their rate of mortality through time. But they absolutely do age. And I've witnessed it firsthand because I was very curious about the same question. And you can see that they no longer regenerate as good as they once could. And they just kind of, there is some visible kind of looks around aging. But like, you know, the part of why they're most interesting about aging is they show you that regeneration is possible.

13:35And regeneration can be possible in humans. Like we regenerate over 70 % of our liver. You know, if we took out 70 % of liver, it'll grow back. And in a remarkably short time period. And so I just think this notion is really powerful and fundamental of, you know, one day being able to enable a whole other level of regeneration in humans that our genomes may be capable of doing if they're modified or controlled and in the right way.

14:00Alex Colville: Yeah. I mean, they're all the, well, okay. So I get it. Yeah. I mean, there's all these signs all over the place that things people might think are fantastic and impossible really are possible. And even I remember I was doing a story, which on a topic we're going to get into on kind of this idea of partial reprogramming, taking your cells back to a sort of peak state. And yeah, I was with the guys over at RetroBio. And I think some of this work came out of the DM's lab at Harvard, but just showing that in the womb, it's like obvious in hindsight, or I guess we always like intuitively knew this happened, but I don't think we'd witnessed the process that like when you have two oldish people make a baby.

14:47Alex Colville: The baby doesn't come with all the baggage, you know, from their genes. There is this reset moment that takes place. Right. And, and if you, so we know the body does this and it kind of goes back to this pure state so that the baby has a fresh start in life. And, and so like, you know, and now we're getting ways to kind of program that in a little bit. So yeah, I mean, there's evidence in nature that amazing things are possible. I really appreciate you calling attention to old people reproducing. More attention needs to be brought to this subject. I feel very passionate about that. But on a serious note, yeah, I'm obsessed with the phenomenon that you're describing.

15:23It is the reason, I think, that Jeff Bezos and Yuri Milner and many of these other figures put, and even I think Bill Gates, put very significant amounts of money into Altos Labs, right? $3 billion seed round, pretty much, tranched out, but still. um i think it's this notion of and where clausner has talked about this this notion of like a reset and that like you know i think a lot of people think oh like rejuvenation or turning back the clock is insane can't be done and yet presumably it's an experiment that humans have done millions of times and other animals have done many many times uh we don't really know if it's actually rejuvenation and turning the clock back it could be some sort of like a selection of the healthiest cells.

16:07Alex Colville: But there's some, all this degradation and junk on the end of the parents' DNA is getting cleaved off somewhere. Right? I mean, I mean, that's, that's you, there is this moment where you're getting rid of this, this baggage. Yes. You're looking at me skeptic. You don't have to pretend like I know what I'm talking about. You can fix it. You're mostly right. You're mostly right? The words, you know, cleaved off, you know, it's like, yeah, I guess you're describing telomeres. I'm trying to decode, be the decoder here. No, I just mean you have parents who have had their, they've accumulated damage to their DNA over the years and that is somehow getting erased in some sense.

16:53Yeah, precisely. But the reason I hesitate a bit is that I think people really haven't done very comprehensive research or analyses on aged gametes. So sperm and egg cells in humans. I would really love to see like a much deeper analysis of this done showing like, here's the extent of age that you can go. And then it's reversed back when you actually have a baby or like fertilize an embryo. And I just haven't seen it to that extent. But I, what you're describing is, yeah, absolutely correct. Like, like you would really guess that there's been a ton of damage that has accumulated based on what we know about the rest of the body, uh, that would have to be reset through the process.

17:33And there's a, and it's like a really dramatic, intricate, like reset of the entire methyl, uh, methylation patterns of DNA. Um, so just like really dramatic events, which also would kind of go with this, you know, fact, uh, you know, likely scenario that there's a rejuvenation event. Um, but it's one of the most understudied phenomenon in the entire aging field, in my opinion, with like the highest upside

17:51Alex Colville: because it's hard to study, but you're, you're, you're proving my point. See, you're, you're a, longevity VC. You should just be talking your book. You should just be hyping all this up, and here you are. You're looking for evidence. This is my whole point. People can trust you. This episode is brought to you by Brex. I spend all of my time inside of the world's most ambitious companies making rockets, semiconductors, robots. Very often, the business is struggling and then all of a sudden things click and take off, then the company's expenses spin out of control. They either have to clamp down, start counting pennies, or cross their fingers, hope for the best that the quarter or the year comes out okay.

18:37Alex Colville: Brex was built to handle exactly these situations. It helps you move fast, spend smarter at the same time. They've got credit cards, banking, expense management all in one place. They've got AI technology, looking over everything, taking care of tasks for you. No more chasing down receipts. We use Brexit Core Memory. It has been a godsend and given me back so much time. Giants like Anthropic and Zoom use Brexit as well, and so do tens of thousands of startups. You should use Brexit and you can find out exactly how to do that by going to brex.com slash core memory. I kind of want to get you to walk through a few things and tell us what's real, what's not, what's exciting, what's not.

19:25Alex Colville: I mean, super broadly, people have been hunting for a fountain of youth for literally thousands of years. So the aging field is kind of like hard to tell where you want to start on defining things. But, you know, I would say kind of like, I don't know, 20 years ago, I remember, you know, there was this guy, Aubrey de Grey, I felt like was kind of elevating, not quite mainstream, but like in tech circles, this idea of looking for things that you could go to repair the body and clear out cells that senescence, like these dysfunctional cells. Anyway, he was kind of like starting to get this discourse a little bit more, at least in my world of tech people.

20:11Alex Colville: And then we've gone through these weird ups and downs because there's like science and then obviously there's all the pills and everybody's preaching this and that. But then now I feel like we're in this kind of new era that's interesting, which is, yeah, you've sort of got people like Brian Johnson who – whatever. I mean, folks are opinionated on him, but putting this stuff very much in the mainstream discussion. And then you also have just, for me, at least, this is my feelings, like real biotech companies doing like, it's a very interesting time. You know, people are throwing billions of dollars around at stuff that may or may not work.

20:53Alex Colville: But like, this is not fringe anymore to a large degree. And then things like GLP ones that couldn't be bigger and more obvious as like multi-billion dollar industries and apparently helping people out like on a quite large scale. So I guess my thrust is like an exciting time. I was kind of curious how you would characterize it in terms of hype versus real versus like for the general person in the public, you know, how excited they should be in this moment or if we're still actually in the overhyped, you know, maniacal phase of this. Yeah. And I'll admit, I got things very wrong in terms of mentally how I thought things would play out.

21:38So like back in 2014, when I started getting, you know, doing research in the field, getting really involved in it, the way I kind of mentally thought things would play out is like you'd have these technological advances, they'd hit humans, and then that's when it would go really mainstream in terms of the interest around the space. And then what ended up happening was the technology is still on the way to do that and has made really dramatic leaps on the way to do that. But that wasn't what catalyzed like people's level of knowledge or like excitement broadly about the space. It was really like the rise of the influencers and podcasters.

22:13And it was like, you know, David with his book, Lifespan, it was Huberman and Atiyah and Brian Johnson. And that's really what like just like thrusted this notion of like aging and longevity totally on people's, you know, the front of their brains. But I think it was almost more in a way of like here, you know, you need to exercise, right? You need to sleep, right? You need to be really careful about your habits and doing the right things. Which like everyone knew. Which everything, everybody already knew. That's what blew my mind about it. I was like, people just like find it mentally satisfying to like tell you the things you should be doing but are not doing.

22:47Alex Colville: Well, I mean, they can tell you in like one minute that you should exercise and sleep and eat right. But if you have a five-hour podcast, I guess it really drives Des Moines home. I don't know. Yeah. Yeah. Buckle up, everybody. We're going. Let's go in the distance, this podcast. No, like to me, what it has screamed is people want control. And that's what I've learned from the biohacking peptides movement as well, Chinese peptides. It's like everybody is desperately looking for control. they're dissatisfied with the pace of randomized controlled trials and evidence and technology to get there and so they're gonna you know it's just that much pent-up demand for control over our decline with age that people are experimenting they're testing everything and yeah it's just like that to me just screams there's a massive demand for these things that can control the way we decline with age or our biology of aging and and i think that you know it's the boring stuff getting in the way of like the controlled trials, the evidence generation, the manufacturing, all these sorts of things that are boring to a lot of people.

23:53But that's what's going to catalyze this like whole next era of excitement and joy about the field. So, you know, your question of if we're hyped or not, like it's just like the AI field or any other frontier field or crypto, like you go through waves, you know, you go through a wave where people get really excited about it. And maybe that wave of excitement got a little bit ahead of the technology and then it goes down and up and up and up. There's like zero doubt in my mind the aging field is going to be one of the most impactful technologies that's ever existed in the history of humanity. And are we fully there yet?

24:25No. But will we make huge leaps there over the next five and 10 years? Absolutely.

24:30Alex Colville: So what did you see in 2014 that made you excited? Yeah. In 2014, I mean, honestly, I was so out there. It was just like that people were working on the problem. That to me blew my mind. I was like, oh, this is so cool that there's like a research community. It was very small. But there's, you know, a handful of these leading pioneer professors that were working on this. And, you know, technology-wise, what can be really excited is it was like, you know, the work that had been done in the 1980s and early 2000s just showing that aging was modifiable. This is, you know, when we talk about that, like, you know, the villain is vibes of like people, you know, being kind of complacent about decline with age is because no one thinks it's modifiable and so then when it hits them they're like oh my god this is terrible this is horrible but if people believed it was modifiable they would do something before and 1980s uh there was professor tom johnson and uh one of his uh colleagues michael glass they published a paper showing that you could mutate one gene in worms uh right age one and actually increase lifespan by 40 to 110 percent uh eventually that same gene was shown to be able to be mutated in 2008 uh with a with a kind of complete mutation that could 10x lifespan of worms literally we've been able to like 10x lifespan of an organism uh aging is modifiable yeah but although this is one of the most frustrating things i feel like we've made worms live you know until infinity and i you know calorie restriction all this stuff and then yeah yeah Yeah, and then it just doesn't seem to replicate.

26:06Alex Colville: But you're saying the sign is there. This replicates. That's right. Yeah, yeah, yeah. I'll be very clear. This is a replication. This finding has replicated over the past 50 years. I didn't mean replicate. I mean translate to humans. Yes. Yeah, yeah, yeah, yeah. I mean, you've covered Celine Halyua and Loyal's story really closely. They're going to be a big test of this hypothesis and how it translates. So Loyal's doing therapies for dogs, for people who haven't seen our work. Yeah. So you, right. So going to a new class of animal to see how this plays out. Yeah. So Loyal, yeah, targeting lifespan and healthy lifespan in dogs and developing therapeutics to do that and eventually shifting to humans.

26:52And they've made some really exciting progress with the FDA, as you've covered, in terms of the FDA is now on board with them doing this, which is really cool for the field. But a part of the interventions that they're testing are related to the same exact pathway that in the 1980s was the first to show that aging was modifiable. So when I mentioned age one, it's - Which is the name of your firm?

27:14Alex Colville: Which is the name of our firm. Yeah. Yeah. It's a nod to, well, it's kind of related to PI3K biology in humans. And so this is a member of insulin growth factor like signaling. So IGF-1 like signaling insulin and IGF-1 signaling pathway. And one of Loyal's pipeline programs is going after the same biology and dogs. Gotcha. And so when you say it hasn't translated, well, it's taken us 50 years because, you know, we were, the world was waiting for people badass enough like Celine to step up and be really creative and pragmatic about how to translate it. But yeah, we're starting to go on the path of translating these.

27:51Alex Colville: Yeah, that's always weird to me. It just seems like there would obviously be so much money in the field. So, yeah, it's like when you came along first kind of investing some of James' money and then partnering with Laura Deming really closely. And, you know, she was a pioneer in all of this, raising one of the biggest VC funds around this field. I mean, it wasn't very long. Yeah, this just strikes me as nuts. I mean, I mean, I felt like this is a thing Silicon Valley would be chasing with billions of dollars. But I guess it was just seen as too fringe or just too impossible or something. It's, it's, it is insane to me as well.

28:35But like you get into the nitty gritty of translating these things and then you quickly understand why it has taken so long to happen. It's expensive.

28:43Alex Colville: It takes a long time. Human trials are hundreds of millions of dollars sometimes, depending on your size and scope. And you're just dealing with really complicated operations and logistics problems and just bets. You learn in therapeutics, it's so hard to go zero to one that everything kind of falls to the local minimum, I guess, local maximum of the most de-risk thing. right like every biotech vc right now they want to fund like i don't know the past three years it's just been trying to fund the next glp ones that are like slightly better right everything is like a me too uh or like a multi-agonist off of like an established thing uh and it's just very hard to go and do something radically different than that and go out there and so but but i think the bottleneck has been like there's hasn't been the salines of the world to go do it and the people who have tried to do it uh just unfortunately have have you know either had gotten unlucky with their approach or just been grifters with a lot of those, or just like weren't very pragmatic about the approach.

29:42Alex Colville: Yeah. Yeah. Okay. Well, okay. So we're going to go through what we should maybe be excited about and what's real, but we'll start with you because I find that the most serious people I know in this field actually like take almost nothing that everybody else is trying. So I imagine you do some form of calorie restriction or you're, careful on your diet? Definitely, definitely pretty careful on my diet. Uh, but no, I don't do anything too out of the ordinary. I used to do the, like, you know, the zero app. I used to do the zero app. So 16, 18, uh, 16, eight hour fasting. Um, I do think there's probably good evidence for like longer fasts, like a three day fast or something like that, or even longer.

30:23Um, but I, I just don't personally do it because I did like, and it's a lame reason, but the, The effect size, I just don't think is dramatic on longevity and lifespan. I think the effect size is like semi dramatic on like energy levels and things like this on a week to week basis. But the mental trade-off for me is like, I would rather just be like mentally more happy and like more productive on working on the massive effect size things for human aging.

30:46Alex Colville: Okay. Okay. Cause I always thought calorie restriction was at least one of these things where everyone's like, yeah, that probably works. Oh, I think it works. Okay. I think it works in, you know, the primate data, there was one study by the NIA and one study in a wisconsin study and there's like still disagreement as to you know one was seemingly positive one was seemingly uh negative in terms of a positive effect on primates humans there's been the calorie study uh but there really hasn't been a test of this in humans because it's just so hard for people to adhere to yeah um glp1s you mentioned really interesting because they could do this in some respect they could be the first test of calorie restriction in humans um but yeah We don't really know in humans for color restriction.

31:28The jury is still out, which is insane because it is, you know, one of the gold standard interventions in the aging space of what positively works.

31:34Alex Colville: Okay. Okay. And you don't have to rate all these things yet because we will get to them. But this is just a quick lightning round. Metformin, rapamycin, anything. Do you take any pills? Nothing. No. No, I take nothing. Like, you know, metformin is interesting. Rapa, like I could see the 0.5 mg every other week or every week, but we just don't know. We don't have the data. And, and yeah, I want to see it. Anything that like on Brian Johnson's litany of, do you take, you take anything, you take nothing? Really? Right. No, I take nothing. So you like eat healthy. Yeah. Cause you're vegetarian or you eat?

32:10I eat mostly vegetarian, but I eat meat. I eat meat as well.

32:13Alex Colville: Yeah. Okay. And then do you drink alcohol? Uh, occasionally. Yeah. Occasionally. And then otherwise what? You're exercising, you're sleeping. Not, not sleeping. I'm working. You're working. It's terrible. You're just, you're. Nobody should follow you. You're just a workaholic venture capitalist. Okay. No, it's literally like the dilemma of aging researchers, which is either like, you know, you can go and you can try to be like a nun in terms of your practices and be perfect about your own health. And I guess that's kind of like the Brian Jatson approach. Or you can lock in and be like, we're not satisfied with small effect sizes.

32:49Like we want huge effect sizes.

32:51Alex Colville: So you want the big pill. Yeah. Well, or any, you know, I don't know what, if it's a pill, it's another. sort of intervention, but like, I want us to be able to all live to 120 and amazing health. And, uh, you know, being a vegan who sleeps 10 hours a day and, uh, and doesn't ever drink, that's not going to get me there. And that's not going to get my parents there. And that's not going to get any of my friends there. And so I'm just like, no, we need to do something more ambitious. Okay. Okay. All right. Well then there we go. There's our baseline. All right, pod friends. I am here to tell you about Send Cut Send.

33:21Alex Colville: They are a manufacturing phenomenon. Whether you're working on your own car or you're a giant automotive company, a rocket maker, if you need metal cut, machine, or bent, you're going to SendCutSend. They'll do it for you right and they will do it for you fast. Go to SendCutSend.com slash core memory for a 15 % discount on whatever you're trying to make. We love SendCutSend. Go visit them today. All right, let's do GLPs first since they're so massive. Thoughts? Net good, net bad? Pros and cons? How should we feel about these things? Yeah, I mean, one of the most positive medicines to society from like a society level impact that we've ever had.

34:12I think they're remarkable. There's a reason that they're so talked about. the long-term outcomes are really dramatically positive in terms of the cardiovascular outcomes trials, the risk reduction for cardiovascular disease for people that are overweight or have obesity or have type 2 diabetes. And seemingly, you know, if you were to describe what an aging drug looks like, you'd probably be like, well, if, you know, if I tested it long-term in humans, it would have beneficial effects across many different aspects of aging. um glv ones have done that they have a mechanism that kind of fits with what mentally you would think of as an aging intervention and that they somewhat phenocopy calorie restriction like a gold standard intervention in the field um they have these effects against inflammation which are really dramatic and exciting uh inflammation for those that don't know inflammation is is and low-grade inflammation is thought to be in part like a hallmark of aging or a driver of aging um so i think it's like the aging field has been working really hard for 50 years to get aging interventions and then just like villa monster totally other field you know eli lily novo come along and they're like oh here's something like better than anything you've created to date uh if you know what the aging field is going to do is going to end up being way more dramatic and exciting than glp1s but it is still funny the irony of like serendipity and you know another field coming along and providing something that's probably better so i still have

35:38Alex Colville: like doctor friends though who are like they're like oh god you know don't do it and uh and then i have other i see other people who are i guess educated but i don't know that they're experts in this they're like oh it's gonna like lower your tolerance for risk and change your personality you know you i mean we all see all these different things and we have no i guess we kind of know how it plays out over the long term because why because people were taking this for diabetes for a long, I think for a while, right? I mean, okay, I'm just listing off things, but like, so good on all these fronts.

36:11Alex Colville: How concerned should people be though that, you know, 30 years from now, it turns out you've got something horrendous happening to you as a result of taking these. Yeah, so I mean, there's some height effects there. You know, there's a really good review that came out last week summarizing some of these. Like, you know, there's the, there's a specific ophthalmology eyesight effect that does seem to have a consistent signal, albeit like extremely rare. But the evidence is kind of built in that direction. But other than that, you know, with a lot of these, it's like so many people have been tested for so long.

36:41Like Ozempic was not the first GLP-1, right? We've had FDA approved GLP-1s for way longer time horizon. And so just with the number of patients treated, we kind of like, we know that like the rare events will have popped up by now. So I am really not that concerned about some sort of mystery side effect that hasn't been seen yet in the data. And so, I mean, the data looks great. You know, we work with one of the first authors of the SELECT trial in semaglutide that was that cardiovascular outcome trial that got semaglutide approved. That was in, you know, a massive data set, way over 10 ,000 patients for over, for about four years, medium follow-up.

37:19We have a lot of data now.

37:21Alex Colville: So, but like this risk-taking thing, I mean, you hear people, oh it stops them drinking doing drugs yeah how what a shame yeah no that part is good but i had never seen somebody argue before that this is but that it's changing your personality too though and you're becoming less usually i mean i didn't like the idea of that of like like oh i'm in my personality is gonna shift and i'm gonna i'm gonna like i don't know you know i'm like in the middle trying to run a business is like do you want to uh stop taking risk and daring and i don't know So yeah, is that bullshit? Have you heard anything like that?

37:55I mean, we have an extremely smart mutual friend who's an influential academic at Stanford that I will not name that, you know, has tried this out for like time spent on smartphone and found that, you know, they really reduced the amount of time that they were doom scrolling.

38:12Alex Colville: Yeah. So yeah, I've heard a lot of anecdotal evidence in this direction. And there's some really exciting new approaches like Lily's developing a trial for a backup for Terzapatide called Brennapatide. uh, for alcohol use disorder. Um, so we're going to get to see a lot of this addiction trial, uh, addiction, uh, data play out in trials to see if there is, you know, a really robust effect there, but anecdotally, yeah, that's like, I don't know. It seems like a good thing to do scroll less. Yeah. Yeah. Yeah. Yeah. I mean, it's just, it is weird, but it's very weird. Personality's changing. I mean, yeah, obviously in good ways, sometimes, um, you mentioned a whole bunch of things already, but like, what is the most exciting thing you see on the horizon directly as like an outcrop of the GLP-1s and where they're going, like advancements with these therapies or the next most exciting thing that's come as a result of studying them.

39:05Yeah.

39:05Alex Colville: Does that make sense? Yeah, absolutely. I mean, I think in one part, we're going to see variants of them put to the test in terms of being measured in trials that are reflective beyond just a single disease population. So I think this is one of the biggest things that the aging field can accomplish. And this is something we're working on very directly is to say, you know, can we design trials with the FDA that are reflective of aging as opposed to a singular disease? This is what Loyal has been the pioneer for in terms of showing as possible. I think we're going to see that with humans in the next decade, and it's going to be really cool.

39:41And GLP-1s are kind of related variants may be a part of that. I think another exciting wave with GLP-1s is just kind of like next generation mechanisms that could be paired with them, could go beyond them. I mean, something that is, it's not necessarily concerned based off of the data so far, but is always a lingering concern in people's minds is the lean body mass loss. And this fact of when you yo-yo with GLP-1s in terms of go on GLP-1s, go off GLP-1s, go back on, go back off, the weight that comes back is a little bit disproportionately fat and adipose as opposed to the muscle mass coming back.

40:19And people theorize this could be a bigger problem longer term. And so it's like, it's one of these memes in pharma land right now of everybody's looking for the things that could help either have less of a negative effect on lean body mass, or help just like build back lean body mass. And I think something we're betting really big on is, is there some sort of intervention that can help improve muscle function or muscle size, uh, that also is just long-term really good for you. Um, so over like 90 % of glucose is, is, is kind of metabolized process by muscle has all these physiological benefits.

40:56Um, you know, can we, uh, is this like a, you know, a next GLP one wave of, you know, what we learned from GLP ones is that people love things that make them look good and are good for their long-term health. Uh, you know, is our muscle interventions the next wave of that?

41:12Alex Colville: And you said, do you have a startup that's doing that or you're just looking, you're surveying the field? We have multiple. Can we disclose any of these or are they stealthy ones? They're a little bit more on the, on the stealthier side. Uh, but, but what I can say is, yeah, what, one of them, uh, we've been building with Nova Holdings, uh, extremely excited about that, uh, moving more in that direction. Um, And another one we just signed on today with a big multi-stage VC firm located in California and literally signed the paperwork today. That's what can help. Yeah, where no VC firms exist. And so, yeah, this is something that I think is going to be huge.

41:56Alex Colville: So these are therapies that would help build muscle mass? Yeah. In part, build muscle mass for some of the therapies and interventions we're focusing on. And others would focus more on the function improvement side of things. Okay. So in kind of getting to the place, like an example, one of them, the one with Nova Holdings, we've seen preclinically evidence to improve exercise capacity in mice. Oh, okay. And so that's something that we're really interested in is, you know, can we translate some of these sorts of interventions to humans? And how were, you know, there was like that era where it was like the Uber for this and everybody was making some new app and it was always the Uber for whatever.

42:39Alex Colville: I feel like I'm hearing it already from all these startups. Like I'm the Ozempic of this, you know, of, of sleep of whatever. Um, I mean, like, I feel like we should, this is going to be kind of too easy, um, for companies for a bit. Is that something you're seeing? Yes. Yes. Yeah. I think it's a little bit, but the funny part is as, as like, as meme-y as that phrase has been, and as many times as it has been used, it works on VCs every single time. Well, I mean, it's so much money. It's like, why not? Well, because every VC is wired to just be like, I only care about the biggest possible outcome.

43:16Everything is, you know, this, this distribution where you're looking for the outliers that drive all the returns. And so when you hear somebody talking about something as ambitious of, we're going to build, you know, the next, you know, we have a phrase internally at the fund that we always say civilization defining companies. Uh, that's what we're looking for. And so, yeah, when you hear somebody say it was MPEC for X or is MPEC for Y, that is there inherently in implying a civilization altering trajectory.

43:41Alex Colville: Yeah. Yeah. Okay. Okay. Um, another topic we talk about a ton on the show and our videos is this idea of partial. So reprogramming, if you've heard me do my spiel before, I apologize, but for people who haven't, there was a famous Japanese scientist, Yamanaka, who came up with these proteins called the Yamanaka factors. It's kind of this combination of four proteins. Alex will fix everything that I butcher here, but you kind of hit, you can take a skin cell from an old mouse, hit it with these four proteins, take it back to basically like creating a stem cell. So to this kind of pure, um, early state.

44:22Alex Colville: And then there's this hope with like partial cell reprogramming that, that you take a old liver cell or brain cell and you hit it with some combination of proteins. And instead of going all the way back to a blank slate, you get like the platonic ideal, like whatever it is, 18 to 25 year old version of that, that cell is all healthy and doing everything at maximum capacity. Um, tons of research showing these things in practice working, and then also huge issues, um, with this process kind of running away sometimes and forming tumors, you know, cancerous tumors where we're still in this process where we're trying to control, um, learn which proteins to use, learn how much, um, how to control what's happening with these cells.

45:11Alex Colville: And we haven't quite perfected it, although lots of interesting things going on. You mentioned earlier, Jeff Bezos, Yuri Milner, other folks have put billions of dollars into Altos Labs. It's at least thought to be quite secretive, but thought to be chasing this as one of its major programs. Sam Altman's funded retro bio is doing some work in this area. New Limit funded by Brian Armstrong and others. also here. So, and there's more players, but we're talking billions upon billions of dollars have gone into this. Yeah. And I, you know, when you and I have talked, I think you're, I don't know if it's fair to call you skeptic.

45:49Alex Colville: I guess we'll hear what you think about this, but I've noticed at least in our discussions, I felt like some caution as to how effective this would be. So first, please fix anything that I butchered. And then, yeah, how should we, this i always get excited because it's like amazing what happens to these cells to be able to like start from scratch or to rewind um seems incredible and and and so yeah i mean how exciting not exciting where where are we yeah so i'll say in the in the context of like news cycles and events uh there were just two approved therapies with ipsc technology so today we have one today yeah i think i think it was like the past two days out of japan okay yeah yeah yeah uh which is remarkable it's like a huge milestone now of course that's like was it full reprogramming yeah tell us what was it spinal or this was uh i think one was cardiac okay uh but i'm not sure actually yeah okay no keep talking i'm gonna look it up while you're talking all right love it uh so so that is in the context of full reprogramming of this like can we just generate uh you know new healthy cells you know one of my North stars or like obsessions long-term on like a 40 year time scale is, can we replace every single cell in the human body?

47:01Uh, you know, we have 30 trillion cells. Can we get to a point that just at any point, uh, that we have damaged cells, can we just swap in a new, fresh, healthy cell? And it sounds insane, but there are a couple of companies, uh, that have shown that this is somewhat possible in the context of specific cell types. So like there's a company, Blue Rock therapeutics and Aspen Neuroscience that Sam Altman is a funder of that are going after replacing dopaminergic neurons for Parkinson's disease. And they've been able to show in phase one trials from Blue Rock that you can implant these cells, even remove immunosuppression, and the cells still engraft and function long term.

47:36That's remarkable. There's another company here in the Bay Area called Neurona Therapeutics that's working on implanting inhibitory neurons for epilepsy. and they've shown efficacy, pretty dramatic efficacy in just a very early trial at being able to implant these cells derived from pluripotent stem cells into the brain. And so that's like, if we're just talking about reprogramming, one of the things is just like, wow, can we replace every single cell in the body? Maybe.

48:02Alex Colville: Wait, and explain that first. Okay, pluripotent stem cell is this stem cell, this kind of human-made stem cell, this process that I was talking about, right? I mean, and they get called pluripotent stem cells. Yeah, it doesn't necessarily have to be human-made in that, like, you know, at various times throughout our life, you know, we have pluripotent stem cells and embryonic stem cells are one of the types of pluripotent stem cells. And another type is iPSCs, so induced pluripotent stem cells and kind of ESCs and iPSCs. There are different companies using each approach and they have their pros and cons.

48:38iPSCs are the ones using OSKM, the Yamanaka factors you described. And so there's specific nuances around it. And for example, like big pharma companies that are in traditional red states, like historically haven't loved like embryonic stem cells because of the connotation there. But like, at any rate, it's yeah, those are kind of like the high level technologies used for replacement. And then as you kind of described on the partial reprogramming side, that's saying like, okay, instead of going all the way from taking a somatic cell, aka like a skin cell or a blood cell or a hepatocyte liver cell, instead of taking one of those and turning it into a pluripotent stem cell that can then divide into many different cell types, let's just take that like skin cell and try to make it younger.

49:24So harness the rejuvenative benefits of reprogramming while maintaining the same identity. So the skin cell is still skin cell, still does skin cell things, but is younger. Okay.

49:34Alex Colville: And then I did, I found the story from Japan today. I mean, so yeah, it's, it's, it's induced pluripotent stem cells, two therapies receiving approval for Parkinson's and, and cardiomyocyte patches for heart failure. um so like in in i don't know if you know the details on this but the two examples you mentioned so those were both in the brain right yeah and so in there you're getting what you're getting an injection of these um neurons in in into the brain that are replacing the damaged ones or how is that process working yeah so this is i am not an expert at all but i'll say for like neurona i think it's really interesting in that there's the i believe it's these like neuronal precursor cells that then naturally kind of migrate to where they're supposed to go in the brain um and and for the parkinson's companies right now i think they're currently placed in the region that dopaminergic neurons actually normally don't lie uh and so they're in actually a different region but it doesn't matter because they're they're there just to secrete uh dopamine uh and and that is enough to have this beneficial effect.

50:47And so there are some companies working to optimize the placement of them to put them where they're supposed to do and they have theories as to why that'll be more beneficial. Yeah, so it's kind of like a mix of just putting like the direct neuron type or it's sort of precursor. So we see startups doing these,

51:04Alex Colville: putting these healthier cells in brain. We just read about, well, one was Parkinson's, probably quite similar. And then heart, I've seen spinal. So it's kind of like taking these stem cells that we're creating, fixing problems here and there. But like the holy grail that everyone's chasing is, can I have like a 25-year-old's liver or lungs or brain, right? I mean, that's kind of the mega quest. Yeah. I think they're both the mega quests, but just in parallel. Like one is saying like, okay, like, you know, if we can't figure out how to just like intrinsically at a cell turn back its age, then like we now have the technology somewhat to just replace it with a young cell.

51:50Right. And so there's this like field of aging that's focused on replacement, which is kind of like the, you know, it's so hard to fix all the thousands of macromolecular damages that accumulate in a cell. But if we can just swap it out, then it doesn't even matter. We don't even need to really understand everything that's going on. And then there's kind of like a parallel school of thought of like, okay, like there's all these things going wrong in a cell. We know in the process of reprogramming that it looks like a lot of that molecular damage is reverted or cleaned up somehow, you know, via autophagy processes or via the epigenome changing.

52:29And, you know, can we just do that instead and have this kind of like fast track to a rejuvenated young cell? uh and so it's kind of like parallel fields uh pushing along both are in the earliest of innings in their trajectories and both are incredibly exciting uh but just look very differently but but i mentioned the companies like brulewark and neurona because i think a lot of people don't realize this because everyone hears stem cell technology and they think like bahamas they think

52:55Alex Colville: they think like you know they're going to go somewhere pay a lot of money gets you know random cells injected into them and then they're just going to die and and like who knows if it's working or not. And I think it's been a hyped up. Which you can't do, by the way. Yeah. Okay. But different here. Yeah. Okay. Yeah. So it's been a field like hyped up for such a long time and now it's like working in phase one trials. I just don't think that's clicked for a lot of people yet. No. I mean, this drives me absolutely actually kind of bonkers. I think, yeah. Anyway, we're doing, I feel like we're doing our part over here.

53:27Alex Colville: So, but, but then if I'm not wrong, I mean, when you and I've talked in the past, you, my sense was always that you felt like there actually is so much complexity in the body that, um, like my read was that you were kind of skeptical on, on how, uh, how far these technologies could go. Yeah. So, so in the lane of, uh, partial reprogramming, uh, so this is something that I actually sought out when I first came to Stanford. So like 2016, I was like, I really want to work on reprogramming. In part, I selected my PhD lab because it was working on this project. So I did my PhD in Dr. Tom Rando's lab.

54:09So he's a muscle stem cell expert and one of the first movers, I'd say, in the aging field. You know, not in the 80s per se, but he really dipped into the field in the late 1990s, early 2000s. He's famous because his lab published in 2005 Nature paper that young blood was rejuvenative to old mice. so this really creepy notion of like blood boys and parabiosis and a lot of that energy and excitement came from both the lab at my phd and then the lab that was directly beneath us downstairs which was dr tony vizcaray who also did a lot of similar lines of research on the brain but i didn't choose the lab because of that i chose the lab because they were working on this project with dr vittorio sebastiano at stanford looking at partial reprogramming and its effects on aging.

54:56And so at that exact time, Juan Carlos Belmonte, previously kind of down in San Diego, Salk Institute, now at Altos Labs, he had a cell paper that showed you could increase lifespan by progeric mice by 50%. So mice with progeria, genetically engineered to kind of mimic human progeria, which are your humans that age extremely rapidly, die in the teens or 20s, depending on the type of bacteria you have. And this technology was shown to dramatically increase those mice's lifespan. And so we were working on that same problem in parallel and kind of really trying to disentangle just how good the effects were and in what ways and how the mechanisms worked.

55:38And maybe in part, the skepticism you're referring is just, you know, worked in the field for two years, got a sense of what it was like doing these things in cells and mice to some extent, But it was just very early days in terms of trying to disentangle like single from noise, trying to disentangle like where things were going to go. And so I was shocked when we had all these companies working on it at the end of my PhD. Not necessarily in a bad way. Like I'm thrilled that people are really pushing it forward and investigating it. And I think there's this meme in the aging field of like, oh, like reprogramming is overfunded.

56:13Therefore, people shouldn't fund it. And I'm like, no, pretty much everything in the aging field, even reprogramming with these billions of dollars is totally underfunded because reprogramming could be tailored to each individual cell type or tissue in your body. And I remember Jacob Kimmel, who some people may know, some people may not, but you should know him, one of my top five favorite people in the field. When I was first starting working with Laura on our kind of latest fund, he was like, 70 % of your portfolio should be reprogramming companies. How much is it? There's so many angles.

56:44Alex Colville: How much of your portfolio is reprogrammed? None. Right now, none. None. Yeah. And I really want to change that because if we talk about holy grails of the aging field, everybody wants something that can turn the clock back. This is one of the closest paths to being able to do that. Yeah. But okay. So why is it none? And because it's a really hard problem. But you haven't seen something you're convinced by yet, right? I haven't seen something that we're convinced by yet. I'll say like, for example, New Limit, like massive super fan of Jacob and Brian and Blake. And I think what they've built is extraordinary.

57:27And I would say follow very closely along with what they're doing. because I think they've done it in a really, really intelligent and smart way. It's just like a very inherently tough problem to translate to humans given, for those that don't know, like you're just, you're triggering, you're messing around with pathways in cells that involve proliferation. And so there's these risks of teratomas or kind of cancer, inducing cancer. And so inherently, it's just like a, it's something that demands a lot of study before translating it to humans. Um, and, and new limit is, you know, they're not going in the direction of OSKM and Yamanaka factors as much as they are kind of orthogonal, different transcription factors and non-transcription

58:13Alex Colville: trying to find their own proteins. Yeah, exactly. Yeah. Okay. Okay. All right. All right. We got out of that one. Okay. Um, I don't usually, I try, well, I guess I do let people talk their book a little bit. I try not to make this like a advertisement for your, your companies, but Fauna Bio, you guys are invested in. I mean, tell me what they do. Cause it's, it's just fascinating. Yeah. So, um, and I know, I know you don't like to invite VCs on, so I'm trying to like earn my keep here and. Who do I not like? VCs. Oh, no, no. Wow. I don't usually let VCs on the podcast, but you, you, you were an easy decision cause you're legit.

58:55Yeah. So fauna bio, they study hibernating species. So this goes back to that obsession with axolotls or with, you know, gilla monsters, this extreme biology. Naked mole rat. Naked mole rats, exactly. And, you know, bowhead whales. Like, so bowhead whales, they just have this, there's been a series of publications recently covering the stability of their genome. and and there's a lot of animals like elephants and whales that for their size you would assume they would be dealing with cancer incessantly um and they they're not uh because they have better ways to maintain genome stability than we do um and why big animals get more cancer or they should

59:35Alex Colville: it should just because they have more cells oh okay uh and and i never thought about it okay yeah and so it's a little bit of a paradox in some animals that that's not the case or they You know, just looking at different rates of cancers in different species can teach us a ton about human biology and ways that we could potentially have levers to dial up or dial down rates of cancer. I don't know why you'd dial up, but let's go with dial down. Let's not do that. And so, yeah, Fauna Bio, they study hibernators. So 13-line ground squirrel series. They have a huge data set across hundreds of different types of hibernators.

1:00:13And the reason is like just extreme biology can teach you so much about human therapeutics and human disease. And so, you know, some examples are just like the amount of cardiac stress that these animals go through through the hibernating process of going from, you know, extreme temperatures down to low extreme temperatures, dealing with really dramatic differences in things like heart rates. and they'd have no issues doing it versus like human systems, you'd put them through those same stresses or temperature changes or physiological changes and we would die instantly or we'd get some horrific disease or some horrific fibrosis.

1:00:54And so fauna has been studying this in a really cool way.

1:00:58Alex Colville: So they're trying to pinpoint the genes or the mechanisms behind some of this. Yeah, they're like building a human genetics data set and saying, okay, like what genetic modifiers in humans help prevent us from getting diseases? What genes are different in these hibernating species? And what do they do differently to prevent getting similar conditions to in humans? Overlapping the two and saying, okay, what can we learn from the intersection of these two to take targets that have human relevance and that we know in like the 13 ground line squirrel or something can give them a remarkable ability not to get a disease.

1:01:33Alex Colville: I feel like I remember writing a story about a company called Variant Bio almost, I don't know, I want to say it was like eight years ago. I can't remember. And they were running around the world finding unique populations of humans, people in Chile who could do similar things to your describing. I mean, they could be in the snow in relatively little clothes and sort of deal with hypothermia and stuff like no problem. People that can be hypoxic, you know, up in who live in mountains and can be without oxygen and still function at a really high level. Trying to find the genes behind some of those things to see if you could make a therapy populations that just didn't get like diabetes and things like that.

1:02:18Alex Colville: And then, um, so I feel like I run across startups kind of chasing these outlier type functions, animals, humans, and then like how successful have we ever been at translating something like that into a therapy? Yeah. So during my PhD, I consulted for a year and a half for the business development group of, uh, maze therapeutics. So this was a third rock ventures build. Uh, for those that don't know, third rock is one of the biggest biotech VC funds, uh, based out of Boston, you can think of, and SF, they're kind of like a corollary to flagship, which gave us Moderna. So they do these big builds.

1:02:55May's Therapeutics partnered with a bunch of different prolific professors, including Aaron Gittler at Stanford, who's kind of the ALS group of the world, I would say, expert on ALS. And they focused in large part on genetic modifiers. So that in part locked my brain into the power of that platform. So very similar to variant bio in terms of looking for these extreme examples and translating that to humans. To your question, has that been successful?

1:03:23Alex Colville: Remarkably so. So there's like a cardio company, cardiomyopathy company called Myocardia that's had a lot of success with this kind of human genetics driven approach. You may have heard of PCSK9 inhibitors, which is an example of using human genetics to say, oh, people with a human mutation in PCSK9 have 88 % fewer cardiovascular events lifelong. Well, okay, where's the downside? Okay, you look into the genetics, there's not really a downside. Why aren't we all doing this? Why don't we all mutate our PCSK9 to lower our risk of atherosclerotic disease later in life, right? So I do think there's just like, there has been a number of very successful examples of this.

1:04:06And there's also cool papers in Nature Reviews direct discovery that show it's like you have a 50 % higher chance of getting a drug approved if your target has human genetic evidence supporting it.

1:04:17Alex Colville: So it just, it just takes a while. I just feel like I've been writing about this stuff forever that I don't, yeah, you know, I just don't see like people living, walking through the snow in shorts yet. Yeah. On the way, you know, but like there, there are the really cool examples of dramatic improvements and breakthrough, like cystic fibrosis, right? Where, you know, another one where in part human genetics played a big role and we've had people brought, you know, had like 50 year improvements and expected lifespan with this disease. So there are the success stories, but like it hasn't reached the common man yet.

1:04:54You know, something we think a lot about is like, you know, like how do we get to this human enhancement, right? You know, there's this baseline, we all live our lives where, you know, we have this certain risk of decline with age that's certain and we're most likely going to get cardiovascular disease and neurodegeneration and all these bad things like when are we going to get to the point where we can just modify things so that just baseline we can prevent cognitive decline or experience better cognition or be way more resilient to cardiovascular disease or any of these things and yeah what is that i think i think the next 10 years for real yeah i don't i don't know if you've heard of sRNA or RNA therapy, but there's a company, Alnylam, in Boston, has been a pioneer.

1:05:33John Ragnore is really pushing along this technology. It's gotten to the point there. We mentioned in glycerin or PCSK9 inhibitors, there's an sRNA for PCSK9 that you can administer once every six months. And I think it's really very minimal in terms of off-target side effects. I think we're getting really close to an era where we're going to see people be able to experience baseline enhancement using these targeted RNA therapies.

1:06:00Alex Colville: Okay. I mean, I, cause yeah, well, I mean, that's exciting. Jesus. I mean, you think, you think like in the next, I am, God, I forget how old I am. I mean, that was a part of the problem, like 48 ish. Um, I think, and, um, I'm just, I'm going through it now. Uh, yes, I think that's right. And, and, uh, you know, to that point worried about cognitive decline do you think do you think like when you're saying this i mean you think in the next 10 years 20 years how realistic would it be on my part to expect something that not only kind of like holds me at the state i'm at but but but improves me back to where i was yeah i mean especially like mental yeah health 20 or 20 years extremely uh optimistic about it.

1:06:5010 years, pretty optimistic, but it's going to take a lot of effort. But I think we can get there. And we're working with a founder who's developing therapies that you could do, potentially even like a subcutaneous injection to deliver an RNA therapy to the brain uniformly. So this has been one of the biggest developments in drug development and medicine in the past decade is we now have this blood brain barrier shuttle technology that can allow pretty uniform and deep penetration into the brain delivery of these RNA medicines. And we think that's going to be huge along these lines of prevention.

1:07:27And so it's going to be like probably going to start out for genetic subsets of disease. But I think it'll increase in terms of prevalence of the population that it's benefiting pretty quickly.

1:07:38Alex Colville: Wait, and that one was a stealth startup or that one's public? That one's public. We announced... Which one was it? It's called Erska. Erska. So Irish founder... In Boston? it? Uh, company is split between Boston and Ireland and London. Okay. Okay. All right. I'm writing that down. Last week we led, uh, co-led their, uh,$39 million series a. Well, you didn't tell me that. Did you? No, I didn't mention that one. No. Come on, man. That's good. Um, I asked my question a lot better if I had these drugs. Um, I could, I could use that. Okay. Um, and then, okay we had jennifer dowden on the podcast not long ago that's a brag um but you know we were talking so much about i mean chrisbury feels like look i get excited about these things i mean in many ways it has lived up to its hype in many ways it has not in and um yeah where are you on she was arguing and a lot of people argue this to me finally we're getting better editors, doing bigger swaths of DNA, doing more, less, less damage to the DNA when you're making cuts, getting better delivery mechanisms, which I think is partially what you're talking about.

1:08:54Alex Colville: I mean, yeah. So obviously you're kind of bullish that, that, um, I mean, it's sort of like when we sequenced the genome, it was, it was like overnight that was meant to be a cure to every disease. You just had to like, look at one person's DNA and, and it would, everything would reveal itself. It turned out to be much harder. I feel like CRISPR's fallen into that category where everyone hears about this magical cheat editor. Then it turns out you have to do lots of work to make this all function well. But yeah, so where are you on kind of the state of CRISPR? Yeah, I think that's right. I think in part, like the second half of my PhD that I wasn't working on reprogramming and aging, I was working on high throughput CRISPR genetic screens in aging.

1:09:35And I think CRISPR has had just like a revolution in terms of basic biology or even like slightly translational biology in terms of looking for new targets in terms of just understanding cellular biology. It's been unbelievably impactful. And then I think in the human side, I think expectations got out ahead of what was realistic or feasible from a progress perspective. I think what you described in terms of DNA double-stranded breaks and genomic damage and off targets have been a huge hindrance. And I think, you know, maybe rightfully so the FDA has taken pretty conservative stance in terms of saying, all right, show me very long-term outcomes to prove that there aren't risks of rare events or cancers or something being caused by these off targets.

1:10:17And in some cases they have been caused, which I think there has been a huge cooling effect on that space. Where we've been extremely excited is, you know, an example, you had a lot of news not on the podcast uh so she's one of our founders uh building company general control using crisper technology hasn't aired yet but but it will it will have by the

1:10:39Alex Colville: time by the time this one is i think i'll make sure it does well i think you wrote a piece maybe that's what i meant to say oh no no no sorry yes yes yes no yes we did yes wrote a piece uh about her sorry i said pod piece uh you wrote a piece about her uh but so what she's doing is she's harnessing CRISPR technology, making, I'd say, invariance of it to enable a world and that you can modify the epigenome without inducing DNA breaks or DNA damage or double-stranded breaks. And so that's something we're extremely excited about right now in terms of this ability for finite control and potentially longer endurance therapies.

1:11:21So maybe one-time therapies or very long acting inhibition or activation of any gene in the genome or not every, but like a lot that weren't previously able to be targeted. And so I think we're just, you know, with a lot of technologies, we're about to see just like the next wave and the technology is going to end up being extremely impactful in humans. It was just slightly different. You know, the first generation, we didn't know at the time, but it just wasn't really ready. But yeah, like, you know, I've been, I'm not very active in terms of investing in traditional CRISPR companies right now.

1:11:53I think that's very reflective of most of the investor base uh at some point you know i think localized delivery targeted delivery these sorts of things will end up being really promising and great short term uh longer term the technology is just going to have to evolve to like epi editing or other sorts of approaches to enable the large-scale impact okay all right let's go rapid fire for a

1:12:13Alex Colville: second um yeah i mean i'll throw a few things at you and you tell me if they're hot or not um altos labs been super secretive for a long time now do we have a and if i put you in too uncomfortable of a position i'll i'll give you at least one pass yeah where's like the whiskey bottle i need like to take a shot if i don't answer we could do that if you like um yeah like i mean i've heard kind of like nothing for a while how do we do we have any sense as to to what's going on over there, how they're doing. Yeah. And for, I don't know, maybe a little bit of background for the listeners. Like I had a, I'd say a period in my life, maybe a year or two or a year or two ago where I was digging and doing a lot of journalistic work on Altos and it was going well in terms of public reception, because I think a lot of people wanted to know.

1:13:11And I got told by a couple of people that management at Altos was not very happy. Oh, I didn't know that. Of my journalistic work. But, so no, I'm very happy to talk about it. Like, I think Altos, look, they need to be held to a high standard, just like with Calico. That's, you know, a whole other topic we can talk about later.

1:13:27Alex Colville: That was next on the lightning round. Oh, perfect. So you can just do both if you want. Yeah, I mean, in the spirit of lightning round, I'll try to keep it short where, yeah, these companies have taken a lot of resources for the space. they're seen as the bearweathers or the kind of barometers of whether the field's going to do well or not or is doing well or not, they should have extremely high expectations on them in terms of doing well. In the case of Altos Labs, they had a recent publication at a scientific conference that I thought was really interesting where this will be new to a lot of people, but they took organs for transplant and they showed that they could improve those organs using traditional OS cam reprogramming before transplanting them into patients.

1:14:07Alex Colville: Whoa. And so they're focused, their new model in humans. So they had an organ donor, hit it with the Yamanaka factors before it went into the person and sort of juiced it up. Yes. Okay. I believe this is a part of the direction they're going with reprogramming. And they presented that at a scientific conference recently. Wow, I didn't see that. in the past week, the Mayo Clinic announced that they have a transplantation center focused on aging. Oh no, wrong sound effect. I was going to celebrate that. Hang on. Okay, wait. All right, there we go. Sorry, I'm an idiot. Warranted for human organ rejuvenation, I think.

1:14:47Alex Colville: Other people do that for like stock bumps, but we do it for organ replacement. Okay. Yeah. So, you know, they presented this. I thought it was really cool. You know, beside that, some of my past Twitter threads, they've been working and publishing on like line one ASOs. So line one is a retrotransposon. So if you've heard of like jumping genes, there was a Nobel prize for this. Like in our genome, there's a lot of genes that just like jump around and cause DNA damage in the process of doing so. It's thought that maybe damping those down could help us long-term in terms of specific diseases or long-term health outcomes if we could not have, our genes jumping around causing a bunch of damage.

1:15:26So that was one of their approaches that I think is pretty cool, but there's a bunch of other companies in the space and I haven't seen a lot of activity pushing it along. They kind of very stealthily acquired a company that we were an investor in, but it was very under the radar in terms of that happening. They've been extremely quiet and they have very smart people. Hal Barron is incredibly sharp, really smart in terms of how he's thinking about clinical trial design for humans. These three centers across UK, SF, San Diego. There's been some rumors about, you know, people being cut from some of these sites recently.

1:16:04We still don't really know. And at the same time, you know, the Aspen Ideas Festival, I think Rick Klosner was making pretty exciting claims about, you know, treating thousands of mice with reprogramming factors and seeing really dramatic effects in terms of lifespan. Hopefully we'll find out soon.

1:16:21Alex Colville: Okay. Well, you can just publish your findings under a pseudonym on core memories no problem we i i was enjoying your journalistic work if they weren't and i guess that is awkward you're like a vc and then you're kind of rubbing some people the uh the wrong way that you might you might be interacting with or or running into some some people respect it i think there's definitely some people at altos that are like appreciate you bringing light to our hard work and like getting people excited about what we're doing uh and i like to hear those people versus yeah i think the other take is they want the competitive advantage of they don't want other people doing what they're doing they don't want other people to you know it's a bigger moat for them if people don't know what they're doing yeah so i mean i get it i totally get it well just tell me everything man let's be um for real uh and and calico been around forever do we do we know at all what they are actually doing yeah yeah so calico is an interesting one and that like it was uh core to me even in undergrad i like when there was this time magazine uh cover that was like can google solve death yeah and i literally like printed it out i like kept it on my desk for like three years of my life just being like this is so cool like a huge organization you know google is is willing to work on aging and not just that they're bringing art levitton who is a legend at genentech and and just like top of the top in terms of drug developers and bringing a lot of these experienced people into this organization.

1:17:51I applied to Calico before I actually applied to my PhD programs. And I was like, please give me a job. I'll sweep the floors for free, literally said that. And they said, go get a PhD. And so I got a PhD. So yeah, I've been following Calico extremely closely over the past decade. We've got an awesome founder, Adam Froyin, who used to work at Calico. Jacob Kimmel used to work at Calico. Their alumni is cracked like their talent for their early positions. And, you know, this is obviously why I got turned down. They had like 10 ,000 applications for every one position. It was crazy. Uh, and, and so, yeah, it's, it's been, uh, I don't know what, like 13 years, uh, of, of Calico now AbbVie just recently walked away from their big partnership.

1:18:33We don't know why yet, but AbbVie was putting in like billions of dollars. I think it was like$4 billion that they were splitting on this. So that's a big question mark. We need to find out what happened there. Calico switched strategies in that for the first, I'd say 10 years, they were extremely secretive. Maybe like first eight or nine years, extremely secretive. The aging field, I think, didn't really like that. And so there was a little bit of a tension, a healthy tension. Calico did publish a lot. And so I highly encourage everyone to go check out Calico's publications. I think they've and extremely high quality science, really productive and great for the field.

1:19:11But I think Calico kind of realized like, oh, we made a mistake in being super secretive and people don't like it. And Calico is one of their own founders, you know, publicly was in the media criticizing them as an organization and saying they didn't accomplish what, you know, the goals of the founding Calico, Google members and kind of creating the organization was. And so I think they're doing really cool stuff now. um you know i think they're working on things that people would be surprised to hear they're working on i think the public pipeline right now is really impressive um but i think it's just this question of are they ever going to really move the needle and and really be more aggressive

1:19:49Alex Colville: um we'll see yeah okay okay then um what's like the most exciting thing you think people will see in the next, like, call it two years in this field? Like, is there something you see right on the horizon that's amazing? I hope it's these transplantation results, uh, and, and whether that's either, uh, my co-founder, Laura at, and, and until labs and the work they're doing in cryo or it, you know, loyal with, I think that the dog thing, I think it's, it's really hard to say the dog thing is not going to be the turning point. Yeah. Because I think the second that loyal gets a green light from the FDA, I think that's our chat GBT moment of just this entering thousands and millions of people's homes.

1:20:36I think the aging field has been waiting for a win for a very long time to be able to say like, yes, we can do this. We can modify aging beyond mice. and for me i think it's the loyal moment of uh hopefully millions of of households and and dogs in the u.s experiencing that aging can be modified and and just like the beauty of that psychological shift for people of oh wow like i don't have to accept decline with age there might be some better future where we can have our physical independence longer and run and play and all so close to that moment yeah um and and knock on wood that happens next year yeah with with oil

1:21:15Alex Colville: how do you how do you stay on top of like when you're i'm sure when the startups come to you i mean you have people knocking on your door all the time and then you guys are trying to do your due diligence and and research them and everything but like to for you do you go hunting for outliers um scientists in some lab that have a big idea like how do you what do you read or how How do you, are you just doing papers all the time? How do you stay on top of everything? Yeah. So, I mean, in part of it, uh, I think one of Laura and I's superpowers is, uh, attracting some of the best, most ambitious young talent, uh, of any field that you'll find.

1:21:58Um, so I think one of like the most proud of things in my whole career is just like the team we have right now at, at age one in terms of the young talent. You know, we have a bunch of venture fellows and principals that are undergrads and grad students. Kat, Sophic, Soleil, Lynetta. It's like they're just unbelievably talented, Maggie. And I think they just have this superpower of being in the inn and all their individual spheres and knowledge circles. And so it's like it's not a one person job. It's a team thing. And I think as a team, we just have a lot of fun being able to catalyze anything we can find in the field.

1:22:42So, yeah, we're constantly getting forwarded or, you know, having people say, oh, you really got to hear about this or check this out.

1:22:49Alex Colville: Yeah. I think it's that. And then, yeah, neurotic scrolling of papers comes along with that. And we definitely do a lot of that, too. So it's a little bit of both. But, yeah, it's a lot of hunting. We definitely are hunting in terms of, like, if we hear that some professor has something really cool, we want to go investigate. Yeah. Okay. Um, well, I always try to be respectful to people's time. I've dragged you all over the place. Is there anything, I mean, I know you're into so many interesting things. Is there something that I just, just top of mind that I just grossly ignored or that we should bring up?

1:23:21I think, I think maybe this like translation to humans thing is, is maybe the one thing, which is like, I think this next five years is going to be really pivotal moment for seeing these aging therapies translate to humans. And in part, like the federal government has been really interesting in terms of their motion in this area. ARPA-H is like the DARPA, but for health, they have a number of program managers working in this space. And I'd say that's something that I think people should be more aware of is that now is the time for human trials and testing things in humans.

1:24:00Alex Colville: Why? Like just because we've been researching this for so long and now it's, it's baked and ready to be tested. Yeah. I think, I think it's been an Overton window thing in part. And the FDA has been for their part, you know, willing to engage on it, but there just hasn't been a lot of practical things and pragmatic things brought to them. I think we're going to see a lot more pragmatic things brought to them over the next two or three years. And I think through Arbor H and others, uh, we're, we're going to see really exciting efforts funded in the space to put a lot of these hypotheses to the test in humans.

1:24:29And like to have more things that work, you need to test more things and to test more things, we need costs to decrease, to test things and cycle times to get faster. Uh, that I think is going to be a big focus in the next five years.

1:24:41Alex Colville: I always ask this question. People probably get tired of it i mean do you think uh i mean is china who who you know when you're talking about human enhancements and um so many of these promising things i mean there's just no question that running trials is immensely cheaper in china yeah um they are more you know for better or worse adventurous with running experiments on people um and primates but but you know willing to do things we're quite cautious about. And I think it's fair to say, well, I'm sure it is fair to say, kind of coming from behind on terms of the pure science, but catching up and advancing very quickly.

1:25:23Alex Colville: And so, yeah, I mean, like in 20 years, I mean, is the U.S., for all these things that you've just been talking about, is the U.S. the driving force or is China the driving force of this bio revolution. That is a bit of the irony of all the companies that have pitched the AI platforms and this and that, that is reducing, you know, dramatically reducing truck discovery costs and truck development costs. Uh, and, and then, you know, despite all of that excitement and hype and some under promising and over promising China comes in for the past five years, really dramatically lowers the cost of trials by like 5 to 10x and the speed and investigator-initiated trials and all these sorts of things.

1:26:06And it's like, oh, wow, like all this hype about like technology, being able to do this in the US, and then China just does it for totally different reasons.

1:26:13Alex Colville: It's like, we don't need a virtual cell. We have one. We just test more things and faster and cheaper. And it's been revolutionary. Uh, yeah. So, I mean, I think we're seeing some cool efforts by the FDA right now to try to catch up and, and to try to do our own unique things. Uh, Marty McCary, uh, published, uh, in, in New England Journal of Medicine, some discourse yesterday about, uh, the kind of push to, instead of having two confirmatory trials, have one, these sorts of things. I think the U S is going to make a pretty dramatic shift, but ultimately, like, I think that impact has already been felt and it'll like continuously, you know, be nice, but I don't think it's going to have like Like, you know, the change that's going to happen is China has been flipping to outnumber the U.S.

1:26:58in terms of basic research. Right now, China has been innovating on development, but they haven't necessarily been innovating on target discovery to the same extent as the U.S. is still the leader in. That's going to flip. If you just look at the publications of the basic science and the amount of funding going into it and like where the top talent is, like they're also going to get to a point where a lot of the new targets, a lot of the exciting new discoveries are going to come out of China. so that i think is going to be the next wave that's going to hit the u.s is that realization and that's going to be a pretty stark and heavy hitting realization when that happens but but i think i think like the cool part of all the ai platforms and this sort of stuff is that like i don't think the upside of that you know we haven't seen it yet like it will hit but over the next five to ten years so i think like the the amount of dramatic change that can come from ai it's going to be a steeper curve in terms of impact but we just like haven't hit the inflection point yet versus like china has had its inflection point of impact there and like when you see

1:27:52Alex Colville: the chan zuckerberg initiative or i don't know any number of groups our institute um working on things like virtual cells uh the idea that we could simulate a lot of these processes and get get biology to the level of detail that we need to do this i do do you believe we're making i mean yeah does that excite you i mean i'm sure it excites you but like does it you know does it uh i don't know what excites me but the um to you yeah i mean i can't tell how real some of that stuff is or how um how real to take it yet yeah i mean i'd say like virtual cell i think was a misnomer like like what was his name andrew white from uh future house uh cso there he had a really cool blog post breaking down like if you were to model a virtual human cell how long would it take you uh and i believe his conclusion was to like model it for just like one day it would take you to like 2070 or something like that if you even with like extrapolating what data is going to do and you know what computability is going to change and so that was just like one cell for one day but so so the virtual cell thing i think a misnomer In terms of predictions on like you make a perturbation, here's what it causes at the level of the genome or like RNA gene expression.

1:29:15I think those models have been really exciting and really impactful. And I think that's kind of what people mean when they talk about virtual cell and what we're seeing right now. Protein-protein interactions, AI has come a long way. Obviously, AlphaFold has been completely revolutionary. And it's like a lot of things like, you know, we take it for granted so fast. It's like with Waymos, it's like, oh, onto the next thing. Like it's like completely revolutionary. And then like the next month you're like, okay, yeah, duh. Like what's next? So yeah, I think it's going to be insanely impactful, but I don't think we're going to be able to just model cells or whole organisms to the fidelity that we do to replace trials in the next 10 years.

1:29:55Alex Colville: I don't know if you can talk about this. What's the most batshit crazy idea someone has come to you with? You know, I mean, you can name names if you want, but I mean, we're, we're like starting to run up against stuff where, you know, you're talking about the right having concerns with like stem cells things. I mean, you know, I think you and I both know people who are growing headless bodies to harvest organs and, and, you know, I mean, there's going to be some big, um, big stuff to talk about. Yeah. I mean, what's, what's the craziest idea that comes to the top, top of mind? I'm supposed to top that one?

1:30:32Yeah.

1:30:33Alex Colville: I figure you must get the best, the best shit. Well, I mean, yeah. I mean, why not? Like why I'm destroying my own reputation. Like, you know, something I've always been fascinated by is, uh, there's a company that we funded out of Yale technology, not at age one, but my previous job with James called Becksword, you know, keeping brains alive outside the body. Um, we have an episode coming. Oh, okay. That's really, really exciting. So, you know, they had two nature papers showing that you can keep pig brains alive outside the body and entire pigs bring them back from cardiac arrest. And it's really cool.

1:31:12Something that I've always wondered about and been really excited about, is there a way to enable a kind of, you know, for somebody that has an incurable disease or a metastatic cancer, is there a way to, gosh, I don't want to say Futurama, but like, you know, keep a head alive without the body, right? We have these amazing ECMO machines that are in most emergency centers around the world that are a way to kind of replace certain organ functions. Certain people have been kept alive on ECMO without their own organ functions for like months, like six months, I think four to six months in some cases.

1:31:47You know, is there a world in the future in that like somebody that has no other options, metastatic cancer, it's all over their body. Is there a way that you could keep someone's head alive in Futurama style on like, you know, some sort of like a robot or, you know, mobile machine?

1:32:02Alex Colville: Would they be like alive or kind of coma until something better comes along? I think they could be alive. Like just chatting. Yeah. Yeah. I think like the lymph system is the hardest part to solve there. Yeah. But in terms of most, I mean, the problem, lungs, you're right. Like you'd have to do silent speech. But I think you could still have vision and taste and hearing. Um, but, but like, this is something that I think, um, I think, you know, I don't think it's like a 10 year thing, but, but I think like a 20 to 30 year thing, it like could be really interesting. It could be like a head eating stuff, but like, I don't think you'd eat stuff.

1:32:42Alex Colville: We used to be talking about tasting. I was like, how is this going to work, man? I just mean that like physically your tongue could like put it against your tongue and be like, oh, okay. I taste that. Yeah, I was about to ask you where that, it's like how you're not gaining weight, I guess. Yeah, you'd get nutrients shot up. I think you'd get like nutrients ejected in your system, right? So I mean, this is something I've long been obsessed with because it's just like horrific in terms of, you know, you know, somebody with metastatic cancer, they have no option. Stage four, like, I don't know how much time you've spent on the Facebook groups in terms of some of these rare terminal illnesses.

1:33:18It's horrifying. It'll like literally, you know, just gut wrenching to read these stories. I'm extremely excited about reversible cryopreservation as a way to kind of give people with a curable illness the chance to come back when they have a chance to have a cure for their illness. I think that's going to be, you know, one of the most traumatic impacts to medicine that's ever happened. You know, I wonder if there's some other option of, you know, people have been in like iron lungs for, I don't know, 40 years of their life happily. this seems even more improved state to me in terms of like being mobile and being able to integrate.

1:33:54I don't know. You know, it's a crazy sci-fi idea. Beside that, you know, all the things you mentioned.

1:33:58Alex Colville: You're like a head in a Waymo. He's just cruising, road tripping, man. Why not? Why not? Like, I think people should have the choice. You know, anybody that has a relative with a terminal on this, I think a lot of them would probably agree. They'd wish they, you know, that their mom or their dad or their sister or brother, you know, I think they want them to have the choice. I'm just laughing because I'm trying to think to my head. Oh, God, that's good. I mean, it is weird. I am extrapolating too far. But yeah, between Bexorg and I think Becoming, I mean, it feels like we're these perfusion devices that sort of replicate functions of the body.

1:34:43Alex Colville: Again, I think I'm going maybe too far. but you were hinting at it. Yeah. Like it seems like we're getting better at replicating these functions of the body. Um, and because we, yeah, I mean, Bexorg is the only one that I know of that can keep a brain going and becoming, doing all kinds of interesting stuff. Um, yeah, I don't think you are getting too ahead of yourself. Like it was the, you know, science magazine breakthrough of the year or two years ago, right. Or three years ago of, uh, synthetic embryos or integrated stem cell models where we can now, you know, instead of needing egg and sperm to create potentially, you know, a new embryo system to study.

1:35:17Uh, we have another way using embryonic stem cell technology. Uh, and I mean, that's revolutionary. Like I think, I think this world of, of having replacement, uh, parts and organs. I mean, right now it's pretty much only discussed by, uh, Xi Jinping and, uh, and Putin together, which is like probably the worst PR that the aging field could ever have to have those two talk about this. Um, I think it's like very easy to have a dystopian lens to the field. But at the end of the day, I think it's like, it's just going to bring so much quality of life and happiness. And like, I'm confident we will do it in a very equitable and distributable way.

1:35:55And yeah, I don't think it's that far off. I think it is time to dig into these sorts of things.

1:36:02Alex Colville: Well, you did it, man. You answered the call. That was fantastic. it is sort of a shame that Futurama has already depicted some of this things going around in my head were amazing that was fantastic well Alex thank you so much I guess people can find you on age one and on X and I'm sad that they've clamped down on your journalism though I mean really come on just send it to me send it to us we got you we got you um but yeah no man it's been so fun getting to know you you are you're just like encyclopedic on your knowledge of this stuff and and um it's rare to i'm gonna have a guest on in a couple weeks who i think of in a similar way around nuclear energy it's just it's rare to kind of find these people that i just really really trust on their subject matter and that can go so deep and, and, um, and, and so it's just, it's amazing.

1:37:05Alex Colville: And I'm glad everyone got to kind of meet you a little bit. Appreciate you having me on a bunch. Uh, and, uh, yeah, can't, so excited for the next decade and, uh, having you revealed to the world, the crazy stuff that we're going to do as a field. We're going to do it. We're going to do it. Um, okay. So everyone check out Alex. Thank you very much. And yeah, we will have, I don't know when this will air, but if it's out and you haven't seen it, you must watch our Bexorg episode. And I think I'm going to write a big, long feature story because it is probably easy. Definitely in my top five companies I've run across in years and probably like possibly one.

1:37:44Alex Colville: I don't know. I'm not going to rank them all off the top of my head, but amazing stuff. And with that, thank you all for listening and we will see you again soon. Love it. Thanks, man. We use Brex and they're amazing. oh do we'll say that shout out wait wait do you use brex we actually we use brex uh we most of our portfolio companies use brex and we fucking love them oh not supposed to say that part but they're great well this is good this is like this now this is like a real guest man i mean answering the call on the tough questions and then coming through with the totally natural brex shout out it's kind of like a war right now going on between the two of them with the acquisition.

1:38:27It's been like the talk of the town. So I'm like, you know, I had to make clear what side we were on. It's important.

1:38:32Alex Colville: It is a war. And we will only say Brex's name. We will not say who this war involves. Okay, well done. You get bonus points for that. Very well done. Thank you so much, Alex. Thanks, Ashley. the core memory podcast is hosted by me ashley vance and or kylie robison or both of us together it is produced by me and david nicholson our theme song is by james mercer and john sortland and the show is edited always by the john sortland thank you so much to brex and send cut send for all your support and thank you most of all to everybody for listening or watching we love you please leave us a like a review a subscribe all those tremendous things thank you and we'll see you again