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Well, I'll go I'll go have an armchair expert, experts on Earth expert, I'm Dan Shepherd. I'm joined by what's your new name we just came up with last night, two nine six party pants.


No, no. As a play on Monica.


Monica, Monica. Oh, that's mother Monica.


Monica. Try to say that three times. Monomaniacal. Monica.


Monica no longer. Yeah. Monica Monarchal. Monica. Monica. Monica Monarchal.


No, I can't do that. Gary Hart is very. Oh right. We have a show to do. We have a glorious expert today by the name of David Sinclair. He is an Australian biologist and professor of genetics. Best known for his research on ageing and longevity mechanism. Now. Gang, I got interested in this off of a 60 Minutes episode.


You can't stop talking about it if I'm going to be honest.


Well, the stakes are high. We're talking about living forever. I can't think of a topic I'm more interested in than living forever. I'd really like to meet you also.


He has a p h d from the University of New South Wales, Sydney, and received the Australian Commonwealth Prize. He was hired at Harvard Medical School in 1999 and he has a great book called Life Span. Why We Age and Why We Don't Have To. And he has a new book coming this year called Just in Time. The Discovery of 021 and How it Will Change Everything.


Did you ever when you were a kid? Part of my fing nose and smell. Well, we all did that just in time.


Just Justin. Oh, it's a first name. Oh, hi. Oh, second.


No, just in time. Your.


Yeah. I can't wait. Please enjoy. Mr David Sinclair. We are supported by motion. These days there's no shortage of stressors. That is for certain. We just found out today that LAUSD is a and no school in the fall. Right. You can talk about stress pegged, Max, yet another half year of homeschooling. I can't do it. Well, isn't with everything that's going on in the world. It's more important than ever to carve out personal time and space for yourself.


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Hey, Dex. Hey, Monica. How are you? I'm great, actually. How you doing? Great.


We are so flattered to have your ear to talk about this topic. I got to say. Where did this come from, Adam Grant? Yes. Yeah, I did. We wouldn't have a show at this point without Adam Grant. I'm just going to own that right now. Like, we see something that excites us and we think, oh, we could never talk to that person. And we just email Adam Grant. Then we're talking to him.




Adam knows everybody is real social at best. Email responder I've ever met my life. Yeah, I was just checking. He's still married somehow now.


That's exactly what I think every time he emailed me back. I think, my God, how does he do it with the marriage and the curriculum and the whole nine. So are we talking to you? Are you in Boston? I'm on sunny Cape Cod.


Oh, and are you getting roadside lobster sandwiches? That's my best memory of Cape Cod.


We are actually Scituate Harbor. It's cold. What whereabouts did you spend your time?


Well, I was in Boston and I got on a motorcycle and I rode out to the Cape. I don't know where I went. I don't know what stand I stopped at. But, boy, does that stick out because I don't know that I love lobster before I had it on the side of the road like that. I think I thought it always tasted chlorine, but this was real nice.


Yeah, I still don't like it, but I eat it and the French fries. But you got to have it right. Otherwise you don't blend in. Now, I do wonder.


Let's just talk personal stuff for a minute, cause I find it it'll be informative to why you study what you study and where you're at in life. But you're from Australia. You're from Sydney. Yeah. Correct. And is it freaky to have these children that are American? This I always imagined like I moved to England. I meet an English girl and then my son's got this charming accent. I don't have it. There must be some weird dissonance there.


It is interesting. So, you know, in my family, we have three accents. My wife has a German accent. And then there's me. And then the kids. But the kids are picking up some Australian isms. They say, I can't do it. I can have a bath.


Do they say sweet ass? Or that's more of a Kiwi thing. Yeah. That we is. We don't say that. We'd say you gone down to the beach, the side. I might pick up some some beer, some beer.


So when you look at your children and there's and I imagine as a as someone who at least minimally viewed this country as another on the other side of the world, you wouldn't be human if you didn't have some judgements of the American national character. And when you see your children exemplifying some of those traits that you probably view differently from the outside. How do you make peace with all that? And is it something you laugh at or go like. This is concerning?


Well, it's both.


I moved here because this is the freest place and you can be who you want to be. And it's a real meritocracy. And I've thrived here because that and actually when the kids were young, it was it was perfect. You know, you can be whatever you want to whatever you want. I mean, it's wonderful because when they become adults, true adults know that they believe they can do anything and change the world. But when there is part of a family unit, it's actually much harder, I think, to raise American kids.


Yet the individuality being prized and rewarded. And we write biopics of people who are staunch individuals and in the face of consensus said, fuck you like that. Those are our heroes, right? Much more than I think people recognize anywhere else in the world. Do we do we perv out on that? We love it.


That is true. And so, as you know, as a parent, if you say, well, you know, this is what dad thinks and you can't have this soda or whatever, they're like, screw you. I, I do what I want. This is America. That's always been tough now.


But in this country, you know, I left my family and my best friends behind to come here. And I was supposed to only come in for two years. But I really I fell in love with it, especially in a town like Boston where you can thrive on just being intellectual and you don't have to hide it because most people around you, even on the train or on the T, are smarter than you are.


So it's it's the opposite. I went from Australia where people didn't want to talk about anything but sport and the weather and. Well, that's an exaggeration, but that's typical. And then you come to Boston and people are talking about artificial intelligence and viruses and all this stuff on trains. And I thought, OK, this is pretty cool. This is like, yeah, the Athens of ancient Greece. I like this place.


Yeah. And I wonder if you appreciate this. So I'm from Detroit suburb and in Detroit is is similar to many, many American cities. The ultimate status achievement is just wealth. That's like how you go to alpha status. So, you know, it's just very celebrated and talked about. And I moved here to L.A. and I'd be in the line at the grocery store. And I'm like, there's five dudes ahead of me. Three are homeless in two are billionaires.


They've created TV shows and I don't know which is which. And I think there's something very beautiful about that. I came to really love that about L.A. It's just like you don't know who has. The status or the value or the what? Right. Actually, it's probably the worst dressed person who is the billionaire who has their own couple of jets. Yeah, I do. Yeah.


And then but then, of course, the clerks then have to give everyone some modicum of respect because it could again. Person could have created Two and a Half Men or something and we'll probably hear about it. So I just there's some kind of leveling the playing field given that that's our industry and I dig it. OK, let's talk about. Did you study gerontology? Was that your major originally?


Yeah, I don't call it gerontology. That's more doctors treating the elderly. I'm in a field that really just blossomed since I became an adult, which is longevity research, or sometimes you call it aging research. Just make sure you don't call it anti aging research, okay? Because then you're an atheist.


No, it's got a bad connotation because anti aging, there's a lot of snake oil out there. And yet we scientists at these universities are trying to say we're something different than that. And you know what, really? We're publishing these papers in the world's top scientific journals. We don't want to get mixed up with people who are selling stuff on the Internet that's just made up. We're aging. Research is not anti aging research. Yeah.


And you are shouldered with the history. You know, since the dawn of Homosapien Sabien. One hundred and fifty thousand years ago, all we've always wanted to live longer and every attempt to do so. His failed. Well, it was erroneous at best. So you're coming into something pretty deep in and you're saying, no, now we actually have an understanding of it and we actually can make some moves. And it's just hard for people to shrug off, as you say, all the snake oil salesmen that preceded you.


Yeah, well, it's been an uphill battle for sure to convince the average person who comes in with this healthy skepticism and even doctors. You know, I'm an academic at Harvard University. Most people there are trained in the traditional way, which is we don't care about aging. That's a natural process. We should just accept it. And when bad stuff happens, we get diseases. Then we apply medicine. Whereas I'm saying hold on. Let's not wait till people get too sick to be able to fix things.


But also, let's understand why they get sick in the first place. A 10 year old doesn't get heart disease or Alzheimer's. Why is that? And if you could make an 80 year old be as physically fit and resilient as a 10 year old, would they still get those diseases? I absolutely think that they wouldn't. And that's why I think it's it's an important approach to medicine. But traditional medicine, you know, dealt Teletech cancer, heart disease and Alzheimer's with billions of dollars.


But as soon as you say aging, they go, oh, that's natural. Which is B.S. because these other diseases are natural, too. Yes.


A cancer cell is as natural as anything else in the body. Right. It's just a cell that's dividing and replicating. And I would say, yeah, there's there's this kind of implied vanity to the pursuit. Right. That you must be interested in it cause either you're just vain or spiritually. You can't accept the reality that we're all going out in a body bag. You know, there's there's all these weird implications.


That's also an obstacle. Yeah. DAX, you're very intuitive that way. And that's been a huge obstacle. And even philanthropists who we survive on their donations, many of them, I think Bill Gates would be in this category, even though they're intrigued with this topic. They're afraid that they'll be perceived as being selfish. But if Bill Gates is listening, I want to explain the situation.


He is listening. Our biggest fear. Yes.


So here's the thing. Let me start with something personal. I'm not afraid of death. Absolutely not. I fly a lot. I've almost crashed many times. I don't even get worried about that. I'm fine with it. I'm not trying to live. Four hundred and fifty years. It's a good experiment. I wouldn't mind trying. So let's just make that clear. I'm not doing this for myself. What I am doing it for is I think this is the best way to approach medicine, that it can have the biggest impact for the dollar.


And it's actually been calculated that the cost of one of these medicines, if we're successful, would give us an extra year of life for about seven thousand dollars, whereas a pacemaker costs society a few hundred thousand dollars and some go up to millions. So this is an economic solution. It makes social sense because we don't want people to be sick and look at today's society. We know that elderly are dying a lot more frequently from even Kova 19. So all of that makes sense.


And that's why I wrote my book, is that, you know, I can speak to small numbers of people. And I kept saying the same thing over and over again. So I said, OK, I'll put it down on paper and hopefully reach more people and try to help them see things from from my angle.


Well, to me, it seems like you're in the pursuit of the ultimate upstream solution for all these things, which should appealed everyone on some level. Now, I'm going to start by saying I have not had a biology class since nineteen ninety nine in college, so my understanding could be flawed. In fact, and I'm sure you'll point out some misconceptions, but I have some very general questions based on my very general and aging knowledge of biology. When it was explained to me in biology how the body goes through my ptosis, right.


It either goes through meiosis, which is sexual reproduction, or my ptosis words creating what I was told is an exact mirror copy of itself that the cell divides and then RNA comes in and it reads the DNA and then it takes off and it creates a protein and then it ends up creating the exact same cell. Oh, do we. Do I have it right thus far? Well, it's never exact. You can't make a perfect copy of anything easily.


But, yeah, that's that's the principle of life in theory that. Well, in theory. But there are mistakes that accumulate. Right.


Which is where will we'll get to with your research, which I find so fascinating. But just right on the surface, if you know nothing but that, or when I was 19, learning that in a biology class, my first thought was, well, then what? How could we ever age if if my body's making exact copies of every cell? Then why did those cells change shape elasticity, all these different things? What happens in between that replication and what I see?


I guess the pheno typical results of it being aging. How does that happen? Yeah.


Well, the problem is that there's this thing called entropy and things just follow. You know, everything around us falls apart unless we rebuild it now. Biological organisms shouldn't be alive for more than 30 seconds. If we stopped breathing or if we took a cyanide pill, we'd be gone. But what we are very good at is using food, mostly, you know, other organisms we consume to overcome entropy, at least temporarily. You can't do it forever.


Even the universe can't. But at least for 80 years, a human being can repair itself and rebuild things and expand and divide cells, like you said. But it's not perfect. And it could be a lot better if there was evolutionary pressure on our species that we had to live 300 years. Let's say we never caught a disease. We never had a sabertooth tiger kill us. We would have evolved the lifespan of a whale, which can be 300 years, or a Greenland shark.


Five hundred years or tree two thousand. But we didn't. We usually died in our 40s from infection or war or starvation. So our bodies are not evolved to live much beyond that, unfortunately. But it's biologically possible to live. I think for many thousands of years it's not against the law or biology or even physics because we're consuming energy and using it to rebuild.


Well, minimally, if just looking at a tree, I remember walking through the redwoods and they bisected a tree and they're showing you, oh, Jesus was alive here on this ring, and you get a real scope of like, wow. Well, that's possible. You know, a living organism could have been here when Jesus was here and I was still on my hike.


Yeah, well, it will be possible for us as a species if civilization lost long enough for us to figure it out. But I do think we're on the cusp of finally figuring out why these organisms are able to live so long. And you're right. It's got to do with a copying process, the ability to maintain the information that you have when you're born and keep that going for decades. You know, sometimes for thousands of years. But there's a new ones to that.


Right. You're talking about copying the DNA, whereas the new theory that's coming out of my lab and a few others is that there's another type of information that we lose over time that's even more important for our long term survival and health. Is that the epigenome? It is, yes. OK. So really quick just to give a second grade explanation of this. So your DNA is literally the recipe and anyone who's baked anything knows that you could have all the perfect ingredients measured out correctly, but you do got to bake it.


And that's kind of nurture. Some things can happen in the cooking process and you don't necessarily get what you want. But we have a kind of complicated system. But in general, it is your recipe that makes you the human you are that you see in the mirror. And then now on top or this is always explained to me again, I'm probably got it wrong. But on top of the DNA is the epigenome. And it's basically deciding what's going to be read from the recipe list.


Is that accurate?


Yeah, you're doing extraordinarily well for someone who hasn't found one yet.


Oh, good. So now this epigenome. We'll look at this, you know, nearly infinite long of strand of DNA and it's deciding what it's going to read and not read. So over time, this epigenome collects errors.


It has a lifetime of its own right in it. And by the time you're 70 or 80, it's actually not reading your DNA efficiently. Is that what's happening?


That's what we see. It's a pretty new idea in biology, but it's catching fire. And I think within five years it's going to be standard dogma in the field, is my prediction. So you're describing it Dax's layers, where the DNA is a strand, which is about six feet long. Purcell with 26 trillion cells in our body. There's a lot of it can go to the moon and back. I think at least eight times. So a lot of it.


But it's not really layers. It's actually got to think of it in three dimensions. The DNA isn't just a string pulled out. It's wrapped up in bundles and loops. And the loops are with the genes that are on stay on. And then the bundles are like a hose real on your driveway. You spool it up or like a like a fishing rod, you spool it up and then those genes stay off. And every cell, literally every cell has a different programs set out.


So the DNA is in different patterns of loops and bundles that the different string your eyeball in your ear lobe in your liver.


Right. Every single cell has the full recipe, but only some percentage of them recipes being used to create that exact cell. Yeah.


And it has to be that way for life on Earth because we start out as one cell and that DNA has to be copied. But if we didn't have the epigenome would just be a giant bowl of egg cells rag. Right. We would never be an organism. So the only way to do that is to institute this program like software in a computer to say, all right, you're going to be a brain cell. And when you become a brain cell, you're going to stay that way for 80 years.


The problem is that. Over time, that instruction booklet, the recipe becomes badly bread. So. Think of it as a chef. So the recipe is to largely intact in each cell. But the chef comes along and the chefs now lost her eyesight and she's throwing in the wrong ingredients. And instead of this beautiful souffle, it looks like it S.O.S. So it's not working well anymore. And we see that now that we think we understand what's going on.


We so we we work on mice in the lab. We treat them as kindly as we can. We can change the epigenome and cause aging to accelerate and we can measure it. There's now a DNA clock. We can measure an epigenetic clock, actually can take it forwards and backwards now, which is to me now that we can do that, we are beyond what anybody in history has been able to do. I'm not saying I'm a pharaoh or anything, but but everyone who tried to change the course of aging was unsuccessful.


But in the last few years, my colleagues and I have done that. We can take aging forwards and backwards.


I was introduced to this and I got to applaud 60 Minutes because my understanding comes solely from that episode. So anything I'm getting right. I got to credit them. But they, of course, in in the episode I saw, they were talking a lot with George Church. Do you know, George, are you guys enemies or do you have been or are your friends or your colleagues?


We are very, very good friends. We we collaborate all the time. And this reversal of aging. He was a great collaborator on that project. Great.


So in that that segment, he said that we as a species have executed this in eight different species other than ourselves. Right. Done mice. And they're working with dogs now already. Thus far, it's proving consistent. The results over these eight different species that this technology's been tried on. Is that is that expanded since I saw it?


Well, if he was talking about gene therapy, yeah, it's working in a variety of animals. And and there's even gene gene therapy working in humans now for the eye, restoring blindness. But aging technology or longevity technology, it ranges from taking a pill in the case of mice, putting in their food or their water all the way to human clinical trials where there have been some really interesting success stories. Now, we don't have drugs on the market that your doctor can prescribe to you for aging yet, and in large part because aging isn't yet considered a treatable condition.


But yet we've seen that this likely translates to humans. And it's not just pills and potions that I'm talking about. We can look at the genes that control longevity in things like yeast cells and worms and flies and mice. And we have those same genes in our body. And the different variants, say, between you and me, can actually predict how long we're going to live in part. Wow.


OK. So could you give me a quick history of our breakthroughs leading up to this? Because I have to imagine the fact that your behind the helm during the biggest breakthrough in all this, if it doesn't make you question whether or not we're in a simulation. I think it should. I mean, I think it's very crazy, right. That you and I and Monacan, our lifetimes are witnessing as well.


There have been a lot we know that the time in the womb and early life actually impacts you many decades later. And that's not the genetic influence. That's the epi genetic influence. So that's important to know. Actually, only about 20 to 25 percent of your lifespan is determined by your parents' genomes, by the DNA. The rest is epigenetic, which is good news because it means how we live our lives, whether we're exercising, we're eating the right things that can have a massive impact more than even your your genes.


And there's some proof.


Am I wrong? We've had a couple of different trauma experts on that have talked about that. The epigenome can be passed down. This really kind of flips the whole Darwinian paradox. All right. So early, early, evolutionary biologists were thinking about it backwards, right? They were going, oh, a giraffe's neck is long because the parents stretch to reach that leaf and then somehow passed on that stretching to their offspring. And then we concluded, no, you can't alter your genes in your lifetime, no matter how much you stretch towards a leaf.


But now, weirdly, is looking like it's going backwards, right. Like that. The accumulation of this epigenome may be transferred on in your lifetime. Behavior may end up getting transferred, which is fascinating.


Yeah, yeah, yeah. DNA is not your destiny. Keep that in mind. It's the most liberating thing you can think of. But it's pretty much agreed upon by all scientists that you inherit some of your health and longevity from your parents. Actually, that the male sperm has the biggest influence on people's life, by the way.


How so? I think my recollection it was the age of the sperm has an impact on how long you live more than the mother.


Yeah. Oh, wow. Oh, wow.


How does a man the older. You know this berm. That's how I roll. OK? I want fresh sperm in the day. Yeah, I can see a lot of guys right into the freezer right now to store some. So I've got a small lab in Australia. And what we did there was we made mice or rats. I forget which one. We made them fat. And then these were mums and they gave birth to offspring. And those offspring from the fat mums were much more prone to diabetes than the mothers that within when they were pregnant.


And that's probably true for us as well. And we often don't think about that as how we can influence the future health of our kids by what we eat. And that would have been a type two diabetes if I had to use the human kind of analogy, which is how you made them. The mouse have diabetes through fucking up its diet, right. It wasn't born with a disposition not to make insulin and its pancreas right.


It's type two diabetes. So the body wasn't able to take up the sugar and it put on more weight, became obese much more easily and then pass that on.


Yes. Yeah, it is amazing. And that's what what the epigenome does. But you can counter it. So we have longevity molecules that we've developed that we could now treat these offspring and overcome what bad things the mother did to the offspring.


Wow. Fucking mindblowing now. So if I'm understanding correctly. So aging in essence, is that epigenome just as a bad job at reading that DNA as it gets older or it's not reading the stuff we would want it to prioritize and that the technology that you guys are playing with is that you're kind of a race scene in all these defects or imperfections that accumulate over a lifetime so that it will go back to reading the DNA as if it's fresh.


Yeah, that's exactly it. We think of it as a reset button. Now, we spent the better part of 20 years figuring out why aging probably happens, that the epigenome is involved. And one of the breakthroughs that was made by actually a good friend of mine, Steve Horvath at UCLA, is that there's a particular chemical that accumulates on our DNA as we get older, called methyl methylated DNA. And he found he's a mathematician. He found that if he could plot where these were changing, he could predict the age of a person.


Oh, I now think of it like plac that gloms onto your teeth over time. You don't brush your teeth. That's what happens to our DNA. And this so-called DNA methylation pattern very accurately predicts your biological age, not your chronological or birthday age. And what's interesting is you can speed that up by smoking and being overweight and vice versa, which, first of all, that was an important breakthrough in the field. And then what we realized was that we we could use some genes from embryos to reset that clock to get the plaque off the teeth or off the DNA and basically restore the clock back to a much younger age.


And we're hoping to publish this soon. A lot of what's in my book isn't actually yet published, which is an unusual situation. I didn't think in the book.


The book is Lifespan Why We Age and Why We Don't Have To. That's the one referring to.


Yeah. And so is writing the book. And my student texted me a picture of an AI that had its age reversed and from an old mouse to a young mouse and the nose were growing back and then these other mice were getting their eyesight back. And I wrote that down with my co-author Metal Plant. He's a good friend and brilliant writer. And so in an unusual situation, a scientist myself was able to record what it was like to make a discovery for everyone to experience.


And only now, because it takes a couple of years to get this work published in top journals. It's only now seemingly going to come out soon.


I mean, it's so exciting. I try and do a bridle my enthusiasm about the future because so often we get a little too excited. But I remember learning about crispier and going like, well, that's that. I will never have a disease as long as I live. Yeah, it is. Okay. So is my understanding correct that early on into this research it became obvious that you could kind of erase these layers of the epigenome that would allow the body to start producing these cells as if they were 20 years old or whatever?


But that, in fact, it was it was possible to go to erase too much of it. And you're basically having the cell do what it does in vitro or early on where it would make the organs grow out of control. All this all this like the burst of growth you get as you're becoming an adult, that you could go too far back and get this kind of hyper organ growth. Yeah. Yeah. Right.


So that that's the key step that we figured out. A big breakthrough around the same time as my friend Steve Horvath was made by a Japanese scientist, probably the most famous Japanese scientist currently, Shinya Yamanaka discovered that there are four genes in early life. When you fertilize an egg that can be put into adult cells to erase their adulthood and get them back to being a stem cell, that you can turn into anything. So that that now we use that in the clinic of people, we you could take a skin cell moniker and turn that into a stem cell and then turn that.


If I wanted to, I could make an egg and sperm and fertilize that and make a new copy of you if I wanted to.


Not only do we need to run out of hers. Yeah, you kind of have too many Monika's, that's for sure. But. We could make new skin, we could make nerve cells, put them back into your brain if he had Parkinson's, so that that's amazing technology and rightly so. Shinya Yamanaka won the Nobel Prize for that in 2012. But what I don't believe he realized was that these same genes can drive aging backwards. But like you said, Dachsie can't just throw these four genes into a mouse or a human and expect good things to happen because you'll just have a giant bowl of stem cells and probably the world's biggest tumor.


It's very dangerous to play with that. But what one of my students, brilliant student, one Chang Lou, he realized that instead of using four of the Yamanaka factors, if you just left out the dangerous one. Hold mic, which is a known cancer causing gene. Then the other three Yamanaka factors. They took the cells back in age, but not so far that it caused any trouble. And so now we could wind the clock back in a safe way.


And now now we're having a lot of fun being able to see what happens when you reverse aging in complex parts of the body like the eye.


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That makes me think of the early kind of t cell treatments in that it was like so I was on one for arthritis. It's kind of you're just carpet bombing the immune system, right? So then you're opening yourself up to infection and all these different things. But they've they've slowly started kind of pinpointing which t cells they want to turn off. And it's getting narrower their focus. And it feels like that's similar to this or it's like just honing in on exactly what we want to be activated and not.


Yeah, well, there was a lot of luck involved, right. Didn't have to work. But I've spoken to someone who's I, I don't namedrop. But this is someone who you'd know a wealthy individual was speaking to him the other day and he said, how is it possible that there were these three genes? This is like a wormhole discovery. It shouldn't be possible for humans to do this. Why is it possible? And my explanation to him was that I think a lot of species still have this system.


You chop off the tail of a lizard. It grows back. You chop off the limb of a salamander. It goes back. I think that life has had the ability to regenerate, but we've lost that ability and now we're rediscovering how to use it.


Oh, my God, it's crazy. It's so fascinating. Can you can you be very precise into how far back you go? Like, at one point at some point we can be like, I just want to be twenty five looking for the rest of my life.


Yeah. Is that, is that on the horizon. Can I pick my age.


I don't see why not. We built the system that we've used in mice at least, and hopefully in the next two years we'll put into patients who have eye disease. We built the systems so it's you can turn it on and off very easily. So in theory, you could go back as far as you want and then stop and then age out 10 years and go back another 10 years and keep repeating.


Can I ask how that actually happens process wise? So are you taking some cells out and then adding some stuff like Chris Burri type stuff and then putting it back in the body and then that cell in itself replicates and starts taking over? What are the mechanics of it?


That's been done, but that's way too complicated. What we do is very simple. We we have a domesticated virus colder and a V which is used in patients in the eye and others. It's very safe virus. And it's a it's a delivery vehicle for genes. And that's how crispier is being delivered into people. Now, we don't use crisper. What we're doing is adding in those three embryonic genes. They have three names short for, oh, české.


And these OSKAY genes are the reset button. And all we do is let's say we want to turn the age of the eye back from a mouse that's one year old and blind back to a six month old eye that can see what we do is we take I think it's 10 to the 14th virus particles that are carrying the oskay genes and just one injection into the eye. They go to the retina and then they sit there. OK. So now you've got this transgenic genetically modified eye.


But then we've built it so that if you just take an antibiotic that's very safe, you've probably, you know, Toxi cycling, you can take it for malaria. We turn it on with an antibiotic. So when we give them mice three weeks of antibiotic in their water with a food, they get their eyesight back.


Then we stop the antibiotic and they can see monarch on it. Oh, my God. Do you feel like we're dreaming a little bit? Yeah, we are. We think we're living in my dad's simulation, and it's proving more and more and more to be true. But I mean, I'm sure we'll talk about this. But there's fear around this.


Yeah, hold on. I got a whole I got a whole collection of that. Before I ask that, I have this one question. And we've we've got to have some pretty awesome biologists on this podcast. Dawkins being one of them. Where I posed this question and still boggles me is why isn't there any thing in the archaeological record? Why isn't there any animal that mutated to just not age? It just seems like something that would have to have happened numbers wise.


If there's something we're now doing in the lab, it seems like it could have existed over the millennia. Why isn't anything ever mutated into living forever?


Well, first of all, there are species that have what's called negligible senescence, which means they really don't age trees. Obviously, you know, there are some trees that are five thousand years. They still have seeds that seem young. Lobsters. All right. New England, where. Where I'm at right now. This helps us just get bigger and bigger. And they seem to be just as healthy as when they were young. And there are so lots of examples of those kinds of animals.


But are they immortal? Probably not. No one's ever kept a lobster for a thousand years in a tank. We don't know. But there is a reason why we tend not to have species that live forever. And the reason is that evolution builds what's necessary. And that's it. And it is not necessary to be immortal to replace yourself. By the time you've had two or three kids you're done for. So I'm I just turned 50. So I'm basically now expendable.


My kids are almost grown up.


Well, Woods made sense to me is obviously. It almost couldn't happen in females in the way that we've conventionally thought of female reproduction having a window. But men I see nine year olds getting women pregnant in the news. It is conceivable is that the male of that species would be incentivized to spread that mutated gene where it never changes.


Yeah, but but once you've got children, they can go ahead and spread it. The force of natural selection that keeps you alive declines with time with aging. And there's a cost to being immortal energetically. If you're only putting your energy into living forever, you're probably going to breed very slowly. And, you know, think about whales. Think about trees that they tend to breed very slowly, whereas a little mouse that lived two years and a rabbit pumping out the babies.


So there's a tradeoff between longevity and reproduction that you have to get. Right. And that's determined on your environment and how likely you are to die. Yeah. One interesting thing about women is so no, no men have ever died in childbirth that I'm aware of. And women used to die often in childbirth. So it's a dangerous business for women to have kids. And so you find that the ovary is one of the first things to age out in a woman to protect them from dying in childbirth.


That's one reason we. Oh, interesting. Why there's a difference between males and females. But interestingly, we found that by turning on the set of longevity genes that we work on, we can actually in animals such as mice and probably horses, we think we can reverse the age of of the ovary. And now those animals become fertile again.


Oh, my goodness. We just published this. If anyone wants to look it up. And so we think that the old idea that women run out of eggs needs to be re-examined.


Yeah. So instead of, like, freezing eggs, which is commonplace now, maybe the treatment would just be new eggs. Forty five. Is that where you're. Yeah.


Well, if the Ludy mouse results are true for four humans of forty five year old could take a month's worth of pills and produce very healthy eggs either for IVF or natural birth. How? Oh, Mike Bowers.


OK, I think I have this elementary understanding that you're gonna kind of you're gonna go back to an earlier state of the cell bite by erasing some of this epigenome. But but how does the cell know what it was?


Well, that that's the million dollar question. And what we're chasing that right now, we call this thing The Observer, because there's a very famous mathematician from I.T., Claude Shannon. I'm a big disciple of his back in the nineteen thirties and forties, he was basically figuring out how to maintain information. And he was talking about radio signals. But today, basically that the the Internet is built on his theory. And what he said was, OK, we can have a perfect signal at the other end.


We need a backup copy. So if we lose a little bit of it, we get the full copy and we call this the TPP IP protocol of the Internet. And it's why we can't pretend that we didn't get that email. It always comes in now.


And that's our challenge. Right. And so he called this the observer, we'd call it these days, probably a backup copy, hard drive or even a hard drive is old fashioned now. But you know what? So so we think that there's somewhere in the cell the equivalent of this observer, a backup copy of Youthfulness. But we don't know where and how it's stored, but it must be there because he's a new thing that we discovered in my lab that will publish soon is that these marks on the DNA, this scum, this plaque that accumulates, it's not just five or six.


It's about 20000 different changes that occur across the big six, four strand of DNA in each cell. Now, when we reset the cell, we had a look recently, how many of those little sites got reversed and by how much? And what we discovered was that pretty much all of those many thousand got reset nearly perfectly. And the little sites that changed a little bit got reversed a little bit. And the others that went crazy went the other way, got reverse back to where they were.


So there's there's not just a message somewhere in the cell that says this. Piece of DNA needs to change. It's by how much? As well. So there's two types of information we're looking for. Now, if you want me to speculate, what is the observer physically? And I'll probably be proven wrong in history, but I think it's probably a chemical that is on our DNA that we haven't found yet, or we or we know it exists, but we've ignored it for the last 50 years.


Or it could be something else. Like you mentioned, RNA, DACs, this other type of genetic material like Corona virus has as its genetic material. Maybe there's RNA that stuck between the two strands of our DNA and that says this is a region that needs to be reset. And maybe the information in that RNA strand is telling the cell that it needs to be fully reset, not just a little bit. In which direction as well? But yeah, I think that, you know, if we talk again in a year or two, I might have the answer for you.


But that to me is the one thing I need to figure out before I die.


The Herculean task, I'd label it now. So even for people who are maybe bumping on, like living forever.


There was other stuff in that same 60 Minutes piece with your buddy, Dr. Church, where he was saying that we could make changes to our DNA that would virtually make it impossible to get any virus also. Are you familiar? Yeah.


Can you walk us through the mechanics of that? Because I think that's something that could really appeal to people without the kind of ethical dilemma that will we'll get into in a second. But, yeah, how how could that work?


Well, I don't know what's on George's mind, but off the top of my head, I could imagine ways to engineer ourselves so that we we block all of the receptors so they can't get in or we engineer ourselves to have a natural immunity against all viruses. And there are we have very strong antiviral mechanisms that take a while to ramp up, but we could engineer ourselves to turn them on at will. There's plenty of ways. So, for instance, HIV gets into cells through a certain receptor called CCR five.


And there are naturally people who don't have this receptor a few percent and they're luckily unable to be infected and get AIDS. Did he tell you about genetically modifying that baby in China? That's no. Tell me that. So the doctor who got into a lot of trouble, he made a crisper modification of twin girls. And what he did was he he knocked out, got rid of this CCR five gene. And so they cannot catch HIV, which all sounds great, but it's pretty useless because the chance of catching HIV is very low.


And it's like one in a thousand or less. But the chance of this going wrong, you know, we know very little about what what this procedure does long term. We don't even know what what the CCR five receptor does as well. So I think the risks were way higher than the benefits. I think if he was going to do that, I'll just go out on a limb. If you're going to do it, why not change genes for longevity or heart disease or Alzheimer's?


These are things that you definitely are going to have to suffer through.


Yeah. You stated that you have slowed down a gene in mice, but you've also made my smarter. You've made mice run twice as far.


Oh yeah. That was fun. Yeah. I can't imagine what it's like in your words are you have this idea. And it probably seems harebrained at first. And then you figure out some way to execute it. And then just watching the results must be a very unique experience, to say the least.


Well, what usually happens in my lab is I ask somebody to do something right. I'm useless. I wouldn't know my way around a mouse if you gave me one. But I have these ideas and I have a very smart group of 20 or so P HD who will often do what I ask them to do. Not always.


And so when I say I'll look, let's just try making a mouse run twice as far. Usually they'll say, David, that's crazy. I got more important things to worry about than doing that. And then I just keep pestering and pestering and three months later they try it. I'm not always right, but I do find occasionally I am. And when when I am right, it's a lot of fun. And in this case of the mice running along time, what actually happened was the scientist Michael Bankowski called me up and he said, David, we've got a problem.


He said the old mice kept running so long that the treadmill has stopped running.


It broke my ear on a treadmill treadmill. And I said, oh, no, we've wasted, you know, two months of our time. And it turns out the treadmill didn't break. It's just that the software that was written for it never expected a mouse to run so far. And these were old mice and they were outpacing even the young ones.


Oh, wow. OK. I don't know. This has nothing to do with anything. But you've mentioned now several of your students who have proven themselves to be geniuses or pioneers in the. What is the interpersonal experience of recognizing one of your students who's been looking to you for guidance? There must be a moment right where clicks like this dude is smarter than I am. I've now got to transfer this relationship into you. Go further and tell me how this works.


What is that dynamic like? Well, that's the best part about being a scientist, is to have your trainees go off into bigger and better things than you do. And it's very easy to be smarter than me. I'm just a kid from Sydney who has an imagination. I don't actually do the really hard work. The work that I did when I was a student was with yeast cells, you know, making beer. And we did make beer, but we also discovered why they grow old.


But what they do is really difficult. I love that. The turning point, typically student goes through very stages of grief and anger and whatever. Denial in my lab. And if they get a broken down and we rebuild them into the real scientists, they can be. I mean, really true. A grad program at Harvard is like West Point training because most students who come into Harvard have been the smartest people in their class. Yeah, and they come in not all, but there's often some arrogance like, oh, I'm here, everybody.


Let me win a Nobel Prize and show you how it's done. And then after about two years of them failing and I had this actually with this brilliant student launching, he was about to give up because the reprogramming was just making the cells into cancer and not stopping at youthfulness. And I said, don't give up. Everybody goes through this. Let's try one more thing. And we did we did the I and it worked. And this is time and time again, really.


I find two jobs. One is to put them on challenging questions because it's very easy to answer a basic question. If you know what the answer to the question is already, it's not worth doing. You want to you want to do something that has a 10 percent chance of working or less.


Which, by the way, gets harder and harder in science. The more we learn, it's it's like an escalating issue.


Right. Well, that's why we took on reversing aging, because there's not a lot of things you can do.


But then they then they start to hate you because they think they've wasted their lives and they should have gone somewhere else. And David's crazy and he's got no good ideas. But then they then they break because then they get this beautiful result where they are. Now I know what David was talking about. And then they blossom. Then they go off and they can do amazing things.


And you've just described the exact trajectory for every actor in Hollywood, which is like they're the hottest person in their town. And then they got here and I fuck everyone's up. What are you going to do now?


And then they've got to figure out what's unique and beautiful. Yes. Yeah.


But you got to have resilience in both industries, right? Because it's tough, really. Yeah. It'll break you if you don't keep getting out of bed every day. Okay.


Now, as I was watching you speak today in numerous interviews, I could not help but draw the parallel between a book I'm currently reading about Oppenheimer.


You're at the cusp of this really monumental scientific breakthrough, and it's going to have these humongous implications. And to watch how Oppenheimer and surrounded by all these very thoughtful, intelligent people were both solving the problem and, you know, when free time permitted evaluating the downstream consequences of it. And in that situation, of course, we were up against the fact that had not they done it, someone else would do it. So that's just an imperative that they're working under.


It's like all your ethical dilemmas aside, best we have the technology, not everyone else. I couldn't help but think that you guys are on this amazing path. And then there will be all this societal outcome from it that I wonder when you're working on this, what percentage of your brainpower is dedicated to that? The downstream outcome of all this?


Well, more than you might think. So the last third of my book is about the implications and what the future could look like if we don't do anything and if we do succeed in what we're doing. And actually, in my view, the future looks much better if we're successful. It's not all good. Right. There are some people who don't want to live a lot longer and politicians are getting older and older. And, you know, there's a lot.


But but the overarching benefit to society, if we utilize this, is that I mean, who wouldn't want to spend an extra year with their parents and prevent them from getting cancer in their 80s? This is what we're talking about in reality, about drugs that help people live healthier and more productive lives. And so I think a lot about it. But I also do think about the downsides as well about population growth and what are we going to do about jobs if there aren't enough to go around.


So I'm working with mathematician's right now over in London, trying to actually build mathematical models to understand what society will look like. And even the impact of. On the economy of the globe? Well, first and foremost, let's acknowledge that if it all comes to market within the first decade, it's certainly going to favor people with money. I mean, all all medical advances do favor first those of means.


Well, yeah, it's similar to the Wright brothers in that if you wanted to fly on a plane, it wasn't cheap, but still not cheap, but it was incredibly expensive. And cars as well, the rich had the cars. It's a little bit different in this case in that the drugs that we're developing, some of them, the pills don't have to be expensive. They could be actually quite cheap. So it would about to start a clinical trial to treat Koven 19, for example.


And we are, if we're lucky, very lucky. In a year, that drug could be on the market. And it would be sold for, I don't know, let's make up a number. Twenty dollars a pill, a maybe one hundred. But that's not outrageous. Right. And then we're we're also looking at trying to get it quickly over the counter so everybody in the planet can have it. Now, if that plan works, then it's going to be great.


First of all, we'll have this possibly five to 10 years earlier than we otherwise would. But also because it's being used for an infectious disease, you cannot charge tens of thousands of dollars for it. No one would buy it. Yeah, and in fact, most of the downstream treating the symptoms cures are horrendously expensive. I'm on different arthritis. And I don't think one of them's been under a thousand dollars a month.


You know that the reversal of aging as we do it in the eye right now. That will be expensive and it's unavoidable because gene therapy right now, there are so many hurdles and safety issues you have to go through just to to get a drug on the market. It probably close to 700 million dollars. So that's fair enough. But here's the good news is that I don't think it has to stay gene therapy. There are about four of us in the world who do this age reversal right now.


And we talk all the time, every day. It's a bit like Oppenheimer and his crowd, actually. And we are working very hard to figure out how can we do this with a combination of safe molecules. And eventually it should be a pill that can do this.


OK, so sensing that 60 Minutes thing, I've probably dedicated 300 hours of my free time thinking about it because I'm a writer by trade and I'm always thinking of movie concepts. And so I can't help but funnel it into that thought process. And one of the things I thought of is like, OK, in the world where this is widely available and you can basically revert back to your 24 year old self, what would a world look like in which everyone's virtually the same age in that you're going to see your doctor who's been practicing medicine for 40 years and he looks the same age as you, and then your parents look the same age as you.


It's a very fascinating concept, right, of just having everyone virtually at their peak and how you're going to recognize was the easy strategy identify as a source of wisdom and stuff.


If you thought of that aspect, probably not as much as you have. But what I find is that, first of all, it's been really heartwarming that in the last few months, the world has shown its respect for older people. That being revelation, which is great, but I think it's going to be even bigger than that. If older people in their 80s, 90s and 100 are still as healthy as the young people, so playing tennis, hanging out with a great grandkids, then we're in a world similar to the line at L.A. where you can tell how rich somebody is in a world where you can't tell how old somebody is, then you don't have this ageism right out.


We only look at someone who's shuffling along and go, oh, God, kill me when I get to that point. You know that that's that's not nice. Speaking of the brain, one of the experiments we're currently doing is asking if you turn back the age of a brain. So we're going to take an old mouse that's lost its memory, has dementia. If you reverse aging in the brain, what happens? Do you lose your memory? Do you die?


That's exactly what we regain. Lost memories. Yes. And really quickly, what?


Again, going back twenty five years since I learned this, but I was told that there was some Madoc cells and there was grey cells in your brain was these grey cells that didn't go through mitosis and didn't replicate. And the ones you were born with are the ones you were going to have for life. Is that still the the belief or do they do more than we thought they did 20 years ago that they do grow?


So there is neurogenesis, but not in large parts of the brain. It's usually only in the center section. So you can grow new nerve cells, but you're not going to be able to grow enough to replace all the damage that's occurred over 80 years. So I think we need a treatment like I'm talking about where every nerve cell in the body remembers how to read the genes to be a nerve cell. And what's up? So the treatment that we did for the eye, so the eye is an extension of the brain.


And part of the central nervous system. So if we can turn the clock back in the retina and the optic nerve, it should work just as well, I think, in the rest of the brain. And that's what's exciting.


Well, this must be very exciting for, like spinal cord injury people, because that's, again, the material we thought we couldn't really grow back or limited options there. Exactly right.


So one of the experiments was to pinch the optic nerve. And we saw it grow back to the brain. And the same thing we hope will happen in spinal cord injury, but maybe it's even bigger than that. Maybe one day if we have our finger cut off, we'll apply this technology and you'll get a new finger to grow back.


So but OK, so if you're going back, what if you go back to like a 15 year old brain, which is not early and God forbid, develop? Exactly. And so then would it develop again? Well, yes. Feels like a pansy five.


Yeah, this is interesting. I haven't thought about this, but what if your brain starts producing hormones like you're a teenager again?


Was this going to say I do miss the horniness as much as it was? I don't need any more. Right.


Having your brain develop over and over and over again and releasing more chemicals over it. Like how? That's crazy.


Well, we will. And I think in our lifetime we'll be able to know the answer that.


OK. Here's another one I thought of. On our hundred, which was OK. This technology exists. Everyone has access to it. You don't have to die. It is unexpected for you to die of a virus of, you know, any of these numerous ailments that this technology could prevent. In a world where the expectation is you won't die. Does it? Change our relationship with death. And then I thought of this in a very selfish way, right?


Let's say I had the procedure. My wife was like, well, you now can live to 250 years old. And if you keep riding motorcycles, what a fucking you can't do that. Like now. It heightens all this acceptable risk we take on. Because we we live in a paradigm where we have a life expectancy and we expect to die of diseases. So you put motorcycle riding into that equation. You're like, yeah, well, I'd rather die from that than cancer.


But now when all those are off the table, do you think it makes people hyper neurotic about dying through accidents? Because there'd be an expectation of longevity.


Yes, absolutely. I mean, just look at what's happened over the last hundred years. People didn't care so much about protecting their kids and whatever now because kids are expected to live for 80, 90 years. We put them in bubble wrap. I think the same would be true if we lived forever. We'd be scared to cross the road. It'd be that right?


I really think so. And it would feel like a much deeper loss. It's too. Yeah. It didn't have to happen. It would be irresponsibility. So there'd be this moral character judgments, right. If I kept riding motorcycles. Right. Well, that guy's a selfish asshole because he could live to 500.


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Also, like, what about suicide, like that will probably rise that time, because if you feel like this is literally for ever. I want to get off the road. I'm choosing to get off.


Right. Some some people have said they they may not get married. Oh, this is the joke. I've been saying to my wife, which is, hey, I'm going to be able to afford this procedure and I promise I will live with you. Do you die of an old lady? But I will remarry many, many times after is my commitment to you morally as I'll be by your side till you die. But just know I will be off to the races after that.


And so I guess I'm wondering, do you guys invite in the super esteemed folks in your philosophy department at Harvard and and do any kind of like workshopping synthesis of these different disciplines to wrap your head around with all the downstream effects would be.


No, not often enough. Occasionally I debate bioethicists. I debated Lee on Cass, who was President Bush's bio ethicist and scientific adviser. And we clashed terribly. He thought that treating aging was was abhorrent and would reduce the agency of life. And we wouldn't wake up every morning with joy. We would just be lethargic. And I totally disagree. But I don't get out of bed every morning because I know I could die. I get out of bed in the morning because I got stuff to do.


I'm enjoying my life. I'm healthy and I'm excited about it. And that's can be true if I'm 100 or 200 or whatever, you know.


Yeah. My gratitude is not rooted in the inevitable death I'm gonna experience. No, no.


We could all die tomorrow. I mean, that's enough motivation. Look the wrong way. Crossing the road. But it's a it's an incredible thought that we may be able to have multiple careers and multiple lifetimes. And for people who make the wrong choices when they're young and go and do the wrong career if you have extra time. Yes. Reinvent yourself at 60.


Yeah. The panic and people throwing in the towel and all these things. We think of it too late. I like the notion of that being off the table. Right.


And, you know, if you've been breaking rocks either physically or metaphorically your whole life, it's not fair to expect someone to keep doing that for another 50 years. But that's why I think we should have the chance to start again and have a skill battle kind of thing where you're allowed to take a couple of years off, maybe hide to go and learn something new. Yeah, yeah.


This system will need to evolve with this technology, because if we live in our current system with this, I do think it's going to be disruptive. Yeah. So we have to have the whole thing has to evolve. Yeah.


Actually that the most exciting thing for me is that I might outlive all my enemies.


Sure. Sure. Are they numerous?


I have a list of people that I'm not fond of this about. But generally I forgive people. I don't have a lot of enemies. I think what we're all in this together, it's a hell of a ride. It's difficult. And, you know, we've got other problems then, too, to hold grudges. So I don't think I've a lot of enemies. I've a lot of people who, you know, in science take potshots at our work.


Oh, that's what we're paid to do as scientists. So, you know, sometimes you take it personally. But as I've gotten older, I've realized it's not personal. It's just business.


Yeah, that's the underpinning of peer review. Right. You're not doing your job if you're not critical of everyone else's research and claims and.


Yeah, but it's a tough career, especially when you're young. No. Similar to your career as a young scientist. You don't know if you going to make it. And at a place like Harvard, your chances of staying are probably less than 30 percent. And you have to be the best at what you do. And every time somebody writes, all Sinclairs follow it or whatever, it it really hurts because you could lose your job. Yeah. Lose the city you you live in.


You have to move. But once you get tenure, which means you cannot be dismissed. That's a wonderful thing because all of that fear of getting kicked out goes away. And then you can just dream up this crazy stuff. And actually, George Church gave me the best advice of my career. He said, once you get tenure, just do the stuff you want to do, do it. And that's what has led me here. I'm just doing what I want to do rather than what I think I should be doing.


Yeah, well, I am so grateful you're doing it now. A, have I not thought of a moral conundrum that you want to bring up? Is there one that vexes you like home? I don't have a great response to that problem. It'll create.


Not really. I'm a I'm a glass half full kind of guy and I think humanity can solve any problem it puts its mind to, whether it's social or economic or medical. I think the biggest one is that people may become more politically one direction. The older they get. Yeah, well, we'll look out.


Disheartening covered was it only had about a two week window where it was a political and then it just everyone lined up, which was so discouraging.


It is so. So I'm thinking of how I'm gonna do an experiment to test whether a mouse becomes more right wing or left wing and then reversed.


I ask it to vote again while I have to imagine people are more liberal in their youth. I'm more conservative, right.


They are so a world with lot of older. People may be more conservative, but then again, if you have your brain reset, who knows? Yeah. And if you're if your journey is not over, there's things that are ahead of you that alters all the things.


Well, here's one of the benefits, which is if the politicians today we're going to see the 22nd century, I think they pay more attention to climate change.


Yeah, exact. Yeah. Yeah, I totally agree. Now, the question you hate the most. I got to ask it. It's my responsibility. What is the the window of this happening? If you had to say how many years out is this, you know, is this something I'm going to be able to do in my 50s or am I going to be doing it my 70s? Where will I be at?


All right. Well, you're in your 20s right now, 45, 45. You're doing great. So it's always dangerous making these predictions because drug development is so hard and things fail and the FDA makes things really difficult. That said, I'm more optimistic than I've ever been. And why is that? It's because it's not just me working on this. There's hundreds of labs and dozens and dozens of companies who have different approaches to longevity and ageing research. And so I think somebody is going to break through within the next probably five years in terms of total age reset.


Well, the timeline that's been set is I started a company we've been working for a year on reprogramming the eye and hopefully within two years we'll have some results as to whether it works or not. Then it could expand, you know, start reprogramming the skin or the liver or the kidney. Eventually, I hope within 20 years we'll be able to reset large parts of our body, if not the whole thing.


I hate to keep drawing these parallels, but I keep seeing them. So you're very much like a movie director, writer directors. I spent two years of my life writing and directing this movie and then literally I'll find out on a Friday whether it was a total waste of my time is the best thing I could have done. It's very rare scenario or zone that it gave that much time, you know, and get potentially an unfavorable outcome. Yeah, well, that's why we need to live longer, because it's hard to have have these failures and there's a lot of work to do both in your industry and mine.


But it is true. It it really is true. Sometimes I, I freak out because we work for 10 years on a project and then you send it into the journal to be reviewed by your peers and then it comes back and gets rejected and you think, what other profession do you work for 10 years a and get a rejection. It's tough sometimes.


Yeah. It's it's really an all or nothing endeavor. The rewards are huge and the downside is is also huge. Well, David, thank you so much for taking the time to talk to us. It's one of the most exciting things happening in science. I'm so fascinated with this. And I constantly bring up that 60 Minutes and people are, in my experience, is generally unaware that any of this stuff is happening. And I think it's best that we start these debates now so that we have some sense of what our ethical blueprint is once it hits the marketplace, as opposed to reacting to some things that pop up.


Yeah, yeah. 100 percent. That's that's also why I wrote the book is to start the discussion now. But what's really helping are guys like you. You two getting information out directly from scientists and big thinkers. You know, we used to live in a world even just five years ago where you'd go to a newspaper and newspaper reporters couldn't report about stuff until it was fully published. Whereas now you can speak to me and I'm saying, hey, scientist, don't even know this stuff yet.


I'll let you in on a secret. I love that world that we can now. You know, bounced between the public and our ivory tower.


Oh, yeah. The world of the middle man has is evaporating. And I know one's more excited about that than than me and you. Even the notion here that there's no intermediary between us recording this and it being in people's ears. There is no corporate board. There's no you know. Yeah, that part's pretty great.


And so I love podcasts and I rarely talk to newspapers anymore because I found that every time I said something, it would get twisted or hyped up. And my colleagues would be mad at me for saying we're going to live for 200 years. And I would say I didn't say that. And it doesn't matter. It's out there. Yeah. And so I'm just like old media. It's just frustrating as hell that that's my greatest frustration.


And increasingly with my publicist on my I don't want to do anything print because it's going to pass through their filter no matter how I present myself. It has to go through the filter of their body before it comes out their pen or their keyboard. And that's just a lot to risk when you've dedicated so much of your time in life to something and they're incentivized to have that be a flashy thing.


So click be an economy. Yeah.


So true. You know, I worked on my career for 25 years and some jerk can come along and like in your your situation, just write something that makes you look really bad. And you don't even say that it's not worth it. Right. Twenty five years is a long time to work on a reputation. And then they move on to the next story and don't care. That's happy at number of times in my career. So I applaud what you're doing.


Thank you for showing the world what's possible and allowing people like me to talk directly to people. Yeah. What I please.


This is forever at your disposal. Any time you think there's info that people need to know, please let us know. And we would love to have you back as many times as you'd like to come back.


Thanks text. And thanks, Monica. All right. We'll be well. Thank you so much.


There are days and now my favorite part of the show. The fact check with my soulmate, Monica Padman. We're rolling, Monica. So don't do that. L don't do that. Okay, I'll stop farting loudly right into the mike. You're disgusting. You disgust me.


Oh, you know what I really like. What do you like, McKayla Cole? And it's. I may destroy you. Yeah. And HBO, we are obsessed. We love it.


Oh, my gosh. We've so much housekeeping because that's old news.


That is old news, but it's new news because I didn't know anything about her. And Joy Bryant, our good friend, Joy Bryant, for me in an interview with her in Vulture. That was so funny. It was it was really top notch. And she basically says in there that the world can be divided into two people, the people who like talking about poop and people who don't. She's in the liking to talk about poop category. She's a shoo in to be on this show.


Oh, my. She's all right. I'll do two hours on poop if she wants to talk too much about.


No, we had. Now I know that we don't. That's right. Well, honestly, I felt a little better reading that. So when I assessed as being a genius.


Yeah. I was about boudi. We should tell people about Pooty. OK. So we had puppies for a while. Two weeks or something for pup. Three, three.


Three players. So cute.


They were really cute. And then when they would take a shit you know, is a baby poop. It was a puppy poop. Yeah. So it's kind of runny and a mess and stinky and it varies thinking very specifically stinky. And I started referring it to Pudi like someone smell Pudi. It just felt like it'd be right to call it that because of the dog. And we were really going off on saying Pudi like like oh I think this pooty might be in my shoe, something I'm putting on their shoe.


And then we got to talking about that. It sounds really gross.


It's pretty much the worst word you could possibly. Yes. Think of Bhiku. And I'm going to have you explain why some massah like I can do it.


I will just talk in code. OK. The reason it's disgusting is cause it kind of sounds like a mix between poop and also a female. Yeah. Erogenous zones as well. Yeah. You also Jema. All right. This is my.


Yeah. So we're like, oh, that's Kelly. Wah, you are. And it's combining poop with that word. It kind of sounds like maybe Whitewell, I think. And there was a substance that was made and it's called beauty. I'm so sorry. I'm so sorry.


But not sorry. Oh my gosh. Of our fat. Our fact checks have been nasty recently. Yeah, that's all right. Isn't the booty pretty pretty good. That's Pudi. That's one of our housekeeping's. Another is. I got Jordans. Oh yeah.


Yeah. Burs Perigord. Yep.


You pick them out for me cause you are a connoisseur. I don't have an eye for a lot of things, but I happen to have an eye for Gytis.


That's right. And you pick them out there. Animal instinct to two point toes there. Gorgie, we bought one for you and Christian as well.


There's sack. Soon as I got him for you, I started looking for him, for me. And then I couldn't find him. And then, like, gifted the magic style. You found him for me so early. You didn't get a free per gytis. Yes.


I was going to push my more broadly even more expensive because this is like a blog.


Yeah. They're caught, chise. And there is something so special about that box arriving, especially now that I've watched The Last Dance. I feel even more connected to him than ever.


Wow. And I said, correct me if I'm wrong, but you're gonna kind of just get your shoes out. And I was like, no, no, this is a thing. You get the box and Jordan in the air and you stare at it for us.


Yeah. You want me to, like, really safer than I did. Yeah. Yeah. And build in the 23 number is all over with a little packaging.


And then you pop. You crack that top in it. Yes. Yes. Jordan and only a Jordis thing like that. So is she. Oh, it's really the funnest box open.


It is. It was really fun. And I love wearing them. OK, another update were in Sedona, Arizona. That's a crime.


And gang, get in your car and go to Sedona. I had never been here. Me either. Outrageously gorgeous.


So unbelievably beautiful. It does not go at all. We've been here for about nine days. Yes. And it is not old and we're not on vacation, OK?


We're not like vacationing during COVA. No. Where I'm working, I'm shooting top here and we wanted to still be able to record a bit.


Know I came. And that is a commitment to you, the listener. That's right. That's right. And the family of your man about Pooty now, you should be even about this.


The family came and we're all here. And it has been so wonderful and beautiful.


I'm not going to go so far as to say I have like felt the energy for tax. But I will tell you, I've been content.


Yeah. At Paea my mood has been so good. Whole time I've been here. Definitely a notch above what my mood. No, I can't. Me too. You too I think.


Yeah. In fact, everyone here by Muswell Tired presents huge house cleaning and this will really embarrass the fuck out of him. OK, we got. Here, day one. Oh, yes, huge mountain behind the ice with some dangerous rocks to climb. And Erik said if you climb it. And I said, no, I had this terrible experience climbing something like that Joshua Tree. And I was stuck. And I thought I was going to get airlifted.


Then my friend Scott Johnson rescued me and I was on the verge of tears. It's the as I've been those five and got lost. Yeah. So I tell this long winded story, people leave during it, it's too long. And then the next day I go to work. Yep. You sure do. I go down to Phoenix and I start getting videos sent to my phone of a helicopter circling the mountain behind her house. And I think, you know, why are they sending me these big dollars helicopter?


There's a million in L.A. in the sky. Then I start thinking that helicopter must be looking for somebody. And then I thought, if anyone in our group has lost its right. Hanson and it was not that he was lost, it was that he climbed up into this very precarious situation and used a rope. When he got to the top, the fucking rope snapped. Well, now let's be OK. This is what I'm trying to dress it up for.


I know. Well, I going to tell the truth. OK, so I'm on the porch.


This story is not about you. Go ahead. It's actually not about you. You are even there. I on the porch and they come out.


Where if you go. So I had eggs for breakfast. So they came out and they're like, we're gonna go on a hike. And they're like, we're gonna try to hike up there. And I looked up there and I thought, that is the dumbest thing. It's trouble close. Just like, that's so dumb. Like, you're gonna try for five minutes. You're not gonna make it. It's gonna be dumb. And I made a joke about 127 Hours.


Oh, yeah.


Oh. So you kind of jinx them. No, I'm just smart and predicted what was about to happen again. Or Zarno. Some people call it whatever. And then three of them went Ryan, his wife Amy and our Molly and we. OK, also, we've had a few disasters this year, personal disasters amongst the group.


Molly had surgery. I fell off a cliff. OK. Well aware. And I'm actually not counting either of those. Although there was the most significant one. Go ahead. There was a seizure. There was a dog death.


And now there was this year. You're right. Those are the hugely right. You're absolutely right. And Molly has been there for every single one.


We're starting to see a little bit bad luck. She's also a I thought. Yeah. OK. So anyway, they left and they had been gone a bit. And then I went to shower. I came out, Eric said, did you hear that?


Oh, no.


Did she here?


Oh, they're stuck up there in a search. And rescue is coming.


Oh, my. Oh my God. Then I immediately look at my phone. Ryan has tried to call me on WhatsApp. We have zero service. Sedona, Arizona. So he's tried to call me on WhatsApp. I call him back. Amy answers. I was like, what's going on here? I said, yes. Ryan climbed up this one part. There was a rope there. And he was like, Oh, I think I can go in.


So he started climbing it. And then it snapped. Yeah, well, he was almost at the top. He was almost at the top and it snapped.


And he caught himself using this crevice like a luckily because it was it was there's literally a life or death.


It was 100 feet on one side and like 30 to 40 feet on the other side. And he could only stand on one. That's what he was balancing.


So I said, oh, my gosh. She said, yes. Search and rescue is coming. So then we flew our drone out.


Eric had a dream found and say, we are insane. Eric had a drone out a drawer. It didn't come.


It had a half battered city, so he couldn't get very far. But we did see the search and rescue people, but we couldn't find them. Then I called her back. She said, yeah, I guess a helicopter is from Flagstaff.


Two hours goes by. Well, Ryan is on one foot in a crowd. Oh, my God.


For two hours, I keep checking in with Amy. She's like, he's he's OK. He's panicking little. The girls are fine. They're not stuck. And she's like he's panicking a little. And every time she said that, I was like, oh, what if he passes out because he's for you? Oh, my gosh. It's hard to get so scary. Finally, the helicopter calms. We're like, hey. And even still after the helicopter comes, it's like 20 minutes before we see Ryan's tiny body hanging from the helicopter on a rope.


Just soaring. We've all seen this image. You see it on the edge. Once he was airlifted out. Oh, my God. Like a 100 foot rope.


Oh, my God. It was something. Yeah.


It's been a big year and over with my Jordans, I almost dropped them in a lake and I was variable. Yeah.


We hiked to a cool river to this chapel is a little misleading. Protip I would like to give out any time you get to a new city. Google best swim holes in. Oh I swear. Almost everywhere I go ends up having some like of. Fluted swim holes, and they're always great and you know what we've learned? I'm not a very adventurous person. Did we learn it? I already knew it. Did you admit it or did we learn?


Oh, I don't need to admit. I feel totally confident in that because people get airlifted and people are getting hurt and.


Well, you do have such a paradoxical personality because, you know, you also a high flyer for sure.


You have all these elements where your total is taken and then some that you're you're not. It's inconsistent with the high flyer.


I don't consider it a risk, which is so stupid. That is way more dangerous than any car stuff.


There's no preparation before you get up in that air. Okay. Okay, okay. All right, Rumana. Okay. Next thing. Okay. David Davy, you love this. And so did I. Oh, my God. I loved it.


I mean, if he's not completely lying. I mean, I really believe this is going to happen.


I hope so. I mean, it's a DUI. If you don't like it, shoot yourself. Hey, one that's Zulu's.


Know that. That is what I brought up. I said, I think this might lead to more suicide. I don't like that.


Well, why would it lead to more suicide?


Because if you're living on Earth for 400 years. Yeah. If you're 100 in and you're like, this thing fucking sucks. Yeah. And I have 300 left. I'm done.


Well, but I don't even think we can call that a suicide. I mean, anything past 100. We got a label at something else. You were supposed to be dead anyways.


Well, OK. Now I just got a was.


Yes, it is. If you give us a 300. OK. If a tattered euro man shoots himself. You think that's a loss?


If I'm that person's kid and I get up 200 more years with them. Yes. That's a huge loss. OK.


Well, this person was a tycoon with a No one liked him and he only bought himself the procedure.


Wow. All right. There are a lot of ethical questions. Oh, you bet. I mean, they Berman is they don't stop. What could be a bigger ethical quite now? Yeah.


Well, because even after we were done with him, I kept thinking about it and I thought, well, knows because we had all these kind of major Supreme Court decisions recently. And I was like, oh, my God, if we live to 300 years, what are we gonna do about the Supreme Court? We can't have those people on the Supreme Court for 300 years.


Well, although I got to tip my hand to them. They've been doing up a pretty darn good job of Islam. I've seen both sides. I've been more impressed than I've been disappointed.


But if you're on whatever side you're on of this political spectrum, like, it's scary to think you have the same people make decisions for 300 years about how slow progress would have.


They would have to put term limits on that. And so exactly. Which will become more political. Yeah. Yeah. So. Oh, man. I just never stop. And it was.


Well in the way you know, it's completely unethical. This is black and white unethical because, you know, we all think should it be available for everyone and you go no. That obviously we can't have seven billion people live forever and have new babies. So that's a non-starter. So you go, no, I don't think everyone should have this.


And then. Do you think. Use it? Yes, I said it. So, you know right away that you're on real shaky footing. Yeah. Now, are you wearing a mask right now or on your neck?


Yeah. Phone one in the mini miniature van. It's an eye mask and I think I am going to use it tonight.


Oh, it's an eye mask. Okay, got it. But, you know, like a Dracula mask.


No, I thought it was a Cauvin mask. Oh, no, no, no. I thought you were wearing it for, like, security. And I liked that.


I wear it at work. I'm so I'm a stickler. I love it. OK. So he said that was some of these medicines. They can increase life by a year for seven thousand dollars. And the peacemakers are a hundred thousand dollars. Sometimes millions. Pacemaker. Yeah. Because he's like making an equivalent. Yeah. Yeah.


So Tucker, I just heard. I thought you said peacemaker. Oh I probably did. He's a pacemaker.


I mean, ironic for a bomb wouldn't it, the peace maker.


Oh no.


That's how you see my right wing side. I brought up guns a minute ago and I'm talking about bombs. I see your right wing.


So all that. It's what I fight every day. What are you talking about?


So I saw a few numbers. Total costs for pacemaker implantation range from nine thousand six hundred sixteen to nineteen thousand seven hundred twenty six, with an average cost of fourteen thousand two hundred ninety four patients not covered by insurance. A pacemaker and heart assist implant can cost nineteen thousand to ninety six thousand or more, depending on the type of pacemaker that makes zero sense.


Why would you get charged ten times as much for not having insurance?


Well, the price is right. What's the whole thing? It's a racket.


Right now it's almost like health care has gotten to the point that the derivative market in the stock market is like where there's only three or four people who can explain the product that they sell or truly understand the product that they sell. There's so. Strike. Yeah. Puter modeled. Yeah. Yeah, I know. OK. So he said the age of the sperm has an impact on longevity for the offspring. And I cannot find any backup on that.


So just f why I could not. If that's true. I think we could immediately propose a theory that you're way better off if your parents were young when they had you.


Well, yeah, because when you're younger, you're you're either fucking or jerking off every day. You're not going like this old man who might go a week and a half. Well, then there's Gerkin heading there.


How long do they last?


I don't know, but I'm a great person to test it on.


I think my kids, they got me at a point when I would, you know, maybe once a week. So these kids could have been made from six day olds.


Worm. Interesting. That's good or bad. Terrible.


Oh, if they if I were to have them in my 20s, they would have had two hour olds. Right. Right, right. Right, right, right. But those old sperm die.


Well, the hope he's seen. I mean olders only can only be whatever ten. That's what I'm saying.


I wonder what the actual length that they can live in. OK. It says most men make millions of new sperm every day, but men older than 40 have fewer healthy sperm than younger men. The amount of semen and sperm motility decreased continually between the ages of 20 and 80. Mm hmm. OK. He said no man has ever died in childbirth. That is true from what I could find. There have been some trans men who've had babies.


But I'm going to propose also that a man has certainly died in childbirth. Yallock a heart attack. Yeah. Yeah. Watching in the news over a guy.


That's what I was trying to look for. I truly cannot find any stories about that. But I'm sure it's having a stroke, a heart attack. Actually, I don't think this was childbirth, but I do have this horrible, horrible story. My friend's sisters friend, you get a call. One of those sisters. No, no, no. I want to be sure.


So the mom, I think, was in the hospital or something. Maybe I want to say having a baby, cause it's pertinent to this battle and why she was in the house. Okay. But the dad, like, rush to the heart because she was a doctor.


You fucking massage, you know. She was not a doctor. She she could be if she's in a hospital and she's a woman, is it a riddle or is it the. The woman was in the hospital for a reason and then the dad rushed to the hospital and then got run over in the parking lot of.


Yeah. Of the house. Yes.


Because he was he was not paid because I think something horrible was happening with his wife or whoever.


We'd have to agree. That's the most ironic now. But it's the sad is. Yes, but and then also, if the mom died, I kind of think that happened.


Wait, now you think the mother.


I think the person that was in the how you say, oh, I just I just want to point out that you think the only way a woman could be in the hospital would be to be ill.


And what I'm saying is that women are there as doctors.


You fucking massage and you're I couldn't even comprehend. I won't be in there unless she was terminally ill.


No, I think the reason the dad fucking rushed out of the car so fast I got hit by a car is because something horrible was happening inside. She wasn't a doctor. This is an episode of Grey's Anatomy. I think it might be. Well, actually, I do think it might be OK. OK. What percentage of people don't have the receptor for H. I b. C c. R five. Yeah. It is estimated that the proportion of people with some form of resistance to HIV is under 10 percent.


Under 10 percent. Huh. That's still good size of oxy. I know. How do you find out if you're that person? You kind of have to risk it.


Well, I bet you could. Maybe you could get tested. I bet Eric Topol could have the results of that.


And he could do the body scan for sure. OK. That was it. That's the last one.


It's just the last one is. What's the chance of getting HIV? He said one in a thousand or less. This is just hard. Yeah, it's it's very, very hard to say.


Varies country to country. It varies.


And it's like, what's the chance of having it getting HIV if you have unprotected sex or what's the chance you know it. Right. Intervene it. I know it's just all gets very complicated to find out. Yeah.


It was my Rojos percent chance. If you're a virgin who doesn't shoot. Correct.


Exactly. It's just so you know, you can do some research if you'd like on that. It cannot be one in a thousand or I would have gotten it.


Well, you might have it. Oh wow.


Measle Thomas on. I love you. I've had the best time out here. Don't try to rob the house. I have ringy. I'll see you be we'll be home by the time you'll hear this, and I'll be there waiting with my firearm. Oh, right.