The Problem With Jon Stewart - This CEO Wants a Fountain of Youth for Dogs. Can We Be Next? Please?

Episode Date: November 30, 2022

Jon turned 60 this week, which had him asking: “Can I live longer?” So we’re talking with Celine Halioua, the founder and CEO of Loyal, a biotech start-up with a mission to extend a dog’s lifespan. She believes that if they’re successful, it could work on humans too. Jon and Celine talk about Silicon Valley culture and ask the big tech question: Just because we can do something, should we? Plus, writers Kasaun Wilson and Alexa Loftus discuss the latest Twitter happenings, and Jon gives them a fashion show—which is great content for a podcast. The first half of Season 2 is streaming now on Apple TV+.CREDITSHosted by: Jon Stewart Featuring, in order of appearance: Kasaun Wilson, Alexa Loftus, Celine Halioua Executive Produced by Jon Stewart, Brinda Adhikari, James Dixon, Chris McShane, and Richard PleplerLead Producer: Sophie EricksonProducers: Zach Goldbaum, Caity GrayAssoc. Producer: Andrea Betanzos Sound Engineer & Editor: Miguel CarrascalSenior Digital Producer: Freddie MorganDigital Coordinator: Norma HernandezSupervising Producer: Lorrie BaranekHead Writer: Kris Acimovic Elements: Kenneth Hull, Daniella PhilipsonTalent: Brittany Mehmedovic, Marjorie McCurry, Lukas Thimm Research: Susan Helvenston, Andy Crystal, Cassie MurdochTheme Music by: Gary Clark Jr. The Problem with Jon Stewart podcast is an Apple TV+ podcast, produced by Busboy Productionshttps://apple.co/-JonStewart

How was your Thanksgiving? It was wonderful. Delicious. How was yours? It's my favorite hot. We have all our cousins, probably about 30 people. Really nice. Are you the host home?

We are the host home. That's fun. That's a lot of power. Oh, it's why we do it. Hello, everybody. Welcome to the podcast, The Problem with me. The show is out on Apple TV Plus there, and you can check out season two.

And we've got new shows coming out, I think early next year, some such thing. This is our first post Thanksgiving podcast. We are all basking in the glow of family and friends and wonderful. We're joined by our writers, Kason Wilson and Alexa Loftes. Hey, what's going on? What's happening?

Hello. And later, we'll be joined. Guys, this is going to be, I'm so looking forward to this. We are talking to a woman named Celine Halewa. She's the CEO and founder of Loyal. This is a biotech startup. They're working on, I shit you not, a pill that could help your dog live longer.

Like, I don't mean live longer like, oh, it's for arthritis. And they go, like a longevity pill. Like a fountain of youth pill? Yes, Kason. And if you think that I'm going to give that to my dogs and then take it myself, why, Kason, how could you accuse me of such a thing?

I'm in, I'm taking it. I'm absolutely taking it. Can you imagine if that worked on your dog and you'd be like, mm, peanut butter flavor, and it makes me live longer? I'd be happy to. Am I not supposed to link you doing this around your birthday? Or...

Yeah, it's a little rough. And this one was 60, which there's just no getting around that one. Time that happens, you know, you see that shit in the paper and you're like, he was in his 60s and people are like, you know, I could see that. I could see him dying.

That's 10 years over the hill. Is over the hill 50? I thought, I think so. I did not know I was officially over the hill. Now I'm 10 years past over the hill. So I'm not even on the back, like five. I'm on the back too. I'm on, I'm just about to go into the clubhouse.

Your last podcast of 59 was Hillary Clinton and Condoleezza Rice. You turned 60 and you're like, we got to interview somebody who can make you live longer. As soon as you turn 60, you're like, guys, we need to switch this up. Right. That was figuring out how so many people got to die sooner.

And then I immediately jump in and start talking about how I can hopefully get to live longer. But did you guys have, I know you didn't reach a epochal birthdays during that time, but did you have good thanksgivings? Did you have a nice holiday? Did you spend with family and friends, et cetera? It was beautiful.

Yeah, I had a great time. My mom hosted, it was in Delaware, which obviously means everything closes at 6.45 p.m. So there's nothing to do but. Not the rest stop on 95, baby. John, you got to stop talking about it like a club. You talk about rest stops like they're clubs that you used to play back in the day.

I love them, baby. It is great to play Uno and Spades. My grandma turned 91 this weekend. So that's great. Yeah, this was good stuff. And how is she doing? Is she doing good? Oh yeah, she told me I was fat.

So that's always grandma. Yeah, that's always. I mean, she's still with it. 100%. My step-grandma is 94. What? Yeah. And she's, she made a whole Thanksgiving dinner.

Crazy. She made it. Yes. You know what? Fuck 60. 60 is nothing. Now that I've heard these stories, I feel re-energized.

I may go back to school, knowing that I have so much time left on this earth. Maybe it's time to get a grad degree. It's absolutely time to switch careers. I've got plenty of time. Now, when you go to the family thing, are they discussing, like, are they like, do they pull you aside and be like,

what's going on with Kanye and Elon Musk? Like, is it, are they, are they current eventy? Oh yeah, yeah. My grandpa has lots of articles that he clips and has me read. He has you read them while you're- He hands them across the table and- Are you graded on this? He probably mentally.

Yeah. Mentally graded. What have you guys been thinking of? Are you following the ups and downs of this? Well, yeah. I mean, Twitter is falling apart, right? Is it falling? Now, how could you tell?

Well, there's a lot of ruckus. There's a lot of ruckus happening. More of a ruckus, because I've always found it to be, like, a pretty incessant shithole. So I, like, I'm just trying to think, like, is the panic justified or is this just people noticing for the first time, like, oh, everyone hears mean? Yeah, well, one of the things is in China,

everyone's getting spammed with porn, so that people can- Say that again? Everyone in China? Are you sure they're getting spammed with porn or they're in lockdown and looking up porn? Like, I'm not sure that's spammed. I think that's, I'm in lockdown.

No, no, because, so that people can't organize. They can't use Twitter to organize demonstrations against the intense COVID lockdown. I see what you're saying. The government is spamming them with porn. Yes, yes. You thought I was lying. For a second, I thought you were lying.

I apologize. Now, is that happening because of a loss of guardrails in the new Twitter? Yes, exactly. Now, okay, this is all coming together now. Thank you. That wouldn't happen had the team- Yes, I think there was like a safety guidelines team

that seems to be- In case of porn, break this glass kind of a team. Exactly, exactly. And they were working hard, you know. So this is perhaps a real-world implication of now the loss of manpower. Yes. If you show up to a protest in China,

you know you really earned it. Everybody's like, are you, how are you doing? You're like, I'm exhausted. I've been jerking off for like 12 hours. It's a very dehydrated protest. I don't even know what to say anymore to anybody. I don't have COVID, but I also don't have any moisture left in my body.

It's a terrible situation. So obviously this week is like very big Elon Musk week, which obviously we want to ask you about, John, your thoughts up because- I love the way he's portraying this. And he's like, I bought this, it's like this super weird like, you know, human bulletin board thing where everybody talks.

And he's like, this is a choice between tyranny. And civilization. If you don't advertise on Twitter, the Western world as we know it ends. Like it's just such an incredibly manipulative, like that's the kind of shit that you do like baby, if you don't let me go to this game tonight. Some say it's a little toxic.

Some say, yeah, it's the most manipulative, bizarre framing of this. Like it just so happens that Western civilization depends on, this is a coincidence, the app he bought. It turns out, like I have a feeling if he had bought Angry Birds, he'd have been like, if there's any taking down of the anger of these birds, democracy dies.

And it's such, like, and isn't he, everybody keeps saying, you know, he's for free speech. He's the last person for free speech. He's not for free speech. I don't know what this is. I really don't. Because as soon as people started clowning him on Twitter, he was like, we can't have that.

People are like, Elon Musk sucks. Right, he removed them, right? What I don't understand is, if you're going to spend time validating identity, why wouldn't you spend time validating information? What's the difference? First of all, he says he wants it to be a town square. But town squares don't have algorithms.

Town squares don't recommend other people to talk to that have crazy shit to say. It's probably a bad time to mention, but I'm actually having Elon Musk's next baby. What? Yeah. Well, Alexa, this is the perfect time to mention it. Alexa had a choice between Elon Musk and Nick Cannon,

and she made her choice. I said, let's go Musk, you know? You know, here's what I don't understand. If I control the media and all that, why isn't anybody coming to me first with this shit? Why does Elon Musk now get to control Twitter? I thought it was the Jews. I would like to assert my Fifth Amendment right.

But it's just interesting that a cabal that controls things, you could say that Silicon Valley, you could say that, I mean, if anybody has control right now, it's those social media companies. It's actually pretty damning to me that Elon Musk would be like, hey, Apple doesn't want to advertise on Twitter, which I don't like free speech anymore. It's like, that's not how advertisement works.

You could still, your app is fine. It would be the equivalent of Alexa and I being like, come check us out at New York Comedy Club next Tuesday. But if you don't come, you don't believe in free speech. It's like, no, that's not, just because I don't want to. I think everyone should advertise that way. And that's a great way to mention we have a show next Tuesday. But that is, I think all advertising should just be

that direct manipulation. Have a Pepsi unless you don't like children. And listen, no one wants to take the side of Apple as the little guy in this. No one wants to come out and be like, hey, man, stop bullying Apple because they're unbulliable. I would suggest when your market cap is that many trillions, you're relatively unbulliable, even by most governments,

I would assume. So for Elon to be out there and be like, well, how are they going to handle a thousand alt-right pepe means when they, when the trolls come at Apple, they're going to be like, what? We've never faced anything like this. It's Nick Fuentes and a frog smoking a cigar, abandon ship. He says he's going to make his own phone.

Make your own fucking phone. I don't know if he knows this. Everybody makes their own phones. Somebody makes them that fold. Has he never heard of Nokia? Like we could, you could go try. I'm making my, you know what? If you don't watch this show, I'm making my own television sets.

And I'm just starting sending them out. And if you don't watch them, you hate democracy. Man, though, to any, you know what it always strikes me as? To any of these fucking people have anybody in the room that goes, I think you might be turning into an asshole. Yeah. Like I think, so this whole thing, this messianic thing, it's kind of a downer outside of just the people you control.

Silicon Valley, you know, we're having on a guest from Silicon Valley, but she's doing her thing for good. She's coming up with a pill to make dogs live longer. And if you don't like it, you hate democracy in America. And I'm just going to build my own dogs. Why, uh, John, why did you want to speak with her specifically? Because I have dogs, Alexa, and I love them. Yeah.

I just wanted to hear you say it. It has nothing to do with what's happening here. Sure. We were like, man, John might want to talk about the implications of Silicon Valley, the effects on capitalism. No, I want my dogs to live longer. Fair. That's very fair. And you should be allowed to do that.

You know, Google now makes a foldable dog. It's so much better than the regular dog. If Elon Musk can attack free speech and just tell people Thanksgiving is delicious whenever he feels like it at 2am, you know what, go on your podcast, go save your dogs, John. Thank you. All right. I'm going to go talk to her and then we'll check back in.

Beauty. We're going to talk to our guests now. We're very excited about this. We're talking to Celine Halewa. She's the CEO and founder of Loyal, which is like a biotech startup, developing drugs to increase, and the people, if you're watching this at home or you're listening to it, you're going to freak out, to increase the health span of the most beloved things in your house.

And it's not your children. And it's not your spouse, your dogs, your dogs. Celine, welcome to the program. Thank you. This is a biotech startup that is looking to increase the lifespan of dogs. And one of the most heartbreaking things that people go through is the loss of their dogs. Lifespans between sometimes six years to maybe 15 years to 18 years,

if you're incredibly lucky. What, how, why, how, why? I mean, it's a good first question. I'm really interested in general on working on problems that are at the combination of sounding incredibly crazy, to the point that when I started Loyal about three years ago, I was actually embarrassed to say the phrase, dog longevity. What is your background in terms of work or education or those things

that would put you in a position to make people's dogs live longer? Yeah, so I grew up in Austin, Texas. I'm half Jewish Moroccan, half German. First gen. We grew up with 15 cats, you know, multiple dogs, a dog named Highway that we rescued off the highway, three different puppies that we rescued, found the street. We used to take care of gerbils and turtles and squirrels

and grackles with broken arms. So you were that house? I was that house, yeah. You were the refuge, you were the wild refuge house. Yeah, we had, we had a lot of animals. And so the animal side has been there since day one, but I definitely did not grow up thinking I would start a company or a biotech company or work on dog longevity.

I actually got into college for art school, but then the summer. Wait, what? Yeah, yeah, college. So you're not like, are you a biomedical engineer, neuroscientist? I am, I got there. I got there, yeah. All right, let's go. So I got a full scholarship to UT Austin for art.

And then the summer before I started my undergrad, I decided to do an internship in a neuro-oncology clinic, in part because I was actually really fascinated by MRIs. They were very beautiful, the ability to see the inside of a body. What 17-year-old kid isn't fascinated by MRIs and neurological oncology? That's, you know, if I've heard this story once, I've heard it a million times. So I decided to do this internship and I, I mean, honestly, I just met a number of terminal patients.

And I kind of, I don't know, when you're 16, 17, 18, you kind of think that the adults can always fix everything, right? And I realized that with most diseases and kind of, you know, spoiler, most age-related diseases, there isn't anything anybody can do for you, no matter how much effort, time, care you put into the problem. Yeah, sorry, man, I know your birthday was yesterday. Jesus, this is, this is the wrong time for me to be having this conversation. I think this is the right time to be having this conversation.

You know, I am, I just figured this out. I think I am 420 in dog years, if we were counting. Well, Elon would like that. Seven. He would, he would like that. He would, he's, he's going to save us all or, or make sure we have... Something like, something like that. Yeah, yeah. I mean, we'll definitely be able to talk about dog one, Jev, on Twitter.

No question about that. You get involved with sort of this idea of you're watching a geriatric process or a disease process and you're thinking to yourself, well, well, adults can't fix this. And then this, this puts you in the mind space to focus on biomedical engineering when you go to UT instead of art. And you take up your, you become a, a neuroscientist. Neuroscience and chemistry double major, yeah.

Sure. No, you can't have one without the other. I wouldn't, I was not suggesting that you would go into neuroscience and not have a chemistry double major. I know you're not a slacker. So, so, so you do that, you get out. And do you go immediately to this idea of starting a company to keep people alive? Or was this always about animals and dogs? No, John said it's a lot more complicated than that.

Well, I would think so. You're a double major for God's sake. I picked neuroscience because it was the class where the like neuro 101 to be like, yeah, we don't know how any of this works, but it's important. And I was like, great, that's where I want to be. And I started working in a lab in Southern California called Sanford Burnham. And we were working on basically replacing, so people have Parkinson's disease. The disease is primarily driven by a loss of a certain type of neuron.

Neurons that produce dopamine, which are kind of popularly known as like, you know, happiness, but it's also actually really important for movement. I see. So that, is it providing like the liquidity of your neurons? Is that the, is that what we're doing? I will make no comments on finance or fintech. But it's more around the idea that it rewards the, the, the correct intention, right? So when you see somebody who's Parkinson's, they often will be catatonic or trembling and it's in part due to these kind of misfireings and loss of firings of the,

the movement regulation. But that's all to say, we were working on replacing those neurons. And it was just such a hard problem, right? You had to like source, you had to source the stem cells, you had to put them into the patient and not be a, you know, they had to turn into the right kind of neuron. They have to, you know, re-neurons have these like long branches where they all kind of bind. Talking about, what are you talking about, the dendrites?

Is that what we're talking about? Yeah, look at you. Axons. Got some myelin sheath going. That's all I, that's all I eat. So you're trying to figure out these, these problems. How does that get you into the space of, of aging? Yeah, obviously it is very worthy.

We will always work on helping people who are at the end stage of a disease. But why were we trying to help these Parkinson's patients after they had already lost a significant amount of their neuronal mass, of their, of their brain function, right? So I got really interested in, okay, well, why aren't we looking earlier? And why are we looking at prevention? Why are we looking at reducing the risk of developing it? And long story short, this all kind of brought me to this field that I thought was crazy for a couple of years.

It took a while to convince me of research around understanding the ways we age and specifically the ways we age unhealthily over time and how the processes by which our bodies age lead to the diseases that we've classically defined today. Does that make sense? Does this put you into the Silicon Valley transhumanist movement? Like does this, do you end up like draining the blood of adolescents to like feed into Peter Thiel's eyes? Like that's only, that's Peter's thing.

That's Peter's thing. That is, that is not the standard issue thing in Silicon Valley. But there is, so you're in this whole movement now about aging and is that the sort of, I made a telomere, uh, not unravel. And so an nematode can live forever. Like what's, well, I actually have one of those tattooed on my arm. A nematode? All right.

That's commitment right there. And in a black Labrador, which is the first dog that they showed lifespan extension. No, that's the, I have the same open mic night and then move on to MTV. And then, yeah. So, so you get into the aging thing and, and, but why then dogs? You're, so the idea is you're at this foundational point, uh, transhumanism or the anti aging movement or any of those things, there's an enormous amount of energy and money behind that. What made you then flip to dogs is that are they a great analog for human genomes?

Are they something close, not close? What, why then? Yeah. I mean, so there was two, there was two drivers. One was the pull of dogs and how dogs age and the science of dog aging, but also the push and they're the best. I have a soft spot for old dogs. I think they're cuter than puppies.

Controversial opinion, potentially. We'll see. That's going to, that's going to get spammed on there. Yeah. Yeah. Celine, how did you get canceled? Oh, well, you know, I think old dogs are cuter. How dare she?

She's out. So you're, you're in this, this movement about aging. Do you come up with a discovery that makes you think, oh, here's a mechanism by which aging occurs. I think if we interrupt it there, we can extend life in a dog. 00:21:56,720 --> 00:21:56,720 00:21:56,720 --> 00:21:58,720 So, so tell me about that.

It was two things. It was two things. We, so there, there is this industry as you, you know, you're talking about around trying to understand aging and longevity and lifespan extension, but fundamentally every single company and group, including the ones that have like a billion plus dollars looking at you, Callico, it's Google's big aging thing. They're not actually trying to develop drugs for aging. They are like looking at aging and then they're developing drugs for cancer or

osteoarthritis or ocular diseases or what have you. And so I was. So they're looking at the effects of aging when you're looking at actually the aging process. Well, so my, my thing. So for context, I just, I, I, I had done a bit of grad school in England, came to Silicon Valley and I was there. And I was like, why is nobody trying to actually get a drug approved for aging itself? Like, why are we, you know, targeting these end stages diseases?

Why aren't we just targeting, you know, you, you living a longer health care life. You want to go to the root. You want to go to the root of the problem. I want to go to the root of the problem. And so I started in people because that's where I was been working. But I kind of quickly realized that it wouldn't, unless I had a billion dollars or more. And even then, honestly, I didn't see a way to develop an aging drug for people because fundamentally people live a damn long time.

Right? Like if I, if I gave you an aging drug, it's going to be, you know, 20, 30, 40 years before I know, I might be flattering you a little bit there. Whether the drug works or not. That's painful. I didn't need to know that. Sorry, man. Sorry, man.

No, I get it. It's, you're not telling me anything I don't already see every morning. So not to worry. But it's all about like we, it just is way too long of a feedback loop. So I was like, okay, how can we have a shorter feedback loop? How can we get the first of a drug approved, you know, for aging, for lifespan extension? And it was at the same time that I was thinking about this problem, that I was just reading into dogs and how dog ages and specifically how big dogs age.

So you referenced it earlier, but some dogs might only live six, seven, eight years of age. Sure, you're great gains here. Isn't that counterintuitive that the larger dogs, I was always under the impression that larger mammals lived longer and that the little mammals lived shorter because of their metabolisms, that they, they process everything so quickly. So isn't that why when you're doing, you know, people study in labs that the fruit fly was such a, you know, such a tremendous mutagenic study because you could go through like 10 generations in a weekend.

Exactly. It is, but the opposite happens in dogs. And there's actually at the edges, a two X difference between the average lifespan. So, you know, a gray day might live six to nine years and they actually age faster too, like a three to four year old gray day and we'll start going gray in the muzzle already, while a Chihuahua will live, you know, 15, 17, 18 years. And some people say it's just fueled by spite and that might be potentially true. But if you actually look into the genetics of dogs and dog size, and this was kind of the

aha moment for me, we, so there's no one gene that controls, you know, the size of a human and being, you know, six and a half feet tall isn't going to make you live a much shorter life than, you know, being five and a half feet tall. But if you look into the genetics, that actually makes me sad because I thought that was the only advantage I had. Are you Ashkenazi or are you Sephardic? Ashkenazi, I believe, right? Isn't that Eastern European? Eastern European is Ashkenazi. Yeah, that's right. I ask because there's actually-

You're not going to tell me what I'm going to die, are you? No. Is this going to get super weird? This is good news, John. There's some longevity centenarian genes in Ashkenazi. So actually- Boom! Yeah. So this all comes together because the genes that control dog size and specifically make big dogs live a shorter life is all connected to one of the most well understood and OG

longevity pathways there is. So that's why I have the worm tattooed on my arm because the first time they showed was a single gene mutation that they could make a worm live longer. They made that worm genetically like a Chihuahua. And the inverse was true too. Yeah. So let me ask you a question though. So ethically, extending a nematode isn't necessarily going to burn out societal resources or a Chihuahua, but we all know where this is going. So once you figure out how to do it with a Chihuahua, there's no question that people are going to be banging down your door going, make this into a gummy and give it to me now. There must be. Yeah, probably. I mean-

That's got to be the end game. So when did you start- have you tested this drug on a dog? Uh-huh. We actually dozed our first companion dog a couple weeks ago and we've shown age-related disease or age-related negative impact benefit in dogs treated with our drug. Okay. Yeah. This is where the rubber meets the road. So you've given this dog- not only does it- well, it's only been a couple of weeks. I don't know how you figure something like that out, but the idea would be that it's not even just suspending the aging process. You're rolling it back in a dog. So we've- we dosed the first companion dog with specifically our second drug program that's for

dogs of any size, mostly any size, any breed who are already showing signs of aging. And in our first drug program is trying to make bigger dogs have a longer lifespan by correcting for- what- basically when people were breeding for size, they- our thesis is that they accidentally gave dogs an accelerated aging disease, basically the things that control the dog growing really quickly in puberty, don't fully turn off, then the dog ages at a faster rate and dies sooner. And this is where it all connects. So the Ashkenazi mutation makes the- that some Ashkenazi Jews have- makes them more like the Chihuahua. And they actually are shorter too. Well, I got that. That's for sure. So- Let me ask you this. Are you testing it on good boys and bad boys or just good boys?

All of them. All dogs are equal to us. Cute dogs and cute dogs. So they're all- they're all good boys. You're saying- what you're saying is all dogs go to heaven, but you would just like to make them go a little later. You would like them to- And a little bit happier, right? So it's not just about like the aging field has such a- Right. Because our- listen, hip dysplasia, the- the breeding on dogs has been astronaut. I mean, we've done so many weird things to them and created all kinds of- of issues. The idea that this could help them have more helpful lives is man. Well, that's exactly it, right? Like when we- like, it's not like we domesticated the wolf and a pug popped out, right? Like they- we created all of

these dog breeds because we wanted dogs that were, you know, protectors like my roddy, protectors like your pity, or, you know, whatever other breeds we wanted, retrievers, but this had genetic consequences on these dogs. And one of them is that the bigger a dog is, the shorter their lifespan is. And so we are trying to fix it. But what is it doing? What- what, like, this is the holy grail of- of the human condition. I mean, I- I assume you're- you're aware that you were on the tightrope ethically and otherwise, but- but this is the holy grail that man has, you know, Ponsadillian was searching for the fountain of youth. Like, this is what everyone has. For God's sakes, Walt Disney froze himself for this moment.

I have a friend working on that, too. Oh, for God's sakes. Silicon Valley is the most fucking weird place. Oh, yeah. I can't even imagine the messianic tendencies of that entire region. But- but- but- but the gravity of this has that- and the idea that it's a pill seems crazy to me. Yeah. Yeah, I mean- What does the pill do? So the first one, the one for big dog short lifespan, we're basically- so we're basically the thing that

drives the dog to grow faster. We're just trying to turn that off or turn it down after the dog is fully grown. So we don't- we're not shrinking the dogs or anything like that. We're not making medium Danes. Wouldn't that already be turned off once they- once they grow? It- It should be, but it's not. But it doesn't. It stays- Yeah.

I see. Basically it's like- So you're- that- that part of that process you're going to try and turn down. Yeah. So we're basically damping it down. So we're making a- the- the biology of a Great Dane look maybe more like an Aussie Shepherd or a medium sized dog. So we're not going to make these Great Danes live till, you know, two hours lifespan. I think that's pretty unlikely. But hopefully we can add a few more healthier years and specifically help them-

But that people don't have that- The active longer. That- that mechanism going. So that's not- what's the other pill? That's probably more akin to- So that was actually the thesis. So we wanted to start with something that connected something the world already understands and knows, which is genetic diseases. And specifically- Right. Genetic associated diseases in dogs because of inbreeding. So you mentioned hip dysplasia before that's genetically controlled. So that's why we started there, right? Because we're

introducing something really weird. We're like, hey guys, we're getting this drug approved hopefully for aging and nothing else. But don't worry, it's around things that you already understand. It's around genetics and all of that. Our second drug, exactly as you said, we wanted to be more broad. Something that's more broadly applicable. And something that's also will teach us more about how humans age and how other organisms age. And so this one is looking at metabolic fitness and specifically the reversal and the halting of metabolic decline as an animal gets older. The other thing it's looking at, what's really interesting is- So if you look at an older- some older individuals will often have very skinny

legs but in a bigger belly. With age, you actually get a redistribution of fat- You know, the bellybell is almost entirely pie. I don't know if you knew that. As you age- Pie. But generally, the legs stay the same. But the midsection begins to fill with a variety of pies. Pumpkin pie? Apple pie? The actual breed of the pie is not the question. But it's merely mostly pie. At least in my case. I really like pie. So that sounds great to me. What's not to like about- if you could create a pill, this is the next project that could make short people live longer and somehow be impervious to pie,

then you'd really have something. Are you gonna- Here, Selene, you've got to answer me this. Yes. This seems so crazy. I just want to make sure, like, I'm not going to read about you three years from now going to jail. Like, I don't- I mean, me too. I could not handle jail. I don't want- I don't want this to be one of those Silicon Valley situations where they're like, she's a super genius. She's got a pill that makes you younger and her own Bitcoin. And then it's all going to turn out that, you know, you actually did just go to art school

and you really don't know anything about it. No, no, no, no. So there's a- This is actually something I care a lot about because it's- look, Silicon Valley is weird. Like, I always say that I feel like despite the fact that I am a woman, I have some of the biggest balls with the people I hang around, right? Because they all- they're like these giant brains and super talented and have all the opportunities in the world and they go work on increasing revenue of like some stupid B2B SaaS product or whatever. And I think it's actually really important that if you have the skill sets, the desire, the opportunity that you work on things that help push forward humanity and help push forward things that will materially

impact society. And so- Are there any break- can I ask you, are there any breaks in Silicon Valley? Like, I wonder sometimes because, you know, I think about like artificial intelligence. We've been warned since Asimov that artificial intelligence is going to be the thing, you know, rise of the Terminator and it's going to become sentient and it's going to destroy us. And so far, all we figured out how to use it for is like recommendations for who to follow on Twitter. So like, are there people there who are focused on the consequences of this ambition? There's so much ambition in Silicon Valley and there's certainly an incredible amount of

intelligence and money. But is there anybody in the room who raises their hand and goes, wouldn't that blow up Sacramento? Like, how much of the ethical and larger consequence is taken in? Or are people so enamored of the possibilities that it's actually a dangerous place? I don't think it's a dangerous place, but I do think there has been- So one of the things when I decided to build loyal is I wanted to align my economic incentives with something that would also be positive for society. And I think that's something that you don't often- So for example, if I, you know, if we are successful and we do get this drug FDA approved for lifespan extension, we will make more money if your dog lives longer because your dog

will be on our drug longer, right? We are aligned with your dog living a longer, healthier life, even if I'm just this cold capitalist who doesn't give a shit about dogs versus, for example, you know, Zuck, I don't think when Zuck was in his dorm room, he was like, yeah, I want to, you know, destabilize international politics and election integrity, right? No, that's my point. The incentives- I guess my point is how many people in the room, if you were looking at it, how many people in the room are on the unintended consequence beat? That, that basically game out as everybody's gaming out the process. Like if we gamed out this drug, right? If this works, which by the way, like I've got a 13 year old dog and an 11 year old dog

and like if this works, and God, it better fucking work soon for these guys. But like, and then people get it, the unintended consequences, people are, we're generally locus to begin with. And if you, if you take an 80 year old and put them and make them all 100 or 120, like clearly we're going to have a resource problem in this world. I don't think that's true though. So I would actually push back on that. So it's the, when people think about aging drugs and extending lifespan because of the way a lot of age-related disease drugs work, like let's think about chemotherapy, right? Chemotherapy in most cases does not extend your quality life as much as more around, you know, the number of years of the patient has. It tries to balance killing the

cancer with killing everything else around it. Yeah. But that's not how an aging drug works. It's not pulling out the last unhealthy years of a person or a dog. It's extending the healthy middle years. And so a society where you have a more productive class that's able to work, that's able to take a second career potentially, or like for example, before Obamacare and all of that, you know, not everyone in my family had health insurance. And I had pretty bad health insurance and I had a lot of medical debt for a long time. And thank God I was able to come to the valley and I was able to pay it off. But like things like medical debt or my parents being ill or being financially responsible, they disproportionately impact people who don't come from, you know,

financially strong backgrounds because it's not like. But you do realize like this will, this will, there's no question that a drug like that will be more available to the wealthier. I don't think that's true, actually. Oh, Celine. No, no, no, no, no. So, you know what we are right now? We're so in between utopia and dystopia. And that's, this is the, I feel like we're all in like an Aldous Huxley novel right now. So, so you're saying there is a utopia. And I'm saying, well, turn it into a dystopia, Celine. That's what we do. I mean, I know people suck. So, all right, but you want them to suck longer. I want them to suck less. So,

one of my pet theories actually, they're going a little bit of a tangent and I'm going to answer your economics question is, you know, one of the challenges of society is like you kind of have this crystallization at each generation, right? You know, their biases and the way they view their world. And I'm really curious, like, what would an aging drug do to cognitive flexibility? Like, is there a world where the biases of the generations, you know, one above us actually can be relearned and that it's not inherent that you have to hold on to the biases of the generation that you were raised with? And the reason I bring this up is because one of the studies we looked at- You're saying this is a drug that actually alleviates prejudice?

I don't know, but it could at least facilitate potentially, like, I'm not saying our drugs necessarily do this, but one of the things we look at is cognition in aged dogs treated with our drug. And one of the ways you- actually, one of the things that changes the most was age-related cognitive decline in dogs, by the way, dogs do get dementia, is the ability to relearn something, right? So, they'll learn- I think there's a saying about that. Yeah, exactly. I believe there may be something that has crystallized around that. Potentially. Potentially. Yes, the difficulty of teaching.

Exactly. So, dog. But one thing is we're looking at teaching these, like, old dogs is seeing whether an aging drug that impacts cognitive impact helps those dogs learn new tricks better, faster. I would think that would absolutely- I mean, I think it's been pretty clear that as you age, it becomes more difficult to make those kinds of connections, you know, I tried to learn music at 50, right? I'm getting my ass handed to me by 13-year-olds in music class. Like, they just pick it up quicker, they have it- you know what it is?

It's a fluency that is harder to happen in your brain. But I guess the one thing I wonder is, would we be unleashing the part of our society that has already accumulated the most resources in our society? And would we be putting our younger members of the society at even more of a disadvantage by competing against super people at 70 or 80 as opposed to- they got a hard enough time climbing the ladder. Should older people not bow out necessarily, but you get my point. I totally get your point.

So, we didn't quite get to this, but after I did the stem cell Parkinson's work, I actually started a PhD at Oxford because I was interested in exactly this question, because I was pissed, honestly, that I had at that point at least $30,000 of medical debt, and not to mention all the medical care you don't get when you know you have to pay a shit ton just to walk in, right? And I was like, screw this, like screw the US, I'm going to Europe, I'm going to the NHS, and I'm never going to have a medical bill again, right? And so, I went to Oxford because I wanted to study the differences between the NHS,

you know, single-payer healthcare system where the incentives are aligned, right? The NHS cares about your healthcare now, and also in 30 years from now, versus the US, where there's more money to pay per patient, depending on the kind of care you have, but they're not a long-term incentivization. And I bring this up because there is absolutely, I 100% agree, inequity in healthcare access in the US. And actually, some of the worst inequity is in around how we treat age-related diseases. There are these cancer drugs and new CAR-T therapies that are, you know, half a million dollars.

Not to mention you have to be able to access this very specific facilities where this happens. It's insane. Basically, the industry around elder care is parking lots. We basically find a lot, you know, you go to these facilities if you can afford it, but other than that, like, it's parking lots. Like, they place you in a room, and God bless the people that do their best to take care of them, and their families, but like, people struggle with resources. And as you get older and you're no longer able to provide those resources,

you know, as that space expands of the amount of time you live without being able to do that, without being able to earn your own keep there, it becomes more and more fraught, I would think. It's terrible. It's absolutely terrible. But the- Did you find the NHS had a better system on that? I don't know about elder care, so I was really interested in the preventative care before the person became ill.

And so that's how I think about aging drugs. So there are definitely groups that are working on super expensive types of aging drugs that, you know, if they ever get approved, they're going to be a million dollars, half a million dollars. And I agree there will be inequitable access to those drugs. One of the cool things about, at least how we're trying to approach it, is that we're looking at preventative medicine. And specifically, like, one way to think about it is statins. You know, a large portion of the adult US population is on statins to reduce their risk

of future cardiac events. That's what I think an aging drug should be. It should be a cheap, daily pill that somebody takes to reduce their risk of a future disease that would be extremely expensive to take care of. The lesser side of a statin is a relatively safe drug with very few side effects. And your anti, you know, when they talk about certain Alzheimer's drugs, they're like, now there is one thing that does happen is your brain seizes and then your nose explodes and you die.

So balancing that, I imagine, is difficult. Yeah, that's exactly it. So you're dealing with all these ethical questions. While you're also dealing with the question of, is this going to work? And is it going to shut off the gene? You want it to shut off and open up the gene? You want it to open up? And this has nothing to do with telomeres unraveling.

This is literally looking at the programming of the individual species, seeing where the program advances aging and slowing that down. Exactly. We are working on slowing the rate by which an animal, in this case, dogs, maybe one day people, ages over time to reduce their risk or dampen the probability of a future age-related disease. But it's not necessarily met a ball. In other words, it's not like, and you can only have, if you go on this drug,

you can only have half a brownie every week. Because we've so slowed down your, it doesn't slow down your process of other biological processes, respiration, digestion, all that other kinds of stuff. Hilariously, actually, one of the biggest flops in animal health was a weight loss drug, because people like their dogs fat. So we looked at this explicitly to make sure that our drug wouldn't cause weight loss and it doesn't. See, I'm the opposite. My dogs, so every night they step up on the scale.

We do like a little swimsuit competition. 00:45:52,000 --> 00:45:52,640 No, of course. I was going to say, I have a tripod. One of the pitties is a tripod. And so we do have to manage his weight because he's got the one arm in the front. And so if he gets too heavy, it creates a real arthritic and muscular problem in his front. So that's the only one to do there.

Is this at the FDA your drug or no? Yeah. So we've been working and talking with the FDA since day one. And I think that's actually been super, like we didn't want to get a drug approved, like we didn't want to get a supplement or something that didn't require the FDA because it's because the field is so weird. You don't want this to be like a ginseng ginkgo beloved thing that's in the fucking back of a apotheca.

Yeah, you want this to be on the up and up. I want it to be legit. I want to prove the point that unhealthy aging is a disease that you can target with the drug, and in and of itself is worth developing medicines against. We don't only have to develop medicine once somebody has gotten old and frail or developed cancer, we can develop medicines that reduces what's happening. Why do you keep talking about me? That seems like it's very rude.

So is the FDA, do they work with you? Like, do you submit to them and then they'll say, oh, this, change this, do this, this could help? Yeah. So there are actually, there's a lot of public opinions of the FDA. But what I've actually found in our experience with them is that they're just a bunch of scientific nerds who are excited to work on interesting problems that have good science behind them, right? Like, they're never going to prove something that doesn't work.

00:47:33,520 --> 00:47:38,160 But they've also been very, to date, collaborative in helping us. I mean, because we're deciding everything from the ground up. Nobody has ever asked the question of how to extend for getting a drug approved, how to extend a dog's lifespan, how to quantify their currently current health state, how do we prove that it doesn't? Yeah, what are the metrics of aging in a dog to begin with? So that's, even that's probably a difficult question.

Oh, it's a super difficult question. It's like, it's, and you, it's, it's so hard when you're working on problems like this, because you have to, the way I always tell the team is like, you have to pick which hills to die on, right? Like, we can't fix everything about how you develop drugs today. So we, but we also need to get that drug developed to have the right to work on the next problem in aging. And so now, so you're, you're in a double blind study. You're, you're in a study right now where you're giving this drug to a dog,

and now you're testing it with, is this, because don't you have to reach certain, like the FDA has, you have to reach this level to be eligible for a double blind study or a single blind, you know, whatever it is that they're, that they're allowing you to go through. Yeah. So we, we have a pilot study going on right now in companion dogs, which is, I believe, blinded to the, the pet parents. It's, it's not the, like the highest rigor because it's more around just like learning how to run a study and making sure we're running it correctly and manufacturing a drug.

And then we have the full placebo control, double blinded longevity and health span study that I'll be starting next year. And so the timeframe on, uh, when this, uh, might be available, all things going perfectly, and I'm not talking about getting, yeah, all things going perfectly. Are we talking about this is a three to five year process? This is a five to 10 year process. What, what, what kind of time span are we looking at? Well, we're closer than that, John.

So if, if everything, so actually interestingly, one of the hardest parts of all of this, so we've shown, uh, what, what we believe and what we're currently working with the FDA to see if they also believe compelling reason to believe that our drug will extend data to support that our drug will extend health, fancy quality of life, uh, in dogs. And therefore that's extrapolatable to lifespan extension in dogs. The actual rate limiting thing that's really a pain in my ass is manufacturing. So I, I don't have definitive proof of this, but I have said sneaking suspicion that one of the reasons why the manufacturing standards for dog drugs are so damn high, uh, is because

people take them too, uh, specifically the ivermectin craze with COVID. Oh, really? Oh yeah. So people would take the horse dewarmer. But isn't that, that's a, that's a different form of the drug. Like the ivermectin that we use on our farm is different than the ivermectin that a person would take. Yeah. Yeah.

But people who were buying, so I have a, I have a horse and I obviously do you warm my horse regularly. And when you go to tractor supply to buy dewarmer, they have disclaimers saying, do not take this. Oh, I see what you're saying. I see what you're saying. Yeah, you're right. Because people were taking it. And so, uh, when you manufacture a drug, you have to show that each pill is the same

and it has the same amount of drug in it and it's at a high standard, there's no contaminants, and that's actually the rate limiter. So if we have delays, it's most likely going to be due to, we, we've never, you know, build up dog drugs in zero to one. They're going to be looking to make sure that the manufacturing standards are, and in the way that some like supplement things are unregulated. Completely unregulated. You don't have to prove what's in them.

You know, you don't know if you're just getting solidized. Where's, where's the, I'm coming out. First of all, how ironic that you'd be doing this in a lab. I mean, a lab. We, we do have something called loyal labs and like lots of little lab puns. I mean, there's just a lot of, I don't have a kid, but I'm definitely a bit of a dad. Yes. No, I think, I, I think, oh, is she up?

Della, are you up? Hey friend. This is Della Della. Hey, come say hi to John. Look at that sweetie pants. Hey friend. Della. How you doing?

Back up. Hey, can you show your tricks? Nope. Sit. Nope. Look at that mug. Come on. That dog is beautiful. She's such a good girl.

Yeah. She's so good. Where's your last encounter? Are you in Silicon Valley? I'm in SF. I'm one of the last few holdouts. All right. I'm coming out there and getting some free samples.

I'm going to come out. I don't know if you got him at the front desk. I'm going to come out in that little, whatever that little basket is, you just take one, take it back to my doggies, get this thing going. But it's a fascinating story. And I just wish you all the best. Thank you. And I love the idealism of it.

And I really hope you don't go to jail in three years. That's my concern. I won't. I won't. And I think one of the things I'm excited to show is that you can work on ambitious, crazy problems and do it in an ethical way that helps. Like you need to be clear.

Like, loyal might not work. You can do this without becoming a megalomaniac? Loyal might not work. You can't force a drug to work. Like, I always say there's like a definite God in biology, right? And the truth is already predetermined whether our drugs will extend lifespan or not. We're just trying to catch up with biology in reality.

That's right. But it's important to, like, the company and me and the way I think about this is like, we're working on developing drugs to extend dog lifespan. We're not working on getting one specific drug approved, approving my thesis that I have had my entire life. Like, if my big dog short lifespan thesis doesn't work, sucks.

That's a little bit awkward. You know, people are going to quote this podcast, but I don't actually care, right? What I care about is getting a drug approved for aging. And I think having those incentives built in and also having to, giving the team then permission, right? The scientists are inherently honest at something we've seen in all of these kind of infamous crash stories.

It says that the management, the leadership didn't give them permission to be honest. And there has to be honesty. And I think that's the right way to look at it, which is that life is just a biological puzzle we haven't quite solved yet. And these are riddles, and you're working on different riddles,

and it's exciting. And it doesn't help anyone if the drug doesn't extend lifespan, right? Like, it doesn't, you know, it doesn't work. Like, it just doesn't work. But it's, boy, it's an exciting world to be in. And we thank you so much for spending some time with us. And little Della and such a sweetie pants.

And I just, I wish y'all the best. Thank you. I appreciate it. I expected her to be weirder. Like, Shai was very, like, I think, thrown off by her lack of, you're like, oh, you're just a smart person. Yes, he's trying new things. Trying new things.

If it works, it works. That's great. It's an interesting idea. We thought we'd put it through this process. Like, I think I'm so conditioned now about that part of the world from, like, the FTX thing and from Peter Thiel and from Elon Musk, that, like, you just expect them to go, I will start with dogs and I will move my way up the hierarchy of species.

Man will live to be 150. His dog, 120. Like, it just, I can't wait to see her Netflix documentary. Can I tell you something? That's what I said to me. Think, oh, please tell me. Please tell me you're not going to be going to jail in three years. I know.

Elizabeth Holmes, she ruined this is, you know. I felt like I was, not just her or the FTX guy, like all these people, you're like, oh, this is just a fucking house of cards. The whole time I felt like I was watching Bernie Madoff at a vision board party. I was like, wow, this is, am I, was I, am I? No, no, no. You want to break me? No, no, no.

Am I the vision board? You were the host. I was hosting Bernie Madoff. You were the host, you were hosting the vision board party and she was, you kept trying to tell her like, please don't go to jail because. Yeah, I wasn't sure what the grounding principles of this were. Seem like she had, you know, describing the science. But I also think that when you're a neuroscientist talking to non neuroscientists,

you probably choose your language carefully as to make it accessible. So I think that hesitation, I'm hoping, is less grift and more. How do I put this to a little brain? The utopia, dystopia comment stood out to me. What about, I'm curious, what about the Silicon Valley environment scares you for her? You did turn into a dad halfway through like, they're going to do it, please. So you've had a culture. Look, this is most reminiscent of the early industrial revolution,

robber barons, right? Vanderbilt, Rockefeller, Aster, like all those people that accumulated wealth and power beyond what any human beings that were not monarchs had ever accumulated based on things as simple as like, what if I put fucking steam through a camshaft? What would that do? Hey, hey, what if I took a water wheel and attached it to, you know what I'm saying? Like a shovel. So they accumulate all this, right?

So what happens with innovation is, I think they lose sight of that they are still bound by the laws of man. So like, and Silicon Valley is this, is a incredibly concentrated. It's like innovator resin. It's like at the bottom of that, remember that bong and you'd have it for like a year and you never know, I'm old school and you'd clean it out with the pocket knife and then scrape that resin out, like that concentrated, then you'd fucking smoke that. Like that's what Silicon Valley is robber baron resin.

Nobody's coming with me on this one. This is probably a bad time to pitch you my idea, which is a hat that you wear when you're getting picked up at the airport that lights up. They have those. What? Yeah, I mean, I would do this right now, except it would waste too much time. I could run downstairs and get one. Are you serious?

John, I would want nothing more than you to go get that hat right now. It lights up so that people. All right, you guys hang in there. Are we just going to fast forward through this part until you come back? I hear like clanking back there. I know I'm hearing things. What? For the listeners, John is now wearing a beanie that does in fact light up.

He looks like a Jamaican coal miner. Wow. When do you wear this, John? Always. So imagine you got to go outside at night and clean up poop. Yeah, I get it. My problem is when I'm at the airport, no, the person picking me up can't see me. Alexa is trying to invent an airport locator and you came with your poop cleaning hat?

I know. I should be insulted. Not at all. I'm trying to raise money for my invention. All right, hold on. I'm at the airport right now and I need a ride. All right, that would, I mean, okay. Everyone, what a wonderful post Thanksgiving program.

I want to thank Celine Halewa for joining us. I want to thank K-Sod and Alexa for their intelligence, for their wit, and for their inventions. Make sure to check out the problem. Erin right now at Apple TV Plus there. That's going to be going. And by the way, speaking of the show, this is an update on the Afghan episode. I don't know if you remember the Afghan translators that have been trapped over there, the allies that we promised to never leave behind and then promptly left behind.

One of the people that we spoke to on the program, Mosa, I don't know if you remember Mosa, obviously not his real name, but we spoke to him on the program live from Afghanistan. We received word the State Department that he can complete his visa to the U.S. now that he and his family escaped Afghanistan. They escaped Afghanistan. They will complete, I think, their visas at the U.S. Embassy in Pakistan and then have their interview this week. And hopefully continue their journey to the United States after that.

So that is a little bit of good news in a sea of nonsense. And so we're thrilled for Mosa and his family, and hopefully Godspeed to them and they get here. Thanks again, everybody, and we will see you next week. All right, y'all later. Ta-ta. The Prima John Stuart podcast is an Apple TV plus podcast and a joint bus boy production.