Latest / Core Memory / The Realest Longevity Guru - EP 85 Alex Colville

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The Realest Longevity Guru - EP 85 Alex Colville · Core Memory

0:00
SPEAKER_00: There's a dude in the longevity and aging field who is,
0:03
SPEAKER_00: he's not super well known outside of those worlds.
0:07
SPEAKER_00: He's not a Brian Johnson.
0:09
SPEAKER_00: He's not a Andrew Huberman,
0:11
SPEAKER_00: but I would say he's actually maybe one of, if not the most influential.
0:17
SPEAKER_00: He's very quietly been investing money in this field for a long time.
0:23
SPEAKER_00: And he's a major player.
0:24
SPEAKER_00: His name is Alex Colville.
0:26
SPEAKER_00: He is the co-founder and general partner of age one, a venture capital firm.
0:32
SPEAKER_00: He's been investing even before he started running this firm.
0:36
SPEAKER_00: He's the guy that I kind of go to when there's a new startup or a new branch
0:42
SPEAKER_00: of science and I'm trying to reality check it.
0:45
SPEAKER_00: Alex has a PhD in genetics from Stanford.
0:49
SPEAKER_00: So he's got the cred, but he's also, he's just very even keeled.
0:52
SPEAKER_00: He's not religious about this stuff.
0:54
SPEAKER_00: He digs in incredibly deep.
0:57
SPEAKER_00: I just use him to ground myself and to try to figure out what
1:02
SPEAKER_00: to really spend my time on and care about.
1:06
SPEAKER_00: I think you will find him fascinating.
1:08
SPEAKER_00: We get into his life,
1:10
SPEAKER_00: his career,
1:11
SPEAKER_00: obviously,
1:12
SPEAKER_00: The science that he thinks is real and that you should be paying attention to.
1:18
SPEAKER_00: If you were going to trust anyone, I would put my reputation behind Alex.
1:24
SPEAKER_00: I think he's the real deal here and that you should listen to what he says.
1:28
SPEAKER_00: He's nice.
1:30
SPEAKER_00: He's enthusiastic.
1:31
SPEAKER_00: He's just a good dude.
1:32
SPEAKER_00: I will confess that we are friends and you can do with that what you will.
1:39
SPEAKER_00: Come listen.
1:40
SPEAKER_00: We're going to get into longevity land.
1:42
SPEAKER_00: I am Ashley Vance.
1:44
SPEAKER_00: This is Core Memory.
1:45
SPEAKER_00: Here we go.
2:01
SPEAKER_00: Welcome to the Core Memory Podcast.
2:03
SPEAKER_00: This is Ashley Vance.
2:05
SPEAKER_00: We are joined today by Alex Colville.
2:08
SPEAKER_00: Alex, hello.
2:09
SPEAKER_01: Hey, Ashley.
2:10
SPEAKER_01: How are you?
2:11
SPEAKER_01: I am doing fantastic.
2:12
SPEAKER_01: Good.
2:13
SPEAKER_00: You're always cheerful, I think.
2:17
SPEAKER_01: Yeah.
2:17
SPEAKER_01: Well, it's like curling is on right now.
2:19
SPEAKER_01: Like this is the best time of the year.
2:21
SPEAKER_00: Oh God.
2:22
SPEAKER_00: Cause you're from like Maine or New Hampshire or something, right?
2:24
SPEAKER_00: Which one is it?
2:25
SPEAKER_00: It's from Maine.
2:26
SPEAKER_00: From Maine.
2:26
SPEAKER_01: Yes.
2:27
SPEAKER_00: So did you actually do curling?
2:30
SPEAKER_01: No, but I'm just a super fan.
2:31
SPEAKER_01: Anything with ice, I'm like, this is the best thing ever.
2:33
SPEAKER_01: It's the most exciting sport.
2:34
SPEAKER_01: I don't know if you ever played like broomball or anything like that.
2:37
SPEAKER_00: No, I grew up warm places.
2:39
SPEAKER_00: I did not snow or ice.
2:41
SPEAKER_00: No, you did.
2:43
SPEAKER_01: Yeah.
2:44
SPEAKER_01: I mean, it's, it's, it's how you survive mentally through the season.
2:47
SPEAKER_01: So you gotta do what you gotta do.
2:49
SPEAKER_01: Do you, did you hockey?
2:51
SPEAKER_01: Um, all my friends did, but I was a big skier.
2:53
SPEAKER_01: Okay.
2:53
SPEAKER_01: So I grew up ski racing, competitive ski racing, um, was, was really into it.
2:58
SPEAKER_01: Uh, you know,
2:58
SPEAKER_01: which is particularly crazy when it's like,
3:01
SPEAKER_01: Minus five degrees and you're wearing a skin tight race suit
3:04
SPEAKER_01: and flying down literally a sheet of ice.
3:07
SPEAKER_01: It's a good time.
3:07
SPEAKER_00: Yeah.
3:08
SPEAKER_00: Yeah.
3:08
SPEAKER_00: I never did any of that.
3:09
SPEAKER_00: I've never, I've never skied.
3:10
SPEAKER_00: It's terrible.
3:12
SPEAKER_00: And we have ski week in California and all the kids go off and I feel like
3:16
SPEAKER_00: a terrible parent because I, I was never taught this.
3:19
SPEAKER_00: And so I could not teach my children.
3:22
SPEAKER_00: I've just abandoned them.
3:23
SPEAKER_01: I've abandoned my child.
3:24
SPEAKER_01: Yeah.
3:26
SPEAKER_00: Okay, Alex, dude,
3:29
SPEAKER_00: I feel like we've known each other three years, four years, something like that.
3:32
SPEAKER_00: I consider you my, I mean,
3:35
SPEAKER_00: I'm always bioteching and longevity reporting,
3:39
SPEAKER_00: but I consider you my source of truth,
3:43
SPEAKER_00: my kind of level setter for all these things that I encounter.
3:49
SPEAKER_00: And so I want people to know
3:53
SPEAKER_00: I find you very rational in a field that is not always specializing in rationality.
4:00
SPEAKER_00: And I appreciate that you go deep on the science.
4:03
SPEAKER_00: And yeah, I'll just be like, what do you think?
4:06
SPEAKER_00: This, that, that.
4:07
SPEAKER_00: And I feel like you're always just really even-keeled and knowledgeable
4:11
SPEAKER_00: on all things longevity, aging related.
4:16
SPEAKER_00: And so you're kind of my oracle on some of this stuff.
4:20
SPEAKER_01: I've been called the Switzerland of Aging.
4:23
SPEAKER_01: Okay.
4:25
SPEAKER_01: I think I want to branch beyond that, but I'm happy with that as a base.
4:28
SPEAKER_00: Well, throw some hot takes out here.
4:30
SPEAKER_00: Totally undermine what I said and this moniker.
4:35
SPEAKER_00: But you're also, you run Age One, which is a longevity aging related venture capital firm.
4:44
SPEAKER_00: You run
4:47
SPEAKER_00: We're young, are young.
4:48
SPEAKER_00: You used to manage a very large fund before that for,
4:53
SPEAKER_00: I don't know if we're supposed to name him or not,
4:55
SPEAKER_00: James Fickle, who's invested super deep in science, brain, aging, all that.
5:02
SPEAKER_00: And you,
5:03
SPEAKER_00: like at a very young age,
5:04
SPEAKER_00: in your 20s,
5:05
SPEAKER_00: were managing some ridiculous amount of money for him and where it was going
5:09
SPEAKER_00: to be directed.
5:10
SPEAKER_00: And you got a PhD at Stanford, I believe, in genetics?
5:15
SPEAKER_01: Genetics.
5:15
SPEAKER_01: Genetics.
5:16
SPEAKER_01: Yes.
5:16
SPEAKER_00: Um, so you kind of, you know, I hear Stanford's good.
5:21
SPEAKER_00: I think you probably know what you're talking about on some of this stuff.
5:25
SPEAKER_00: And so, so, but these days are, are kind of a venture capitalist.
5:29
SPEAKER_01: Yeah, exactly.
5:30
SPEAKER_01: I mean, it's,
5:31
SPEAKER_01: it's a common theme,
5:31
SPEAKER_01: like from,
5:32
SPEAKER_01: you know,
5:32
SPEAKER_01: you're describing like growing up on ice and in Maine and Maine's actually
5:36
SPEAKER_01: the oldest state in the country.
5:38
SPEAKER_01: Uh, it's like by, by median age of the population.
5:41
SPEAKER_01: This is news.
5:42
SPEAKER_01: Okay.
5:45
SPEAKER_01: I have to fact check this on Chappie WBC Lifetime.
5:48
SPEAKER_01: Yeah, so oldest state by immediate age of the population.
5:51
SPEAKER_01: And I think that surprised a lot of people because they're like, oh, everyone thinks of Florida.
5:54
SPEAKER_01: No, it's actually Maine.
5:55
SPEAKER_01: And so you just grow up and you're surrounded by people that have their quality
5:59
SPEAKER_01: of life reduced by aging.
6:01
SPEAKER_01: And, you know,
6:03
SPEAKER_01: that was just pretty shocking to me because I was like, wow, that seems suboptimal.
6:09
SPEAKER_01: And then everyone's kind of like, oh, Yeah, that's that's life.
6:11
SPEAKER_01: Like this is natural part of life.
6:14
SPEAKER_01: And so I was kind of like growing up being like, wow,
6:16
SPEAKER_01: like the villain is the vibes of like most people just being like,
6:22
SPEAKER_01: oh, yeah, decline with age is natural.
6:25
SPEAKER_01: And then when they actually experience that decline with age,
6:28
SPEAKER_01: everyone's like, oh, my gosh, this is like the worst thing ever.
6:30
SPEAKER_01: Yeah.
6:31
SPEAKER_01: And that like premise has been like my whole life with all the stops
6:35
SPEAKER_01: that you described is like trying to shift that vibe.
6:39
SPEAKER_00: Do the young people just flee Maine, or are people retiring there?
6:43
SPEAKER_00: I mean, that seems like a crazy place.
6:45
SPEAKER_00: I mean, it's very pretty, I'm sure, but...
6:47
SPEAKER_00: Yeah, it's both.
6:50
SPEAKER_01: It's like, it's both of those are combining to cause it to be the oldest by median age.
6:55
SPEAKER_01: Because most of the employers, like,
6:56
SPEAKER_01: you know,
6:57
SPEAKER_01: there was Fairchild Semiconductor that's had a couple of acquisitions
7:00
SPEAKER_01: and Texas Instruments.
7:01
SPEAKER_01: But then the monetary industries are like lobstering and logging,
7:04
SPEAKER_01: paper mills, you know, blueberries and potatoes.
7:09
SPEAKER_01: There's not a lot of young, exciting industries.
7:12
SPEAKER_01: It's changing and pretty rapidly.
7:14
SPEAKER_01: Like Portland has become a really cool place.
7:17
SPEAKER_01: Uh, but yeah,
7:18
SPEAKER_01: just by and large,
7:18
SPEAKER_01: there hasn't been the industry to keep young people around and
7:20
SPEAKER_01: then like older people love it because it's beautiful.
7:22
SPEAKER_01: It's serene.
7:23
SPEAKER_01: You don't have to, to deal with noise and pollution and yeah, it's just beautiful nature.
7:28
SPEAKER_00: But okay.
7:29
SPEAKER_00: But you were legit, um,
7:32
SPEAKER_00: noticing this as like a teenager and, and just got interested in aging as a result.
7:37
SPEAKER_01: Yeah.
7:38
SPEAKER_01: Yeah.
7:38
SPEAKER_01: I mean, like in part,
7:39
SPEAKER_01: the thing I think that happens to everybody at some point,
7:41
SPEAKER_01: uh, it's like had grandparents get cancer.
7:44
SPEAKER_01: And started asking one why it happened, like how we get cancer, why it comes to be.
7:49
SPEAKER_01: And then just was really kind of mad at the answers.
7:51
SPEAKER_01: I'm like, well, that seems silly that we just like accept this as status quo.
7:56
SPEAKER_01: And then from there, there was a really pivotal journalist that I am forever grateful for.
8:01
SPEAKER_01: That wrote the challenge of our age.
8:04
SPEAKER_00: Okay.
8:04
SPEAKER_01: So it was like a 10 part series in the Portland Press Herald about the challenge
8:08
SPEAKER_01: of aging and the demographic shifts and the burden on caregivers.
8:11
SPEAKER_00: So this is a local journalist.
8:13
SPEAKER_01: Local journalist.
8:14
SPEAKER_01: Yes.
8:14
SPEAKER_00: There we go.
8:15
SPEAKER_00: Okay.
8:16
SPEAKER_01: Yeah.
8:16
SPEAKER_01: Love to see it.
8:17
SPEAKER_01: And this like, I don't know, it was just like perfectly hit my brain.
8:21
SPEAKER_01: At that point, actually, I was kind of in undergrad.
8:26
SPEAKER_01: So it was kind of like came out like at the end of high school and in undergrad.
8:30
SPEAKER_01: And it just like hit me like a ton of bricks.
8:33
SPEAKER_01: And I was like, wow, okay, I need to go back to this.
8:35
SPEAKER_01: Like, cause I,
8:35
SPEAKER_01: at the time I was really interested in cancer because
8:37
SPEAKER_01: the perfect personal connection, that's what I was grappling around.
8:41
SPEAKER_01: And then the aging thing really hit.
8:43
SPEAKER_01: And then I was like,
8:43
SPEAKER_01: wow, okay, there's like so many other things being caused by aging that a problem.
8:47
SPEAKER_01: Like, how can we get to that root cause?
8:49
SPEAKER_01: Started just Googling endlessly, like, what is aging?
8:52
SPEAKER_01: What causes it?
8:53
SPEAKER_01: What drives it?
8:53
SPEAKER_01: How did it evolve?
8:54
SPEAKER_01: All these sorts of things.
8:56
SPEAKER_01: And that pretty much led me down the path now.
8:59
SPEAKER_00: But like, instead of I would think maybe become a doctor, but no, you were more root-causing.
9:07
SPEAKER_01: Yeah, it was more root-causing.
9:08
SPEAKER_01: And during undergrad, I worked with David Sinclair at Harvard Medical School.
9:13
SPEAKER_01: So he's famous for his New York Times bestseller, Lifespan.
9:17
SPEAKER_00: Slightly controversial figure.
9:19
SPEAKER_00: Yes.
9:21
SPEAKER_01: Absolutely.
9:21
SPEAKER_00: Not too crazy, but a little.
9:22
SPEAKER_00: Yeah.
9:23
SPEAKER_01: Yeah, he's one of these pioneers that has like totally,
9:27
SPEAKER_01: you know,
9:29
SPEAKER_01: I think he probably can say that more people are in the field because of him
9:33
SPEAKER_01: than anybody else.
9:34
SPEAKER_01: You know, maybe Brian Johnson can compete with him now for that claim.
9:38
SPEAKER_01: But he was a real pioneer in terms of putting this on the map
9:41
SPEAKER_01: and getting everybody excited about what's possible.
9:43
SPEAKER_01: And I think naturally in that role,
9:45
SPEAKER_01: you can sometimes get a little bit too excited about what's possible or
9:48
SPEAKER_01: the timelines.
9:49
SPEAKER_01: And that may have happened along the way at various points.
9:53
SPEAKER_01: But yeah, I certainly brought more people in the field than anybody.
9:55
SPEAKER_00: I've always wondered if he kind of hates me just because he was doing this and then.
10:01
SPEAKER_00: Then I showed the spotlight on Brian and then I feel like he overtook David a bit
10:06
SPEAKER_00: on all this stuff.
10:07
SPEAKER_00: Yeah.
10:08
SPEAKER_00: I've never talked to David for some reason.
10:10
SPEAKER_00: He's like one of the few people.
10:12
SPEAKER_00: Yeah.
10:14
SPEAKER_00: I've been curious
10:14
SPEAKER_01: about that.
10:16
SPEAKER_00: Okay.
10:17
SPEAKER_00: Well, this all makes sense.
10:19
SPEAKER_00: You've got an axolotl on your shirt.
10:21
SPEAKER_01: Yeah.
10:22
SPEAKER_00: Because...
10:24
SPEAKER_01: Yeah, I mean, I'll say it's a pretty regular basis that I have axolotl attire on.
10:28
SPEAKER_01: This was a little bit special in that not only it's the shirt,
10:31
SPEAKER_01: but I actually brought socks, which I'm quite proud of.
10:35
SPEAKER_01: I may like rip out the headset here, but I
10:37
SPEAKER_00: feel like they must be
10:39
SPEAKER_01: demoed.
10:40
SPEAKER_00: Oh, jeez, you're not joking around.
10:42
SPEAKER_00: Wait, let me see if we can see.
10:43
SPEAKER_00: Yes, we can see this on the camera.
10:45
SPEAKER_00: Yeah, both.
10:45
SPEAKER_00: Okay, that's great.
10:46
SPEAKER_00: Wow.
10:47
SPEAKER_00: So for people who are just listening,
10:49
SPEAKER_00: these are not, I mean, I guess all socks are three-dimensional.
10:55
SPEAKER_00: These are very three-dimensional socks.
10:57
SPEAKER_00: They have an actual axolotl growing out of the edge.
11:01
SPEAKER_01: Yeah, they're little crocheted axolotls that are hugging your legs.
11:06
SPEAKER_01: My mom got me them for Christmas.
11:08
SPEAKER_01: Okay.
11:08
SPEAKER_00: But why the axolotl?
11:10
SPEAKER_01: Why the axolotl?
11:11
SPEAKER_01: You know,
11:12
SPEAKER_01: in this frustration with everyone's kind of complacency about aging and,
11:16
SPEAKER_01: you know, I think a big part of the problem is showing that something can be done.
11:20
SPEAKER_01: I think the world is going to continue to be very complacent until you're able
11:24
SPEAKER_01: to show people like, oh, the aging field has had like one win.
11:27
SPEAKER_01: Like we can modify aging.
11:29
SPEAKER_01: We could delay aging, prevent aging, could reverse aspects of aging.
11:32
SPEAKER_01: If we can do that like credibly,
11:35
SPEAKER_01: I think everyone's going to pile in and it's going to be one of the biggest,
11:37
SPEAKER_01: best transitions ever.
11:39
SPEAKER_01: But until that happens, We're going to struggle to do that.
11:42
SPEAKER_01: So, I mean,
11:42
SPEAKER_01: why axolotls,
11:43
SPEAKER_01: like a lot of the coolest stories ever in medicine have been catalyzed
11:48
SPEAKER_01: by discoveries from animals.
11:50
SPEAKER_01: So famously with GLP-1s came in part from the Guillemots.
11:58
SPEAKER_01: And there's many examples of this through the history of medicine
12:04
SPEAKER_01: because it turns out that millions and millions of years
12:08
SPEAKER_01: of evolution can do things biologically that it would take PhD students
12:13
SPEAKER_01: a little bit longer.
12:16
SPEAKER_00: I've known this and I've forgotten it.
12:18
SPEAKER_00: What's the axolotl famous for in this field?
12:21
SPEAKER_01: Uh, regeneration.
12:22
SPEAKER_01: So it can regenerate almost every organ in its body,
12:25
SPEAKER_01: uh, can regenerate parts of its spinal cord, which I find particularly really crazy.
12:30
SPEAKER_01: Uh, there's like the lamprey eel can regenerate a whole centimeter of a spinal cord,
12:35
SPEAKER_01: like complete transection.
12:37
SPEAKER_01: Axolotl can't quite do that,
12:38
SPEAKER_01: but they're,
12:38
SPEAKER_01: they're really cool and they can regenerate parts of their brain,
12:41
SPEAKER_01: parts of their heart.
12:43
SPEAKER_01: Uh, remarkable entire limbs is like the most famous one.
12:46
SPEAKER_00: And do they live really long?
12:51
SPEAKER_01: Let me put on my Switzerland of Aging hat.
12:55
SPEAKER_01: It's one of these that people will refer to them as like,
12:57
SPEAKER_01: oh, they're really resistant to aging and these sorts of things.
13:02
SPEAKER_01: And I think that is true.
13:04
SPEAKER_01: They have some varieties of what we call negligible senescence,
13:08
SPEAKER_01: where they don't seem to accelerate in their rate of mortality through time.
13:14
SPEAKER_01: But they absolutely do age.
13:15
SPEAKER_01: And I've witnessed it firsthand because I was very curious about the same question.
13:18
SPEAKER_01: And you can see that They no longer regenerate as good as they once could.
13:22
SPEAKER_01: And they just kind of, there is some visible kind of looks around aging.
13:29
SPEAKER_01: But like,
13:30
SPEAKER_01: you know,
13:30
SPEAKER_01: the part of why they're most interesting about aging is they show you
13:33
SPEAKER_01: that regeneration is possible.
13:35
SPEAKER_01: And regeneration can be possible in humans.
13:37
SPEAKER_01: Like we regenerate over 70% of our liver.
13:41
SPEAKER_01: You know, if we took out 70% of liver, it'll grow back.
13:43
SPEAKER_01: And in a remarkably short time period.
13:46
SPEAKER_01: And so I just think this notion is really powerful and fundamental of,
13:50
SPEAKER_01: you know,
13:51
SPEAKER_01: one day being able to enable a whole other level of regeneration in humans
13:55
SPEAKER_01: that our genomes may be capable of doing if they're modified or controlled in
13:59
SPEAKER_01: the right way.
14:00
SPEAKER_00: Yeah, I mean, they're all, well, okay, so I get it.
14:03
SPEAKER_00: Yeah, I mean, there's all these signs all over the place that things...
14:08
SPEAKER_00: People might think are fantastic and impossible really are possible.
14:11
SPEAKER_00: And even I remember I was doing a story,
14:14
SPEAKER_00: which on a topic we're going to get into on kind of this idea
14:18
SPEAKER_00: of partial reprogramming, taking yourselves back to a sort of peak state.
14:26
SPEAKER_00: And yeah, I was with the guys over at Retro Bio.
14:30
SPEAKER_00: And I think some of this work came out of Vadim's lab at Harvard,
14:34
SPEAKER_00: but just showing that in the womb, Um, we,
14:38
SPEAKER_00: it's like obvious in hindsight,
14:39
SPEAKER_00: or I guess we always like intuitively knew this happened,
14:41
SPEAKER_00: but I don't think we'd witnessed the process that like when you have two old,
14:45
SPEAKER_00: oldish people make a baby,
14:47
SPEAKER_00: the baby doesn't come with all the baggage, you know, from their genes.
14:51
SPEAKER_00: There is this reset moment that takes place.
14:54
SPEAKER_00: Right.
14:54
SPEAKER_00: And, and if you,
14:55
SPEAKER_00: so we know the body does this and it kind of goes back to this Pure state so that
15:00
SPEAKER_00: the baby has a fresh start in life.
15:03
SPEAKER_00: And so like, you know, and now we're getting ways to kind of program that in a little bit.
15:08
SPEAKER_00: So yeah, I mean, there's evidence in nature that amazing things are possible.
15:12
SPEAKER_01: I really appreciate you calling attention to old people reproducing.
15:16
SPEAKER_00: More attention needs to be brought to this subject.
15:18
SPEAKER_00: I feel very passionate about that.
15:20
SPEAKER_01: But on a serious note, yeah, I'm obsessed with the phenomenon that you're describing.
15:24
SPEAKER_01: It is the reason,
15:25
SPEAKER_01: I think,
15:25
SPEAKER_01: that Jeff Bezos and Yuri Milner and many of these other figures put,
15:30
SPEAKER_01: and even, I think, Bill Gates, put very significant amounts of money into...
15:35
SPEAKER_01: Altos Labs, right?
15:36
SPEAKER_01: $3 billion seed round, pretty much, tranched out, but still.
15:41
SPEAKER_01: I think it's this notion of,
15:43
SPEAKER_01: and where Klauser has talked about this,
15:45
SPEAKER_01: this notion of like a reset and that like,
15:47
SPEAKER_01: you know,
15:47
SPEAKER_01: I think a lot of people think,
15:48
SPEAKER_01: oh, like rejuvenation or turning back the clock is insane, can't be done.
15:53
SPEAKER_01: And yet,
15:54
SPEAKER_01: Presumably it's an experiment that humans have done millions of times
15:58
SPEAKER_01: and other animals have done many, many times.
16:00
SPEAKER_01: Uh, we don't really know if it's actually rejuvenation and turning the clock back.
16:04
SPEAKER_01: It could be some sort of like a selection of the healthiest cells.
16:07
SPEAKER_00: But there's some,
16:08
SPEAKER_00: all this degradation and junk on the end of
16:11
SPEAKER_00: the parent's DNA is getting cleaved off somewhere.
16:16
SPEAKER_00: Right?
16:16
SPEAKER_00: I mean, I mean, that's, that's,
16:18
SPEAKER_00: that's you, there is this moment where you're getting rid of this, this baggage.
16:23
SPEAKER_00: You're looking at me,
16:26
SPEAKER_00: you don't have to pretend like I know what I'm talking about.
16:28
SPEAKER_00: You can fix it.
16:32
SPEAKER_01: You're mostly right.
16:33
SPEAKER_01: You're mostly right.
16:35
SPEAKER_01: The words,
16:35
SPEAKER_01: you know,
16:35
SPEAKER_01: cleaved off, you know, it's like, yeah, I guess you're describing telomeres.
16:39
SPEAKER_01: I'm trying to decode, be the decoder here.
16:42
SPEAKER_00: No, I just mean you have parents who have had their,
16:46
SPEAKER_00: they've accumulated damage to their DNA over the years and
16:50
SPEAKER_00: that is somehow getting erased in some sense.
16:53
SPEAKER_01: Yeah, precisely.
16:55
SPEAKER_01: But the reason I hesitate
16:56
SPEAKER_01: a bit is I think people really haven't done very comprehensive research or analyses
17:02
SPEAKER_01: on aged gametes, so sperm and egg cells in humans.
17:07
SPEAKER_01: I would really love to see like a much deeper analysis
17:10
SPEAKER_01: of this done showing like here's the extent of age that you can go and
17:13
SPEAKER_01: then it's reversed back when you actually...
17:16
SPEAKER_01: Have a baby or fertilize an embryo.
17:18
SPEAKER_01: And I just haven't seen it to that extent.
17:21
SPEAKER_01: But what you're describing is, yeah, absolutely correct.
17:25
SPEAKER_01: You would really guess that there's been a ton of damage that has accumulated based
17:29
SPEAKER_01: on what we know about the rest of the body that would have to be reset through
17:33
SPEAKER_01: the process.
17:33
SPEAKER_01: And it's like a really dramatic, intricate reset of the entire methylation patterns of DNA.
17:40
SPEAKER_01: So just like really dramatic events,
17:42
SPEAKER_01: which also would kind of go with this likely scenario that there's
17:46
SPEAKER_01: a rejuvenation event.
17:47
SPEAKER_01: But it's one of the most understudied phenomenon in the entire aging field,
17:50
SPEAKER_01: in my opinion, with like the highest upside.
17:51
SPEAKER_00: Because it's hard to study.
17:53
SPEAKER_00: But you're proving my point.
17:55
SPEAKER_00: See, you're a longevity VC.
17:58
SPEAKER_00: You should just be talking your book.
18:01
SPEAKER_00: You should just be hyping all this up.
18:02
SPEAKER_00: And here you are, you know, you're looking for evidence.
18:06
SPEAKER_00: This is my whole point.
18:08
SPEAKER_00: People can trust you.
18:10
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18:12
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19:17
SPEAKER_00: I kind of want to get you to walk through a few things and tell us what's real,
19:22
SPEAKER_00: what's not, what's exciting, what's not.
19:25
SPEAKER_00: I mean, super broadly.
19:27
SPEAKER_00: People have been hunting for a fountain of youth for literally thousands of years.
19:33
SPEAKER_00: So the aging field is kind of like hard to tell where you want to start on defining things.
19:38
SPEAKER_00: But, you know,
19:39
SPEAKER_00: I would say kind of like,
19:41
SPEAKER_00: I don't know,
19:42
SPEAKER_00: 20 years ago,
19:43
SPEAKER_00: I remember,
19:43
SPEAKER_00: you know, there was this guy, Aubrey de Grey, I felt like was kind of elevating.
19:49
SPEAKER_00: Not quite mainstream,
19:50
SPEAKER_00: but like in tech circles,
19:52
SPEAKER_00: this idea of looking for things that you could go to repair the body
19:57
SPEAKER_00: and clear out cells that senescent, like these dysfunctional cells.
20:03
SPEAKER_00: Anyway, he was kind of like starting to get this discourse a little bit more,
20:08
SPEAKER_00: at least in my world of tech people.
20:11
SPEAKER_00: And then we've gone through these weird...
20:14
SPEAKER_00: Ups and downs because,
20:15
SPEAKER_00: you know,
20:15
SPEAKER_00: there's like science and then obviously there's all the,
20:17
SPEAKER_00: you know, pills and everybody's preaching this and that.
20:21
SPEAKER_00: But then now,
20:22
SPEAKER_00: you know,
20:22
SPEAKER_00: I feel like we're in this kind of new era that's interesting,
20:25
SPEAKER_00: which is, yeah,
20:26
SPEAKER_00: you've sort of got people like Brian Johnson who,
20:30
SPEAKER_00: whatever, I mean,
20:32
SPEAKER_00: folks are opinionated on him,
20:35
SPEAKER_00: but putting This stuff very much in the mainstream discussion.
20:40
SPEAKER_00: And then you also have just, for me,
20:42
SPEAKER_00: at least this is my,
20:43
SPEAKER_00: my feelings, like real biotech companies doing like, it's a very interesting time.
20:48
SPEAKER_00: You know, people are throwing billions of dollars around at stuff that may or may not work.
20:52
SPEAKER_00: And, and, but like, this is not fringe anymore, you know, to, to a large degree.
20:57
SPEAKER_00: And then things like GLP,
21:00
SPEAKER_00: GLP ones that couldn't be bigger and more obvious as,
21:03
SPEAKER_00: as like multi-billion dollar industries and, and.
21:07
SPEAKER_00: Apparently helping people out like on a quite large scale.
21:11
SPEAKER_00: So I guess my thrust is like an exciting time.
21:13
SPEAKER_00: I was kind of curious how you would characterize it in terms
21:17
SPEAKER_00: of hype versus real versus like for the general person in the public,
21:24
SPEAKER_00: you know,
21:24
SPEAKER_00: how excited they should be in this moment or if we're still actually in
21:28
SPEAKER_00: the overhyped, you know, maniacal phase of this.
21:32
SPEAKER_01: Yeah.
21:33
SPEAKER_01: And I'll admit,
21:33
SPEAKER_01: I got things very wrong in terms of mentally how I thought things would play out.
21:38
SPEAKER_01: So like back in 2014,
21:40
SPEAKER_01: when I started getting,
21:41
SPEAKER_01: you know,
21:42
SPEAKER_01: doing research in the field,
21:43
SPEAKER_01: getting really involved in it,
21:44
SPEAKER_01: the way I kind
21:44
SPEAKER_01: of mentally thought things would play out is like you'd have these technological
21:48
SPEAKER_01: advances and They'd hit humans and then that's when it would go really mainstream
21:52
SPEAKER_01: in terms of the interest around the space.
21:55
SPEAKER_01: And then what ended up happening was the technology is still on the way to do that
21:59
SPEAKER_01: and has made really dramatic leaps on the way to do that.
22:01
SPEAKER_01: But that wasn't what catalyzed like people's...
22:05
SPEAKER_01: Level of knowledge or like excitement broadly about the space.
22:09
SPEAKER_01: It was really like the rise of the influencers and podcasters.
22:14
SPEAKER_01: And it was like, you know, David with his book, Lifespan.
22:16
SPEAKER_01: It was Huberman and Atiyah and Brian Johnson.
22:20
SPEAKER_01: And that's really what like,
22:21
SPEAKER_01: just like,
22:22
SPEAKER_01: Thrusted this notion of like aging and longevity totally on people's,
22:26
SPEAKER_01: you know, the front of their brains.
22:28
SPEAKER_01: But I think it was almost more in a way of like here, you know, you need to exercise, right?
22:31
SPEAKER_01: You need to sleep, right?
22:32
SPEAKER_01: You need to be really careful about your habits and doing the right things.
22:37
SPEAKER_01: Which like everyone knew.
22:38
SPEAKER_01: Which everything, everybody already knew.
22:40
SPEAKER_01: That's what blew my mind about it.
22:41
SPEAKER_01: I was like,
22:42
SPEAKER_01: people just like find it mentally satisfying to like tell you
22:44
SPEAKER_01: the things you should be doing but are not doing.
22:47
SPEAKER_00: Well, I mean,
22:47
SPEAKER_00: they can tell you in like one minute that you should exercise and sleep
22:50
SPEAKER_00: and eat right.
22:52
SPEAKER_00: But if you have a five-hour podcast, I guess it really drives Des Moines home.
22:58
SPEAKER_00: I don't know.
22:59
SPEAKER_00: Yeah.
22:59
SPEAKER_01: Yeah.
23:00
SPEAKER_01: Buckle up, everybody.
23:01
SPEAKER_01: We're going.
23:01
SPEAKER_01: Let's go in the distance, this podcast.
23:03
SPEAKER_01: No, like to me, what it has screamed is people want control.
23:09
SPEAKER_01: And that's what I've learned from the biohacking peptides movement as well, Chinese peptides.
23:13
SPEAKER_01: It's like everybody is desperately looking for control.
23:16
SPEAKER_01: They're dissatisfied with the pace of randomized controlled trials and evidence
23:22
SPEAKER_01: and technology to get there.
23:23
SPEAKER_01: And so they're going to,
23:24
SPEAKER_01: you know,
23:25
SPEAKER_01: it's just that much pent up demand for control over our decline with age
23:29
SPEAKER_01: that people are experimenting, they're testing everything.
23:31
SPEAKER_01: And yeah,
23:32
SPEAKER_01: it's just like that to me just screams there's a massive demand for these things
23:37
SPEAKER_01: that can control the way we decline with age or our biology of aging.
23:42
SPEAKER_01: And I think that,
23:43
SPEAKER_01: you know,
23:44
SPEAKER_01: it's the boring stuff getting in the way of like the controlled trials,
23:47
SPEAKER_01: the evidence generation,
23:49
SPEAKER_01: the manufacturing, all these sorts of things that are boring to a lot of people.
23:53
SPEAKER_01: But that's what's going to catalyze this like whole next era.
23:56
SPEAKER_01: There's an era of excitement and joy about the field.
24:00
SPEAKER_01: So your question of if we're hyped or not,
24:03
SPEAKER_01: it's just like the AI field or any other frontier field or crypto.
24:06
SPEAKER_01: You go through waves.
24:08
SPEAKER_01: You go through a wave where people get really excited about it and maybe that wave
24:11
SPEAKER_01: of excitement got a little bit ahead of the technology and then it goes down and up
24:15
SPEAKER_01: and up and up.
24:16
SPEAKER_01: There's like zero doubt in my mind the aging field is going to be one of
24:19
SPEAKER_01: the most impactful technologies that's ever existed in the history of humanity.
24:23
SPEAKER_01: And are we fully there yet?
24:25
SPEAKER_01: No, but will we make huge leaps there over the next five and 10 years?
24:29
SPEAKER_01: Absolutely.
24:30
SPEAKER_00: So what did you see in 2014 that made you excited?
24:33
SPEAKER_01: Yeah, in 2014, I mean, honestly, I was so out there.
24:38
SPEAKER_01: It was just like that people were working on the problem.
24:40
SPEAKER_01: That to me blew my mind.
24:42
SPEAKER_01: I was like, oh, this is so cool that there's like a research community.
24:45
SPEAKER_01: It was very small,
24:46
SPEAKER_01: but there's,
24:47
SPEAKER_01: you know, a handful of these leading pioneer professors that were working on this.
24:51
SPEAKER_01: And, you know,
24:52
SPEAKER_01: technology wise,
24:53
SPEAKER_01: what can be really excited is it was like,
24:56
SPEAKER_01: you know,
24:56
SPEAKER_01: the work that had been done in the 1980s and early 2000s just showing
25:00
SPEAKER_01: that aging was modifiable.
25:01
SPEAKER_00: Okay.
25:02
SPEAKER_01: This is,
25:02
SPEAKER_01: you know,
25:03
SPEAKER_01: when we talk about that, like,
25:04
SPEAKER_01: you know,
25:04
SPEAKER_01: the villain is vibes of like people,
25:06
SPEAKER_01: you know, being kind of complacent about decline with age.
25:09
SPEAKER_01: It's because no one thinks it's modifiable.
25:11
SPEAKER_01: And so then when it hits them, they're like, oh my God, this is terrible.
25:14
SPEAKER_01: This is horrible.
25:16
SPEAKER_01: But if people believed it was modifiable, they would do something before.
25:19
SPEAKER_01: And 1980s,
25:21
SPEAKER_01: there was Professor Tom Johnson and one of his colleagues,
25:26
SPEAKER_01: Michael Glass,
25:26
SPEAKER_01: they published a paper showing that you could mutate one gene in worms at age one
25:31
SPEAKER_01: and actually increase lifespan by 40 to 110%.
25:36
SPEAKER_01: Eventually,
25:37
SPEAKER_01: that same gene was shown to be able to be mutated in 2008 with a kind
25:41
SPEAKER_01: of complete mutation that could 10x lifespan in worms.
25:45
SPEAKER_01: Literally, we've been able to like 10x lifespan of an organism.
25:49
SPEAKER_01: Aging is modifiable.
25:51
SPEAKER_00: Yeah, but although this is one of the most frustrating things.
25:55
SPEAKER_00: I feel like we've made worms live,
25:56
SPEAKER_00: you know, until infinity and, you know, calorie restriction, all this stuff.
26:02
SPEAKER_00: And then, yeah, and then it just, it doesn't seem to replicate.
26:06
SPEAKER_00: But you're saying the sign is there.
26:09
SPEAKER_01: This replicates.
26:10
SPEAKER_01: Yeah, yeah, yeah.
26:11
SPEAKER_01: I'll be very clear.
26:11
SPEAKER_00: This is a replication.
26:14
SPEAKER_01: This finding has replicated over the past 50 years.
26:16
SPEAKER_00: I'm sorry.
26:16
SPEAKER_00: I didn't mean replicate.
26:17
SPEAKER_00: I mean, translate to humans.
26:18
SPEAKER_00: Yes.
26:19
SPEAKER_01: Yeah, yeah, yeah, yeah.
26:20
SPEAKER_01: I mean, this is, you've covered Celine Hallua and Loyal's story really closely.
26:26
SPEAKER_01: Yeah.
26:27
SPEAKER_01: They're going to be a big test of this hypothesis and how it translates.
26:30
SPEAKER_00: So Loyal's doing therapies for dogs, for people who haven't.
26:34
SPEAKER_00: Seeing artwork.
26:36
SPEAKER_00: Yeah.
26:38
SPEAKER_00: Right.
26:38
SPEAKER_00: So going to a new class of animal to see how this plays out.
26:43
SPEAKER_01: Yeah.
26:44
SPEAKER_01: So loyal, yeah,
26:45
SPEAKER_01: targeting lifespan and healthy lifespan in dogs and developing therapeutics to do
26:50
SPEAKER_01: that and eventually shifting to humans.
26:53
SPEAKER_01: And they've made some really exciting progress with the FDA,
26:55
SPEAKER_01: as you've covered,
26:56
SPEAKER_01: in terms of the FDA is now on board with them doing this,
26:59
SPEAKER_01: which is really cool for the field.
27:02
SPEAKER_01: But a part of the interventions that they're testing...
27:05
SPEAKER_01: are related to the same exact pathway that in the 1980s was the first to show
27:10
SPEAKER_01: that aging was modifiable.
27:11
SPEAKER_01: So when I mentioned age one- Which is the name of your firm?
27:14
SPEAKER_00: Which is the name of our firm, yeah.
27:17
SPEAKER_01: It's a nod to, well, it's kind of related to PI3K biology in humans.
27:22
SPEAKER_01: And so this is a member of insulin growth factor like signaling.
27:26
SPEAKER_01: So IGF-1 like signaling insulin and IGF-1 signaling pathway.
27:30
SPEAKER_01: And one of Loyal's pipeline programs is going after the same biology and dogs.
27:35
SPEAKER_00: Gotcha.
27:36
SPEAKER_01: And so when you say it hasn't translated, well,
27:38
SPEAKER_01: it's taken us 50 years because,
27:40
SPEAKER_01: you know,
27:40
SPEAKER_01: the world was waiting for people badass enough like Celine to step up
27:44
SPEAKER_01: and be really creative and pragmatic about how to translate it.
27:47
SPEAKER_01: But yeah, we're starting to go on the path of translating these.
27:51
SPEAKER_00: Yeah, that's always weird to me.
27:52
SPEAKER_00: It just seems like there would obviously be so much money in the field.
27:56
SPEAKER_00: So yeah, it's like when you came along...
28:01
SPEAKER_00: First kind of investing some of James' money and then partnering
28:05
SPEAKER_00: with Laura Deming really closely.
28:07
SPEAKER_00: And, you know,
28:07
SPEAKER_00: she was a pioneer in all of this,
28:09
SPEAKER_00: raising one of the biggest VC funds around this field.
28:14
SPEAKER_00: I mean, it wasn't very long.
28:15
SPEAKER_00: Yeah, this just strikes me as nuts.
28:16
SPEAKER_00: I mean, I felt like this was a thing Silicon Valley would be chasing with billions of dollars.
28:24
SPEAKER_00: But I guess it was just seen as too fringe or just too impossible or something.
28:34
SPEAKER_01: It is insane to me as well,
28:36
SPEAKER_01: but like you get into the nitty gritty of translating these things and
28:39
SPEAKER_01: then you quickly understand why it has taken so long to happen.
28:42
SPEAKER_01: It's expensive.
28:43
SPEAKER_00: It takes a long time.
28:44
SPEAKER_01: Human trials are hundreds of millions of dollars sometimes depending on You know,
28:48
SPEAKER_01: your size and scope.
28:49
SPEAKER_01: And you're just dealing with really complicated operations and logistics problems and just bets.
28:56
SPEAKER_01: You know,
28:56
SPEAKER_01: like you learn in therapeutics,
28:57
SPEAKER_01: it's like so hard to go zero to one that everything kind of falls to the Yeah.
29:03
SPEAKER_01: Yeah.
29:03
SPEAKER_01: Yeah.
29:04
SPEAKER_01: Yeah.
29:17
SPEAKER_01: Stuff of like an established thing.
29:20
SPEAKER_01: Uh, and it's just very hard to go and do something radically different than that
29:24
SPEAKER_01: and go out there.
29:24
SPEAKER_01: And so, but,
29:25
SPEAKER_01: but I think the bottleneck has been like,
29:27
SPEAKER_01: there's, hasn't been the Salines of the world to go do it.
29:29
SPEAKER_01: And the people who have tried to do it, uh,
29:32
SPEAKER_01: just unfortunately have, have,
29:34
SPEAKER_01: you know,
29:34
SPEAKER_01: either had to,
29:35
SPEAKER_01: you know,
29:36
SPEAKER_01: gotten unlucky with their approach or just been crifters with a lot of those,
29:40
SPEAKER_01: uh, or just like weren't very pragmatic about the approach.
29:42
SPEAKER_00: Yeah.
29:43
SPEAKER_00: Yeah.
29:43
SPEAKER_00: Okay.
29:44
SPEAKER_00: Well, okay.
29:44
SPEAKER_00: So we're going to go through what we should maybe be excited about and what's real,
29:48
SPEAKER_00: but let's start with you because I find that the most serious people I know
29:53
SPEAKER_00: in this field actually like take almost nothing that everybody else is trying.
29:58
SPEAKER_00: So I imagine you do some form of calorie restriction or you're careful on your diet.
30:05
SPEAKER_01: Definitely, definitely pretty careful on my diet.
30:07
SPEAKER_01: But no, I don't do anything too out of the ordinary.
30:11
SPEAKER_01: I used to do the like, you know, the Xero app.
30:13
SPEAKER_01: I used to do the Xero app.
30:14
SPEAKER_01: So 16, 18, 16, eight hour fasting.
30:18
SPEAKER_01: I do think there's probably good evidence for like longer fasts,
30:20
SPEAKER_01: like a three day fast or something like that, or even longer.
30:24
SPEAKER_01: But I just don't personally do it because I did like it.
30:26
SPEAKER_01: And it's a lame reason,
30:27
SPEAKER_01: but the effect size, I just don't think is dramatic on longevity and lifespan.
30:32
SPEAKER_01: I think the effect size is like semi dramatic on like energy levels
30:36
SPEAKER_01: and things like this on a week to week basis.
30:38
SPEAKER_01: But the mental trade off for me is like,
30:40
SPEAKER_01: I would rather just be like mentally more happy and like more productive on working
30:43
SPEAKER_01: on the massive effect size things for human aging.
30:46
SPEAKER_00: Okay.
30:47
SPEAKER_00: Okay.
30:47
SPEAKER_00: Cause I always thought calorie restriction was at least one of these things
30:50
SPEAKER_00: where everyone's like, yeah, that probably works.
30:52
SPEAKER_01: Oh, I think it works.
30:52
SPEAKER_01: Okay.
30:53
SPEAKER_01: I think it works.
30:54
SPEAKER_01: And you know,
30:54
SPEAKER_01: the primate data, there was one study by the NIA and one study in a Wisconsin study.
30:59
SPEAKER_01: And there's like still disagreement as to, you know, one was seemingly positive.
31:04
SPEAKER_01: One was seemingly negative in terms of a positive effect in primates.
31:08
SPEAKER_01: There's been the calorie study.
31:10
SPEAKER_01: But there really hasn't been a test of this in humans because it's just so hard
31:14
SPEAKER_01: for people to adhere to.
31:16
SPEAKER_01: GLP-1s, you mentioned, really interesting because they could do this in some respect.
31:21
SPEAKER_01: They could be the first test of calorie restriction in humans.
31:25
SPEAKER_01: But yeah, we don't really know in humans for calorie restriction.
31:28
SPEAKER_01: The jury is still out,
31:29
SPEAKER_01: which is insane because it is one of the gold standard interventions in
31:32
SPEAKER_01: the aging space of what positively works.
31:34
SPEAKER_00: Okay.
31:35
SPEAKER_00: Okay.
31:35
SPEAKER_00: And you don't have to rate all these things yet because we will get to them,
31:37
SPEAKER_00: but this is just a quick lightning round.
31:40
SPEAKER_00: Metformin, rapamycin, anything.
31:42
SPEAKER_00: Do you take any, any pills?
31:45
SPEAKER_00: Nothing.
31:46
SPEAKER_01: No, no, I take nothing.
31:47
SPEAKER_01: Like, you know, metformin is interesting.
31:49
SPEAKER_01: Rapa, like I could see the 0.5 mig every other week or every week, but we just don't know.
31:55
SPEAKER_01: We don't have the data and, and yeah, I want to see it.
31:59
SPEAKER_00: Anything that like.
32:00
SPEAKER_00: I'm Brian Johnson's litany of, do you take anything?
32:04
SPEAKER_00: You take nothing?
32:05
SPEAKER_00: Really, right?
32:06
SPEAKER_01: No, I take nothing.
32:07
SPEAKER_00: So you like eat healthy?
32:08
SPEAKER_00: Yeah.
32:08
SPEAKER_00: Because you're vegetarian or you eat?
32:11
SPEAKER_01: I eat mostly vegetarian, but I eat meat.
32:12
SPEAKER_01: I eat meat as well.
32:13
SPEAKER_00: Yeah.
32:13
SPEAKER_00: Okay.
32:14
SPEAKER_00: And then do you drink alcohol?
32:17
SPEAKER_01: Occasionally.
32:17
SPEAKER_00: Occasionally.
32:18
SPEAKER_00: And then otherwise what?
32:19
SPEAKER_00: You're exercising, you're sleeping.
32:22
SPEAKER_01: Not sleeping.
32:23
SPEAKER_01: I'm working.
32:23
SPEAKER_01: You're working.
32:24
SPEAKER_01: It's terrible.
32:26
SPEAKER_00: Nobody should follow you.
32:28
SPEAKER_00: You're just a workaholic.
32:30
SPEAKER_00: Venture capitalist.
32:31
SPEAKER_00: Uh, okay.
32:32
SPEAKER_01: No, it's, it's,
32:33
SPEAKER_01: it's literally like the dilemma of aging researchers,
32:36
SPEAKER_01: which is either like,
32:37
SPEAKER_01: you know,
32:37
SPEAKER_01: you can go and you can try to be like a nun in terms of your practices
32:41
SPEAKER_01: and be perfect about your own health.
32:42
SPEAKER_01: And I guess that's kind of like the Brian Johnson approach.
32:45
SPEAKER_01: Or you can lock in and be like, we're not satisfied with small effect sizes.
32:49
SPEAKER_01: Like we want huge effect sizes.
32:50
SPEAKER_00: So you want the big pill, yeah.
32:52
SPEAKER_01: Well, or any, you know, I don't know what, if it's a pill, it's another sort of intervention.
32:56
SPEAKER_01: But like, I want us to be able to all live to 120 and amazing health.
33:00
SPEAKER_01: And, you know,
33:01
SPEAKER_01: being a vegan who sleeps 10 hours a day and doesn't ever drink,
33:07
SPEAKER_01: that's not going to get me there.
33:08
SPEAKER_01: And that's not going to get my parents there.
33:09
SPEAKER_01: And that's not going to get any of my friends there.
33:11
SPEAKER_01: And so I'm just like, No, we need to do something more ambitious.
33:14
SPEAKER_00: Okay.
33:14
SPEAKER_00: Okay.
33:15
SPEAKER_00: All right.
33:15
SPEAKER_00: Well, then
33:16
SPEAKER_01: there we go.
33:16
SPEAKER_01: There's our baseline.
33:18
SPEAKER_00: All right, pod friends.
33:19
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33:22
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33:41
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33:41
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33:48
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33:49
SPEAKER_00: Go visit them today.
33:52
SPEAKER_00: All right, let's do GLPs first since they're so massive.
33:57
SPEAKER_00: Thoughts?
33:58
SPEAKER_00: Net good, net bad?
34:01
SPEAKER_00: Pros and cons?
34:02
SPEAKER_00: How should we feel about these things?
34:04
SPEAKER_01: Yeah, I mean,
34:05
SPEAKER_01: one of the most positive medicines to society from like a society level impact
34:11
SPEAKER_01: that we've ever had.
34:13
SPEAKER_01: I think they're remarkable.
34:14
SPEAKER_01: There's a reason that they're so talked about the long term outcomes.
34:20
SPEAKER_01: Are really dramatically positive in terms of the cardiovascular outcomes trials,
34:25
SPEAKER_01: the risk reduction for cardiovascular disease for people that are overweight
34:28
SPEAKER_01: or have obesity or have type 2 diabetes.
34:33
SPEAKER_01: And seemingly,
34:33
SPEAKER_01: you know,
34:34
SPEAKER_01: if you were to describe what an aging drug looks like,
34:36
SPEAKER_01: you'd probably be like, well,
34:38
SPEAKER_01: you know,
34:38
SPEAKER_01: if I tested it long term in humans,
34:40
SPEAKER_01: it would have beneficial effects across many different aspects of aging.
34:46
SPEAKER_01: GLP ones have done that.
34:47
SPEAKER_01: They have a mechanism that kind of fits with what mentally you would think of as
34:51
SPEAKER_01: an aging intervention in that they somewhat phenocopy calorie restriction,
34:54
SPEAKER_01: like a gold standard intervention in the field.
34:57
SPEAKER_01: They have these effects against inflammation, which are really dramatic and exciting.
35:03
SPEAKER_01: Inflammaging,
35:03
SPEAKER_01: for those that don't know,
35:04
SPEAKER_01: inflammation and low-grade inflammation is thought to be in part like a hallmark
35:09
SPEAKER_01: of aging or a driver of aging.
35:12
SPEAKER_01: So I think it's like the aging field has been working really hard for 50 years
35:15
SPEAKER_01: to get aging interventions.
35:16
SPEAKER_01: And then just like Villa Monster,
35:18
SPEAKER_01: totally other field,
35:19
SPEAKER_01: you know,
35:19
SPEAKER_01: Eli Lilly,
35:20
SPEAKER_01: Novo come along and they're like,
35:22
SPEAKER_01: oh, here's something like better than anything you've created to date.
35:26
SPEAKER_01: Uh, you know,
35:26
SPEAKER_01: what the aging field is going to do is going to end up being way more dramatic
35:29
SPEAKER_01: and exciting than GLP ones.
35:31
SPEAKER_01: Uh, but it is still funny,
35:32
SPEAKER_01: the irony of like serendipity and,
35:34
SPEAKER_01: you know, another field coming along and providing something that's probably better.
35:37
SPEAKER_00: So I still have like doctor friends though, who are like, they're like, oh God.
35:41
SPEAKER_00: You know, don't do it.
35:43
SPEAKER_00: And, uh,
35:43
SPEAKER_00: and then I have other,
35:44
SPEAKER_00: I see other people who are,
35:46
SPEAKER_00: I guess, educated, but I don't know that they're experts in this.
35:49
SPEAKER_00: They're like, oh, it's going to like lower your tolerance for risk and change your personality.
35:53
SPEAKER_00: You know, you, I mean,
35:54
SPEAKER_00: we all see all these different things and we have no,
35:57
SPEAKER_00: I guess we kind of know how it plays out over the longterm because why?
36:00
SPEAKER_00: Because people were taking this for diabetes for a long, I think for a while.
36:04
SPEAKER_00: Right.
36:04
SPEAKER_00: I mean, okay.
36:07
SPEAKER_00: I'm just listing off things, but like, so yeah.
36:10
SPEAKER_00: Good on all these fronts.
36:11
SPEAKER_00: How concerned should people be, though,
36:13
SPEAKER_00: that 30 years from now it turns out you've got something horrendous happening to you
36:18
SPEAKER_00: as a result of taking these?
36:19
SPEAKER_01: Yeah.
36:19
SPEAKER_01: So, I mean,
36:20
SPEAKER_01: there's some height effects there,
36:21
SPEAKER_01: you know,
36:21
SPEAKER_01: there's a really good review that came out last week, uh,
36:23
SPEAKER_01: summarizing some of these, like,
36:25
SPEAKER_01: you know,
36:25
SPEAKER_01: there's the, uh,
36:26
SPEAKER_01: there's a specific ophthalmology eyesight effect that does seem to have
36:30
SPEAKER_01: a consistent signal, albeit like extremely rare.
36:33
SPEAKER_01: Um, but, but the evidence is kind of built in that direction.
36:36
SPEAKER_01: But, but other than that,
36:37
SPEAKER_01: you know,
36:37
SPEAKER_01: with a lot of these,
36:39
SPEAKER_01: it's like so many people have been tested for so long,
36:41
SPEAKER_01: like Ozempic was not the first GLP-1, right?
36:44
SPEAKER_01: We've had FDA approved GLP-1s for Way longer time prize.
36:48
SPEAKER_01: And so just with the number of patients treated...
36:51
SPEAKER_01: We know that the rare events will have popped up by now.
36:55
SPEAKER_01: So I am really not that concerned about some sort of mystery side effect
36:59
SPEAKER_01: that hasn't been seen yet in the data.
37:02
SPEAKER_01: And so, I mean, the data looks great.
37:04
SPEAKER_01: We work with one of the first authors of the SELECT trial in semaglutide that was
37:08
SPEAKER_01: that cardiovascular outcome trial that got semaglutide approved.
37:12
SPEAKER_01: That was in a massive data set, way over 10,000 patients for about four years, medium follow-up.
37:19
SPEAKER_01: We have a lot of data now.
37:22
SPEAKER_00: So, but like this risk-taking thing,
37:23
SPEAKER_00: I mean, you hear people, oh, it stops them drinking, doing drugs.
37:27
SPEAKER_01: Yeah.
37:28
SPEAKER_01: How, what a shame.
37:29
SPEAKER_00: Yeah, no,
37:29
SPEAKER_00: that part is good,
37:31
SPEAKER_00: but I had never seen somebody argue before that it's changing your personality too,
37:36
SPEAKER_00: though, and you're becoming less.
37:38
SPEAKER_00: I mean, I didn't like the idea of that,
37:40
SPEAKER_00: of like, oh,
37:42
SPEAKER_00: my personality is going to shift and I'm going to like,
37:45
SPEAKER_00: I don't know, you know, I'm like in the middle of trying to run a business.
37:47
SPEAKER_00: It's like, do you want to...
37:49
SPEAKER_00: Stop taking risk and daring.
37:51
SPEAKER_00: And I don't know.
37:52
SPEAKER_00: Yeah.
37:53
SPEAKER_00: Is that bullshit?
37:54
SPEAKER_00: Have you heard anything like that?
37:55
SPEAKER_01: I mean,
37:56
SPEAKER_01: we have an extremely smart mutual friend who's an influential academic at Stanford
38:02
SPEAKER_01: that I will not name that,
38:04
SPEAKER_01: you know,
38:04
SPEAKER_01: Just tried this out for like time spent on smartphone and found that,
38:09
SPEAKER_01: you know, they really reduced the amount of time that they were doom scrolling.
38:12
SPEAKER_01: Yeah.
38:12
SPEAKER_01: So yeah, I've heard a lot of anecdotal evidence in this direction.
38:15
SPEAKER_01: And there's some really exciting new approaches.
38:17
SPEAKER_01: Like Lily's developing a trial for a backup for terzapatide called Brenapatide
38:22
SPEAKER_01: for alcohol use disorder.
38:24
SPEAKER_01: So we're going to get to see a lot of this addiction trial,
38:28
SPEAKER_01: addiction data play out in trials to see if there is,
38:31
SPEAKER_01: you know, a really robust effect there.
38:33
SPEAKER_01: But anecdotally, yeah, that's like, I don't know.
38:35
SPEAKER_01: It seems like a good thing to do scroll less.
38:37
SPEAKER_00: Yeah.
38:37
SPEAKER_00: Yeah.
38:38
SPEAKER_00: Yeah.
38:38
SPEAKER_00: Yeah.
38:39
SPEAKER_00: I mean, it's just, it is weird.
38:40
SPEAKER_00: But it's very weird.
38:41
SPEAKER_00: Personality's changing.
38:42
SPEAKER_00: I mean, yeah, obviously in good ways sometimes.
38:44
SPEAKER_00: Um, you mentioned a whole bunch of things already, but.
38:48
SPEAKER_00: Like what is the most exciting thing you see on the horizon directly as like
38:52
SPEAKER_00: an outcrop of the GLP-1s and where they're going?
38:56
SPEAKER_00: Like advancements with these therapies or the next most exciting thing that's come
39:02
SPEAKER_00: as a result of studying them?
39:05
SPEAKER_00: Yeah, absolutely.
39:07
SPEAKER_01: I mean, I think in one part,
39:09
SPEAKER_01: we're going to see variants of them put to the test in terms of being measured
39:15
SPEAKER_01: in trials that are reflective beyond just a single disease population.
39:19
SPEAKER_01: So I think this is one of the Biggest things that the aging field can accomplish,
39:23
SPEAKER_01: and this is something we're working on very directly,
39:25
SPEAKER_01: is to say,
39:26
SPEAKER_01: you know,
39:26
SPEAKER_01: can we design trials with the FDA that are reflective of aging as opposed to
39:31
SPEAKER_01: a singular disease?
39:32
SPEAKER_01: This is what Loyal has been the pioneer for in terms of showing as possible.
39:36
SPEAKER_01: I think we're going to see that with humans in the next decade,
39:39
SPEAKER_01: and it's going to be really cool.
39:41
SPEAKER_01: And GLP-1s or kind of related variants may be a part of that.
39:45
SPEAKER_01: I think another exciting wave with GLP-1s is just kind
39:49
SPEAKER_01: of like next generation mechanisms that Could be paired with them,
39:52
SPEAKER_01: could go beyond them.
39:53
SPEAKER_01: I mean, something that is,
39:56
SPEAKER_01: it's not necessarily concerned based off of the data so far,
40:00
SPEAKER_01: but is always a lingering concern in people's minds is the lean body mass loss.
40:04
SPEAKER_01: And this fact of when you yo-yo with GLP-1s in terms of go on GLP-1s,
40:09
SPEAKER_01: go off GLP-1s, go back on, go back off.
40:11
SPEAKER_01: The weight that comes back is a little bit disproportionately fat and adipose
40:16
SPEAKER_01: as opposed to the muscle mass coming back.
40:19
SPEAKER_01: And people theorize this could be a bigger problem longer term.
40:22
SPEAKER_01: And so it's like,
40:25
SPEAKER_01: it's one of these memes in pharma land right now of everybody's looking for
40:28
SPEAKER_01: the things that could help either have less of a negative effect on lean body mass
40:34
SPEAKER_01: or help just like build back lean body mass.
40:38
SPEAKER_01: And I think something we're betting really big So over 90% of glucose is kind
40:41
SPEAKER_01: of metabolized processed by muscle, has all these physiological benefits.
40:57
SPEAKER_01: You know, can we,
41:00
SPEAKER_01: is this like,
41:01
SPEAKER_01: you know,
41:01
SPEAKER_01: a next GLP-1 wave of,
41:03
SPEAKER_01: you know,
41:03
SPEAKER_01: what we learned from GLP-1s is that people love things that make them look good
41:06
SPEAKER_01: and are good for their long-term health.
41:09
SPEAKER_01: You know, are muscle interventions the next wave of that?
41:12
SPEAKER_00: And you said,
41:12
SPEAKER_00: do you have a startup that's doing that or you're just looking,
41:16
SPEAKER_00: you're surveying the field?
41:17
SPEAKER_00: We have multiple.
41:19
SPEAKER_00: Can we disclose any of these or are they stealthy ones?
41:22
SPEAKER_01: They're a little bit more on the stealthier side,
41:26
SPEAKER_01: but what I can say is, yeah,
41:28
SPEAKER_01: one of them we've been building with Nova Holdings,
41:32
SPEAKER_01: extremely excited about that, moving more in that direction.
41:36
SPEAKER_01: And another one we just signed on today with a big multi-stage VC firm located
41:44
SPEAKER_01: in California and literally signed the paperwork today.
41:46
SPEAKER_00: That doesn't help.
41:48
SPEAKER_01: Yeah, where no VC firms exist.
41:53
SPEAKER_01: And so, yeah, this is something that I think is going to be huge.
41:56
SPEAKER_00: So these are therapies that would help build muscle mass?
42:01
SPEAKER_01: Yeah, in part build muscle mass for some of the therapies and interventions we're focusing on.
42:07
SPEAKER_01: And others would focus more on the function improvement side of things.
42:10
SPEAKER_00: Okay.
42:13
SPEAKER_01: Kind of getting to the place,
42:14
SPEAKER_01: like an example,
42:15
SPEAKER_01: one of them,
42:16
SPEAKER_01: the one with Nova Holdings,
42:17
SPEAKER_01: we've seen preclinically evidence to improve exercise capacity in mice.
42:22
SPEAKER_00: Oh, okay.
42:24
SPEAKER_01: And so that's something that we're really interested in is,
42:26
SPEAKER_01: you know, can we translate some of these sorts of interventions to humans?
42:30
SPEAKER_00: And how were,
42:31
SPEAKER_00: you know,
42:32
SPEAKER_00: there was like that era where it was like the Uber for this
42:34
SPEAKER_00: and everybody was making some new app and it was always the Uber for whatever.
42:39
SPEAKER_00: I feel like I'm hearing it already from all these startups.
42:42
SPEAKER_00: It's like, I'm the Ozempic of this, you know, of, of sleep, of whatever.
42:46
SPEAKER_00: Um, I mean, like,
42:47
SPEAKER_00: I feel like we should,
42:49
SPEAKER_00: this is going to be kind of too easy, um, for companies for a bit.
42:53
SPEAKER_00: Is that something you're seeing?
42:55
SPEAKER_00: Yes.
42:55
SPEAKER_01: Yeah.
42:56
SPEAKER_01: Yeah.
42:56
SPEAKER_01: I think it's a little bit, um,
42:58
SPEAKER_01: but the funny part is as,
42:59
SPEAKER_01: as like, um,
43:01
SPEAKER_01: As meme-y as that phrase has been,
43:03
SPEAKER_01: and as many times as it has been used, it works on VCs every single time.
43:08
SPEAKER_00: Well, I mean, it's so much money.
43:10
SPEAKER_00: It's like, why not?
43:11
SPEAKER_01: Well, because every VC is wired to just be like, I only care about the biggest possible outcome.
43:16
SPEAKER_01: Everything is,
43:17
SPEAKER_01: you know, this,
43:18
SPEAKER_01: this distribution where you're looking for the outliers that drive all the returns.
43:22
SPEAKER_01: And so when you hear somebody talking about something as ambitious of,
43:25
SPEAKER_01: we're going to build,
43:26
SPEAKER_01: you know,
43:26
SPEAKER_01: the next,
43:27
SPEAKER_01: you know,
43:27
SPEAKER_01: we have a phrase internally at the fund
43:29
SPEAKER_01: that we always say civilization defining companies.
43:31
SPEAKER_01: Uh, that's what we're looking for.
43:33
SPEAKER_01: And so, yeah,
43:33
SPEAKER_01: when you hear somebody say it was Olympic for X or Olympic for Y,
43:37
SPEAKER_01: that is, they're inherently implying a civilization altering trajectory.
43:41
SPEAKER_00: Yeah.
43:41
SPEAKER_00: Yeah.
43:42
SPEAKER_00: Okay.
43:42
SPEAKER_00: Okay.
43:43
SPEAKER_00: Um, Another topic we talk about a ton on the show and our videos is this idea of partial.
43:50
SPEAKER_00: So reprogramming, if you've heard me do my spiel before, I apologize.
43:53
SPEAKER_00: But for people who haven't,
43:56
SPEAKER_00: there was a famous Japanese scientist,
44:00
SPEAKER_00: Yamanaka, who came up with these proteins called the Yamanaka Factors.
44:04
SPEAKER_00: It's kind of this combination of four proteins.
44:06
SPEAKER_00: Alex will fix everything that I butcher here.
44:09
SPEAKER_00: But you kind of hit,
44:11
SPEAKER_00: you can take a skin cell from a,
44:14
SPEAKER_00: Old mouse hit it with these four proteins,
44:17
SPEAKER_00: take it back to basically creating a stem cell, so to this kind of pure early state.
44:22
SPEAKER_00: And then there's this hope with partial cell reprogramming that you take
44:29
SPEAKER_00: an old liver cell or brain cell and you hit it with some combination of proteins.
44:34
SPEAKER_00: And instead of going all the way back to a blank slate,
44:37
SPEAKER_00: you get the platonic Ideal,
44:39
SPEAKER_00: like whatever it is,
44:40
SPEAKER_00: 18 to 25 year old version of that cell is all healthy and doing everything
44:44
SPEAKER_00: at maximum capacity.
44:47
SPEAKER_00: Tons of research showing these things in practice working and then also huge issues
44:55
SPEAKER_00: with this process kind of running away sometimes and forming tumors,
44:59
SPEAKER_00: you know,
44:59
SPEAKER_00: cancerous tumors where we're still in this process where we're trying to control Um,
45:05
SPEAKER_00: learn which proteins to use,
45:07
SPEAKER_00: learn how much, um, how to control what's happening with these cells.
45:11
SPEAKER_00: And we haven't quite perfected it, although lots of interesting things going on.
45:16
SPEAKER_00: You mentioned earlier,
45:17
SPEAKER_00: Jeff Bezos,
45:18
SPEAKER_00: Yuri Milner, um, other folks have put billions of dollars into Altos labs.
45:22
SPEAKER_00: It's at least thought to be quite secretive,
45:25
SPEAKER_00: but thought to be chasing this as one
45:27
SPEAKER_00: of its major Sam Altman's funded retro bio is doing some work in this area.
45:34
SPEAKER_00: New Limit funded by Brian Armstrong and others also here.
45:40
SPEAKER_00: And there's more players,
45:41
SPEAKER_00: but we're talking billions upon billions of dollars have gone into this.
45:44
SPEAKER_00: Yeah.
45:45
SPEAKER_00: And I, you know,
45:45
SPEAKER_00: when you and I have talked,
45:46
SPEAKER_00: I think you're, I don't know if it's fair to call you skeptic.
45:49
SPEAKER_00: I guess we'll hear what you think about this.
45:51
SPEAKER_00: But I've noticed,
45:52
SPEAKER_00: at least in our discussions,
45:53
SPEAKER_00: I felt like some caution as to how effective this would be.
45:58
SPEAKER_00: So first, please fix anything that I butchered.
46:01
SPEAKER_00: And then, yeah, how should we?
46:03
SPEAKER_00: I always get excited because it's amazing what happens to these cells to be able
46:07
SPEAKER_00: to start from scratch or to rewind seems incredible.
46:13
SPEAKER_00: And so, yeah, I mean, how exciting, not exciting?
46:16
SPEAKER_00: Where are we?
46:19
SPEAKER_01: Yeah, so I'll say in the context of like news cycles and events,
46:23
SPEAKER_01: there were just two approved therapies with IPSC technology.
46:27
SPEAKER_01: Today, we have one today.
46:28
SPEAKER_01: Yeah, I think it was like the past two days out of Japan.
46:31
SPEAKER_01: Okay, yeah, yeah, yeah.
46:33
SPEAKER_01: Which is remarkable.
46:34
SPEAKER_01: It's like a huge milestone.
46:35
SPEAKER_01: Now, of course, that's like full reprogramming.
46:37
SPEAKER_00: Yeah, tell us, was it spinal or this was?
46:40
SPEAKER_01: I think one was cardiac, but I'm not sure actually, yeah.
46:44
SPEAKER_00: Okay.
46:44
SPEAKER_00: No, keep talking.
46:44
SPEAKER_00: I'm going to look it up while you're talking.
46:46
SPEAKER_01: All right.
46:46
SPEAKER_01: Love it.
46:47
SPEAKER_01: Uh, so, so that is in the context of full reprogramming of this,
46:50
SPEAKER_01: like, can we just generate, uh, you know, new healthy cells?
46:54
SPEAKER_01: You know,
46:54
SPEAKER_01: one of my North stars are like obsessions long-term on like
46:58
SPEAKER_01: a 40 year time Can we replace every single cell in the human body?
47:02
SPEAKER_01: We have 30 trillion cells.
47:04
SPEAKER_01: Can we get to a point that just at any point that we have damaged cells,
47:08
SPEAKER_01: can we just swap in a new, fresh, healthy cell?
47:10
SPEAKER_01: And it sounds insane,
47:12
SPEAKER_01: but there are a couple of companies that have shown that this is somewhat possible
47:17
SPEAKER_01: in the context of specific cell types.
47:18
SPEAKER_01: So there's a company,
47:19
SPEAKER_01: Blue Rock Therapeutics and Aspen Neuroscience that Sam Altman is a funder of,
47:23
SPEAKER_01: that are going after replacing dopaminergic neurons for Parkinson's disease.
47:27
SPEAKER_01: And they've Been able to show in phase one trials from BlueRock
47:30
SPEAKER_01: that you can implant these cells.
47:32
SPEAKER_01: Even remove immunosuppression and the cells still engraft and function long-term.
47:37
SPEAKER_01: That's remarkable.
47:37
SPEAKER_01: There's another company here in
47:38
SPEAKER_01: the Bay Area called Neurona Therapeutics that's working
47:40
SPEAKER_01: on implanting inhibitory neurons for epilepsy.
47:45
SPEAKER_01: And they've shown efficacy,
47:47
SPEAKER_01: pretty dramatic efficacy in just a very early trial at being able
47:50
SPEAKER_01: to implant these cells derived from pluripotent stem cells into the brain.
47:55
SPEAKER_01: And so that's like,
47:56
SPEAKER_01: if we're just talking about reprogramming,
47:57
SPEAKER_01: one of the things is just like, wow, can we replace every single cell in the body?
48:00
SPEAKER_01: Maybe.
48:01
SPEAKER_01: Maybe.
48:02
SPEAKER_00: Wait, and explain that for a second.
48:03
SPEAKER_00: Okay, pluripotent stem cell is this stem cell,
48:08
SPEAKER_00: this kind of human-made stem cell, this process that I was talking about, right?
48:13
SPEAKER_00: I mean, and they get called pluripotent stem cells.
48:16
SPEAKER_01: Yeah, it doesn't necessarily have to be human made in that like,
48:19
SPEAKER_01: you know,
48:19
SPEAKER_01: various times throughout our life,
48:21
SPEAKER_01: you know,
48:21
SPEAKER_01: we have pluripotent stem cells and embryonic stem cells are one of the one of
48:24
SPEAKER_01: the types of pluripotent stem cells.
48:27
SPEAKER_01: And another type is iPSCs.
48:29
SPEAKER_01: So induce pluripotent stem cells and and and kind of.
48:33
SPEAKER_01: ESCs and IPSCs,
48:34
SPEAKER_01: there are different companies using each approach and they have their pros and cons.
48:38
SPEAKER_01: IPSCs are the ones using OSKM, the Yamanaka factors you described.
48:42
SPEAKER_01: And so there's specific nuances around it.
48:44
SPEAKER_01: And for example,
48:45
SPEAKER_01: like big pharma companies that are in traditional red states,
48:48
SPEAKER_01: like historically haven't loved like embryonic stem cells because of
48:52
SPEAKER_01: the connotation there.
48:54
SPEAKER_01: At any rate,
48:55
SPEAKER_01: it's yeah, those are kind of like the high level technologies used for replacement.
49:00
SPEAKER_01: And then as you kind of described on the partial reprogramming side,
49:03
SPEAKER_01: that's saying like, okay,
49:04
SPEAKER_01: instead of going all the way from taking a somatic cell,
49:08
SPEAKER_01: aka like a Let's just take that skin cell and try to make it younger.
49:13
SPEAKER_01: So harness the rejuvenative benefits of reprogramming while maintaining the same identity.
49:17
SPEAKER_01: So the skin cell is still skin cell, still does skin cell things, but is younger.
49:34
SPEAKER_00: Okay.
49:34
SPEAKER_00: And then I did, I found the story from Japan today.
49:37
SPEAKER_00: I mean, so yeah,
49:38
SPEAKER_00: it's induced pluripotent stem cells,
49:42
SPEAKER_00: two therapies receiving approval for Parkinson's and cardiomyocyte patches
49:50
SPEAKER_00: for heart failure.
49:52
SPEAKER_00: So like in,
49:54
SPEAKER_00: I don't know if you know the details on this,
49:56
SPEAKER_00: but the two examples you mentioned, so those were both in the brain.
50:01
SPEAKER_00: Right.
50:02
SPEAKER_00: Yeah.
50:02
SPEAKER_00: And so in there you're getting what you're getting an injection of these, um,
50:08
SPEAKER_00: neurons in, in,
50:10
SPEAKER_00: into the brain that are replacing the damaged ones or how is that process working?
50:14
SPEAKER_01: Yeah.
50:15
SPEAKER_01: So this is,
50:15
SPEAKER_01: I am not an expert at all,
50:17
SPEAKER_01: but I'll say for like neurona,
50:18
SPEAKER_01: I think it's really interesting in that there's,
50:20
SPEAKER_01: I believe it's these like neuronal precursor cells that then naturally kind
50:24
SPEAKER_01: of migrate to where they're supposed to go in the brain.
50:28
SPEAKER_01: And for the Parkinson's companies right now,
50:31
SPEAKER_01: I think they're currently placed in the region
50:33
SPEAKER_01: that dopaminergic neurons actually normally don't lie.
50:36
SPEAKER_01: And so they're in actually a different region.
50:39
SPEAKER_01: Uh, but it doesn't matter because they're,
50:40
SPEAKER_01: they're there just to secrete,
50:42
SPEAKER_01: uh, dopamine, uh, and, and that is enough to have this beneficial effect.
50:47
SPEAKER_00: Okay.
50:47
SPEAKER_01: And so there are some companies working to optimize the placement of them
50:50
SPEAKER_01: to put them where they're supposed to do.
50:51
SPEAKER_01: And they have theories as to why that'll be more beneficial.
50:54
SPEAKER_01: Um, yeah,
50:55
SPEAKER_01: so it's,
50:56
SPEAKER_01: it's kind of like a mix of just putting like the direct neuron type or it's sort
50:59
SPEAKER_01: of precursor.
51:00
SPEAKER_00: So we see startups doing.
51:05
SPEAKER_00: Putting these healthier cells in brain,
51:08
SPEAKER_00: we just read about, well, one was Parkinson's, probably quite similar.
51:12
SPEAKER_00: And then heart, I've seen spinal.
51:14
SPEAKER_00: So it's kind of like taking these stem cells that we're creating,
51:20
SPEAKER_00: fixing problems here and there.
51:22
SPEAKER_00: But like the holy grail that everyone's chasing is...
51:26
SPEAKER_00: Can I have like a 25-year-old's liver or lungs or brain, right?
51:32
SPEAKER_00: I mean, that's kind of the mega quest.
51:35
SPEAKER_01: Yeah, I think they're both the mega quests, but just in parallel.
51:37
SPEAKER_01: Like one is saying like, okay, like,
51:40
SPEAKER_01: you know,
51:41
SPEAKER_01: if we can't figure out how to just like intrinsically at a cell turn back its age,
51:45
SPEAKER_01: then like we now have the technology somewhat to just replace it with a young cell,
51:50
SPEAKER_01: right?
51:51
SPEAKER_01: And so there's this like field of aging that's focused on replacement,
51:54
SPEAKER_01: which is like kind of like the,
51:55
SPEAKER_01: you know,
51:56
SPEAKER_01: it's so hard to fix all the thousands of macromolecular damages that accumulate in
52:01
SPEAKER_01: a cell.
52:02
SPEAKER_01: But if we can just swap it out, then it doesn't even matter.
52:04
SPEAKER_01: We don't even need to really understand everything that's going on.
52:08
SPEAKER_01: And then there's kind of like a parallel school of thought of like,
52:11
SPEAKER_01: okay, like there's all these things going wrong in a cell.
52:14
SPEAKER_01: We know in the process of reprogramming that it looks like a lot of
52:18
SPEAKER_01: that molecular damage is reverted or cleaned up somehow,
52:24
SPEAKER_01: you know, via autophagy processes or via the epigenome changing processes.
52:29
SPEAKER_01: And, you know,
52:30
SPEAKER_01: can we just do that instead and have this kind of like fast track to
52:33
SPEAKER_01: a rejuvenated young cell?
52:35
SPEAKER_01: And so it's kind of like parallel fields pushing along.
52:38
SPEAKER_01: Both are in the earliest of innings in their trajectories and both are.
52:43
SPEAKER_01: Mm-hmm.
52:44
SPEAKER_01: Got it.
53:03
SPEAKER_01: Who knows if it's working or not.
53:05
SPEAKER_00: And I think it's been- Which you can't do, by the way.
53:08
SPEAKER_00: Yeah.
53:09
SPEAKER_00: Okay.
53:09
SPEAKER_00: But different here.
53:10
SPEAKER_00: Yeah.
53:10
SPEAKER_00: Okay.
53:10
SPEAKER_01: Yeah.
53:11
SPEAKER_01: So it's been a field like hyped up for such a long time and now it's like working
53:14
SPEAKER_01: in phase one trials.
53:15
SPEAKER_01: Yeah.
53:15
SPEAKER_01: I just don't think that's clicked for a lot of people yet.
53:18
SPEAKER_00: No.
53:18
SPEAKER_00: I mean, this drives me absolutely actually kind of bonkers.
53:22
SPEAKER_00: I think, yeah.
53:23
SPEAKER_00: Anyway, I feel like we're doing our part over here.
53:27
SPEAKER_00: But then if I'm not wrong, I mean,
53:30
SPEAKER_00: when you and I have talked in the past,
53:33
SPEAKER_00: my sense was always that you felt like there actually is so much complexity in
53:38
SPEAKER_00: the body that,
53:40
SPEAKER_00: like my read was that you were kind of skeptical
53:43
SPEAKER_00: on how far these technologies could go.
53:48
SPEAKER_00: Mm-hmm.
53:49
SPEAKER_01: Yeah, so in the lane of partial reprogramming.
53:53
SPEAKER_01: So this is something that I actually sought out when I first came to Stanford.
53:57
SPEAKER_01: So like 2016, I was like, I really want to work on reprogramming.
54:01
SPEAKER_01: In part, I selected my PhD lab because it was working on this project.
54:06
SPEAKER_01: So I did my PhD in Dr. Tom Rando's lab.
54:09
SPEAKER_01: So he's a muscle stem cell expert and one of the first movers, I'd say, in the aging field.
54:15
SPEAKER_01: You know,
54:15
SPEAKER_01: not in the 80s per se,
54:16
SPEAKER_01: but he really dipped into the field in the late 1990s, early 2000s.
54:20
SPEAKER_01: He's famous because his lab published in a 2005 Nature paper
54:25
SPEAKER_01: that young blood was rejuvenative to old mice.
54:29
SPEAKER_01: So this really creepy notion of like blood boys and parabiosis and And a lot of
54:33
SPEAKER_01: that energy and excitement came from both the lab at my PhD and then the lab
54:37
SPEAKER_01: that was directly beneath us downstairs,
54:41
SPEAKER_01: which was Dr.
54:41
SPEAKER_01: Tony Viscaray, who also did a lot of similar lines of research on the brain.
54:46
SPEAKER_01: But I didn't choose the lab because of that.
54:48
SPEAKER_01: I chose the lab because they were working on this project with Dr.
54:51
SPEAKER_01: Vittorio Sebastiano at Stanford.
54:53
SPEAKER_01: Looking at partial reprogramming and its effects on aging.
54:57
SPEAKER_01: And so at that exact time,
54:59
SPEAKER_01: Juan Carlos Belmonte,
55:01
SPEAKER_01: previously kind of down in San Diego,
55:03
SPEAKER_01: Salk Institute,
55:04
SPEAKER_01: now at Altos Labs,
55:06
SPEAKER_01: he had a cell paper That showed you could increase lifespan by progeric mice by 50%.
55:12
SPEAKER_01: So mice with progeria genetically engineered to kind of mimic human progeria,
55:16
SPEAKER_01: which are your humans that age extremely rapidly,
55:19
SPEAKER_01: die in the teens or 20s, depending on the type of progeria you have.
55:23
SPEAKER_01: And this technology was shown to dramatically increase those mice's lifespan.
55:28
SPEAKER_01: And so we were working on that same problem in parallel and kind of really trying
55:32
SPEAKER_01: to disentangle just how good the effects were and in what ways and how
55:36
SPEAKER_01: the mechanisms work.
55:38
SPEAKER_01: And maybe in part the skepticism you're referring is just,
55:41
SPEAKER_01: you know,
55:41
SPEAKER_01: worked in the field for two years,
55:43
SPEAKER_01: got a sense of what it was like doing these things in cells and mice to some extent,
55:48
SPEAKER_01: but it was just very early days in terms of trying to disentangle like single
55:52
SPEAKER_01: from noise, trying to disentangle like where things were going to go.
55:57
SPEAKER_01: And so I was shocked when we had all these companies working on it at the end
56:01
SPEAKER_01: of my PhD, not necessarily in a bad way.
56:03
SPEAKER_01: Like I'm thrilled that people are,
56:07
SPEAKER_01: And I think there's this meme in the aging field of like,
56:10
SPEAKER_01: oh, like reprogramming is overfunded, therefore people shouldn't fund it.
56:14
SPEAKER_01: And I'm like, no,
56:15
SPEAKER_01: pretty much everything in the aging field,
56:17
SPEAKER_01: even reprogramming with these billions of dollars is totally underfunded
56:20
SPEAKER_01: because reprogramming could be tailored to each individual cell type or tissue
56:25
SPEAKER_01: in your body.
56:30
SPEAKER_01: Some people may know, some people may not, but you should know him.
56:33
SPEAKER_01: One of my top five favorite people in the field.
56:35
SPEAKER_01: When I was first starting working with Laura on our kind of latest fund,
56:39
SPEAKER_01: he was like,
56:40
SPEAKER_01: 70% of your portfolio should be reprogramming companies because there's
56:43
SPEAKER_01: so many angles.
56:45
SPEAKER_00: How much of your portfolio is reprogramming?
56:47
SPEAKER_00: None.
56:48
SPEAKER_00: Right now, none.
56:49
SPEAKER_01: Yeah.
56:50
SPEAKER_01: And I really want to change that because if we talk about holy grails of
56:55
SPEAKER_01: the aging field, Everybody wants something that can turn the clock back.
57:00
SPEAKER_01: This is one of the closest paths to being able to do that.
57:04
SPEAKER_00: Yeah.
57:04
SPEAKER_00: But okay.
57:04
SPEAKER_00: So why is it none?
57:09
SPEAKER_01: It's a really hard problem.
57:10
SPEAKER_00: But you haven't seen something you're convinced by that, right?
57:14
SPEAKER_01: I haven't seen something that we're convinced by yet.
57:18
SPEAKER_01: I'll say like, for example, New Limit, like massive super fan of Jacob and Brian and Blake.
57:25
SPEAKER_01: And I think what they've built is extraordinary.
57:28
SPEAKER_01: And I would say follow very closely along with what they're doing.
57:34
SPEAKER_01: Because I think they've done it in a really, really intelligent and smart way.
57:38
SPEAKER_01: It's just like a very inherently tough problem to translate to humans given...
57:42
SPEAKER_01: For those that don't know,
57:43
SPEAKER_01: you're messing around with pathways in cells that involve proliferation.
57:49
SPEAKER_01: And so there's these risks of teratomas or kind of inducing cancer.
57:55
SPEAKER_01: And so inherently, it's something that...
58:00
SPEAKER_01: Demands a lot of study before translating it to humans.
58:04
SPEAKER_01: And New Limit is,
58:05
SPEAKER_01: you know,
58:05
SPEAKER_01: they're not going in the direction of OSKM and Yamanaka factors as much
58:09
SPEAKER_01: as they are kind of orthogonal different transcription factors
58:12
SPEAKER_01: and non-transcription factors for reprogramming.
58:13
SPEAKER_00: Trying to find their own proteins.
58:15
SPEAKER_00: Yeah.
58:15
SPEAKER_00: Exactly.
58:15
SPEAKER_00: Yeah.
58:16
SPEAKER_00: Okay.
58:16
SPEAKER_00: Okay.
58:17
SPEAKER_00: All right.
58:17
SPEAKER_00: All right.
58:18
SPEAKER_00: We got out of that one.
58:20
SPEAKER_00: Okay.
58:24
SPEAKER_00: I don't usually, I try, well, I guess I do let people talk their book a little bit.
58:28
SPEAKER_00: I try not to make this like a,
58:31
SPEAKER_00: Advertisement for your, your companies, but Fauna, Bio, you guys are invested in.
58:37
SPEAKER_00: I mean, tell me what they do.
58:38
SPEAKER_00: Cause it's, it's just fascinating.
58:40
SPEAKER_01: Yeah.
58:40
SPEAKER_01: So, um, and I know,
58:43
SPEAKER_01: I know you don't like to invite VCs on, so I'm trying to like earn my keep here.
58:47
SPEAKER_00: Who do I not like?
58:48
SPEAKER_00: VCs.
58:49
SPEAKER_00: Oh, no, no.
58:50
SPEAKER_00: Wow.
58:50
SPEAKER_00: I don't usually let VCs on the podcast,
58:52
SPEAKER_00: but you, you, you were an easy decision cause you're legit.
58:55
SPEAKER_01: Yeah.
58:56
SPEAKER_01: So fauna bio, they study hibernating species.
58:59
SPEAKER_01: So this goes back to that obsession with axolotls or with,
59:04
SPEAKER_01: you know, gilla monsters, this extreme biology.
59:07
SPEAKER_01: Naked mole rats.
59:08
SPEAKER_01: Exactly.
59:09
SPEAKER_01: And, you know, bowhead whales.
59:10
SPEAKER_01: Like, so bowhead whales,
59:12
SPEAKER_01: they just have this,
59:14
SPEAKER_01: there's been a series of publications recently covering the stability
59:17
SPEAKER_01: of their genome.
59:19
SPEAKER_01: And there's a lot of animals like elephants and whales that for their size,
59:22
SPEAKER_01: you would assume they would be dealing with cancer incessantly.
59:26
SPEAKER_01: And they're not because they have better ways to maintain genome stability than we do.
59:32
SPEAKER_00: Um, and why big animals get more cancer or the should?
59:35
SPEAKER_01: It should just cause they have more cells.
59:37
SPEAKER_00: Oh, okay.
59:38
SPEAKER_00: Uh, and, and.
59:39
SPEAKER_00: I never thought about it.
59:40
SPEAKER_00: Okay.
59:41
SPEAKER_00: Yeah.
59:41
SPEAKER_01: And so it's a little bit of a paradox in some animals that that's not the case
59:44
SPEAKER_01: or they,
59:45
SPEAKER_01: you know,
59:45
SPEAKER_01: they just,
59:46
SPEAKER_01: just looking at different rates of cancers and different species can teach us a ton
59:52
SPEAKER_01: about human biology and,
59:53
SPEAKER_01: and ways that we could potentially have levers to dial up or dial down rates
59:57
SPEAKER_01: of cancer.
59:57
SPEAKER_01: I don't know why you'd dial up, but
59:59
SPEAKER_00: let's go.
59:59
SPEAKER_00: Yeah.
59:59
SPEAKER_00: Let's go and dial down.
1:00:00
SPEAKER_00: Let's not do that.
1:00:02
SPEAKER_01: And so yeah, Fauna Bio, they study hibernators.
1:00:05
SPEAKER_01: So 13 line ground squirrel series.
1:00:08
SPEAKER_01: They have a huge data set across hundreds of different types of hibernators.
1:00:14
SPEAKER_01: And the reason is like just extreme biology can teach you So much
1:00:18
SPEAKER_01: about human therapeutics and human disease.
1:00:21
SPEAKER_01: And so, you know,
1:00:22
SPEAKER_01: some examples are just like the amount of cardiac stress that these animals go
1:00:28
SPEAKER_01: through through the hibernating process of going from extreme temperatures down
1:00:31
SPEAKER_01: to Low extreme temperatures,
1:00:34
SPEAKER_01: dealing with really dramatic differences in things like heart rates.
1:00:40
SPEAKER_01: And, you know,
1:00:41
SPEAKER_01: they have no issues doing it versus like,
1:00:43
SPEAKER_01: you know,
1:00:43
SPEAKER_01: human systems,
1:00:44
SPEAKER_01: you'd put them through those same stresses or temperature changes
1:00:46
SPEAKER_01: or physiological changes and we would die instantly
1:00:50
SPEAKER_01: or we'd get some horrific disease or some horrific fibrosis.
1:00:54
SPEAKER_01: And so fauna has been studying this in a really cool way.
1:00:58
SPEAKER_00: So they're trying to pinpoint the genes or the mechanisms behind...
1:01:03
SPEAKER_01: Yeah, they're like building a human genetics data set and saying,
1:01:07
SPEAKER_01: okay, like what genetic modifiers in humans help prevent us from getting diseases?
1:01:14
SPEAKER_01: What genes are different in these hibernating species?
1:01:17
SPEAKER_01: And what do they do differently to prevent getting similar conditions to humans?
1:01:22
SPEAKER_01: Overlapping the two and saying, okay,
1:01:24
SPEAKER_01: what can we learn from the intersection of these two to take targets
1:01:26
SPEAKER_01: that have human relevance and that we know in like the 13 ground line squirrel
1:01:30
SPEAKER_01: or something can, can give them a remarkable ability not to get a disease.
1:01:34
SPEAKER_00: I feel like I remember writing a story about a company called variant bio almost, I don't know.
1:01:39
SPEAKER_00: I want to say it was like eight years ago.
1:01:41
SPEAKER_00: I can't remember.
1:01:42
SPEAKER_00: Um, and they were running around the world finding Unique populations of humans,
1:01:48
SPEAKER_00: people in Chile who could do similar things to your describing.
1:01:52
SPEAKER_00: They could be in the snow,
1:01:54
SPEAKER_00: um, in relatively little clothes and, and sort of deal with hypothermia and stuff.
1:02:00
SPEAKER_00: Like no problem.
1:02:01
SPEAKER_00: People that can be hypoxic,
1:02:03
SPEAKER_00: you know, up in,
1:02:04
SPEAKER_00: who live in mountains and can be without oxygen and still function at
1:02:08
SPEAKER_00: a really high level, um,
1:02:10
SPEAKER_00: trying to find the genes behind some of those things to see if you could make
1:02:13
SPEAKER_00: a therapy.
1:02:14
SPEAKER_00: Uh, populations that just didn't get like diabetes and things like that.
1:02:18
SPEAKER_00: And then, um,
1:02:20
SPEAKER_00: so I feel like I run across startups kind of chasing these outlier type functions,
1:02:26
SPEAKER_00: animals, humans,
1:02:28
SPEAKER_00: and then like how successful have we ever been at translating something like that
1:02:32
SPEAKER_00: into a therapy?
1:02:35
SPEAKER_01: Yeah.
1:02:35
SPEAKER_01: So during my PhD,
1:02:36
SPEAKER_01: I consulted for a year and a half for the business development group
1:02:39
SPEAKER_01: of May's Therapeutics.
1:02:41
SPEAKER_01: So this was a Third Rock Ventures build.
1:02:44
SPEAKER_01: For those that don't know,
1:02:45
SPEAKER_01: Third Rock is one of the biggest biotech VC funds based out of Boston,
1:02:48
SPEAKER_01: you can think of, and SF.
1:02:50
SPEAKER_01: They're kind of like a corollary to flagship, which gave us Moderna.
1:02:53
SPEAKER_01: So they do these big builds.
1:02:55
SPEAKER_01: May's Therapeutics partnered with a bunch of different prolific professors,
1:02:58
SPEAKER_01: including Aaron Gittler at Stanford,
1:03:01
SPEAKER_01: who's kind of the ALS group of the world, I would say, expert on ALS.
1:03:06
SPEAKER_01: And they focused in large part on genetic modifiers.
1:03:09
SPEAKER_01: So that, in part, locked my brain into the power of that platform.
1:03:13
SPEAKER_01: So very similar to Variant Bio in terms of looking for these extreme...
1:03:17
SPEAKER_01: Examples and translating that to humans.
1:03:20
SPEAKER_01: To your question, has that been successful?
1:03:23
SPEAKER_00: Remarkably so.
1:03:24
SPEAKER_01: So there's like a cardio company,
1:03:26
SPEAKER_01: cardiomyopathy company called Myocardia that's had a lot of success with this kind
1:03:32
SPEAKER_01: of human genetics driven approach.
1:03:34
SPEAKER_01: You may have heard of PCSK9 inhibitors,
1:03:37
SPEAKER_01: which is an example of using human genetics to say, oh,
1:03:41
SPEAKER_01: people with a human mutation in PCSK9 have 88% fewer cardiovascular events lifelong.
1:03:49
SPEAKER_01: Well, okay, where's the downside?
1:03:50
SPEAKER_01: Okay, you look into the genetics.
1:03:52
SPEAKER_01: There's not really a downside.
1:03:54
SPEAKER_01: Why aren't we all doing this?
1:03:55
SPEAKER_01: Why don't we all mutate our BCS canine to lower our risk
1:03:59
SPEAKER_01: of atherosclerotic disease later in life, right?
1:04:02
SPEAKER_01: So I do think there's just like, there has been a number of very successful examples of this.
1:04:06
SPEAKER_01: And there's also cool papers in Nature Review's Drug Discovery
1:04:10
SPEAKER_01: that show it's like you have a 50% higher chance of getting a drug approved
1:04:14
SPEAKER_01: if your target has human genetic evidence supporting it.
1:04:17
SPEAKER_00: So it just, and it just takes a while.
1:04:19
SPEAKER_00: I just feel like I've been writing about this stuff forever,
1:04:21
SPEAKER_00: then I don't, yeah,
1:04:22
SPEAKER_00: you know,
1:04:22
SPEAKER_00: I just don't see, like, people living, walking through the snow in shorts yet, yet.
1:04:29
SPEAKER_01: On the way.
1:04:31
SPEAKER_01: You know, but, like, they're...
1:04:33
SPEAKER_01: There are the really cool examples of dramatic improvements in breakthrough,
1:04:37
SPEAKER_01: like cystic fibrosis, right?
1:04:39
SPEAKER_01: Where, you know, another one where in part human genetics played a big role.
1:04:43
SPEAKER_01: And we've had people brought,
1:04:45
SPEAKER_01: you know, had like 50 year improvements and expected lifespan with this disease.
1:04:50
SPEAKER_00: So there are the success stories,
1:04:52
SPEAKER_01: but like it hasn't reached the common man yet.
1:04:54
SPEAKER_01: You know, something we think a lot about is like How do we get to this human enhancement?
1:05:00
SPEAKER_01: There's this baseline.
1:05:01
SPEAKER_01: We all live our lives where we have this certain risk of decline
1:05:04
SPEAKER_01: with age that's certain and we're most likely going to get cardiovascular disease
1:05:08
SPEAKER_01: and neurodegeneration and all these bad things.
1:05:10
SPEAKER_01: When are we going to get to the point where we can just modify things so
1:05:13
SPEAKER_01: that just baseline we can prevent cognitive decline or experience better cognition
1:05:18
SPEAKER_01: or be way more resilient to cardiovascular disease or any of these things?
1:05:22
SPEAKER_01: Yeah, when is that?
1:05:25
SPEAKER_01: I think the
1:05:25
SPEAKER_01: next 10 years.
1:05:27
SPEAKER_01: For real?
1:05:27
SPEAKER_01: Yeah.
1:05:27
SPEAKER_01: I don't know if you've heard of SIRNA or RNA therapy,
1:05:30
SPEAKER_01: but there's a company, Alnylam, in Boston, has been a pioneer.
1:05:33
SPEAKER_01: John Mragnore is really pushing along this technology.
1:05:36
SPEAKER_01: It's gotten to the point there.
1:05:38
SPEAKER_01: We mentioned in glycerin or PCSK9 inhibitors, there's an SIRNA.
1:05:43
SPEAKER_01: And I think it's really very minimal in terms of like off-target side effects.
1:05:52
SPEAKER_01: I think we're getting really close to an era where we're going to see people be able
1:05:55
SPEAKER_01: to experience baseline enhancement using these targeted RNA therapies.
1:06:00
SPEAKER_00: Okay.
1:06:00
SPEAKER_00: I mean, yeah.
1:06:02
SPEAKER_00: I mean, that's exciting.
1:06:03
SPEAKER_00: Jesus.
1:06:03
SPEAKER_00: I mean, you think like in the next...
1:06:07
SPEAKER_00: I am, God, I forget how old I am.
1:06:09
SPEAKER_00: I mean, that was part of the problem, like 48-ish, I think.
1:06:13
SPEAKER_00: And I'm just, I'm going through it now.
1:06:19
SPEAKER_00: Yes, I think that's right.
1:06:20
SPEAKER_00: And, you know, to that point, worried about cognitive decline.
1:06:26
SPEAKER_00: Do you think,
1:06:27
SPEAKER_00: like when you're saying this, I mean,
1:06:29
SPEAKER_00: you think in the next 10 years,
1:06:31
SPEAKER_00: 20 years,
1:06:33
SPEAKER_00: how realistic would it be on my part to expect something that not only kind of like,
1:06:37
SPEAKER_00: Holds me at the state I'm at, but improves me back to where I was.
1:06:44
SPEAKER_00: Especially like mental, yeah, health.
1:06:47
SPEAKER_01: 20 years, extremely optimistic about it.
1:06:50
SPEAKER_01: 10 years, pretty optimistic, but it's going to take a lot of effort.
1:06:55
SPEAKER_01: But I think we can get there.
1:06:58
SPEAKER_01: We're working with a founder who's developing therapies
1:07:01
SPEAKER_01: that you could do potentially even like a subcutaneous injection to deliver
1:07:06
SPEAKER_01: an RNA therapy to the brain uniformly.
1:07:08
SPEAKER_01: So this has been one of like the biggest developments in drug development and medicine.
1:07:13
SPEAKER_01: In the past decade is we now have this blood brain barrier shuttle technology
1:07:17
SPEAKER_01: that can allow pretty uniform and deep penetration into the brain delivery
1:07:23
SPEAKER_01: of these RNA medicines.
1:07:25
SPEAKER_01: And we think that's going to be huge along these lines of prevention.
1:07:27
SPEAKER_01: And so it's going to be like probably going to start out for genetic subsets of disease.
1:07:33
SPEAKER_01: But I think it'll increase in terms of prevalence of the population
1:07:36
SPEAKER_01: that is benefiting pretty quickly.
1:07:38
SPEAKER_00: Wait, and that one was a stealth startup or that one's public?
1:07:41
SPEAKER_01: That one's public.
1:07:42
SPEAKER_01: We announced- Which one was it?
1:07:43
SPEAKER_01: It's called Erska.
1:07:45
SPEAKER_00: Erska.
1:07:45
SPEAKER_01: So Irish founder.
1:07:47
SPEAKER_01: In Boston?
1:07:49
SPEAKER_01: Company is split between Boston and Ireland and London.
1:07:52
SPEAKER_00: Okay.
1:07:53
SPEAKER_00: Okay.
1:07:54
SPEAKER_00: All right.
1:07:54
SPEAKER_00: I'm writing that down.
1:07:56
SPEAKER_01: So last week we co-led their $39 million Series A.
1:08:00
SPEAKER_00: Well, you didn't tell me that.
1:08:02
SPEAKER_00: Did you?
1:08:03
SPEAKER_01: No, I didn't mention that one.
1:08:04
SPEAKER_01: No.
1:08:05
SPEAKER_00: Come on, man.
1:08:06
SPEAKER_00: That's good.
1:08:07
SPEAKER_00: I'd ask my question a lot better if I had these drugs.
1:08:13
SPEAKER_00: I could use that.
1:08:14
SPEAKER_00: Okay.
1:08:15
SPEAKER_00: And then, okay, we had Jennifer Doudna on the podcast not long ago.
1:08:18
SPEAKER_00: That's a brag.
1:08:20
SPEAKER_00: But, you know, we were talking so much about, I mean, CRISPR.
1:08:24
SPEAKER_00: Feels like it.
1:08:25
SPEAKER_00: Love.
1:08:27
SPEAKER_00: I get excited about these things.
1:08:28
SPEAKER_00: I mean, in many ways it has lived up to its hype and in many ways it has not.
1:08:32
SPEAKER_00: And yeah, where are you on?
1:08:35
SPEAKER_00: She was arguing and a lot of people argue this to me.
1:08:39
SPEAKER_00: Finally, we're getting better.
1:08:41
SPEAKER_00: Editors doing bigger swaths of DNA, doing less damage to the DNA when you're making cuts.
1:08:49
SPEAKER_00: Mm-hmm.
1:08:50
SPEAKER_00: Getting better delivery mechanisms, which I think is partially what you're talking about.
1:08:54
SPEAKER_00: I mean, yeah,
1:08:55
SPEAKER_00: so obviously you're kind of bullish that,
1:08:58
SPEAKER_00: I mean, it's sort of like when we sequenced the genome.
1:09:00
SPEAKER_00: It was like overnight that was meant to be a cure to every disease.
1:09:04
SPEAKER_00: You just had to like look at one person's DNA and everything would reveal itself.
1:09:09
SPEAKER_00: It turned out to be much harder.
1:09:10
SPEAKER_00: I feel like CRISPR's fallen into that category where everyone hears
1:09:14
SPEAKER_00: about this magical gene editor and then it turns out you have to do lots of work.
1:09:18
SPEAKER_00: To make this all function well.
1:09:19
SPEAKER_00: But yeah, so where are you on kind of the state of CRISPR?
1:09:24
SPEAKER_01: Yeah, I think that's right.
1:09:26
SPEAKER_01: I think in part,
1:09:28
SPEAKER_01: like the second half of my PhD that I wasn't working on reprogramming and aging,
1:09:31
SPEAKER_01: I was working on high throughput CRISPR genetic screens in aging.
1:09:35
SPEAKER_01: And I think CRISPR has had just like a revolution in terms of basic biology
1:09:41
SPEAKER_01: or even like slightly translational biology in terms of looking for new targets,
1:09:44
SPEAKER_01: in terms of just understanding cellular biology.
1:09:47
SPEAKER_01: It's been unbelievably impactful.
1:09:50
SPEAKER_01: And then I think in the human side,
1:09:51
SPEAKER_01: I think expectations got out ahead of what was realistic or feasible from
1:09:55
SPEAKER_01: a progress perspective.
1:09:57
SPEAKER_01: I think what you described in terms of DNA double-stranded breaks and genomic damage
1:10:02
SPEAKER_01: and off targets have been a huge hindrance.
1:10:06
SPEAKER_01: Maybe rightfully so.
1:10:07
SPEAKER_01: The FDA has taken a pretty conservative stance in terms of saying,
1:10:10
SPEAKER_01: all right,
1:10:10
SPEAKER_01: show me very long-term outcomes to prove that there aren't risks of rare events
1:10:15
SPEAKER_01: or cancers or something being caused by these off-targets.
1:10:17
SPEAKER_01: And in some cases,
1:10:18
SPEAKER_01: they have been caused,
1:10:20
SPEAKER_01: which I think there has been a huge cooling effect on that space.
1:10:25
SPEAKER_01: Where we've been extremely excited is,
1:10:28
SPEAKER_01: you know, an example, you had a lot of news on the podcast.
1:10:31
SPEAKER_01: So she's one of our founders, billing company, General Control.
1:10:35
SPEAKER_01: Using CRISPR technology.
1:10:36
SPEAKER_01: Hasn't aired yet, but,
1:10:38
SPEAKER_00: but it will,
1:10:38
SPEAKER_00: it will have by the time, by the time this one, I think I'll make sure it does.
1:10:44
SPEAKER_01: Well, I think you wrote a piece.
1:10:45
SPEAKER_01: Maybe that's what I meant to say.
1:10:46
SPEAKER_00: Oh, no, no, no.
1:10:47
SPEAKER_00: Sorry.
1:10:47
SPEAKER_00: Yes.
1:10:48
SPEAKER_00: Yes.
1:10:48
SPEAKER_00: Yes.
1:10:48
SPEAKER_00: No.
1:10:49
SPEAKER_00: Yes.
1:10:49
SPEAKER_00: We did.
1:10:50
SPEAKER_00: Yes.
1:10:50
SPEAKER_01: Wrote a piece about her.
1:10:52
SPEAKER_01: Sorry.
1:10:52
SPEAKER_01: I said pod piece.
1:10:53
SPEAKER_01: Uh, she wrote a piece about her.
1:10:54
SPEAKER_01: Uh, but so what she's doing is she's harnessing CRISPR technology, uh,
1:10:59
SPEAKER_01: making I'd say invariance of it to enable a world and that you can modify
1:11:04
SPEAKER_01: the epigenome without inducing DNA breaks or DNA damage or double-stranded breaks.
1:11:11
SPEAKER_01: And so that's something we're extremely excited about right now in terms
1:11:15
SPEAKER_01: of this ability for finite control and potentially longer endurance therapies.
1:11:22
SPEAKER_01: Maybe one time therapies or very long acting inhibition or activation of any gene in
1:11:28
SPEAKER_01: the genome or not every, but like a lot that weren't previously able to be targeted.
1:11:33
SPEAKER_01: And so I think we're just,
1:11:34
SPEAKER_01: you know,
1:11:34
SPEAKER_01: with a lot of technologies,
1:11:35
SPEAKER_01: we're about to see just like the next wave and the technology is going
1:11:38
SPEAKER_01: to end up being extremely impactful in humans.
1:11:40
SPEAKER_01: It was just slightly different.
1:11:41
SPEAKER_01: You know, the first generation, we didn't know at the time, but it just wasn't really ready.
1:11:46
SPEAKER_01: But yeah, like,
1:11:47
SPEAKER_01: you know,
1:11:48
SPEAKER_01: I've been I'm not very active in terms of investing
1:11:51
SPEAKER_01: in traditional CRISPR companies right now.
1:11:53
SPEAKER_01: I think that's very reflective of most of the investor base.
1:11:56
SPEAKER_01: At some point,
1:11:57
SPEAKER_01: you know,
1:11:57
SPEAKER_01: I think localized delivery,
1:11:58
SPEAKER_01: targeted delivery,
1:11:59
SPEAKER_01: these sorts of things will end up being really promising and great short term.
1:12:04
SPEAKER_01: Longer term,
1:12:05
SPEAKER_01: the technology is just going to have to evolve to like epi-editing or other sorts
1:12:08
SPEAKER_01: of approaches to enable the large scale impact.
1:12:11
SPEAKER_00: Okay.
1:12:11
SPEAKER_00: All right.
1:12:12
SPEAKER_00: Let's go rapid fire for a second.
1:12:14
SPEAKER_00: Okay.
1:12:18
SPEAKER_00: Yeah.
1:12:18
SPEAKER_00: I mean, I'll just throw a few things at you and you tell me if they're hot or not.
1:12:26
SPEAKER_00: Altos Labs been super secretive for a long time now.
1:12:30
SPEAKER_00: Do we have a,
1:12:32
SPEAKER_00: and if I put you in too uncomfortable of a position,
1:12:35
SPEAKER_00: I'll give you at least one pass.
1:12:38
SPEAKER_01: Yeah.
1:12:38
SPEAKER_01: Where's like the whiskey bottle?
1:12:39
SPEAKER_01: I need like to take a shot if I don't
1:12:41
SPEAKER_00: answer the question.
1:12:42
SPEAKER_00: We can do that if you like.
1:12:44
SPEAKER_00: Yeah.
1:12:44
SPEAKER_00: Like, I mean, I've heard kind of like nothing for a while.
1:12:47
SPEAKER_00: How do we, do we have any sense as to what's going on over there or how they're doing?
1:12:52
SPEAKER_01: Yeah.
1:12:52
SPEAKER_01: And for, I don't know, maybe a little bit of background for the listeners.
1:12:55
SPEAKER_01: Like I had a,
1:12:57
SPEAKER_01: I'd say a period in my life,
1:12:59
SPEAKER_01: maybe a year or two or a year or two ago where I was digging and doing a lot
1:13:04
SPEAKER_01: of journalistic
1:13:05
SPEAKER_01: on Altos and it was going well in terms of public reception
1:13:09
SPEAKER_01: because I think a lot of people want to know.
1:13:11
SPEAKER_01: And I got told by a couple of people that management at Altos was not very happy.
1:13:16
SPEAKER_01: Oh, I didn't know that.
1:13:17
SPEAKER_01: Journalistic work.
1:13:19
SPEAKER_01: But to know, I'm very happy to talk about it.
1:13:20
SPEAKER_01: Like, I think Altos, look, they need to be held to a high standard, just like with Calico.
1:13:25
SPEAKER_01: That's, you know, a whole other topic we can talk about later.
1:13:28
SPEAKER_00: That was next on the lightning round.
1:13:29
SPEAKER_00: Oh, perfect.
1:13:29
SPEAKER_00: So you can just do them both if you want.
1:13:31
SPEAKER_01: Yeah.
1:13:32
SPEAKER_01: I mean, in the spirit of lightning round,
1:13:34
SPEAKER_01: I'll try to keep it short where,
1:13:35
SPEAKER_01: yeah, these companies have taken a lot of resources for the space.
1:13:39
SPEAKER_01: They're seen as the bearweathers or the kind of barometers of whether
1:13:44
SPEAKER_01: the field is going to do well or not or is doing well or not.
1:13:47
SPEAKER_01: They should have extremely high expectations on them in terms of doing well.
1:13:50
SPEAKER_01: In the case of Altos Labs,
1:13:51
SPEAKER_01: they had a recent publication at a scientific conference
1:13:54
SPEAKER_01: that I thought was really interesting where this will be new to a lot of people,
1:13:57
SPEAKER_01: but they took organs for transplant and they showed
1:14:00
SPEAKER_01: that they could improve those organs using traditional OSCAM reprogramming.
1:14:05
SPEAKER_01: Before transplanting them into patients.
1:14:07
SPEAKER_00: Whoa.
1:14:08
SPEAKER_00: And so they're focused in humans.
1:14:11
SPEAKER_00: So they got, so they had an organ donor, hit it with the Yamanaka factors.
1:14:16
SPEAKER_00: Yes.
1:14:17
SPEAKER_00: Before it went into the person and sort of juiced it up.
1:14:20
SPEAKER_01: Yes.
1:14:20
SPEAKER_00: Okay.
1:14:20
SPEAKER_00: Okay.
1:14:21
SPEAKER_01: I believe this is a part of the direction they're going with reprogramming.
1:14:25
SPEAKER_01: And, you know, they presented that at a scientific conference recently.
1:14:28
SPEAKER_00: Wow, I didn't see that.
1:14:30
SPEAKER_01: In the past week,
1:14:31
SPEAKER_01: the Mayo Clinic announced that they have a transplantation center focused on aging.
1:14:35
SPEAKER_00: Oh no, wrong sound effect.
1:14:37
SPEAKER_00: I was going to celebrate that.
1:14:38
SPEAKER_00: Hang on.
1:14:40
SPEAKER_00: Okay, wait.
1:14:41
SPEAKER_00: All right, there we go.
1:14:43
SPEAKER_00: Sorry, I'm an idiot.
1:14:45
SPEAKER_01: Warranted for human organ rejuvenation, I think.
1:14:47
SPEAKER_00: I don't know.
1:14:48
SPEAKER_00: Other people do that for like stock bumps, but we do it for organ replacement.
1:14:52
SPEAKER_00: Okay.
1:14:53
SPEAKER_01: Yeah.
1:14:53
SPEAKER_01: So, you know, they presented this.
1:14:55
SPEAKER_01: I thought it was really cool.
1:14:57
SPEAKER_01: You know,
1:14:57
SPEAKER_01: beside that,
1:14:58
SPEAKER_01: some of my past Twitter threads,
1:14:59
SPEAKER_01: they've been working and publishing on like line one ASOs.
1:15:03
SPEAKER_01: So line one is a retrotransposon.
1:15:05
SPEAKER_01: So if you've heard of like jumping genes,
1:15:07
SPEAKER_01: there was a Nobel prize for this,
1:15:08
SPEAKER_01: like In our genome,
1:15:09
SPEAKER_01: there's a lot of genes that just like jump around and cause DNA damage in
1:15:14
SPEAKER_01: the process of doing so.
1:15:15
SPEAKER_01: It's thought that maybe damping those down could help us long-term in terms
1:15:20
SPEAKER_01: of specific diseases or long-term health outcomes
1:15:22
SPEAKER_01: if we could not have our genes jumping around.
1:15:25
SPEAKER_01: So that was one of their approaches that I think is pretty cool.
1:15:28
SPEAKER_01: But there's a bunch of other companies in the space and I haven't seen a lot
1:15:31
SPEAKER_01: of activity pushing it along.
1:15:33
SPEAKER_01: They kind of very stealthily acquired a company that we were an investor in,
1:15:37
SPEAKER_01: but it was very under the radar in terms of that happening.
1:15:43
SPEAKER_01: They've been extremely quiet and they have very smart people.
1:15:46
SPEAKER_01: Hal Barron is incredibly sharp,
1:15:49
SPEAKER_01: really smart in terms of how he's thinking about clinical trial design for humans.
1:15:53
SPEAKER_01: These three centers across UK, SF, San Diego.
1:15:58
SPEAKER_01: There's been some rumors about people being cut from some of these sites recently.
1:16:04
SPEAKER_01: We still don't really know.
1:16:05
SPEAKER_01: And at the same time,
1:16:06
SPEAKER_01: you know,
1:16:06
SPEAKER_01: at the Aspen Ideas Festival,
1:16:08
SPEAKER_01: I think Rick Klosner was making pretty exciting claims about,
1:16:12
SPEAKER_01: you know,
1:16:12
SPEAKER_01: treating thousands of mice with reprogramming factors
1:16:15
SPEAKER_01: and seeing really dramatic effects in terms of lifespan.
1:16:20
SPEAKER_01: Hopefully we'll find out soon.
1:16:21
SPEAKER_00: Okay, well you can just publish your findings under a pseudonym on Core Memory is no problem.
1:16:29
SPEAKER_00: I was enjoying your journalistic work if they weren't.
1:16:33
SPEAKER_00: I guess that is awkward.
1:16:34
SPEAKER_00: You're like a VC and then you're kind of rubbing some people the wrong way
1:16:40
SPEAKER_00: that you might be interacting with or running into.
1:16:43
SPEAKER_01: Some people respect it.
1:16:45
SPEAKER_01: I think there's definitely some people at Altos that are like,
1:16:47
SPEAKER_01: appreciate you bringing light to our hard work and like getting people excited
1:16:50
SPEAKER_01: about what we're doing.
1:16:52
SPEAKER_01: And I like to hear those people versus, yeah,
1:16:54
SPEAKER_01: I think the other take is they want the competitive advantage
1:16:57
SPEAKER_01: of they don't want other people doing what they're doing.
1:16:58
SPEAKER_01: They don't want other people to,
1:17:00
SPEAKER_01: you know, it's a bigger moat for them if people don't know what they're doing.
1:17:03
SPEAKER_01: So, I mean, I get it.
1:17:04
SPEAKER_01: I totally get it.
1:17:04
SPEAKER_00: Well, just tell me everything, man.
1:17:06
SPEAKER_00: Yeah.
1:17:08
SPEAKER_00: For real.
1:17:10
SPEAKER_00: And, and Calico been around forever.
1:17:13
SPEAKER_00: Do we, do we know at all what they are actually doing?
1:17:16
SPEAKER_00: Yeah.
1:17:17
SPEAKER_01: Yeah.
1:17:17
SPEAKER_01: So Calico is an interesting one in that like,
1:17:19
SPEAKER_01: it was a core to me, even in undergrad, I like when there was this time magazine.
1:17:25
SPEAKER_01: Uh, cover that was like, can Google solve death?
1:17:28
SPEAKER_00: Yeah.
1:17:29
SPEAKER_01: And I literally like printed it out.
1:17:30
SPEAKER_01: I like kept it on my desk for like three years of my life, just being like, this is so cool.
1:17:34
SPEAKER_01: Like a huge organization,
1:17:36
SPEAKER_01: you know,
1:17:37
SPEAKER_01: Google is,
1:17:38
SPEAKER_01: is willing to work on aging and not just that they're bringing Art Levinson, uh,
1:17:42
SPEAKER_01: who is a legend at Genentech and,
1:17:44
SPEAKER_01: and just like top of the top in terms of drug developers.
1:17:48
SPEAKER_01: And bringing a lot of these experienced people into this organization,
1:17:51
SPEAKER_01: I applied to Calico before I actually applied to my PhD programs.
1:17:55
SPEAKER_01: And I was like, please give me a job.
1:17:56
SPEAKER_01: I'll sweep the floors for free, literally said that.
1:17:59
SPEAKER_01: And they said, go get a PhD.
1:18:00
SPEAKER_01: And so I got a PhD.
1:18:02
SPEAKER_01: So yeah, I've been following Calico extremely closely over the past decade.
1:18:06
SPEAKER_01: We've got an awesome founder, Adam Froyin, who used to work at Calico.
1:18:10
SPEAKER_01: Jacob Kimmel used to work at Calico.
1:18:11
SPEAKER_01: Their alumni is Like their talent for their early positions.
1:18:16
SPEAKER_01: And, you know, this is obviously why I got turned down.
1:18:19
SPEAKER_01: They had like 10,000 applications for every one position.
1:18:21
SPEAKER_01: It was crazy.
1:18:24
SPEAKER_01: And so, yeah, it's been, I don't know, what, like 13 years of Calico now.
1:18:30
SPEAKER_01: AbbVie just recently walked away from their big partnership.
1:18:33
SPEAKER_01: We don't know why yet, but AbbVie was putting in like billions of dollars.
1:18:37
SPEAKER_01: I think it was like So that's a big question mark.
1:18:42
SPEAKER_01: We need to find out what happened there.
1:19:02
SPEAKER_01: Calico did publish a lot.
1:19:04
SPEAKER_01: And so I highly encourage everyone to go check out Calico's publications.
1:19:06
SPEAKER_01: I think they've been extremely high quality science, really productive and great for the field.
1:19:11
SPEAKER_01: But I think Calico kind of realized like,
1:19:13
SPEAKER_01: oh, we made a mistake in being super secretive and people don't like it.
1:19:16
SPEAKER_01: And Calico is one of their own founders,
1:19:18
SPEAKER_01: you know,
1:19:18
SPEAKER_01: publicly was in the media criticizing them as an organization
1:19:22
SPEAKER_01: and saying they didn't accomplish what,
1:19:24
SPEAKER_01: you know,
1:19:24
SPEAKER_01: the goals of the founding Calico,
1:19:27
SPEAKER_01: Google members and kind of creating the organization was.
1:19:30
SPEAKER_01: Um, and, and so I, I think they're doing a really cool stuff now.
1:19:34
SPEAKER_01: Um, you know,
1:19:35
SPEAKER_01: I think they're working on things that people would be surprised
1:19:38
SPEAKER_01: to hear they're working on.
1:19:39
SPEAKER_01: I think the public pipeline right now is really impressive.
1:19:42
SPEAKER_01: Um, but I think it's just this question of,
1:19:44
SPEAKER_01: are they ever going to really move the needle and really be more aggressive?
1:19:50
SPEAKER_01: Um, we'll see.
1:19:51
SPEAKER_00: Yeah.
1:19:52
SPEAKER_00: Okay.
1:19:52
SPEAKER_00: Okay.
1:19:53
SPEAKER_00: Then, um,
1:19:55
SPEAKER_00: What's like the most exciting thing you think people will see in the next,
1:19:59
SPEAKER_00: like, call it two years in this field?
1:20:05
SPEAKER_00: Like, is there something you see right on the horizon that's amazing?
1:20:09
SPEAKER_01: I hope it's these transplantation results and whether that's either...
1:20:14
SPEAKER_01: I co-founder Laura at Intel Labs and the work they're doing in cryo or it,
1:20:20
SPEAKER_01: you know,
1:20:20
SPEAKER_01: loyal with,
1:20:21
SPEAKER_01: I think that the dog thing,
1:20:22
SPEAKER_01: I think it's,
1:20:23
SPEAKER_01: it's really hard to say the dog thing is not going to be the turning point.
1:20:26
SPEAKER_00: Yeah.
1:20:26
SPEAKER_01: Cause I think the second that loyal gets a green light from the FDA.
1:20:30
SPEAKER_01: I think that's our ChatGBT moment of just this entering thousands and millions
1:20:35
SPEAKER_01: of people's homes.
1:20:36
SPEAKER_01: I think the aging field has been waiting for a win for a very long time to be able
1:20:40
SPEAKER_01: to say like, yes, we can do this.
1:20:41
SPEAKER_01: We can modify aging beyond mice.
1:20:45
SPEAKER_01: And For me,
1:20:46
SPEAKER_01: I think it's the loyal moment of hopefully millions of households and dogs in
1:20:52
SPEAKER_01: the U.S.
1:20:53
SPEAKER_01: experiencing that aging can be modified and just like the beauty of
1:20:57
SPEAKER_01: that psychological shift for people of,
1:21:00
SPEAKER_01: oh, wow, like I don't have to accept decline with age.
1:21:02
SPEAKER_01: There might be some better future where we can have our physical independence longer
1:21:07
SPEAKER_01: and run and play and all these sorts of things like.
1:21:09
SPEAKER_01: We're so close to that moment.
1:21:12
SPEAKER_01: And knock on wood, that happens next year
1:21:14
SPEAKER_00: with Loyal.
1:21:15
SPEAKER_00: How do you stay on top?
1:21:17
SPEAKER_00: I'm sure when the startups come to you,
1:21:21
SPEAKER_00: you have people knocking on your door all the time and then you guys are trying
1:21:24
SPEAKER_00: to do your due diligence and research them and everything.
1:21:28
SPEAKER_00: But do you go hunting for...
1:21:32
SPEAKER_00: Outliers,
1:21:34
SPEAKER_00: scientists in some lab that have a big idea,
1:21:36
SPEAKER_00: like how do you,
1:21:38
SPEAKER_00: what do you read or how do you, are you just doing papers all the time?
1:21:41
SPEAKER_00: How do you stay on top of everything?
1:21:43
SPEAKER_01: Yeah.
1:21:43
SPEAKER_01: So, I mean,
1:21:44
SPEAKER_01: in part of it,
1:21:45
SPEAKER_01: I think one of Laura and I's superpowers is attracting some of the best,
1:21:54
SPEAKER_01: most ambitious young talent of any field that you'll find.
1:21:58
SPEAKER_01: Um, so I think one of like the most proud of things in my whole career is just like
1:22:02
SPEAKER_01: the team we have right now at, at, at age one in terms of the, the young talent.
1:22:07
SPEAKER_01: Um, you know,
1:22:08
SPEAKER_01: we have, uh,
1:22:10
SPEAKER_01: we have a bunch of venture fellows and,
1:22:13
SPEAKER_01: and principals that are, uh,
1:22:15
SPEAKER_01: undergrads and grad students, um, Kat, Sophic, Soleil,
1:22:20
SPEAKER_01: Lynetta, uh,
1:22:21
SPEAKER_01: that's like,
1:22:21
SPEAKER_01: they're just unbelievably talented, Maggie, uh,
1:22:25
SPEAKER_01: And I think they just have this superpower of being in the inn
1:22:29
SPEAKER_01: and all their individual spheres and knowledge circles.
1:22:33
SPEAKER_01: And so it's like, it's not a one person job, it's a team thing.
1:22:36
SPEAKER_01: And I think as a team, we just have a lot of fun being able to kind of Yeah.
1:22:40
SPEAKER_01: Okay.
1:22:40
SPEAKER_01: Um,
1:23:05
SPEAKER_00: Well, I always try to be respectful to people's time.
1:23:08
SPEAKER_00: I've dragged you all over the place.
1:23:10
SPEAKER_00: Is there anything, I mean, I know you're into so many interesting things.
1:23:13
SPEAKER_00: Is there something that is top of mind that I just grossly ignored or that we should bring up?
1:23:21
SPEAKER_01: I think maybe this like translation to humans thing is maybe the one thing
1:23:27
SPEAKER_01: which is like I think this next five years is going to be really pivotal moment
1:23:34
SPEAKER_01: for seeing these aging therapies translate.
1:23:37
SPEAKER_01: And in part,
1:23:38
SPEAKER_01: like the federal government has been really interesting in terms of their motion
1:23:42
SPEAKER_01: in this area.
1:23:43
SPEAKER_01: ARPA-H is like the DARPA, but for health.
1:23:47
SPEAKER_01: They have a number of program managers working in this space.
1:23:51
SPEAKER_01: And I'd say that's something that I think people should be more aware of is
1:23:56
SPEAKER_01: that now is the time for human trials and testing things in humans.
1:24:00
SPEAKER_00: Why?
1:24:00
SPEAKER_00: Like,
1:24:01
SPEAKER_00: just because we've been researching this for so long and now it's baked and ready
1:24:05
SPEAKER_00: to be tested?
1:24:06
SPEAKER_01: Yeah, I think I think it's been an Overton window thing in part and the FDA has been
1:24:10
SPEAKER_01: for their part,
1:24:11
SPEAKER_01: you know,
1:24:11
SPEAKER_01: willing to engage on it,
1:24:13
SPEAKER_01: but there just hasn't been a lot of practical things and pragmatic things brought
1:24:16
SPEAKER_01: to them.
1:24:16
SPEAKER_01: I think we're going to see a lot more pragmatic things brought to them over
1:24:19
SPEAKER_01: the next two or three years and.
1:24:21
SPEAKER_01: I think through RBH and others,
1:24:23
SPEAKER_01: we're going to see really exciting efforts funded in the space to put a lot
1:24:27
SPEAKER_01: of these hypotheses to the test in humans.
1:24:29
SPEAKER_01: And like to have more things that work, you need to test more things.
1:24:33
SPEAKER_01: And to test more things, we need costs to decrease to test things and cycle times to get faster.
1:24:38
SPEAKER_01: That I think is going to be a big focus in the next five years.
1:24:41
SPEAKER_00: I always ask this question.
1:24:43
SPEAKER_00: People probably get tired of it.
1:24:44
SPEAKER_00: I mean, do you think...
1:24:46
SPEAKER_00: I mean, is China who, who,
1:24:48
SPEAKER_00: you know,
1:24:49
SPEAKER_00: when you're talking about human enhancements and, um,
1:24:54
SPEAKER_00: so many of these promising things,
1:24:56
SPEAKER_00: I mean, there's just no question that running trials is immensely cheaper in China.
1:25:01
SPEAKER_00: Um, they are more,
1:25:03
SPEAKER_00: you know,
1:25:03
SPEAKER_00: for better or worse,
1:25:04
SPEAKER_00: adventurous with running experiments on people, um,
1:25:08
SPEAKER_00: and primates,
1:25:09
SPEAKER_00: but, but, you know, willing to do things we're quite cautious about and.
1:25:14
SPEAKER_00: I think it's fair to say, well,
1:25:16
SPEAKER_00: I'm sure it is fair to say,
1:25:17
SPEAKER_00: kind of coming from behind on terms of the pure science,
1:25:20
SPEAKER_00: but catching up and advancing very quickly.
1:25:23
SPEAKER_00: And so, yeah, I mean,
1:25:24
SPEAKER_00: like in 20 years, I mean,
1:25:25
SPEAKER_00: is the U.S.,
1:25:26
SPEAKER_00: for all these things that you've just been talking about,
1:25:28
SPEAKER_00: is the U.S. the driving force or is China the driving force of this biorevolution?
1:25:36
SPEAKER_01: That is a bit of the irony of all the companies that have pitched the AI platforms
1:25:42
SPEAKER_01: and this and that,
1:25:42
SPEAKER_01: that is reducing,
1:25:44
SPEAKER_01: you know, dramatically reducing truck discovery costs and truck development costs.
1:25:48
SPEAKER_01: And then,
1:25:49
SPEAKER_01: you know,
1:25:49
SPEAKER_01: despite all of that excitement and hype and some under promising and over promising,
1:25:55
SPEAKER_01: China comes in for the past five years.
1:25:59
SPEAKER_01: Really dramatically lowers the cost of trials by like five to 10 X and the speed
1:26:03
SPEAKER_01: and investigator initiated trials and all these sorts of things.
1:26:06
SPEAKER_01: And it's like, oh wow,
1:26:07
SPEAKER_01: like all this hype about like technology being able to do this in the US and
1:26:10
SPEAKER_01: then China just does it for totally different reasons.
1:26:13
SPEAKER_00: It's like, we don't need a virtual cell.
1:26:15
SPEAKER_00: We have one.
1:26:19
SPEAKER_00: We just test more things and
1:26:20
SPEAKER_01: faster and cheaper.
1:26:21
SPEAKER_01: And it's been revolutionary.
1:26:23
SPEAKER_01: Yeah.
1:26:25
SPEAKER_01: So, I mean,
1:26:25
SPEAKER_01: I think we're seeing some cool efforts by the FDA right now to try to catch up and
1:26:30
SPEAKER_01: to try to do our own unique things.
1:26:32
SPEAKER_01: Marty McCary published in New England Journal of Medicine some discourse yesterday
1:26:38
SPEAKER_01: about the kind of push to instead of having two confirmatory trials, one.
1:26:43
SPEAKER_01: These sorts of things, I think the U.S. is going to make a pretty dramatic shift.
1:26:47
SPEAKER_01: But ultimately,
1:26:48
SPEAKER_01: like I think that impact has already been felt and it'll like continuously,
1:26:51
SPEAKER_01: you know, be nice.
1:26:51
SPEAKER_01: But I don't think it's going to have like,
1:26:53
SPEAKER_01: you know,
1:26:54
SPEAKER_01: the change that's going to happen is China has been flipping to outnumber the U.S.
1:26:58
SPEAKER_01: in terms of basic research.
1:26:59
SPEAKER_01: Right now,
1:27:00
SPEAKER_01: China has been innovating on development,
1:27:01
SPEAKER_01: but they haven't necessarily been innovating on target discovery to the same extent
1:27:06
SPEAKER_01: as the U.S. is still the leader in.
1:27:08
SPEAKER_01: That's going to flip.
1:27:09
SPEAKER_01: If you just look at the publications of the basic science and the amount
1:27:11
SPEAKER_01: of funding going into it and like where the top talent is,
1:27:14
SPEAKER_01: like they're also going to get to a point where a lot of the new targets,
1:27:18
SPEAKER_01: a lot of the exciting new discoveries are going to come out of China.
1:27:20
SPEAKER_01: So that I think is going to be the next wave that's going to hit the US is that realization.
1:27:25
SPEAKER_01: And that's going to be a pretty stark and heavy hitting realization when that happens.
1:27:30
SPEAKER_01: But I think the cool part of all the AI platforms and this sort of stuff is
1:27:34
SPEAKER_01: that I don't think the upside of that, we haven't seen it yet.
1:27:37
SPEAKER_01: It will hit, but over the next five to 10 years.
1:27:40
SPEAKER_01: So I think the amount of dramatic change that can come from AI,
1:27:43
SPEAKER_01: it's going to be a steeper curve in terms of impact.
1:27:46
SPEAKER_01: But we just haven't hit the inflection point
1:27:47
SPEAKER_01: yet versus China has had its inflection point of impact there.
1:27:51
SPEAKER_00: And like when you see the Chan Zuckerberg initiative,
1:27:56
SPEAKER_00: or I don't know,
1:27:57
SPEAKER_00: any number of groups,
1:27:58
SPEAKER_00: Art Institute, um,
1:28:00
SPEAKER_00: working on things like virtual cells, uh,
1:28:05
SPEAKER_00: the idea that we could simulate a lot of these processes and get,
1:28:09
SPEAKER_00: get biology to the level of detail that we need to do this.
1:28:12
SPEAKER_00: I do, do you.
1:28:14
SPEAKER_00: I mean, yeah, does that excite you?
1:28:16
SPEAKER_00: I mean, I'm sure it excites you,
1:28:17
SPEAKER_00: but does it,
1:28:18
SPEAKER_00: you know,
1:28:19
SPEAKER_00: does it,
1:28:20
SPEAKER_00: I don't know what excites you,
1:28:20
SPEAKER_00: but do you, yeah,
1:28:24
SPEAKER_00: I mean, I can't tell how real some of that stuff is or how real to take it yet.
1:28:31
SPEAKER_01: Yeah, I mean, I'd say like virtual cell, I think was a misnomer.
1:28:35
SPEAKER_01: Like, what was his name?
1:28:37
SPEAKER_01: Andrew White from Future House, CSO there.
1:28:41
SPEAKER_01: He had a really cool blog post breaking down,
1:28:43
SPEAKER_01: like if you were to model a virtual human cell, how long would it take you?
1:28:48
SPEAKER_01: And I believe his conclusion was to like model it for just like one day.
1:28:52
SPEAKER_01: It would take you to like 2070 or something like that.
1:28:55
SPEAKER_01: Even with like extrapolating what data is going to do and what computability is going to change.
1:29:01
SPEAKER_01: And so that was just like one sell for one day.
1:29:05
SPEAKER_01: So the virtual cell thing, I think, is misnomer.
1:29:06
SPEAKER_01: In terms of predictions on, like,
1:29:08
SPEAKER_01: you make a perturbation,
1:29:10
SPEAKER_01: here's what it causes at the level of the genome,
1:29:13
SPEAKER_01: or like RNA gene expression,
1:29:16
SPEAKER_01: I think those models have been really exciting and really impactful.
1:29:20
SPEAKER_01: And I think that's kind of what people mean when they talk about virtual cell
1:29:23
SPEAKER_01: and what we're seeing right now.
1:29:25
SPEAKER_01: Protein-protein interactions, AI has come a long way.
1:29:28
SPEAKER_01: Obviously, AlphaFold has been completely revolutionary.
1:29:31
SPEAKER_01: And it's like a lot of things, like, You know, we take it for granted so fast.
1:29:35
SPEAKER_01: It's like with Waymos, it's like, oh, onto the next thing.
1:29:38
SPEAKER_01: Like, it's like completely revolutionary.
1:29:39
SPEAKER_01: And then like the next month you're like, okay, yeah, duh.
1:29:42
SPEAKER_01: Like what's next?
1:29:44
SPEAKER_01: So yeah,
1:29:45
SPEAKER_01: I think it's going to be insanely impactful,
1:29:46
SPEAKER_01: but I don't think we're going to be able to just model cells or whole organisms to
1:29:51
SPEAKER_01: the fidelity that we do to replace trials in the next 10 years.
1:29:55
SPEAKER_00: I don't know if you can talk about this.
1:29:57
SPEAKER_00: What's the...
1:29:59
SPEAKER_00: Most batshit crazy idea someone has come to you with,
1:30:04
SPEAKER_00: you know, I mean,
1:30:04
SPEAKER_00: you can name names if you want,
1:30:06
SPEAKER_00: but I mean,
1:30:08
SPEAKER_00: we're like starting to run up against stuff where,
1:30:11
SPEAKER_00: you know,
1:30:11
SPEAKER_00: you're talking about the right having concerns with like stem cells things.
1:30:15
SPEAKER_00: I mean, you know, I think you and I both know people who are.
1:30:19
SPEAKER_00: Growing headless bodies to harvest organs and,
1:30:23
SPEAKER_00: and, you know, I mean, there's going to be some big, um, big stuff to talk about.
1:30:26
SPEAKER_00: Yeah.
1:30:26
SPEAKER_00: I mean, what's, what's the craziest idea that comes to the top, top of mind?
1:30:31
SPEAKER_01: I'm supposed to top that one?
1:30:32
SPEAKER_00: Yeah.
1:30:33
SPEAKER_00: I figure you must get the best, the best shit.
1:30:37
SPEAKER_01: Well, I mean, yeah, I mean, why not?
1:30:41
SPEAKER_01: Uh, like.
1:30:42
SPEAKER_01: Why I'm destroying my own reputation.
1:30:45
SPEAKER_01: Like, you know,
1:30:46
SPEAKER_01: something I've always been fascinated by is there's a company that we funded out
1:30:50
SPEAKER_01: of Yale Technology, not at age one, but my previous job with James called Becksword.
1:30:54
SPEAKER_01: Oh, I love that.
1:30:55
SPEAKER_01: You know, keeping brains alive outside the body.
1:30:57
SPEAKER_00: We have an episode coming.
1:31:01
SPEAKER_00: Oh, okay.
1:31:02
SPEAKER_01: That's really, really exciting.
1:31:03
SPEAKER_01: So, you know,
1:31:03
SPEAKER_01: they had two nature papers showing that you can keep pig brains alive outside
1:31:06
SPEAKER_01: the body and entire pigs bring them back from cardiac arrest.
1:31:10
SPEAKER_01: And it's really cool.
1:31:12
SPEAKER_01: Something that I've always wondered about and been really excited about,
1:31:14
SPEAKER_01: is there a way to enable a kind of,
1:31:17
SPEAKER_01: you know,
1:31:18
SPEAKER_01: for somebody that has an incurable disease or a metastatic cancer,
1:31:21
SPEAKER_01: is there a way to Gosh,
1:31:24
SPEAKER_01: I don't want to say Futurama,
1:31:25
SPEAKER_01: but like, you know, keep a head alive without the body, right?
1:31:28
SPEAKER_01: We have these amazing ECMO machines that are in most emergency centers around
1:31:33
SPEAKER_01: the world that are a way to kind of replace certain organ functions.
1:31:38
SPEAKER_01: Certain people have been kept alive on ECMO without their own organ functions
1:31:43
SPEAKER_01: for like months, like six months, I think four to six months in some cases.
1:31:47
SPEAKER_01: Is there a world in the future in that like somebody that has no other options,
1:31:52
SPEAKER_01: metastatic cancer, it's all over their body.
1:31:54
SPEAKER_01: Is there a way that you could keep someone's head alive in Futurama style on like,
1:31:58
SPEAKER_01: you know, some sort of like a robot or, you know, mobile machine?
1:32:02
SPEAKER_00: Would they be like alive or kind of coma until something better comes along?
1:32:06
SPEAKER_00: I think they could be alive.
1:32:07
SPEAKER_00: Like just chatting.
1:32:08
SPEAKER_01: Yeah, yeah, yeah.
1:32:09
SPEAKER_00: I think like the lymph system is the hardest part
1:32:12
SPEAKER_01: to solve there.
1:32:13
SPEAKER_01: Yeah.
1:32:15
SPEAKER_01: But in terms of most, I mean, the problem, lungs, you're right.
1:32:18
SPEAKER_01: Like you'd have to do silent speech,
1:32:20
SPEAKER_01: but I think you could still have vision and taste and hearing.
1:32:25
SPEAKER_01: Oh, wow.
1:32:25
SPEAKER_01: But like this is something that I think,
1:32:30
SPEAKER_01: you know,
1:32:30
SPEAKER_01: I don't think it's like a 10-year thing,
1:32:31
SPEAKER_01: but I think like a 20 to 30-year thing, it like, Could be really interesting.
1:32:36
SPEAKER_00: You could be like a head eating stuff, but like- I don't think
1:32:41
SPEAKER_01: you'd eat stuff.
1:32:42
SPEAKER_00: When you started talking about tasting, I was like, how is this going to work, man?
1:32:46
SPEAKER_01: What the- I just mean that like physically your tongue could like put
1:32:50
SPEAKER_01: against your tongue and be like, oh, okay.
1:32:52
SPEAKER_01: I taste that.
1:32:52
SPEAKER_01: Yeah.
1:32:52
SPEAKER_01: I think you get nutrients.
1:32:54
SPEAKER_00: I was about to ask you where that is like how you're not gaining weight, I guess.
1:32:58
SPEAKER_01: Yeah.
1:32:59
SPEAKER_01: You'd get nutrients shot up.
1:33:00
SPEAKER_01: I think, I think you'd get like nutrients ejected in your system.
1:33:03
SPEAKER_01: Right.
1:33:03
SPEAKER_01: So I mean, this is something I've long been obsessed with because it's just like.
1:33:07
SPEAKER_01: Horrific in terms of, you know, somebody with metastatic cancer, they have no option.
1:33:11
SPEAKER_01: Stage four, like,
1:33:13
SPEAKER_01: I don't know how much time you've spent on the Facebook groups in terms of some
1:33:16
SPEAKER_01: of these rare terminal illnesses.
1:33:18
SPEAKER_01: It's horrifying.
1:33:20
SPEAKER_01: It'll like literally, you know, just gut-wrenching to read these stories.
1:33:25
SPEAKER_01: I'm extremely excited about reversible cryopreservation as a way to kind
1:33:29
SPEAKER_01: of give people with a curable illness the chance to come back when they have
1:33:32
SPEAKER_01: a chance to have a cure for their illness.
1:33:34
SPEAKER_01: I think that's going to be You know,
1:33:36
SPEAKER_01: one of the most traumatic impacts to medicine that's ever happened.
1:33:40
SPEAKER_01: You know,
1:33:40
SPEAKER_01: I wonder if there's some other option of,
1:33:43
SPEAKER_01: you know,
1:33:43
SPEAKER_01: people have been in like iron lungs for,
1:33:45
SPEAKER_01: I don't know, 40 years of their life happily.
1:33:49
SPEAKER_01: This seems even more improved state to me in terms of like being mobile
1:33:52
SPEAKER_01: and being able to integrate.
1:33:54
SPEAKER_01: I don't know.
1:33:54
SPEAKER_01: You know, it's a crazy sci-fi idea.
1:33:56
SPEAKER_01: Beside that, you know, all the things you mentioned.
1:33:58
SPEAKER_00: You're like a head in a Waymo.
1:34:00
SPEAKER_00: He's just cruising, road tripping, man.
1:34:02
SPEAKER_00: Yeah.
1:34:03
SPEAKER_01: Why not?
1:34:04
SPEAKER_01: Why not?
1:34:04
SPEAKER_01: Like, I think people should have the choice,
1:34:07
SPEAKER_01: you know,
1:34:07
SPEAKER_01: anybody that has a relative with a terminal illness,
1:34:09
SPEAKER_01: I think a lot of them would probably agree.
1:34:11
SPEAKER_01: They'd wish they,
1:34:12
SPEAKER_01: you know,
1:34:13
SPEAKER_01: that their mom or their dad or their sister or brother,
1:34:16
SPEAKER_01: you know, I think they want them to have the choice.
1:34:19
SPEAKER_00: I'm just laughing.
1:34:21
SPEAKER_00: Oh God, that's good.
1:34:26
SPEAKER_00: I mean, it is weird.
1:34:29
SPEAKER_00: I am extrapolating too far,
1:34:31
SPEAKER_00: but yeah,
1:34:31
SPEAKER_00: between Bexorg and I think Becoming, I mean,
1:34:35
SPEAKER_00: it feels like we're these perfusion devices that sort of replicate functions of
1:34:41
SPEAKER_00: the body.
1:34:43
SPEAKER_00: Again, I think I'm going maybe too far, but you were hinting at it.
1:34:47
SPEAKER_00: Yeah, it seems like we're getting better at replicating these Functions of the body.
1:34:51
SPEAKER_00: Um, and because we, yeah, I mean,
1:34:54
SPEAKER_00: Bexorg is the only one that I know of that can keep a brain going and becoming,
1:34:58
SPEAKER_00: doing all kinds of interesting stuff.
1:35:00
SPEAKER_01: Um, yeah, I don't think you are getting too ahead of yourself.
1:35:02
SPEAKER_01: Like it was the, you know, science magazine breakthrough of the year or two years ago, right.
1:35:06
SPEAKER_01: Or three years ago of.
1:35:08
SPEAKER_01: Synthetic embryos or integrated stem cell models where we can now,
1:35:11
SPEAKER_01: you know,
1:35:11
SPEAKER_01: instead of needing egg and sperm to create potentially,
1:35:15
SPEAKER_01: you know,
1:35:15
SPEAKER_01: a new embryo system to study,
1:35:18
SPEAKER_01: we have another way using embryonic stem cell technology.
1:35:21
SPEAKER_01: And I mean, that's revolutionary.
1:35:23
SPEAKER_01: Like, I think this world of having replacement Parts and organs.
1:35:28
SPEAKER_01: I mean, right now it's pretty much only discussed by Xi Jinping and Putin together,
1:35:33
SPEAKER_01: which is like probably the worst PR that the aging field could ever have
1:35:36
SPEAKER_01: to have those two talk about this.
1:35:40
SPEAKER_01: I think it's like very easy to have a dystopian lens to the field,
1:35:43
SPEAKER_01: but at the end of the day, I think it's like.
1:35:46
SPEAKER_01: It's just going to bring so much quality of life and happiness.
1:35:52
SPEAKER_01: And I'm confident we will do it in a very equitable and distributable way.
1:35:55
SPEAKER_01: And yeah, I don't think it's that far off.
1:35:57
SPEAKER_01: I think it is time to dig into these sorts of things.
1:36:02
SPEAKER_00: Well, you did it, man.
1:36:06
SPEAKER_00: You answered the call.
1:36:07
SPEAKER_00: That was fantastic.
1:36:08
SPEAKER_00: Yeah.
1:36:11
SPEAKER_00: It is sort of a shame that Futurama has already depicted some of this.
1:36:15
SPEAKER_00: The things going around in my head were amazing.
1:36:19
SPEAKER_00: That was fantastic.
1:36:20
SPEAKER_00: Well, Alex, thank you so much.
1:36:22
SPEAKER_00: I guess people can find you on Age One and on X,
1:36:27
SPEAKER_00: and I'm sad that they've Clamp down on your journalism though.
1:36:32
SPEAKER_00: I mean, really, come on, just send it to me.
1:36:34
SPEAKER_00: Send it to us.
1:36:35
SPEAKER_00: We got you.
1:36:35
SPEAKER_00: We got you.
1:36:37
SPEAKER_00: But yeah, no, man, it's been so fun getting to know you.
1:36:40
SPEAKER_00: You are just like encyclopedic on your knowledge of this stuff.
1:36:44
SPEAKER_00: And it's rare to...
1:36:48
SPEAKER_00: I'm going to have a guest on in...
1:36:50
SPEAKER_00: A couple weeks who I think of in a similar way around nuclear energy.
1:36:55
SPEAKER_00: It's just,
1:36:55
SPEAKER_00: it's rare to kind of find these people that I just really,
1:36:57
SPEAKER_00: really trust on their subject matter and that can go so deep.
1:37:03
SPEAKER_00: And so it's just, it's amazing.
1:37:05
SPEAKER_00: And I'm glad everyone got to kind of meet you a little bit.
1:37:08
SPEAKER_01: Appreciate you having me on a bunch.
1:37:10
SPEAKER_01: And yeah, can't,
1:37:13
SPEAKER_01: so excited for the next decade and Uh,
1:37:15
SPEAKER_01: have a new reveal to the world, the crazy stuff that we're going to do as a field.
1:37:18
SPEAKER_00: We're going to do it.
1:37:19
SPEAKER_00: We're going to do it.
1:37:20
SPEAKER_00: Um, okay.
1:37:20
SPEAKER_00: So everyone check out Alex.
1:37:23
SPEAKER_00: Thank you very much.
1:37:23
SPEAKER_00: And yeah,
1:37:23
SPEAKER_00: we will have,
1:37:24
SPEAKER_00: I don't know when this will air,
1:37:27
SPEAKER_00: but if it's out and you haven't seen it, you must watch our Bexorg episode.
1:37:32
SPEAKER_00: And I think I'm going to write a big long.
1:37:35
SPEAKER_00: Feature story because it is probably easy.
1:37:39
SPEAKER_00: Definitely in my top five companies I've run across in years and probably like possibly one.
1:37:44
SPEAKER_00: I don't know.
1:37:45
SPEAKER_00: I'm not going to rank them all off the top of my head, but amazing stuff.
1:37:49
SPEAKER_00: And with that, thank you all for listening and we will see you again soon.
1:37:54
SPEAKER_01: Love it.
1:37:55
SPEAKER_01: Thanks, man.
1:37:56
SPEAKER_01: We use Brex and they're amazing.
1:37:58
SPEAKER_01: Oh, do it.
1:37:59
SPEAKER_00: Shout out to Brex.
1:38:01
SPEAKER_00: Wait, do you use Brex?
1:38:03
SPEAKER_01: We actually use Brex.
1:38:05
SPEAKER_01: Most of our portfolio companies use Brex and we fucking love them.
1:38:08
SPEAKER_01: Oh, not supposed to say that part, but they're great.
1:38:10
SPEAKER_00: No, this is good.
1:38:12
SPEAKER_00: Now this is like a real guest, man.
1:38:15
SPEAKER_00: I mean...
1:38:17
SPEAKER_00: Answering the call on the tough questions and then coming through with
1:38:20
SPEAKER_00: the totally natural Brex shout out.
1:38:23
SPEAKER_01: It's kind of like a war right now going on between the two of them with the acquisition.
1:38:27
SPEAKER_01: It's been like the talk of the town.
1:38:29
SPEAKER_01: So I'm like, you know, I had to make clear what side we were on.
1:38:31
SPEAKER_00: It's important.
1:38:32
SPEAKER_00: It is a war and we will only say Brex's name.
1:38:35
SPEAKER_00: We will not say who this war involves.
1:38:39
SPEAKER_00: Okay, well done.
1:38:40
SPEAKER_00: You get bonus points for that.
1:38:43
SPEAKER_00: Very well done.
1:38:44
SPEAKER_00: Thank you so much, Alex.
1:38:46
SPEAKER_01: Thanks, Ashlee.
1:38:49
SPEAKER_00: The Core Memory Podcast is hosted by me,
1:38:52
SPEAKER_00: Ashlee Vance, and or Kylie Robison, or both of us together.
1:38:56
SPEAKER_00: It is produced by me and David Mickelson.
1:39:00
SPEAKER_00: Our theme song is by James Mercer and John Sortland.
1:39:04
SPEAKER_00: And the show is edited always by the John Sortland.
1:39:10
SPEAKER_00: Thank you so much to Brex and SendCutSend for all your support.
1:39:14
SPEAKER_00: And thank you most of all to everybody for listening.
1:39:18
SPEAKER_00: Thank you and we'll see you again.