David Sinclair

[0] Welcome, welcome to armchair expert, experts on expert.

[1] I'm Dan Shepard.

[2] I'm joined by, what's your new name?

[3] We just came up with them last night, two nights ago.

[4] Farty pants?

[5] No, no, no, no. Is it play on Monica?

[6] Monica, Monica.

[7] Oh, that's right.

[8] Monica, Monica, Monica.

[9] Try to say that three times.

[10] Monica, Monica.

[11] No, but I can.

[12] Yeah.

[13] Monica, Monica, Monica.

[14] Monica.

[15] No, I can't do it.

[16] It's very hard.

[17] It's very hard.

[18] Oh, right.

[19] we have a show to do.

[20] We have a glorious expert today by the name of David Sinclair.

[21] He is an Australian biologist and professor of genetics, best known for his research on aging and longevity mechanisms.

[22] Now, gang, I got interested in this off of a 60 Minutes episode.

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

[24] Well, the stakes are high.

[25] We're talking about living forever.

[26] I can't think of a topic I'm more interested in than living forever.

[27] I'd really like to.

[28] Me too.

[29] Also, he has a PhD from the University of New South Wales, Sydney.

[30] and received the Australian Commonwealth Prize.

[31] He was hired at Harvard Medical School in 1999, and he has a great book called Lifespan, Why We Age and Why We Don't Have to.

[32] And he has a new book coming this year called Just in Time, The Discovery of Sir Tuan and How It Will Change Everything.

[33] Did you ever, when you were a kid?

[34] Fart on my fingertips and smell it.

[35] Well, we all did that.

[36] Just in time.

[37] Justin is the first name.

[38] Time is the first name.

[39] Time is the second.

[40] No, just in time.

[41] Yeah, that's a thing.

[42] Yeah, I can't wait.

[43] Please enjoy Mr. David Sinclair.

[44] Wondry Plus subscribers can listen to Armchair Expert early and ad free right now.

[45] Join Wondry Plus in the Wondry app or on Apple Podcasts.

[46] Or you can listen for free wherever you get your podcasts.

[47] Hey, Dax.

[48] Hey, Monica.

[49] How are you?

[50] I'm great, actually.

[51] How are you doing?

[52] Great.

[53] We are so flattered to have your ear to talk about this topic.

[54] I got to say, did this come from Adam Grant?

[55] Yes, it sure did.

[56] We wouldn't have a show at this point without Adam Grant.

[57] I'm just going to own that right now.

[58] Like, we see something that excites us and we think, well, we could never talk to that person and we just email Adam Grant, then we're talking to him.

[59] Yeah, Adam knows everybody.

[60] It's real social act.

[61] Best email responder I've ever met in my life.

[62] Yeah, I was just checking.

[63] He's still married somehow.

[64] I know.

[65] That's exactly what I think every time he emails me back, I think, my God, how does he do it?

[66] With the marriage and the curriculum and the whole nine.

[67] So are we talking to you?

[68] Are you in Boston?

[69] I'm on sunny Cape Cod.

[70] Oh, and are you getting roadside lobster sandwiches?

[71] That's my best memory of Cape Cod.

[72] We are actually, Situate Harbor, it's called.

[73] Whereabouts did you spend your time?

[74] Well, I was in Boston, and I got on a motorcycle, and I rode out to the cape.

[75] I don't know where I went.

[76] I don't know what stand I stopped at, but boy, does that stick out?

[77] Because I don't know that I love lobster before I had it on the side of the road like that.

[78] I think I thought it always tasted chloriney, but this was real nice.

[79] Yeah, I still don't like it, but I eat it, and the French fries are food.

[80] But you got to have it, right?

[81] Otherwise, you don't blend in.

[82] Now, I do wonder, let's just talk personal stuff for a minute because I find 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?

[83] Correct.

[84] And is it freaky to have these children that are American?

[85] I always imagine, like, I moved to England, I meet an English gal, and then my son's got this charming accent.

[86] I don't have it.

[87] There must be some weird dissonance there.

[88] It is interesting.

[89] So in my family, we have three accents.

[90] My wife has a German accent, and then there's me, and then the kids.

[91] But the kids are picking up some Australianisms.

[92] They say, I can't do it.

[93] I'm going to have a bath.

[94] Yeah.

[95] Do they say, sweet?

[96] Sweet airs?

[97] Or that's more of a Kiwi thing, huh?

[98] Sweet ears?

[99] We don't say that.

[100] We'd say you're going down to the beach, the Savo, mate.

[101] Pick up some beer.

[102] Some beer.

[103] 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 judgments of the American national character.

[104] And when you see your children exemplifying some of those.

[105] traits that you probably view differently from the outside.

[106] How do you make peace with all that?

[107] And is it something you laugh at or go like, hmm, this is concerning.

[108] Well, it's both.

[109] I moved here because this is the freest place and you can be who you want to be.

[110] And it's a real meritocracy.

[111] And I've thrived here because of that.

[112] And actually, when the kids were young, it was perfect.

[113] You know, you can be whatever you want, do whatever you want.

[114] I mean, it's wonderful because when they become adults, true adults, you know, they believe they can do anything and change the world.

[115] But when there is part of a family unit, it's actually much harder, I think, to raise American kids.

[116] Yeah, the individuality being prized and rewarded.

[117] And we write biopics of people who are staunch individuals.

[118] And in the face of consensus said, fuck you, like that.

[119] Those are our heroes, right?

[120] More than I think people recognize anywhere else in the world, do we purve out on that?

[121] We love it.

[122] That is true.

[123] And so, you know, as a parent, if you say, well, you know, this is what dad thinks.

[124] you can't have, you know, this soda or whatever, they're like, screw you.

[125] I do what I want.

[126] This is America.

[127] That's always being tough.

[128] No, but this country, you know, I left my family and my best friends behind to come here.

[129] And I was supposed to only come here for two years.

[130] But I really, I fell in love with it, especially in a town like Boston where, you know, you can thrive on just being intellectual and you don't have to hide it.

[131] Because most people around you, even on the train or on the tea, are smarter than you are.

[132] So, actually, if it's the opposite, I went from Australia where people didn't want to talk about anything but sport and the weather.

[133] And, well, that's an exaggeration, but that's typical.

[134] And then you come to Boston and people are talking about artificial intelligence and viruses and all this stuff on trains.

[135] And I thought, okay, this is pretty cool.

[136] This is like the Athens of ancient Greece.

[137] I like this place.

[138] Yeah, and I wonder if you appreciate this.

[139] So I'm from Detroit suburb.

[140] and in Detroit, as is similar to many, many American cities.

[141] The ultimate status achievement is just wealth.

[142] That's like how you go to alpha status.

[143] So, you know, it's just very celebrated and talked about.

[144] And I moved here to L .A. And I'd be in the line at the grocery store.

[145] And I'm like, there's five dudes ahead of me. Three are homeless and two are billionaires.

[146] They've created TV shows.

[147] And I don't know which is which.

[148] And I think there's something very beautiful about that.

[149] 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.

[150] Right.

[151] Actually, it's probably the worst -dressed person who's the billionaire who has their own couple of jets.

[152] Yeah, I do love that too.

[153] Yeah, and then, of course, the clerks then have to give everyone some monocum of respect because it could, again, a person could have created two and a half men or something, and they'll probably hear about it.

[154] So there's some kind of leveling of the playing field, given that that's our industry.

[155] And I dig it.

[156] Yeah.

[157] Okay.

[158] Let's talk about, did you study gerontology?

[159] Was that your major originally?

[160] Yeah, I don't call it gerontology.

[161] That's more doctors treating the elderly.

[162] I'm in a field that's really just blossomed since I became an adult, which is longevity research.

[163] Or sometimes we call it aging research.

[164] Just make sure you don't call it anti -aging research.

[165] Okay, because then you're an agist?

[166] No, it's got a bad connotation because anti -aging.

[167] There's a lot of snake oil out there.

[168] And we scientists at these universities are trying to say we're something different than that.

[169] And, you know, really, we're publishing these papers in the world's top scientific journals.

[170] We don't want to get mixed up with people who are selling stuff on the internet that's, you know, just made up.

[171] We're aging researchers, not anti -aging researchers.

[172] Yeah, and you are shouldered with the history, you know, since the dawn of Homo sapiens sapien 150 ,000 years ago, we've always wanted to live longer.

[173] and every attempt to do so has failed.

[174] Was erroneous at best.

[175] 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.

[176] 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.

[177] You know, I'm an academic at Harvard University.

[178] Most people there are trained in the traditional way, which is we don't care about aging.

[179] That's a natural process.

[180] We should just accept it.

[181] And when banned stuff happens, we get diseases, then we apply medicine, whereas I'm saying, hold on, let's not wait until people get too sick to be able to fix things.

[182] But also let's understand why they get sick in the first place.

[183] A 10 -year -old doesn't get heart disease or Alzheimer's.

[184] Why is that?

[185] 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?

[186] I absolutely think that they wouldn't.

[187] And that's why I think it's an important approach to medicine.

[188] But traditional medicine, they'll attack cancer, heart disease, and Alzheimer's with billions of dollars.

[189] But as soon as you say aging, they go, oh, that's natural, which is BS, because these other diseases are natural too.

[190] Yes, a cancer cell is as natural as anything else in the body, right?

[191] It's just a cell that's dividing and replicating.

[192] And I would say, yeah, there's this kind of implied vanity to the pursuit, right?

[193] Like, you must be interested in it because either you're just vain or spiritually, you can't accept the reality that we're all going out in a body bag.

[194] You know, there's all these weird implications.

[195] That's also an obstacle.

[196] Yeah, Dax, you're very intuitive that way.

[197] And that's been a huge obstacle.

[198] And even philanthropists who we survive on their donations, many of them, I think Bill Gates would be in this category.

[199] Even though they're intrigued with this topic, they're afraid that they'll be perceived as, you know, being selfish.

[200] But if Bill Gates is listening, I want to explain the situation.

[201] He's listening.

[202] He's our biggest fan.

[203] So here's the thing.

[204] Let me start with something personal.

[205] I'm not afraid of death.

[206] Absolutely not.

[207] I fly a lot.

[208] I've almost crashed many times.

[209] I don't even get worried about that.

[210] I'm fine with it.

[211] I'm not trying to live for 150 years, though.

[212] It's a good experiment.

[213] I wouldn't mind trying.

[214] So let's just make that clear.

[215] I'm not doing this for myself.

[216] 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.

[217] 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 $7 ,000, whereas a pacemaker costs society a few hundred thousand dollars and some go up to millions.

[218] So this is an economic solution.

[219] It makes social sense because we don't want people to be sick.

[220] And look at today's society, we know that elderly are dying a lot more frequently from even, you know, COVID -19.

[221] So all of that makes sense.

[222] And that's why I wrote my book is that, you know, I could speak to small numbers of people.

[223] And I kept saying the same thing over and over again.

[224] So I said, OK, I'll put it down on paper and hopefully reach more people and try to help them see things from my angle.

[225] Well, to me, it seems like you're in the pursuit of the ultimate upstream.

[226] solution for all these things, which should appeal to everyone on some level.

[227] Now, I'm going to start by saying I have not had a biology class since 1999 in college.

[228] So my understanding could be flawed.

[229] In fact, I'm sure you'll point out some misconceptions.

[230] But I have some very general questions based on my very general and aging knowledge of biology.

[231] When it was explained to me in biology how the body goes through mitosis, right?

[232] It either goes through meiosis, which is sexual reproduction, or mitosis, where it's creating what I was told is an exact mirror copy of itself.

[233] 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.

[234] Do I have it right thus far?

[235] Well, it's never exact.

[236] You can't make a perfect copy of anything easily.

[237] But yeah, that's the principle of life.

[238] In theory, that.

[239] Well, in theory, but there are mistakes that accumulate.

[240] Right, which is where we'll get to with your research, which I find so fascinating.

[241] 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 how could we ever age?

[242] If my body's making exact copies of every cell, then why did those cells change shape?

[243] elasticity, all these different things.

[244] What happens in between that replication and what I see, I guess the phenotypical results of it being aging?

[245] How does that happen?

[246] Yeah, well, the problem is that there's this thing called entropy and things just fall apart.

[247] You know, everything around us falls apart unless we rebuild it.

[248] Now, biological organisms shouldn't be alive for more than 30 seconds, right?

[249] If we stop breathing or if we took a cyanide pill, we'd be gone.

[250] But what we are very good at is, is using food, mostly other organisms we consume, to overcome entropy, at least temporarily.

[251] You can't do it forever, even the universe can't.

[252] But at least for 80 years, a human being can repair itself and rebuild things and expand and divide cells, like you said.

[253] But it's not perfect.

[254] 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 saber -tooth tiger kill us, we would have evolved the lifespan of a whale, which can be 300 years, or a Greenland shark, 500 years, or a tree, 2 ,000.

[255] But we didn't.

[256] We usually died in our 40s from infection or war or starvation.

[257] So our bodies are not evolved to live much beyond that, unfortunately.

[258] But it's biologically possible to live, I think, for many thousands of years.

[259] It's not against the law of biology or even physics because we're consuming energy and using it to rebuild.

[260] Well, yeah, minimally, if you're 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.

[261] And you get a real scope of like, wow, well, that's possible.

[262] You know, a living organism could have been here when Jesus was here and I was still on my hike.

[263] Yeah.

[264] Well, it will be possible for us as a species if civilization lasts long enough for us to figure it out.

[265] But I do think we're on the cusp of finally figuring out why these organisms are able to live so long.

[266] 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.

[267] But there's a nuance to that, right?

[268] 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.

[269] Is that the epigenome?

[270] It is.

[271] Yes.

[272] Okay, so really quick, just to give a second grade explanation of this.

[273] 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.

[274] Some things can happen in the cooking process, and you don't necessarily get what you want.

[275] But we have a kind of complicated system.

[276] But in general, it is your recipe that makes you the human you are that you see in the mirror.

[277] And then now on top, or this is how was explained to me, again, I've 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.

[278] Is that accurate?

[279] Yeah.

[280] You're doing extraordinarily well for someone who hasn't gone biology in 21 years.

[281] Okay, okay, okay, good.

[282] So now this epigenome will 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.

[283] So over time, this epigenome collects errors.

[284] It has a lifetime of its own, right?

[285] And by the time you're 70 or 80, it's actually not reading your DNA efficiently.

[286] Is that what's happening?

[287] That's what we see.

[288] It's a pretty new idea in biology, but it's catching fire.

[289] And I think within five years, it's going to be standard dogma in the field, is my prediction.

[290] So you're describing it, Dax says layers, where the DNA is a strand, which is about six feet long per cell.

[291] We have 26 trillion cells in our body.

[292] So there's a lot of it.

[293] You can go to the moon and back, I think, at least eight times.

[294] It's a lot of it.

[295] But it's not really layers.

[296] It's actually got to think of it in three dimensions.

[297] The DNA isn't just a string pulled out.

[298] It's wrapped up in bundles and loops.

[299] And the loops are where the genes that are on, stay on.

[300] And then the bundles are like a hose reel on your driveway.

[301] you spool it up, or like a fishing rod, you spool it up, and then those genes stay off.

[302] And every cell, literally every cell has a different program set out.

[303] So the DNA is in different patterns of loops and bundles.

[304] That the difference between your eyeball and your earlobe and your liver, right?

[305] Every single cell has the full recipe, but only some percentage of that recipe is being used to create that exact cell.

[306] Yeah, and it has to be that way for life on earth, because we start out as one cell.

[307] and that DNA has to be copied, but if we didn't have the epigenome, we'd just be a giant ball of egg cells.

[308] Right, right.

[309] We would never be an organism.

[310] 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.

[311] And when you become a brain cell, you're going to stay that way for 80 years.

[312] The problem is that over time, that instruction booklet, the, recipe becomes badly read.

[313] So think of it as a chef.

[314] So the recipe is still largely intact in each cell, but the chef comes along and the chef's now lost her eyesight and she's throwing in the wrong ingredients and instead of this beautiful souffle, it looks like a POS.

[315] So it's not working well anymore.

[316] And we see that.

[317] Now that we think we understand what's going on.

[318] So we work on mice in the lab.

[319] We treat them as kindly as we can.

[320] We can.

[321] We can change the epigenome and cause aging to accelerate.

[322] And we can measure it.

[323] There's now a DNA clock we can measure, an epigenetic clock, actually.

[324] You can take it forwards and backwards now.

[325] Which is, to me, now that we can do that, we are beyond what anybody in history has been able to do.

[326] I'm not saying I'm a pharaoh or anything, but everyone who tried to change the course of aging was unsuccessful.

[327] But in the last few years, my colleagues and I have done that.

[328] We can take aging forwards and backwards.

[329] I was introduced to this, and I got to applaud.

[330] 60 minutes because my understanding comes solely from that episode.

[331] So anything I'm getting right, I got to credit them.

[332] But they, of course, in the episode I saw, they were talking a lot with George Church.

[333] Do you know George?

[334] Are you guys enemies?

[335] Do you have beef?

[336] Are you friends?

[337] Are you colleagues?

[338] We are very, very good friends.

[339] We collaborate all the time.

[340] And this reversal of aging, he was a great collaborator on that project.

[341] Great.

[342] So in that segment, he said that we as a species have executed this in eight different species other than ourselves, right?

[343] We've done mice and they're working with dogs now already.

[344] Thus far, it's proven consistent the results over these eight different species that this technology's been tried on.

[345] Is that expanded since I saw it?

[346] Well, if he was talking about gene therapy, yeah, it's working in a variety of animals.

[347] And there's even gene therapy working in humans now for the eye, restoring blindness.

[348] But aging technology or longevity technology, it ranges from taking a pill or 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.

[349] 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.

[350] But yeah, we've seen that this likely translates to humans.

[351] 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.

[352] And we have those same genes in our body.

[353] And the different variants, say, between you and me, can actually predict how long we're going to live in part.

[354] Wow.

[355] Okay.

[356] So could you give me a quick history of our breakthroughs leading up to this?

[357] Because I have to imagine the fact that you're behind the helm during the biggest breakthrough and all this.

[358] If it doesn't make you question whether or not we're in a simulation, I think it should.

[359] I mean, I think it's very crazy, right, that you and I and Monica and our lifetimes are witnessing this.

[360] Well, there have been a lot.

[361] We know that the time in the womb and early life actually impacts you many decades later.

[362] And that's not the genetic influence.

[363] That's the epigenetic influence.

[364] So that's important to know.

[365] Actually, only about 20 to 25 percent of your lifespan is determined by your parents' genomes, by the DNA.

[366] 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.

[367] That can have a massive impact, more than even your genes.

[368] And there's some proof, am I wrong?

[369] We've had a couple different trauma experts on that have talked about that the epigenome can be passed down.

[370] This really kind of flips the whole Darwinian paradox.

[371] So early, early evolutionary biologists, we're thinking about it backwards, right?

[372] They were going, oh, a giraffe's neck is long because the parents stretched to reach that leaf and then somehow passed on that stretching to their offspring.

[373] And then we concluded, no, you can't alter your genes in your lifetime, no matter how much you stretch towards a leaf.

[374] But now it weirdly is looking like it's going backwards, right?

[375] Like that the accumulation of this epigenum may be transferred on.

[376] and your lifetime behavior may end up getting transferred, which is fascinating.

[377] Yeah, yeah, DNA is not your destiny.

[378] Keep that in mind.

[379] It's the most liberating thing you can think of.

[380] But it's pretty much agreed upon by all scientists that you inherit some of your health and longevity from your parents.

[381] Actually, the male sperm has the biggest influence on people's life, by the way.

[382] How so?

[383] I think by recollection it was the age of the sperm has, an impact on how long you live more than the mother's egg.

[384] Oh, wow.

[385] Oh, wow.

[386] How does a man cultivate really?

[387] It's bad to have an old sperm.

[388] That's how I recall.

[389] Okay.

[390] Do you want fresh sperm on the table?

[391] Yeah, I can see a lot of guys running to the freezer right now to store some away.

[392] So I have a small lab in Australia.

[393] And what we did there was we made mice or rats.

[394] I forget which one.

[395] We made them fat.

[396] And then these were moms.

[397] And they gave birth to offspring.

[398] And those offspring from the fat moms were much more prone to diabetes than the mothers that were thin when they were pregnant.

[399] And that's probably true for us as well.

[400] And we often don't think about that as how we can influence the future health of our kids by what we eat.

[401] And that would have been a type 2 diabetes if I had to use the human kind of analogy.

[402] So you made the mouse have diabetes through fucking up its diet, right?

[403] It wasn't born with a dispositive.

[404] not to make insulin and it's pancreas.

[405] Right.

[406] It's type 2 diabetes, so the body wasn't able to take up the sugar and it put on more weight, became obese, much more easily.

[407] And then pass that on.

[408] Yes.

[409] Yeah.

[410] It is amazing.

[411] And that's what the epigenome does.

[412] But you can counter it.

[413] 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.

[414] Wow.

[415] Fucking mind -blowing.

[416] Now, So if I'm understanding you correctly, so aging, in essence, is that epigenome just does 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 erasing in all these defects or imperfections that accumulate over a lifetime so that it'll go back to reading the DNA as if it's fresh.

[417] Yeah, that's exactly it.

[418] we think of it as a reset button.

[419] Now, we spent the better part of 20 years figuring out why aging probably happens that the epigenomes involved.

[420] And one of the breakthroughs that was made by actually a good friend of mine, Steve Horovath at UCLA, is that there's a particular chemical that accumulates on our DNAs we get older called methyl, methylated DNA.

[421] 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.

[422] Oh, wow.

[423] Think of it like plaque that it gloms onto your teeth over time.

[424] You don't brush your teeth.

[425] That's what happens to our DNA.

[426] And this so -called DNA methylation pattern very accurately predicts your biological age, not your chronological or birthday age.

[427] And what's interesting is you can speed that up by smoking and being overweight and vice versa.

[428] Which, first of all, that was an important breakthrough in the field.

[429] And then what we realized was that 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.

[430] And we're hoping to publish this soon.

[431] A lot of what's in my book isn't actually yet published, which is an unusual situation.

[432] I didn't think.

[433] And the book is Lifespan, Why We Age and Why We Don't Have to?

[434] That's the one you're referring to?

[435] Yep.

[436] And so I was writing the book.

[437] And my student texted me a picture of an eye that had its age reversed from an old mouse to a young mouse.

[438] And the nerves were growing back.

[439] And these other mice were getting their eyesight back.

[440] And I wrote that down with my co -author, Matt LaPlante, who's a good friend and brilliant writer.

[441] 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.

[442] 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.

[443] I mean, it's so exciting.

[444] I try and to bridle my enthusiasm about the future because so often we get a little too excited.

[445] But I remember learning about CRISPR and going like, well, that's that.

[446] I will never have a disease as long as I live.

[447] Yeah.

[448] 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.

[449] But that, in fact, 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.

[450] Yeah.

[451] Yeah.

[452] Right.

[453] Right.

[454] Right.

[455] So that's the key step that we figured out.

[456] 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.

[457] 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.

[458] So now we use that in the clinic or people, you know, you could take your skin cell moniker and turn that into a stem cell and then turn that.

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

[460] Oh, please do.

[461] We need more than one of her.

[462] We've run out of hers.

[463] Yeah, you can't have too many monikas, that's for sure.

[464] But we could make new skin.

[465] We could make nerve cells, put them back into your brain if you had Parkinson's.

[466] So that's amazing technology.

[467] And rightly so, Shinya Yamanan.

[468] won the Nobel Prize for that in 2012.

[469] But what I don't believe he realized was that these same genes can drive aging backwards.

[470] But like you said, Dax, you 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.

[471] It's very dangerous to play with that.

[472] But what one of my students, brilliant student, one Changlu, he realized that instead of using four of the Yamanaka factors, if you just left out the dangerous one called Mick, which is a known cancer -ca -ca -ca -ca -factor, then the other three Yamanaka -factors, they took the cells back in age, but not so far that it caused any trouble.

[473] And so now we could wind the clock back in a safe way.

[474] And 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 eyes.

[475] Stay tuned for more armchair expert if you dare.

[476] What's up guys?

[477] This is your girl Kiki and my podcast is back with a new season and let me tell you it's too good and I'm diving into the brains of entertainment's best and brightest, okay?

[478] Every episode I bring on a friend and have a real conversation and I don't mean just friends I mean the likes of Amy Polar, Kel Mitchell, Vivica Fox, the list goes on so follow, watch and listen to Baby.

[479] This is Kiki Palmer on the Wondery app or wherever you get your podcast.

[480] We've all been there.

[481] Turning to the internet to self -diagnose our inexplicable pains, debilitating body aches, sudden fevers and strange rashes.

[482] Though our minds tend to spiral to worst -case scenarios, it's usually nothing, but for an unlucky few, these unsuspecting symptoms can start the clock ticking on a terrifying medical mystery.

[483] Like the unexplainable death of a retired firefighter, whose body was found at home by his son, except it looked like he had been cremated or the time when an entire town started jumping from buildings and seeing tigers on their ceilings.

[484] Hey listeners, it's Mr. Ballin here, and I'm here to tell you about my podcast.

[485] It's called Mr. Ballin's Medical Mysteries.

[486] Each terrifying true story will be sure to keep you up at night.

[487] Follow Mr. Ballin's Medical Mysteries wherever you get your podcasts.

[488] Prime members can listen early and ad free on Amazon Music.

[489] That makes me think of the early kind of T -cell treatments.

[490] that it was like, so I was on one for arthritis.

[491] It's kind of, you're just carpet bombing the immune system, right?

[492] So then you're opening yourself up to infection on all these different things, but 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, where it's like just honing in on exactly what we want to be activated and not.

[493] Yeah, well, there was a lot of luck involved, right?

[494] It didn't have to work.

[495] But I was talking to someone who's, I don't name drop, but this is someone who you'd know, a wealthy individual.

[496] I was speaking to him the other day.

[497] And he said, how is it possible that there are these three genes?

[498] This is like a wormhole discovery.

[499] It shouldn't be possible for humans to do this.

[500] Why is it possible?

[501] And my explanation to him was that I think a lot of species still have this system.

[502] You chop off a tail of a lizard, it grows back.

[503] You chop off the limb of a salamander, it grows back.

[504] 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.

[505] Oh, my God.

[506] This is so crazy.

[507] It's so fascinating.

[508] But can you be very precise into how far back you go?

[509] Like, at one point, at some point we can be like, I just want to be 25 looking for the rest of my life?

[510] Yeah, is that on the horizon?

[511] Can I pick my age?

[512] I don't see why not.

[513] 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 our.

[514] disease.

[515] But we built the system so you can turn it on and off very easily.

[516] 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.

[517] Can I ask how that actually happens process -wise?

[518] So are you taking some cells out and then adding some stuff like crispery type stuff and then putting it back in the body and then that cell in itself replicates and starts taking over?

[519] What are the mechanics of it?

[520] That's been done, but that's way too complicated.

[521] What we do?

[522] was very simple.

[523] We have a domesticated virus called an AAV, which is used in patients in the eye and in other areas.

[524] It's a very safe virus.

[525] And it's a delivery vehicle for genes.

[526] And that's how CRISPR is being delivered into people.

[527] Now, we don't use CRISPR.

[528] What we're doing is adding in those three embryonic genes.

[529] They have three names, short for OSK.

[530] And these OSK genes are the reset button.

[531] 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.

[532] What we do is we take, I think it's 10 to the 14th virus particles that are carrying the OSK genes, and we're just one injection into the eye, they go to the retina, and then they sit there.

[533] Okay, 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.

[534] You've probably, you know, doxycycline, you can take it for malaria.

[535] Ah.

[536] We turn it on with an antibiotic.

[537] So when we give the mice three weeks of antibiotic in their water or their food, they get their eyesight back.

[538] Then we stop the antibiotic and they can see.

[539] Oh, my God.

[540] Monica, Monica, Monica.

[541] Do you feel like we're dreaming a little bit?

[542] Yeah, we definitely are.

[543] We think we're living in my dad's simulation and it's proving more and more and more to be true.

[544] But, I mean, I'm sure Walt.

[545] talk about this, but there's fear around this, right?

[546] Oh, yeah, hold on, hold on.

[547] Yeah, I got a whole, I got a whole section of that.

[548] Before I ask that, I have this one question, and we've got to have some pretty awesome biologists on this podcast, Dawkins being one of them, where I pose this question, and still boggles me, is why isn't there any thing in the archaeological record?

[549] Why isn't any animal that mutated to just not age?

[550] It just seems like something that would have to have happened numbers -wise.

[551] If there's something we're now doing in the lab, it seems like it could have existed over the millennia.

[552] Why isn't anything ever mutated into living forever?

[553] Well, first of all, there are species that have what's called negligible senescence, which means they really don't age.

[554] Trees, obviously, you know, there are some trees that are 5 ,000 years.

[555] They still have seeds that seem young.

[556] Lobsters, right?

[557] England, where I'm at right now, these lobsters just get bigger and bigger and they seem to be just as healthy as when they were young.

[558] And there are so lots of examples of those kinds of animals.

[559] But are they immortal?

[560] Probably not.

[561] No one's ever kept a lobster for a thousand years in a tank.

[562] We don't know.

[563] But there is a reason why we tend not to have species that live forever.

[564] And the reason is that evolution builds what's necessary and that's it.

[565] And it is not necessary to be immortal to replace yourself.

[566] By the time you've had two or three kids, you're done for.

[567] So I just turned 50.

[568] So I'm basically now expendable.

[569] My kids are almost grown up.

[570] Well, what's 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.

[571] But men, I see 90 -year -olds getting women pregnant in the news.

[572] It is conceivable at least that the male of that species would be incentivized to spread that mutated gene.

[573] where it never ages.

[574] Yeah, but once you've got children, they can go ahead and spread it.

[575] The force of natural selection that keeps you alive declines with time, with aging.

[576] And there's a cost to being immortal.

[577] Energetically, if you're only putting your energy into living forever, you're probably going to breed very slowly.

[578] And, you know, think about whales, think about trees, that they tend to breed very slowly, whereas a little mouse that will live two years and a rabbit pumping out, the babies.

[579] So there's a trade -off between longevity and reproduction that you have to get right.

[580] And that's determined on your environment and how likely you are to die.

[581] Yeah.

[582] One interesting thing about women is, so no men have ever died in childbirth that I'm aware of.

[583] And women used to die often in childbirth.

[584] So it's a dangerous business for women to have kids.

[585] And so you find that the ovary is one of the first things to age out in a woman.

[586] To protect them from dying in childbirth.

[587] That's one reason we think.

[588] I think why there's a difference between males and females.

[589] But interestingly, we've found that by turning on a 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 the ovary and now those animals become fertile again.

[590] Oh, my goodness.

[591] We just published this if anyone wants to look it up.

[592] And so we think that the old idea that women run out of eggs needs to be re -examined.

[593] Yeah, so instead of like freezing eggs, which is commonplace now, maybe the treatment would just be new eggs at 45.

[594] Is that where you're alluding to?

[595] Yeah, well, if the mouse results are true for humans, a 45 -year -old could take a month's worth of pills and produce very healthy eggs, either for IVF or natural birth.

[596] Wow.

[597] Oh, my gosh.

[598] Okay, I think I have this elementary understanding that you're going to kind of, you're going to go back to an earlier state of the cell.

[599] by erasing some of this epigenome.

[600] But how does the cell know what it was?

[601] Well, that's the million -dollar question.

[602] And we're chasing that right now.

[603] We call this thing the observer because there's a very famous mathematician from MIT, Claude Shannon.

[604] I'm a big disciple of his.

[605] Back in the 1930s and 40s, he was basically figuring out how to maintain information.

[606] And he was talking about radio signals, but today, basically, the internet is built on his theory.

[607] And what he said was, okay, if we're going to have a perfect signal at the other end, we need a backup copy so that if we lose a little bit of it, we get the full copy.

[608] And we call this the TCPIP protocol of the internet.

[609] And it's why we can't pretend that we didn't get that email.

[610] It always comes in now.

[611] And that's because of Claude Shannon, right?

[612] And so he called this The Observer.

[613] We'd call it these days probably a backup copy, hard drive, or even a hard drive is all.

[614] old -fashioned now.

[615] But you know what I mean.

[616] 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.

[617] Because here's a new thing that we discovered in my lab that we'll 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 20 ,000 different changes that occur across the big six -foot strand of DNA in each cell.

[618] Now, when we reset the cell, we had a look recently how many of those little sites got reversed and by how much?

[619] 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 and went the other way got reversed back to where they were.

[620] So there's not just a message somewhere in the cell that says this piece of DNA needs to change.

[621] It's by how much as well.

[622] So there's two types of information we're looking for.

[623] 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 know it exists, but we've ignored it for the last 50 years.

[624] Or it could be something else.

[625] like you mentioned RNA DAX, this other type of genetic material like coronavirus has as it's genetic material.

[626] Maybe there's RNA that's 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.

[627] But yeah, I think that, you know, if we talk again in a year or two, I might have the answer for you.

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

[629] Yeah, a Herculean task, I'd label it.

[630] 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.

[631] Oh, sure.

[632] Are you familiar?

[633] Yeah.

[634] 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 we'll get into in a second.

[635] But how could that work?

[636] 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 block all of the receptors so they can't get in, or we engineer ourselves to have a natural immunity against all viruses.

[637] And we have very strong antiviral mechanisms that take a while to ramp up, but we could engineer ourselves to turn them on at will.

[638] There's plenty of ways.

[639] So, for instance, HIV gets into cells through a certain receptor called CCR5.

[640] And there are naturally people who don't have this receptor a few percent.

[641] And they're luckily, you know, unable to be infected and get AIDS.

[642] Did he tell you about genetically modifying that baby in China?

[643] That's...

[644] No, tell me that.

[645] So the doctor who got into a lot of trouble, he made a crisper modification of twin girls.

[646] And what he did was he knocked out, got rid of this CCR5 gene, and so they cannot catch HIV.

[647] Which all sounds great, but it's pretty useless because the chance of catching HIV is very low.

[648] It's like one in a thousand or less.

[649] But the chance of this going wrong, you know, we know very little about what this procedure does long term.

[650] And we don't even know what this CCR5 receptor does as well.

[651] So I think the risks were way higher than the benefits.

[652] I think if he was going to do that, I'll just go out on a limb.

[653] If you're going to do it, why not change genes for longevity or heart disease or Alzheimer's?

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

[655] Yeah.

[656] You stated that you have slowed down aging in mice, but you've also made mice smarter.

[657] You've made mice run twice as far.

[658] Oh, yeah, that was fun.

[659] Yeah.

[660] I mean, I can't imagine when it's like being yours.

[661] Like, you have this idea and it probably seems hairbrain at first, and then you figure out some way to execute it.

[662] And then just watching the results must be a very unique experience, to say the least.

[663] Well, what usually happens in my lab is I ask somebody to do something, right?

[664] I'm useless.

[665] I wouldn't know my way around a mouse if you gave me one.

[666] but I have these ideas, and I have a very smart group of 20 or so PhDs who will often do what I ask them to do, not always.

[667] And so when I say, oh, let's just try making a mouse run twice as far, usually they'll say, David, that's crazy, I've got more important things to worry about than doing that.

[668] And then I just keep pestering and pestering, and three months later they try it.

[669] I'm not always right, but I do find a case.

[670] occasionally I am.

[671] And when I am right, it's a lot of fun.

[672] And in this case of the mice running a long time, what actually happened was the scientist, Michael Bunkowski, he called me up and he said, David, we've got a problem.

[673] He said, the old mice kept running so long that the treadmill has stopped running.

[674] It broke.

[675] Oh my gosh.

[676] You had a treadmill issue.

[677] Yeah, a little thin treadmill.

[678] And I said, oh, no, we've wasted, you know, two months of our time.

[679] And it turns out the treadmill didn't break.

[680] It's just that the software that was written for it never expected a mouse to run so far.

[681] And these were old mice and they were outpacing even the young ones.

[682] Oh, wow.

[683] Okay, I don't know.

[684] 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 field.

[685] What is the interpersonal experience of recognizing one of your students who's been looking to you for guidance?

[686] There must be a moment, right, where it clicks like, hmm, this student is smarter than I am.

[687] I've now going to transfer this relationship into you go further and tell me how this works.

[688] What is that dynamic like?

[689] Well, that's the best part about being a scientist, is to have your trainees go off and do bigger and better things than you do.

[690] And it's very easy to be smarter than me. I'm just a kid from Sydney who has an imagination.

[691] I don't actually do the really hard work.

[692] 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.

[693] But what they do is really difficult.

[694] I love the turning point.

[695] Typically, a student goes through various stages of grief and anger and whatever, denial in my lab, and they get broken down and we rebuild them into the real scientist they can be.

[696] I mean, it's really true.

[697] A grad program at Harvard is like West Point training.

[698] Because most students who come into Harvard have been the smartest people in their class.

[699] Yeah.

[700] And they come in, not all, but there's often some arrogance like, oh, I'm here everybody.

[701] Let me win a Nobel Prize and show you how it's done.

[702] And then after about two years of them failing, and I had this actually with this brilliant student, Wang Chang, he was about to give up because the reprogramming was just making the cells into cancer and not stopping at youthfulness.

[703] And I said, don't give up.

[704] Everybody goes through this.

[705] Let's try one more thing.

[706] And we did.

[707] We did the I. And it worked.

[708] And this is time and time again.

[709] Really, I find I have two jobs.

[710] One is to put them on challenging questions because it's very easy to answer a basic question.

[711] If you know what the answer to the question is already, it's not worth doing.

[712] You want to do something that has a 10 % chance of working or less.

[713] Which, by the way, gets harder and harder in science the more we learn.

[714] It's just like an escalating issue.

[715] Right.

[716] Well, that's why we took on reversing aging because there's not.

[717] of things you can do.

[718] But 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.

[719] But then they break because then they get this beautiful result where they go, oh, now I know what David was talking about.

[720] And then they blossom.

[721] Then they go off and they can do amazing things.

[722] 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 him and they're like, fuck everyone's hot?

[723] What am I going to do now?

[724] And then they got to figure out what's unique and beautiful about them.

[725] Yeah, but you've got to have resilience in both industries, right?

[726] Because it's tough.

[727] Really tough.

[728] They'll break you if you don't keep getting out of bed every day.

[729] 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.

[730] You're at the cusp of this really monumental scientific breakthrough.

[731] and it's going to have these humongous implications and to watch how Oppenheimer and surrounded by all these very thoughtful, intelligent people, we're both solving the problem and, you know, when free time permitted, evaluating the downstream consequences of it and in that situation, of course, we're up against the fact that had not they done it, someone else would do it.

[732] So that's just an imperative that they're working under.

[733] It's like all your ethical dilemmas aside, Best we have the technology, not everyone else.

[734] 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 brain power is dedicated to that, the downstream outcome of all this?

[735] Well, more than you might think.

[736] 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.

[737] And actually, in my view, the future looks much better if we're successful.

[738] It's not all good, right?

[739] There are some people you don't want to live a lot longer.

[740] And politicians are getting older and older and, you know, there's all that.

[741] 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?

[742] I mean, this is what we're talking about, in reality, about drugs that help people live, healthier and more productive lives.

[743] 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.

[744] So I'm working with mathematicians right now over in London, trying to actually build mathematical models to understand what society will look like and even the impact on the economy of the globe.

[745] 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.

[746] I mean, all medical advances do favor first those of means.

[747] Well, yeah, it's similar to the Wright brothers in that if you wanted to fly on a plane, it wasn't cheap.

[748] It's still not cheap, but it was incredibly expensive.

[749] And cars as well, the rich had the cars.

[750] 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.

[751] could be actually quite cheap.

[752] So we're about to start a clinical trial to treat COVID -19, for example.

[753] And we are, if we're lucky, very lucky in a year, that drug could be on the market.

[754] And it would be sold for, I don't know, let's make up a number, $20 a pill, maybe $100.

[755] But that's not outrageous, right?

[756] And then we're also looking at trying to get it quickly over the counter so everybody in the planet can have it.

[757] Now, if that plan works, then it's going to be Right.

[758] First of all, we'll have this possibly five to ten 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.

[759] No one would buy it.

[760] Yeah.

[761] And in fact, most of the downstream treating the symptoms cures are horrendously expensive.

[762] I'm on different arthritis medication.

[763] I don't think one of them's been under $1 ,000 a month, you know.

[764] The reversal of aging as we do it in the eye right now.

[765] That will be expensive.

[766] And it's unavoidable because gene therapy right now, there are so many hurdles and safety issues you have to go through just to get a drug on the market.

[767] It's probably close to $700 million.

[768] So that's fair enough.

[769] But here's the good news, is that I don't think it has to stay gene therapy.

[770] There are about four of us in the world who do this age reversal right now.

[771] And we talk all the time every day.

[772] It's a bit like Oppenheimer and his crowd, actually.

[773] And we are working very hard to figure out, how can we do this with a combination of safe molecules?

[774] And eventually, it should be a pill that can do this.

[775] Okay.

[776] So since seeing that 60 minutes thing, I've probably dedicated 300 hours of my free time thinking about, because I'm a writer by trade, and I'm always thinking of movie concepts.

[777] And so I can't help but funnel it into that thought process.

[778] And one of the things I thought of is like, okay, 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 and 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?

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

[780] Have you thought of that aspect?

[781] Probably not as much as you have.

[782] 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.

[783] That's been a revelation, which is great.

[784] But I think it's going to be even bigger than that.

[785] If older people in their 80s, 90s, and 100 are still as healthy as the young people, still playing tennis, hanging out with their great grandkids, then we're in a world similar to the line at L .A. where you can't tell how rich somebody is, in a world where you can't tell how old somebody is, then you don't have this ageism, you know, right?

[786] We currently look at someone who's shuffling along and go, oh, God, kill me when I get to that point.

[787] You know, that's not nice.

[788] 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're reverse aging in the brain, what happens?

[789] Do you lose your memory?

[790] Do you gain?

[791] Right, that's exactly.

[792] Or do you regain lost memories?

[793] Yes.

[794] And really quickly, again, going back 25 years since I learned this, but I was told that there was somatic cells and there was gray cells.

[795] And your brain was these gray cells that didn't go through mitosis and didn't replicate.

[796] And the ones you were born with are the ones you were going to have for life.

[797] Is that still the belief?

[798] Or do they do more than we think?

[799] thought they did 20 years ago.

[800] They do grow.

[801] So there's neurogenesis, but not in large parts of the brain.

[802] It's usually only in the center section.

[803] 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.

[804] 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 wakes up.

[805] 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.

[806] 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.

[807] And that's what's exciting.

[808] Well, this must be very exciting for like spinal cord injury people.

[809] Because that's, again, the material we thought we couldn't really grow back or limited options there.

[810] Exactly.

[811] Right.

[812] So one of the experiments was to pinch the optic nerve and we saw it grow back to the brain.

[813] And the same thing we hope will happen in spinal cord injury.

[814] But maybe it's even bigger than that.

[815] Maybe one day if we have our finger cut off, we'll apply this technology and you'll get you a new finger to grow back.

[816] So, but okay.

[817] So if you're going back, what if you go back to like a 15 -year -old brain, which is not fully - Oh, man, God forbid.

[818] Develop.

[819] Exactly.

[820] So then would it develop again?

[821] Well, yes.

[822] This feels like a sci -fi brain.

[823] Yeah, this is interesting.

[824] I haven't thought about this.

[825] But what if your brain starts producing hormones like you're a teenager again?

[826] Well, I was just going to say, I do miss the horniness.

[827] As much as it was blinding.

[828] No, we don't need any more of that.

[829] Right.

[830] But having your brain develop over and over and over again and releasing more chemicals over.

[831] Like, how, that's crazy.

[832] Well, we will see.

[833] I think in our lifetime we'll be able to know the answer to that.

[834] Okay.

[835] Here's another one I thought of an hour hundred.

[836] which was, okay, this technology exists, everyone has access to it.

[837] You don't have to die.

[838] It is unexpected for you to die of a virus, of, you know, any of these numerous elements that this technology could prevent.

[839] In a world where the expectation is you won't die, does it change our relationship with death?

[840] And then I thought of this in a very selfish way, right?

[841] Let's say I had the procedure and my wife was like, well, you now can live to 250 years old.

[842] And if you keep riding motorcycles, what a fucking, you can't do that.

[843] Like now it heightens all this acceptable risk we take on because we live in a paradigm where we have a life expectancy and we expect to die of diseases.

[844] So you put motorcycle riding into that equation, you're like, yeah, well, I'd rather die from that than cancer.

[845] But now when all those are off the table, do you think it'd make people hyper neurotic about dying through accidents?

[846] because there'd be an expectation of longevity?

[847] Yes, absolutely.

[848] I mean, just look at what's happened over the last hundred years.

[849] People didn't care so much about protecting their kids and whatever.

[850] Now, because kids are expected to live for 80, 90 years, we put them in bubble wrap.

[851] I think the same would be true.

[852] If we lived forever, we'd be scared to cross the road.

[853] It'd be that.

[854] Right.

[855] I really think so.

[856] And it would feel like a much deeper loss, too.

[857] Yeah, because it didn't have to happen.

[858] And it would be irresponsibility.

[859] so there'd be this moral character judgments, right?

[860] If I kept riding motorcycles and I'm like, well, that guy's a selfish asshole because he could live to 500.

[861] Stay tuned for more armchair expert if you dare.

[862] Also, like, what about suicide?

[863] Like, that will probably rise a ton because if you feel like this is literally forever.

[864] I want to get off the ride.

[865] I'm choosing to get off.

[866] Right.

[867] Some people have said they may not get married.

[868] 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 to you die of an old lady, but I will remarry many, many times after that.

[869] Just so my commitment to you morally is, I'll be by your side till you die, but just know, I will be off to the races after that.

[870] So I guess I'm wondering, do you guys invite in the super esteemed folks in your philosophy department at Harvard and do any kind of like workshoppy synthesis of these different disciplines to wrap your head around what all the downstream effects would be?

[871] No, not often enough.

[872] Occasionally, I debate bioethicists.

[873] I debated Leon Kass, who was President Bush's bioethicist and scientific advisor.

[874] And we clashed terribly.

[875] He thought that treating aging was abhorrent and would reduce the agency of life.

[876] And we wouldn't wake up every morning with joy.

[877] We'd just be lethargic.

[878] And I totally disagree.

[879] I don't get out of bed every morning because I know I could die.

[880] I get out of bed in the morning because I got stuff to do.

[881] I'm enjoying my life.

[882] I'm healthy and I'm excited about it.

[883] And that's going to be true if I'm 100 or 200 or whatever.

[884] Yeah, my gratitude is not rooted.

[885] in the inevitable death I'm going to experience?

[886] No, no, we could all die tomorrow.

[887] I mean, that's enough motivation.

[888] Look the wrong way, crossing the road.

[889] But it's an incredible thought that we may be able to have multiple careers and multiple lifetimes.

[890] 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.

[891] Yeah, the panic and people throwing in the towel and all these things we think of being it too late.

[892] I like the notion of that being off the table.

[893] Right.

[894] 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.

[895] But that's why I think we should have the chance to start again and have a skill batical kind of thing where you're allowed to take a couple of years off, maybe paid to go and learn something new.

[896] Yeah.

[897] Yeah, the system will need to evolve with this.

[898] technology.

[899] Because if we live in our current system with this, I do think it's going to be disruptive.

[900] Yeah.

[901] So we'd have to, the whole thing has to evolve.

[902] Yeah.

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

[904] Sure, sure.

[905] Are they numerous?

[906] I have a list of people that I'm not fond of.

[907] There's about 10 of them.

[908] But generally, I forgive people.

[909] I don't have a lot of enemies.

[910] I think we're all in this together.

[911] It's a hell of a ride.

[912] It's difficult.

[913] And, you know, we've got other problems than to hold grudges.

[914] So I don't think I have a lot of enemies.

[915] I have a lot of people who, you know, in science, take pot shots at our work.

[916] That's what we're paid to do as scientists.

[917] So, you know, sometimes you take it personally, but as I've gotten older, I've realized it's not personal.

[918] It's just business.

[919] Yeah, yeah.

[920] That's the underpinning of peer review, right?

[921] You're not doing your job if you're not critical of everyone else's research and claims.

[922] Yeah, but it's a tough.

[923] career, especially when you're young, similar to your career, as a young scientist, you don't know if you're going to make it.

[924] And at a place like Harvard, your chances of staying are probably less than 30 percent.

[925] And you have to be the best at what you do.

[926] And every time somebody writes, oh, Sinclair is full of it or whatever, it really hurts because you could lose your job, lose the city you live in, you have to move.

[927] 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 to 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 a have i not thought of a moral conundrum that you want to bring up is there one that vexes you like hmm i don't have a great response to that problem it'll create Not really.

[928] 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.

[929] I think the biggest one is that people may become more politically one direction.

[930] The older they get.

[931] Yeah.

[932] Well, look how disheartening COVID was.

[933] It only had about a two -week window where it was apolitical, and then it just everyone lined up, which was so discouraging.

[934] It is.

[935] So I'm thinking of how I'm going to do an experiment to test whether a mouse becomes more right -wing or left -wing and then reverse the age and ask it to vote again.

[936] Well, I have to imagine people are more liberal in their youth and become more conservative, right?

[937] They are.

[938] So a world with a lot of older people may be more conservative, but then again, if you have your brain reset, who knows?

[939] Yeah, and if your journey's not over, if there's things that are ahead of you, that alters all the things.

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

[941] Yeah, exactly.

[942] Oh, yeah, yeah, I totally agree.

[943] Now, the question you hate the most, I got to ask it, it's my responsibility.

[944] What is the window of this happening?

[945] 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 in my 70s?

[946] where will I be at?

[947] Right.

[948] Well, you're in your 20s right now.

[949] 45, 45.

[950] You're doing great.

[951] So it's always dangerous making these predictions because drug development is so hard and things fail and the FDA makes things really difficult.

[952] That said, I'm more optimistic than I've ever been.

[953] And why is that?

[954] It's because it's not just me working on this.

[955] There's hundreds of labs and dozens and dozens of companies who have different approaches to longevity and aging research.

[956] And so I think somebody's going to break through within the next probably five years.

[957] In terms of total age reset, well, the timeline that's been set is I started a company.

[958] We've been working for a year on reprogramming the eye.

[959] And hopefully within two years we'll have some results as to whether it works or not.

[960] Then it could expand.

[961] You know, start reprogramming the skin or the liver or the kidney.

[962] Eventually, I hope within 20 years we'll be able to reset large parts of our body, if not the whole thing.

[963] I hate to keep drawing these parallels, but I keep seeing them.

[964] So you're very much like a movie director, writer -director, whereas 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 or it was the best thing I could have done.

[965] It's a very rare scenario where someone would dedicate that much time, you know, and get potentially an unfavorable outcome.

[966] Yeah, well, that's why we need to live longer because it's hard to have.

[967] have these failures and there's a lot of work to do, both in your industry and mine.

[968] But it is true.

[969] It really is true.

[970] Sometimes I freak out because we work for 10 years on a project.

[971] And then you send it into the journal to be reviewed by your peers.

[972] And then it comes back and gets rejected.

[973] And you think, what other profession do you work for 10 years and get a rejection?

[974] It's tough sometimes.

[975] Yeah, it's really an all or nothing endeavor.

[976] The rewards are huge and the downside is also huge.

[977] Well, David, thank you so much for taking the time to talk to us.

[978] It's one of the most exciting things happening in science.

[979] I'm so fascinated with this and I constantly bring up that 60 minutes and people are, in my experience, just generally unaware that any of this stuff is happening.

[980] 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.

[981] Yeah, yeah, 100%.

[982] That's also why I wrote the book is to start the discussion.

[983] now.

[984] But what's really helping are guys like you, you too, getting information out directly from scientists and big thinkers.

[985] 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, scientists don't even know this stuff yet.

[986] I'll let you in on a secret.

[987] I love that world that we can now you know, bounce between the public and our ivory tower.

[988] Oh, yeah.

[989] The world of the middleman is evaporating, and no one's more excited about that than me. Even the notion, yeah, that there's no intermediary between us recording this and it being in people's ears.

[990] There's no corporate board.

[991] There's no, you know.

[992] Yeah.

[993] That part's pretty great.

[994] And so I'm, I love podcasts, and I rarely talk to newspapers anymore because I I found that every time I said something, it would get twisted or hyped up.

[995] And my colleagues would be mad at me for saying, we're going to live for 200 years.

[996] And I would say, I didn't say that.

[997] And it doesn't matter.

[998] It's out there.

[999] And so, I'm just, like, old media is just frustrating as hell.

[1000] That's my greatest frustration.

[1001] And increasingly with my publicist, I'm like, I don't want to do anything print because it's going to pass through their filter.

[1002] No matter how I present myself, it has to go through the, of their body before it comes out their pen or their keyboard.

[1003] And that's just a lot to risk when you've dedicated so much of your time in life to something.

[1004] And they're incentivized to have that be a flashy thing.

[1005] A click -baby economy, yeah.

[1006] Yeah.

[1007] So true.

[1008] You know, I worked on my career for 25 years and some jerk can come along.

[1009] And like in your situation, just write something that makes you look really bad.

[1010] And you didn't even say that.

[1011] It's not worth it, right?

[1012] 25 years.

[1013] is a long time to work on a reputation.

[1014] And then they move on to the next story and don't care.

[1015] That's happened a number of times in my career.

[1016] So I applaud what you're doing.

[1017] Thank you for showing the world what's possible and allowing people like me to talk directly to people.

[1018] Yeah, well, I please, this is forever at your disposal.

[1019] Anytime you think there's info that people need to know, please let us know.

[1020] And we would love to have you back as many times as you'd like to come back.

[1021] Thanks, Dax.

[1022] And thanks, Monica.

[1023] Thank you.

[1024] All right.

[1025] Well, be well.

[1026] so much today.

[1027] Thank you.

[1028] Bye, guys.

[1029] And now my favorite part of the show, the fact check with my soulmate Monica Padman.

[1030] Monica, so don't do that.

[1031] Ew, don't do that.

[1032] Oh, okay, I'll stop farting.

[1033] Really loudly right into the mic.

[1034] You're disgusting.

[1035] You disgust me. You disgust me. Oh, you know what I really like?

[1036] What do you like?

[1037] I'm a Kayla Cole.

[1038] And it's, I may destroy you.

[1039] Yes.

[1040] An HBO.

[1041] We are obsessed.

[1042] We love it.

[1043] Oh my gosh.

[1044] We have so much housekeeping, because That's old news.

[1045] That is old news, but it's new news because I didn't know anything about her.

[1046] And Joy Bryant, our good friend, Joy Bryant, forwarded me an interview with her in Vulture.

[1047] That was so phenomenal.

[1048] It was.

[1049] It was really top -notch.

[1050] 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.

[1051] And she's in the liking to talk about poop category.

[1052] And I was like, oh, she's a shoeing to be on this show.

[1053] Oh, my.

[1054] She's made for it.

[1055] I'll do two hours on poop if she wants to.

[1056] We talk too much about poop, but now I know that we don't.

[1057] That's right.

[1058] Well, honestly, I felt a little better reading that.

[1059] So when I assess as being a genius, it talks about pooty.

[1060] We should tell people about pooty.

[1061] Okay, so we had puppies for a while, two weeks or something.

[1062] Four pup, three, how many puppies?

[1063] Three puppies.

[1064] They were so cute.

[1065] They were really cute.

[1066] And then when they would take a shit, you know, it was a baby poop.

[1067] It was a puppy poop.

[1068] So it was kind of runny and a mess.

[1069] And stinky.

[1070] And very stinking, very specifically stinking.

[1071] And I started referring it to pooty.

[1072] Like, I'm like, does anyone smell pooty?

[1073] It just felt like it would be right to call it that because of the dog.

[1074] And we were really going off on saying poody a lot.

[1075] Yeah, we're like, oh, I think this poody might be in my shoe.

[1076] Uh -oh.

[1077] Someone got putty on their shoe.

[1078] And then we got to talking about that it sounds really gross.

[1079] It's pretty much the worst word you could possibly think of for poop.

[1080] And I'm going to have you explain why because it was some massagenistic if I do.

[1081] Well, just talking code.

[1082] Okay, the reason it's disgusting is because it kind of sounds like a mix between poop and also a female erogenous zone.

[1083] Well, yeah.

[1084] You always said g -spot?

[1085] Orogyz spot.

[1086] Yeah, so we're like, oh.

[1087] The P word, the P -word.

[1088] Yeah, and it's combining poop with that word.

[1089] Yeah, and it kind of sounds like maybe you didn't wipe well as a girl.

[1090] And there was a substance that was made, and it's called beauty.

[1091] I'm so sorry.

[1092] I'm so sorry.

[1093] But not sorry.

[1094] Oh, my gosh.

[1095] Of our fact, our fact checks have been nasty recently.

[1096] Yeah.

[1097] That's all right.

[1098] That's okay.

[1099] Booty.

[1100] Poodie.

[1101] That's Poodie.

[1102] That's one of our housekeeping.

[1103] Another is I got Jordans.

[1104] Oh, yes.

[1105] First pair of Jordy's.

[1106] Yep.

[1107] You pick them out for me because you're a connoisseur.

[1108] I don't have an eye for a lot of things, but I happen to have an eye for Jordy's.

[1109] That's right.

[1110] And you pick them out.

[1111] They're Animal Instinct 2.

[1112] 2 .0s.

[1113] They're gorgy.

[1114] We bought one for you and Kristen as well.

[1115] They're sack.

[1116] As soon as I got them for you, I started looking for them for me, and then I couldn't find him.

[1117] And then, like, Gifted the Magi style.

[1118] You found him for me. So really, you didn't get a free pair of Jordy's.

[1119] Yes, I did.

[1120] Well, it's kind of a push.

[1121] No, that's fine.

[1122] Mine were probably even more expensive because the size was not about it.

[1123] Yeah, they're gorgeous.

[1124] And there is something so special about that box arriving, especially now that I've watched the last dance.

[1125] I feel even more connected to him than ever.

[1126] Well, and I said, correct me if I'm wrong, but you were going to kind of just get your shoes out.

[1127] And I was like, no, no. This is a thing.

[1128] You get the box with Jordan in the air and you stare at it for a second.

[1129] Yeah, you wanted me to like really savor it.

[1130] And I did.

[1131] Yeah, yeah.

[1132] And build.

[1133] And the 23 number is all over the little packaging.

[1134] Oh.

[1135] And then you pop, you crack that top and it fucking.

[1136] Yeah, it stinks.

[1137] Oh, it's stanky like a Jordan.

[1138] And it's only a Jordy stank like that.

[1139] Oh, yeah.

[1140] It's really the funnest box to open.

[1141] It is.

[1142] It was really fun.

[1143] And I love wearing them.

[1144] Okay.

[1145] Another update.

[1146] We're in Sedona, Arizona.

[1147] That's a rhyme.

[1148] And gang, get in your car and go to Sedona.

[1149] I had never been here.

[1150] Me either.

[1151] It's outrageously gorgeous.

[1152] It's so unbelievably beautiful.

[1153] It does not go.

[1154] We've been here for about nine days, ten days.

[1155] Yes.

[1156] And it is not old.

[1157] And we're not on vacation.

[1158] Okay.

[1159] We're not like vacationing during COVID.

[1160] No, we're not.

[1161] I'm working.

[1162] I'm shooting top year.

[1163] And we wanted to still be able to record a bit.

[1164] So I came and the family came.

[1165] As a commitment to you.

[1166] The listener.

[1167] That's right.

[1168] That's right.

[1169] And the family came.

[1170] So if you're mad about Poodie, now you should be even about this.

[1171] The family came and we're all here and it has been so wonderful and beautiful.

[1172] I'm not going to go so far as to say I've felt the energy vortex, but I will tell you I've been content.

[1173] Yeah.

[1174] At peace.

[1175] Yeah.

[1176] My mood has been so good the whole time I've been here.

[1177] Definitely a notch above what my mood normally is.

[1178] I think me too.

[1179] You too, I think.

[1180] Yeah.

[1181] In fact, everyone here.

[1182] Well, I'm also on antitipresence.

[1183] Huge house cleaning, and this will really embarrass the fuck out of him.

[1184] Okay.

[1185] We got here, day one.

[1186] Oh, yeah.

[1187] There's a huge mountain behind the house with some dangerous rocks to climb.

[1188] And Eric said, did you climb that?

[1189] And I said, no, I had this terrible experience climbing something like that.

[1190] And Joshua Tree, and I was stuck, and I thought it was going to have to get airlifted.

[1191] Then my friend Scott Johnson rescued me, and I was on the verge of tears.

[1192] It's the scared as I've been since I was five and got lost.

[1193] Yeah.

[1194] So I tell this long -winded story.

[1195] people leave during it.

[1196] It's too long.

[1197] And then the next day, I go to work.

[1198] Yep, you sure do.

[1199] And I go down to Phoenix and I start getting videos sent to my phone of a helicopter circling the mountain behind her house.

[1200] And I'm like, you know, why are they sending me these big dealers?

[1201] There's a helicopter.

[1202] There's a million in L .A. in the sky.

[1203] Then I start thinking, that helicopter must be looking for somebody.

[1204] And then I thought, if anyone in our group is lost, it's Ryan Hansen.

[1205] And it was not that he was lost.

[1206] it was that he climbed up into this very precarious situation and he used a rope and when he got to the top the fucking rope snapped.

[1207] Well, no. Let's be, okay, this is what happened.

[1208] I'm trying to dress it up for him.

[1209] I know.

[1210] Well, I'm going to tell the truth.

[1211] Okay.

[1212] So I'm on the porch.

[1213] Yeah, this story's not about you, but go ahead.

[1214] It's actually not about you.

[1215] You weren't even there.

[1216] I'm on the porch and they come out.

[1217] What if you go?

[1218] So I had had eggs for breakfast.

[1219] So they came out and they were like, we're going to go on a hike.

[1220] And they were like, going to try to hike up there.

[1221] And I looked up there and I thought, that is the dumbest thing.

[1222] It's trouble.

[1223] Well, I was just like, that's so dumb.

[1224] Like, you're going to try for five minutes.

[1225] You're not going to make it.

[1226] It's going to be dumb.

[1227] And I made a joke about 127 hours.

[1228] Oh.

[1229] Yep.

[1230] Oh, so you kind of jinx them.

[1231] No, I'm just smart and predicted what was about to happen.

[1232] Okay.

[1233] Or no, I didn't.

[1234] Some people call it a jinx.

[1235] And then three of them went.

[1236] Ryan, his wife Amy, and our.

[1237] from Molly.

[1238] And we, okay, also we've had a few disasters this year, personal disasters amongst the group.

[1239] Molly has been up.

[1240] I've had surgery.

[1241] I fell off a cliff.

[1242] Okay.

[1243] Well, I'm actually not counting either of those.

[1244] Oh, that's weird.

[1245] There was the most significant things that went wrong.

[1246] But go ahead.

[1247] There was a seizure.

[1248] There was a dog death.

[1249] And now there was this.

[1250] And those, you're right.

[1251] Those are the huge ones.

[1252] You're right.

[1253] You're absolutely right.

[1254] And Molly has been there for every single one.

[1255] We're starting to think she's a little bit bad luck.

[1256] She's also AI robot.

[1257] Yeah.

[1258] Okay.

[1259] So anyway, they left and they had been gone a bit.

[1260] And then I went to shower.

[1261] I came out.

[1262] Eric said, did you hear?

[1263] I was like, no. Did she hear?

[1264] Oh, they're stuck up there and a search and rescue is coming.

[1265] Oh.

[1266] What?

[1267] So then I immediately look at my phone.

[1268] Ryan has tried to call me on WhatsApp.

[1269] We have zero service in Sedona, Arizona.

[1270] So he tried to call me on WhatsApp.

[1271] I call him back Amy answers.

[1272] I was like, what's going on?

[1273] Yeah.

[1274] He said, yes, Ryan climbed up this one part.

[1275] There was a rope there and he was like, oh, I think I can go.

[1276] And so he started climbing it and then it snapped.

[1277] Yeah, well, he was almost at the top.

[1278] He was almost at the top and it snapped and he caught himself.

[1279] Uh -huh.

[1280] He was in this crevice.

[1281] Luckily, because it was literally a life or death.

[1282] It was 100 feet on one side and like 30 to 40 feet on the other side.

[1283] Yes.

[1284] And he could only stand on one foot.

[1285] He was bouncing.

[1286] So I said, oh my gosh.

[1287] She said, yeah, search and rescue's coming.

[1288] So then we flew our drone out.

[1289] Eric had a drone.

[1290] We sound insane.

[1291] We are insane.

[1292] Eric had a drone out or drone.

[1293] It didn't have it had half battery.

[1294] So we couldn't get very far.

[1295] But we did see the search and rescue people, but we couldn't find them.

[1296] Then I called her back.

[1297] She said, yeah, I guess a helicopter's coming.

[1298] From Flagstaff.

[1299] Two hours goes by.

[1300] Ryan is on one foot in a crevice.

[1301] Oh, my God.

[1302] For two hours.

[1303] I keep checking in with Amy.

[1304] She's like, he's okay.

[1305] He's panicking little.

[1306] The girls are fine.

[1307] They're not stuck.

[1308] And she's like, he's panicking a little.

[1309] And every time she said that, I was like, uh -oh.

[1310] Like, what if he passes out?

[1311] Because he's freaking.

[1312] Oh, my gosh.

[1313] It started to get so scary.

[1314] Finally, the helicopter comes.

[1315] We're like, yay.

[1316] 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.

[1317] We've all seen this image.

[1318] You see it on the news once a year.

[1319] He was airlifted out.

[1320] Oh, my God, on like a hundred foot rope.

[1321] Oh, my God.

[1322] It was something.

[1323] Yeah, it's been a big year.

[1324] Anyway, but with my Jordans, I almost dropped them in a lake and I was very upset.

[1325] Yeah, we hiked to a cool river to.

[1326] Yeah, and I almost dropped it.

[1327] That's disgusting.

[1328] A little pro tip I would like to give out.

[1329] Anytime you get to a new city, Google best swim holes in.

[1330] Oh.

[1331] I swear, almost everywhere I go ends up having some like 10 secluded swim holes.

[1332] And they're always great.

[1333] And you know what we've learned.

[1334] I'm not a very adventurous person.

[1335] Did we learn it?

[1336] I already knew it.

[1337] Did you admit it or did we learn it?

[1338] Oh, I don't need to admit it.

[1339] I feel totally confident in that because people get airlifted and people are getting hurt.

[1340] Well, you do have such a paradoxical personality because, you know, you're also a high flyer.

[1341] For sure.

[1342] You have all these elements where you're a total risk taker and then some that you're not.

[1343] It's inconsistent.

[1344] With the high flyer, I don't consider it a risk.

[1345] Which is so stupid.

[1346] That is way more dangerous than any car stuff I do.

[1347] There's preparation before you get up in that air.

[1348] Okay.

[1349] Okay.

[1350] Okay.

[1351] All right.

[1352] Moving on.

[1353] Okay.

[1354] Okay, David.

[1355] Davey.

[1356] You loved this.

[1357] And so did I. Oh, my.

[1358] God, I loved it.

[1359] I mean, if he's not completely lying, I mean, I really believe this is going to happen.

[1360] I hope so.

[1361] I mean, it's, but do I?

[1362] Yes, if you don't like it, shoot yourself.

[1363] Hey.

[1364] What?

[1365] That's the solution.

[1366] No, that is what I brought up.

[1367] I said, I think this might lead to more suicide.

[1368] I don't like that.

[1369] Well, why would it lead to more suicide?

[1370] Because if you're living on earth for 400 years, if you're 100 in and you're like, this thing fucking sucks.

[1371] Yeah.

[1372] And I have 300 left.

[1373] I'm done.

[1374] Well, but I don't even think we can call that a suicide.

[1375] I mean, anything past 100, we've got to label that something else.

[1376] You were supposed to be dead anyways.

[1377] Well, okay.

[1378] Yeah.

[1379] That's not a loss.

[1380] Yes, it is.

[1381] If you could have 300, okay.

[1382] If a 200 -year -old man shoots himself, you think that's a loss?

[1383] If I'm that person's kid and I could have 200 more years with them, yes.

[1384] That's a huge loss.

[1385] Okay.

[1386] Well, this person was a tycoon with no one liked him and he only bought himself the procedure.

[1387] Okay.

[1388] Well, all right.

[1389] There are a lot of ethical questions.

[1390] Oh, you betcha.

[1391] I mean, they don't stop.

[1392] What could be a bigger ethical question?

[1393] I know.

[1394] Yeah.

[1395] Well, because even after we were done with him, I kept thinking about it and I thought, well, no, it was because we had all these kind of major Supreme Court decisions recently.

[1396] And I was like, oh my God, if we live to 300 years, what are we going to do about the Supreme Court?

[1397] We can't have those people on the Supreme Court for 300 years.

[1398] Well, although I got to tip my hat to them.

[1399] They've been doing a pretty darn good job.

[1400] Of course.

[1401] I've seen both sides.

[1402] I've been more impressed than I've been disappointed.

[1403] 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 making the decisions for 300 years.

[1404] Think about how slow progress would happen.

[1405] They would have to put term limits on that.

[1406] And so.

[1407] Exactly, which would become more political.

[1408] Yeah, yeah.

[1409] So, oh, man, they just never stop.

[1410] I never stop.

[1411] Well, in the way you know it's completely unethical.

[1412] It's just black and white unethical because you know we all think should it be available for everyone?

[1413] And you go, no, that obviously we can't have seven billion people live forever and have new babies.

[1414] So that's a non -starter.

[1415] So you go, no, I don't think everyone should have this.

[1416] And then do you think you should have it?

[1417] Yes, I think I should have it.

[1418] So you don't right away that you're on real shaky footing.

[1419] Yeah, no, that's not.

[1420] Are you wearing a mask right now or on your neck?

[1421] Yeah, I found one in the miniature van.

[1422] It's an eye mask, and I think I'm going to use it tonight.

[1423] Oh, it's an eye mask.

[1424] Okay, got it.

[1425] Oh, you think it was like a Dracula mask?

[1426] No, I thought it was a COVID mask.

[1427] Oh, oh, no, no. I thought you were wearing it for like security, and I liked that.

[1428] I wear it at work.

[1429] I'm a stickler.

[1430] I love it.

[1431] Okay.

[1432] So, he said that with some of these medicines, they can increase life by a year for $7 ,000.

[1433] And the peacemakers are $100 ,000, sometimes millions.

[1434] Pacemaker.

[1435] Yeah.

[1436] Because he's like making an equivalent.

[1437] Yeah, yeah.

[1438] So totally.

[1439] I just had heard, I thought you said peacemaker.

[1440] Oh, I probably did.

[1441] Pacemaker.

[1442] That'd be an ironic name for a bomb, wouldn't it?

[1443] The peacemaker?

[1444] Oh, no. Now you're seeing my right wing side.

[1445] I brought up guns a minute ago, and now I'm talking about bombs.

[1446] I see your right wing side all the time.

[1447] It's what I fight every day.

[1448] What are you talking about?

[1449] So I saw a few numbers.

[1450] Total cost for pacemaker implantation range from 9 ,6 to 19 ,726 with an average cost of 14 ,290.

[1451] For patients not covered by insurance, a pacemaker and heart assist implant can cost 19 ,000 to 96 ,000 or more.

[1452] depending on the type of pacemaker.

[1453] That makes zero sense.

[1454] Why would you get charged 10 times as much for not having insurance?

[1455] Well, that's the whole problem with the whole thing.

[1456] It's a racket.

[1457] I know.

[1458] It's almost like healthcare 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.

[1459] They're so abstract.

[1460] Yeah.

[1461] Computer modeled.

[1462] Yeah.

[1463] Yeah.

[1464] Yeah, I know.

[1465] Okay, so he said the age of the sperm has an impact on longevity for the offspring.

[1466] And I could not find any backup on that.

[1467] So just FYI.

[1468] I could not find any back on that.

[1469] 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.

[1470] Well, yeah.

[1471] Because when you're younger, you're either fucking or jerking off every day.

[1472] You're not going like this old man who might go a week and a half without jerking off.

[1473] How long do they last?

[1474] I don't know, but I'm a great person to test it on, I think.

[1475] My kids, they got me at a point when I would, you know, maybe once a week.

[1476] So these kids could have been made from six -day old sperm.

[1477] And you're saying that's good or bad?

[1478] Terrible.

[1479] Oh.

[1480] If I would have had them in my 20s, they would have had two -hour old sperm.

[1481] Right, right, right, right, right.

[1482] Right, right.

[1483] But those old sperm die.

[1484] Well, the whole, he's saying, I mean, old is only, can only be whatever 10 days old.

[1485] That's what I'm saying.

[1486] I wonder what the actual length that they can live is.

[1487] Okay, it says most men make millions of new sperm every day, but men older than 40 have fewer healthy sperm than younger men.

[1488] The amount of semen and sperm motility decreased continually between the ages of 20 and 80.

[1489] Okay.

[1490] Okay.

[1491] Okay.

[1492] Okay, he said no man has ever died in childbirth.

[1493] That is true from what I could find.

[1494] There have been some trans men who've had babies.

[1495] But I'm going to propose also that a man has certainly died in childbirth.

[1496] Well, yeah, like a heart attack.

[1497] Yeah, like watching it and then heals over or a guy, you know.

[1498] That's what I was trying to look for.

[1499] I truly could not find any stories about that.

[1500] But I'm sure it's happened.

[1501] A stroke, a heart attack.

[1502] Actually, I don't think this was childbirth, but I do have this horrible.

[1503] horrible story.

[1504] My friend's sister's friend.

[1505] You could have caught one of those sisters out.

[1506] No, no, no. I want to be true.

[1507] So the mom, I think, was in the hospital or something.

[1508] Maybe, I want to say having a baby because it's pertinent to this, but I don't really know why she was in the hospital.

[1509] Okay.

[1510] But the dad, like, rushed to the hospital.

[1511] Maybe because she was a doctor, you fucking misogynist.

[1512] She was not a doctor.

[1513] She could be, if she's in a hospital and she's a woman.

[1514] This isn't a riddle we're living in.

[1515] Okay.

[1516] The woman was in the hospital for a reason.

[1517] And then the dad rushed to the hospital and then got run over in the parking lot.

[1518] Of the hospital.

[1519] Yes, because he was not paying it.

[1520] Because I think something horrible was happening with his wife or whoever it was.

[1521] We'd have to agree that's the most ironic place.

[1522] I know, but it's the saddest.

[1523] Yes.

[1524] But.

[1525] And then also if the mom died, I kind of think that happened.

[1526] Wait, now you think the mom.

[1527] mother.

[1528] I think the person that was in the hospital also died.

[1529] 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 massaginist.

[1530] You couldn't even comprehend how a woman would be in there unless she wasn't terminally ill. No, I'm saying the reason the dad fucking rushed out of the car so fast and got hit by a car is because something horrible was happening inside.

[1531] She wasn't a doctor.

[1532] This is an episode of Grey's Anatomy.

[1533] I think it might be.

[1534] Well, actually, I do think it might be.

[1535] Yeah, okay.

[1536] What percentage of people don't have the receptor for HIV -C -R -5?

[1537] Yeah.

[1538] It is estimated that the proportion of people with some form of resistance to HIV is under 10%.

[1539] Under 10%.

[1540] That's still good chunk of folks.

[1541] I know.

[1542] How do you find out if you're that person?

[1543] You kind of have to risk it.

[1544] Well, I bet you could.

[1545] Maybe you could get tested.

[1546] I bet Eric Topal could have you the results.

[1547] of that in seconds.

[1548] He could do a body scan for sure.

[1549] Okay.

[1550] That was it?

[1551] That's our fact.

[1552] What was the last one?

[1553] It's just, the last one is, what's the chance of getting HIV?

[1554] He said one in a thousand or less.

[1555] This is just hard.

[1556] Yeah.

[1557] It's a very hard one to say.

[1558] It varies country to country.

[1559] It varies.

[1560] And it's like, what's the chance of getting HIV if you have unprotected sex or what's the chance, you know, if someone Some of what has it.

[1561] I know.

[1562] It just all gets very complicated to find out.

[1563] Yeah.

[1564] It is small.

[1565] Because you have zero percent chance if you're a virgin who doesn't shoot.

[1566] Correct.

[1567] It's just.

[1568] So, you know, you can do some research if you'd like on that.

[1569] It cannot be one in a thousand or I would have gotten it.

[1570] Well, you might have it.

[1571] Oh, wow.

[1572] Measel toff.

[1573] Oh, no. you have had the best time out here don't try to rob the house a i have ring and i'll see you b we'll be home by the time you'll hear this and i'll be there waiting with my firearm oh right wing oh gross follow armchair expert on the wondery app amazon music or wherever you get your podcasts you can listen to every episode of armchair expert early and ad free right now by joining wondry plus in the wondery app or on apple podcasts before you go tell us about yourself by completing a short survey at Wondry .com slash survey.