Siddhartha Mukherjee (physician & biologist)

[0] Welcome, welcome, welcome to Armchair, Expert, Experts on Expert.

[1] I'm Dan Shepard, I'm joined by Lily Padman.

[2] Hi.

[3] Hello.

[4] Hey.

[5] One of the most impressive authors were ever going to interview is today.

[6] Pulitzer Prize winner, Sid Arthur Mukherjee, who wrote the most beautiful book called The Emperor of All Malities, a biography of cancer and the gene, an intimate history of cancer research, and probably beautiful book.

[7] An incredible book.

[8] I mean, really like a once in a lifetime.

[9] I couldn't believe what I was reading.

[10] And comes up all the time as like one of the best books on cancer, science books, books.

[11] Books, books.

[12] By the way, so he's incredible, Sir Arthur.

[13] He's also an oncologist.

[14] He's a doctor.

[15] He's a researcher.

[16] He's every single thing.

[17] Yes.

[18] Road Scholar.

[19] Oh, uni.

[20] Uny.

[21] And then a beautiful writer.

[22] What was mind -blowing?

[23] We didn't talk about this in the fact check.

[24] Uh -oh.

[25] What?

[26] The most impressive thing I found about him is how many fucking books he's read and how much he can remember.

[27] Okay, so Sid, he goes by Sid, by the way.

[28] Sid Mukherjee has a new book out called The Song of the Cell, an exploration of medicine and the new human.

[29] He's going to, it's proposed he's going to write four books, basically, on living.

[30] And this is the third of those books.

[31] And it, too, is extraordinarily beautiful and well written.

[32] And so I hope you both read the song of the cell.

[33] And enjoy, Sid Arthur Mukherjee.

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

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

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

[37] Tell me a chair expert.

[38] Can you hear us?

[39] I can hear you through my headphones, yes.

[40] Oh, my gosh.

[41] Okay, now we're ready to party.

[42] This is Monica Padman.

[43] Hello.

[44] Her family's from Kerala.

[45] Okay, where I'm going very soon.

[46] Oh, you are?

[47] What will you do there?

[48] I'm doing the Kerala Literary Festival, but I've been to Kerala many times.

[49] It's a big favorite of mine because I love the food and I love the backwaters and I love being there.

[50] So the kids have been even.

[51] I've never, well, I have been, but I was four, so I have very little memory.

[52] I've heard, too, that ecstasy and psychedelics are, widely available there.

[53] Do you want to comment on that, deny it, confirm it?

[54] I haven't tried them there, but if they were, then, you know.

[55] Okay, first and foremost, you mentioned in the setup of this recording equipment that you do not own a TV, and that might be the most important thing we'll talk about today.

[56] Do you not find that you're left out of a ton of social conversations, like when people are talking about Game of Thrones or making a murderer or any of these zeitgeist shows, Are you completely out?

[57] First of all, I don't know how to spell zeitgeist.

[58] And secondly, I'm actually happy to be out of that zeitgeist.

[59] I do read the New York Times and the Wall Street Journal with great fidelity.

[60] I get enough of my news out of those than I need to.

[61] And I'm not 100 % sure I need to know every single character in the Game of Thrones.

[62] What about movies?

[63] Do you go see any movies?

[64] I do see movies.

[65] I love seeing movies.

[66] I'm a big movie fan.

[67] But nowadays, I see most of them on Netflix.

[68] Okay, now I'm very confused.

[69] So now you have Netflix.

[70] Do you have it on an iPad or something?

[71] I have it on my computer.

[72] Oh, okay.

[73] So you can watch stuff on the computer if necessary.

[74] So, for instance, do you think I missed the Serena Williams match?

[75] No. Okay.

[76] Okay, good.

[77] Good, good.

[78] So do you think I missed Federer's last match?

[79] No. Okay, there's a niche that we're hearing.

[80] You watch only.

[81] Only tennis.

[82] Tennis is not the only example.

[83] I mean, do you think I missed one, two hundredth of the various things that happened during the Queen's funeral?

[84] No, I watched 10 minutes of it.

[85] That's more than we watch.

[86] But I didn't watch it on television.

[87] I watched it on my computer.

[88] Okay, I feel much safer now.

[89] Now it can proceed.

[90] You do have a portal.

[91] I just needed to know that if you needed or wanted to that you had the portal to do it.

[92] Can I say something crazy?

[93] Yes.

[94] I wonder if you've ever heard it.

[95] This is nuts, but this is what we do here.

[96] Has anyone ever said you have a Bradley Cooper vibe?

[97] Oh, wow.

[98] Oh, that's interesting.

[99] Yeah, now we're getting somewhere.

[100] I wasn't expecting it, but I feel it.

[101] For a long time, which is totally inexplicable to me, people have said, I have a Jeff Goldblum vibe.

[102] I'm one of those people, but let's be very clear about it.

[103] You don't have a Jeff Goldblum vibe.

[104] Good, thank you.

[105] You don't look anything like him.

[106] What you have, and I have said this on this podcast when bragging about having met you, was I was at a conference up in Montana that you were at, and I was absolutely intrigued by you.

[107] I did not know yet that you were, Sid.

[108] I had read your book, but I don't know what the author of Emperor of All Malady's looks like.

[109] And I'm just clocking that there's a scientist at this event who's got a leather jacket, wild fucking Elvis hair, a cool beard, a total vibe.

[110] and I was saying to my wife, the scientist from Jurassic Park is here.

[111] Like there's a rock star scientist at this event.

[112] Truly.

[113] And I even said to Adam Grant, who introduced us, I said, who is the rock star scientist at this event?

[114] That's what people mean.

[115] Not that you physically look like him.

[116] Oh, that I breed dinosaurs in my incubator, basically.

[117] That's the point.

[118] No, the point is that you are a punk rock scientist.

[119] I'm going to embrace that.

[120] You should.

[121] And now you have Bradley Cooper to add to the mix.

[122] I've doubled down now.

[123] If this thing goes two hours, we'll be calling you Brad Pitt.

[124] Okay, so you leave India and you go first to Stanford, and then you are a Rhodes Scholar at Oxford, and you get your PhD, and then you go to Harvard and get your medical degree.

[125] My first curiosity is, what is the cultural leap from New Delhi to Stanford?

[126] Is it an easy transition for you?

[127] Does it feel natural, or is it like, whoa?

[128] Because you not just went to an American university, you went to probably the most eclectic one of the group.

[129] Right.

[130] So I just have to push you back in time to 1989.

[131] There are no cell phones.

[132] There's barely email.

[133] There's only landlines.

[134] And I come to Stanford, which is lovely, except I'm out of touch with everyone, including my entire family, who think I've gone to the dead.

[135] Because I don't have a landline set up.

[136] I don't have any way of contacting them.

[137] And so my mother, after four days in a cold panic, She calls the international office.

[138] She says, I have no news of my son.

[139] He's supposedly at Stanford, but I have no idea.

[140] And the guy is like lanky, lots of hair, and looks usually as if he's lost on campus.

[141] Do I get this right?

[142] And my mom says, yes.

[143] And the guy says, he's here.

[144] I'm looking at him now.

[145] He seems to be lost, but he's heading in the right direction.

[146] Okay, you bounce around culturally to go from the Bay Area of California that then shoot over to England in the most historic college in some kind of tie with Harvard, I guess.

[147] Are you feeling like an outsider observing all these places?

[148] Are you getting infected by them?

[149] I didn't ever feel like an outsider.

[150] I just did my work.

[151] I landed up at Stanford, and the next morning I was in my classes.

[152] knocked on Paul Berg's door.

[153] Paul Berg was a preeminent scientist.

[154] He had won by then the Nobel Prize for discovering recombinant DNA for basically an experiment that you would think is obvious, but it's extraordinarily non -obvious in the 1980s, which is can you take a piece of DNA from a lizard and another piece of DNA from a bacteria and stitch them together and put them back in the bacteria and will the bacteria think it's just code, I'm going to read the code.

[155] That was not possible.

[156] Paul found a method to take these two pieces and stitch them together into one single molecule.

[157] And that molecule was called recombinant DNA.

[158] So I think about a week or two when I was at Stanford, I went and knocked on his door and I said, listen, Paul.

[159] I didn't say, listen, Paul.

[160] Paul's a very close friend now.

[161] So I can say this with some degree of temerity.

[162] But I went to Paul.

[163] I said, Dr. Berg, I'm very interested in this kind of work that you're doing.

[164] Can I be in your lab?

[165] if I remember correctly, Paul said, okay, let me ask you three questions in biology, and I answered them.

[166] And he said, okay, you seem to know enough to be able to work in the lab.

[167] So I spent my three to four years at Stanford sort of immersed in that lab.

[168] I learned biology, biochemistry, immunology.

[169] I learned how to write about science.

[170] Then I was given a Rhodes Scholarship and went to work with Alan Townsend.

[171] And Alan was a very, very distinguished immunologist.

[172] And so I worked on virology and immunology there.

[173] So I don't think I felt like an insider or an outsider.

[174] I mean, the questions didn't occur to me. And in fact, to be totally honest, I don't even think that this kind of idea of insider existed in the same form that it does for our children.

[175] It emerged out of the 80s.

[176] It emerged out of a certain sense of reclaiming identity.

[177] What does it mean to be inside?

[178] Who's inside?

[179] Who's outside?

[180] I think it came out of that time, but I'm not sure it existed in that time in the same way.

[181] I'm going to argue against that because I think we would agree, anthropologically speaking, we've had this strong sense of us and them since the beginning, since we've been a hominid.

[182] I think because you were in such an esoteric, finite amount of people that clearly you were the us.

[183] So in that way, I could imagine not feeling any us in them because you were already among the tiniest sliver of people who this topic fascinates.

[184] Fair enough.

[185] The only thing I would say is I do think that much of what we understand today about identity and its importance and how much it shapes us, et cetera, et cetera, were debates that were beginning or questions that were beginning to simmer more acutely in the 80s.

[186] And both Stanford and Oxford happened to be near towns where these questions of identity became very important.

[187] Stanford being near San Francisco, where, again, to remind ourselves medically speaking, it was in the mid of the AIDS rampage.

[188] And Oxford being near London, where, you know, the question of who you are, whether you're Indian, particularly, Bangladeshi, African migrated to London, were also questions that were beginning to sort of resonate through that from which came books like Zadie Smith's White Teeth and Monica Ali's Brick Lane.

[189] So both these places, were proximal to questions of identity, but they were, you know, 50 miles from them.

[190] In some sense, you could watch from a distance, and maybe that's what I meant.

[191] It was there, I could sense it, but it wasn't the chief place in my brain.

[192] Yeah, wow, the AIDS thing is really, really unique in that you'd have to take away from that, that identity was an enormous component and just how the country responded to what was a very brutal illness in any other brutal illness of that caliber, would have been rallied around and fought against.

[193] And yet because it only seemed to affect a certain group of people, the response was very different than the response of other previous diseases.

[194] Yes, absolutely.

[195] And Randy Schilt's book and the band played on details how much of AIDS was ignored by sort of mainstream medicine until people with AIDS started clamoring around it.

[196] And then subsequently, Larry Kramer wrote about it and others have written about it.

[197] But what no one had done before is what Schiltz did.

[198] So one question when you write a book is how do you organize a book?

[199] Do you organize it chronologically?

[200] Is it a series of personalities?

[201] Is there a series of short stories that mingled with each other?

[202] Is there some more sort of modern or even postmodern way of organizing a book?

[203] Schiltz's book was organized as a kind of play by play.

[204] So the chapter would begin April 21st, 1982, 7 p .m. And then he would tell you.

[205] tell you a little story about what happened at 7 p .m. And it was so thrilling to read.

[206] It reads like a thriller.

[207] It's like a police timeline.

[208] And that's how he brought people into it.

[209] He was like, this is what didn't happen.

[210] Here was a meeting that could have happened and maybe someone discussed the fact that there was an immunological collapse going on among certain men and people who had blood transfusions and they moved on.

[211] And it was not until many things happened that you ultimately got the response that was needed for what became a pandemic.

[212] We're living through one right now, actually.

[213] Like, as you're talking about it, it makes me think of the crack epidemic of the 80s and 90s in the response.

[214] It was criminality.

[215] It was a moral shortcoming.

[216] And now the opioid epidemic is an epidemic.

[217] Even that word, it's an epidemic.

[218] It's a health crisis.

[219] Now that it's killing white kids, now the whole lens of addiction has shifted.

[220] It's kind of similar.

[221] Yes, very similar in some ways.

[222] Although, of course, the difference with the opioid epidemic is that it is now becoming clear and clearer that it was incited by very particular forces that wanted to sell opioids as drugs.

[223] They paid off people.

[224] And let me tell you, as an oncologist, I feel the pain in the opposite direction because opioids are very strong drugs and very useful drugs.

[225] And now I feel curtailed in my ability to prescribe them to patients who need them the most.

[226] but there's an equal and opposite crisis in the fact that I can't prescribe these absolutely essential drugs to people who really, really need them.

[227] I've had a father and a stepfather both died of cancer, your specialty.

[228] And yes, it seems that you have to declare I'm going into hospice to get the full cart of help.

[229] But prior to that, they're not going to possibly prescribe you what the person might need to be comfortable.

[230] Is that accurate?

[231] It's just that the bar has risen.

[232] It means filling out more forms.

[233] It means doing a lot more than we were doing, you know, let's say 10 years or 20 years ago.

[234] And in order to become an oncologist, you first have to train an internal medicine.

[235] And one of my toughest patients that I had ever encountered was a frank opioid addict and would come into the hospital saying, I have a headache.

[236] Now, she would come to the emergency room and they would say, you know, rated between 1 and 10.

[237] and she would say 40.

[238] Yeah.

[239] This was 15, 20 years ago.

[240] In the end, she would leave the hospital with five or six or seven percocet.

[241] And then five days later, this pattern would recur.

[242] And I sent her to a specialist.

[243] I hospitalized her to check.

[244] But there's no objective test for a headache.

[245] So because pain lacks an objective test, because there is no pain echocardiogram or pain cat scan, I think the pharma companies that were, particularly pernicious in this epidemic, took advantage of that sort of hole and started asking doctors to prescribe opioids and then obviously this escalated and became what it is today.

[246] Yeah.

[247] Okay.

[248] In addition to being incredibly qualified, in many ways, you have patients, you run a research lab.

[249] You're like incredibly literarily talented.

[250] Your book, the one that you won the Pulitzer for, The Emperor of All Malities, a biography of cancer.

[251] is so impossibly beautifully written.

[252] I have a curiosity, were you putting time into writing commensurate with all this time you were putting into learning about biology?

[253] My life back then was split up and still is very split up.

[254] I do several things and I do them at the same time.

[255] I enjoy it.

[256] So today, for instance, I was in the lab all morning looking at gels and then looking at cells, three, four hours.

[257] Then I came back to my desk.

[258] I wrote a piece of her magazine, then I will do this.

[259] Then I will go back and edit a paper that someone wrote that needs some extra work in it.

[260] I'll try to think of an experiment.

[261] And then I'll have dinner and spend some time with the kids and my wife.

[262] I don't structure my days around, oh, you know, it has to be two hours of writing, three hours of this.

[263] It's just very much sort of responding to what the needs are for that particular day.

[264] I didn't ask the question correctly.

[265] I don't mean schedule -wise.

[266] I mean, did you write letters to people as a kid?

[267] Did you write short stories?

[268] I can't imagine that you thought, okay, finally have all this information.

[269] I'm going to sit down and write Emperor of All Malities, and that's how you wrote.

[270] What I did do, and I always tell people this who ask about sort of writing, I read a lot.

[271] And I think you can't be a writer if you don't read.

[272] And when you read, you've got to read diversely.

[273] You can't say, I'm going to write a book about cancer in the manner of, the emperor of all maladies and say, I'm only going to read science writing.

[274] If you read diversely because people have very different ways of talking and thinking, and all of that comes into our idea of how to write a book.

[275] The fact that the book happens to be about the cosmos, Brian Green's book about the universe, or Richard Rhodes' making of the atomic bomb or a great book of philosophy, all of it has to be read and digested.

[276] And that's what makes, I think a good writer.

[277] It makes you able to write in a way that you couldn't write before.

[278] But within that you have a writer's voice, you seem to have found yours quite quickly.

[279] You have this weird layer of noir over what you write, in my opinion.

[280] There's this very romantic like 20s, black and white, shimmery nitro in the print.

[281] I can see the filter it's going through.

[282] And it's very consistent.

[283] It's a lovely description.

[284] Thank you.

[285] Like I can see why Ken Burns was like, oh, I want to make a doc about both the books you've written, because I can see it as I'm reading Emperor for sure.

[286] I know what the film stock should look like.

[287] I know what the lighting should be like.

[288] Like, it's just there.

[289] Well, it has that thriller quality you were talking about earlier, the police timeline.

[290] It feels like a narrative.

[291] When I write, I try to think of a cinematic quality in the writing.

[292] I love watching films, but I have a very particular kind of film that I like.

[293] And they all come from the 40s and 50s, where lighting was very important.

[294] So Tarkovsky is a big favorite.

[295] And then much later, Kiyoslowski, so I don't actively sit down and say, I'm going to write a novel that sounds like a novel that Tarkovsky would have liked, you know, Andre Rublev or something.

[296] I sit down and say there has to be a quality in the writing so that you feel the place that you're in.

[297] Even the most minimal thing should have atmosphere in it.

[298] I'm going to add to the tonal thing because the structure of your books, and it is clear in The Song of the Cell.

[299] You are telling us a history at all times.

[300] So we're going through many different anecdotal scenarios.

[301] And what has to stay clean through that for it to be cohesive, again, I would analogize it to making a movie.

[302] You might have a funny scene.

[303] You might have a breakup scene.

[304] You might have a death scene.

[305] But there has to be a visual and a tonal cohesiveness through all the different elements.

[306] And I think that you're dropping down and all these different time periods, but that tonal point of view of you as a writer is what makes them all consistent and cohesive.

[307] Well, Song of the Cell is in my fourth book, but really a third in a trilogy of books, Emperor, the Gene, and then now the Song of the Cell.

[308] In nonfiction writing, there's a very old phrase, which is, chronology is your best friend.

[309] It makes life much easier.

[310] I started writing Song of the Cell and realized that I couldn't use chronology because it would have been incredibly bored to read and not atmospheric, and I would not know what to do with chronology.

[311] You know, he discovered this, she then found that cell.

[312] So the song of the cell is organized very, very differently.

[313] So there's a prelude, which is historical, but then each chapter acquires the personality of a cell.

[314] And I didn't realize it, but as I was going through it, the song of a cell makes a very controversial, but I think important claim about knowledge.

[315] A reviewer, recently sort of reminded me of this.

[316] The iconography of life for the last 10 years has been DNA.

[317] The lovely thing about DNA is that it has a very defined structure.

[318] It'll look the same, whether it's here or in the moon, or if we find it in some ectoplasmic alien that comes from another planet, if that ectoplasmic alien has DNA, it will look like DNA, the same DNA that you and I have.

[319] And if Paul Berg had his brothers, he would stitch those two pieces together and produce a piece of DNA, which would be half alien and half human, and it would still look like DNA.

[320] And that's been an incredibly unifying philosophy for science.

[321] The cell is just the opposite, because it doesn't exemplify uniformity, but it exemplifies the enormous diversity that comes out of that molecule.

[322] Now, DNA itself, that molecule is lifeless.

[323] It's a code.

[324] But a cell is the deciphering of that code into something that emerges out of that code and your neuron and your liver cell and your white blood cell, all of which contain the same code look completely different from each other, behave completely differently from each other, occupy completely different spaces, and have completely different functions.

[325] And so the epistemological claim in the song of the cell is that maybe we should be moving from the century of the gene to the century of the cell.

[326] The gene or DNA has become so iconographically identified with the great unification of biology that now we're finding out that beyond that great unification lies a layer of that commonality becoming extraordinarily diverse, acquiring extraordinarily different functions.

[327] And that is where we should be paying a lot of attention because that is the locus as the book claims of life and it is a locus of disease.

[328] You know, the last chapter is going to this in great detail.

[329] It's so satisfying to have a single molecule that looks like a single molecule.

[330] But if someone says to me, draw a picture of a cell, I'd say, well, what cell?

[331] A neuron?

[332] It looks completely different from a skin cell.

[333] But knowing that if I had to be a physician or if I had to do something about the body, yes, of course, I can alter genes.

[334] But ultimately, everything that comes to life.

[335] Life's basic unit is not the iconographic picture of that great unifying molecule, but life's basic unit is the cell.

[336] And it's the cell that we should understand and figure out if you want to figure out both normalcy in life and disease.

[337] That's sort of the punchline that's hidden behind the book.

[338] And that's why this book couldn't be organized chronologically.

[339] It's not a pathway of discovery.

[340] It's like a million starbursts.

[341] And you figure out, of these individual functional properties of a cell, how a neuron is different from a white blood cell, each of these is its own story.

[342] And that's why the book is divided up in this manner in which every single chapter acquires the functional property of a cell.

[343] That makes sense?

[344] Yeah, yeah, yeah.

[345] I do want to, though, put in a layer so that people who aren't familiar with the cell, it is in your preface, which is, so Hook and Lewinhock in the late 1600s, they're looking through these microscopes that they have created themselves.

[346] They're not the ones we get to use there's other people who've done it but they start realizing oh my gosh all living things are really made up of cells this is completely proprietary at that time right we're just looking at bodies in front of us animals plants at best they're dissecting some stuff they see organs oh there's stuff inside these bodies but this is the first time that they're going oh no everything we're looking at is made up of these cells and every single living thing has these That's like a complete paradigm shift.

[347] Lou and Hawk and Hook find cells.

[348] They're very interesting, exciting characters.

[349] But they don't have the wherewithal to make the most audacious claim of all.

[350] And it's not until another 150 odd years before two other scientists, Schwann and Schleiden, who are very close, their colleagues, one studying animals, one studying plants, who make the claim that you're making, that everything, all lives.

[351] is made out of cells.

[352] I guess they were just the first to name it a cell.

[353] Correct.

[354] Right.

[355] God, and I don't want to jump to the end, really, but we all grew up with that understanding that we are an aggregate of all these cells, that all these cells are working in concert, that they come together to make this enormous thing that appears to be its own individual thing, but really it's made up of billions and billions of cells.

[356] I think that is a really profound thing for people who have recognized?

[357] Absolutely.

[358] And at the time, it was very controversial.

[359] Lots of people thought that this is all nonsense.

[360] How could you possibly imagine that when you go down right at the microscopic level, that the microscopic units that build the brain and the heart are basically similar or the same?

[361] Coming back to the last piece of conversation we just had, they don't even look similar.

[362] And yet functionally, metabolically, biochemically, if you go really in, to the heart of it.

[363] They are the same thing.

[364] They're two manifestations of a unit and that unit is a cell.

[365] So it was a really, really bold claim.

[366] And at that point of time, you can imagine lots of skeptics saying, this is complete nonsense.

[367] Well, you're proposing contradictory things, which is our bodies are made up of these self -contained individual items that make one thing or a whole.

[368] So they seem just logically, completely counter to one another.

[369] And that's the leap you're asking at the end of the book to make, which is between autonomism and holism, right?

[370] That it has to be one thing or another, that either this is one cohesive blob or that there's individual things.

[371] How could they possibly be working in concert with the rest of the individual things and creating this body is very hard to comprehend.

[372] Still, it's wild that all the cells are on their own, surviving on their own and self -regulating.

[373] And yet they are a web that creates this greater thing.

[374] And I think that's what's very profound about organisms or bodies, that you have a whole system whose job is to make sure that you don't get invaded by pathogens.

[375] You have a whole system to make sure that the salt in your body doesn't exceed some limit.

[376] You have a brain that is allowing us to have this conversation.

[377] Now, if everything were put into the same unit and made to be the same, If everything was atomistic, everything looked like each other and was like each other, functioned like each other, then you wouldn't have all the things that we can do.

[378] Like walk and talk and defend ourselves against invaders and predators and also make pasta and watch a film, make a film, write a book, all of these things.

[379] Now, what's amazing about it is that these things, when they work well, they work as a cooperative assembly, like a parliament.

[380] And another thing that the book talks about is that over and over again in laboratory experiments, in genetic experiments, etc., scientists have found that this kind of assembly of various parts, cells, carries an evolutionary advantage.

[381] Because evolution over and over again selected for multicellular organisms, even though single -celled organisms like bacteria are extraordinarily successful.

[382] They live in all sorts of places.

[383] They're living in our bodies.

[384] They're living between our teeth.

[385] But somehow, in terms of natural selection, this kind of cooperative assembly with functional specialization, your immune cell defending our body against predators, your brain acting as a master coordinator of your actions and your thoughts, your muscles moving dynamically in space so that you can move yourself in space, all of this cooperative of assembly was of great evolutionary advantage, so much so that people believe that these assemblies evolved separately and independently multiple times.

[386] In other words, multiple times during evolution, there was a leap from single -cellular existence to multicellular existence, because somehow or the other, and we have theories about these now, but they're theories, you can't wind the clock back, but somehow this assembly, this idea of the song of the cell, The fact that these things are singing together, and there is not just sort of one note coming out and another note coming out, but they're singing together like an assembly, somehow or the other creates an incredible evolutionary advantage.

[387] And you could say that is what human beings are.

[388] We lie on top of a certain chain of evolution because these assemblies work.

[389] Yeah, there had to be many iterations that worked for some time.

[390] And then when one of the cells in the system started malfunctioning, the entire thing granated, right?

[391] I mean, the fact that it has the stability to also deal with many of the cells malfunctioning around it in still work as its own crazy mystery.

[392] The book has a huge application to, by looking at ourselves through the lens of the cell, that it's going to lead us in a lot of directions, hopefully with medicine.

[393] And you point out that all these things, hip fracture, heart attack, Alzheimer's, AIDS, cancer, arthritis, they're all the results of systems of cells functioning abnormally.

[394] At the heart of it, that's what's going on, is that in this perfect cohesion in the system, some of them start functioning abnormally, and that's the root of all of our ailments.

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

[396] What's up, guys?

[397] It's 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?

[398] episode, I bring on a friend and have a real conversation.

[399] And I don't mean just friends.

[400] I mean the likes of Amy Poehler, Kel Mitchell, Vivica Fox.

[401] The list goes on.

[402] So follow, watch, and listen to Baby.

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

[404] We've all been there.

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

[406] Though our minds tend to spiral to worst -case scenarios, it's usually nothing.

[407] for an unlucky few, these unsuspecting symptoms can start the clock ticking on a terrifying medical mystery.

[408] 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.

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

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

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

[412] Follow Mr. Ballin's medical mysteries wherever you get your podcasts.

[413] Prime members can listen early and ad -free on Amazon music.

[414] I'm going back to a character who threads the book, Rudolf Verkow, the pathologist, who makes two very simple but two very radical statements.

[415] The first one is that normal physiology is the consequence of cells functioning normally.

[416] It seems like a very simple statement, but we just unpacked it.

[417] It's flip.

[418] It's obverse.

[419] also true that abnormal physiology.

[420] All disease, Verkao claims, is cellular disease.

[421] If you want to understand any disease, any illness, you have to understand its cellular basis.

[422] Now, if you really stretch that point, think about neuropsychiatric diseases, what Verkow is saying, that even depression and schizophrenia, to really understand those diseases and to be able to treat and potentially cure them, what you need to understand is the abnormal cellular physiology in those diseases.

[423] He's saying that I'm not denying the fact that the environment could have something to do with it.

[424] But he's saying that the final common answer in order to have the disease must be that some cell in your body is not functioning the way it's supposed to function.

[425] It seems like a very sort of blasé statement.

[426] Okay, all diseases are cellular diseases.

[427] But when you really begin to think about it, you begin to think, gosh, that really reorients the way I think about medicine, reorienting the way I think about humans, reorient the way I think about making new humans, questions about AI, intelligence, normalcy, abnormality, disability, all of this stuff, all of a sudden, you start thinking about it in a new kind of way.

[428] And that, I think, is the message of the song of the cell.

[429] Well, this ties into the TED talk you did in 2015, which is you can both acknowledge that every single ailment at its core is a cellular issue.

[430] But then we can also have a new way of looking at what creates that cellular health or its functionality.

[431] And so in your TED talk, which is great, is you say, we've been trapped kind of in a model or a paradigm for about 100 years.

[432] Once we discovered antibiotics, our system became really just three parts.

[433] Have a disease, take a pill, kill something.

[434] That's been the model that we've studied everything, that we've researched everything, how we've treated everything.

[435] And that your model, when looking at at the cell might be actually done in reverse.

[436] Can you just tell us how the future of medicine will be a flipping of that?

[437] Yeah, the model will be start from find the cell that's behaving abnormally, find the environment or the circumstances that are making the cell behave abnormally, and that would be the immediate environment of the cell, and ultimately find the macro environment of the cell that is making the person, the organism, behave abnormally.

[438] So it would be something like cell, organ, organism, environment.

[439] Rather than building down, you build up a theory of disease.

[440] You build up a theory of abnormality.

[441] And this is something that my lab does in some ways.

[442] There are extremely strong genetic tools these days.

[443] And you can analyze the world with very strong genetic tools.

[444] You can sequence millions, billions of genes, all of which have been extraordinarily helpful.

[445] But what I'm proposing in this book and have proposed is that that doesn't account for the emergent properties of the cell.

[446] You can't read the Morse code of the human genome and say in this Morse code lies the anatomy of a brain that can write a symphony.

[447] You cannot go from one to the other.

[448] Yeah.

[449] And that's an incredible puzzle.

[450] That's the puzzle of biology.

[451] You cannot read the Morse code, A, C, T, G of the human genome, And from that, based on pure principles alone, you cannot predict that therein lies the code to build a kidney.

[452] You won't know what that kidney does or what that kidney looks like or what it even behaves like.

[453] It just isn't there.

[454] However, you can look at a kidney and its cells and their function and begin to figure out what it does, how it does it, what the physiology is, and how it basically regulates salt and water in your body.

[455] So the book makes the claim that we need to make a step now, moving beyond this very atomistic, which is, in the case of biology, a genetic understanding of humans and our bodies, to a cellular understanding.

[456] And not just one cell, but the parliament of cells, how one cell talks to another, how one cell behaves with another.

[457] And until we understand that, we'll understand simple genetic diseases, but we won't understand real complex diseases, and some of which we talk about.

[458] about.

[459] Well, you give this example of a scientist walking through the forest with an assistant that's out to help him.

[460] He's a local.

[461] And as the scientist is walking with this guy, he's discovering that the local guy knows every single plant species.

[462] And initially, he's really, really impressed and shocked by that.

[463] And he's commending the guy on it.

[464] But the guy is really distraught because he, although knows every single species in there, he laments the fact that He doesn't really know anything because he doesn't understand the song of them.

[465] But as you say, what he really means is he doesn't understand the interconnectedness of them.

[466] He doesn't understand how they're communicating.

[467] He doesn't understand how they're playing off of one another in forming this much larger ecosystem they're walking through.

[468] Exactly.

[469] Here's where I myself struggle.

[470] We just interviewed a guy that was talking about a farmer in England who has spent the last 25 years on a single piece of land.

[471] that was follow, and he's been trying to get it to harvest, and he's discovered all of this stuff about the different fungi that has to grow in the soil around the roots, and then he also found that of these, I forget what he said, 20 ,000, whatever, there's only four that grow on the roots, and they happen to be the four that are in our microbiome.

[472] So for this guy trying to resurrect a farm discovering that you could look at the root for the rest of his life, but the more he focuses out and realizes that the whole thing grows in combination with all these other things, the picture just keeps getting bigger and bigger and more complex.

[473] Now, here's the thing I struggle with.

[474] Like, I can acknowledge that there are cells in my body.

[475] I can go even smaller.

[476] I can say there's electrons.

[477] There's protons.

[478] Okay, then there's atoms.

[479] Now there's these cells.

[480] I get it.

[481] These cells are somehow working together and they're in my body and they form organs and bones.

[482] And I am this thing.

[483] I stop at me. Okay, so I'm this individual creature.

[484] I'm talking to you, but it is really hard for me to make the leap that the scaling up keeps continuing and that I'm a part of all the other animals around me and the other flora and fauna.

[485] That's a hard leap.

[486] Do you think that's hard for everyone?

[487] I think that's the hardest leap, and I think we're not there yet, and this goes back to the TED talk, but in really order to understand us, and by us, I mean human beings in general, I think we need to slowly start making those leaps.

[488] But there's a leap before that leap, finding the interconnectedness of cells.

[489] So I'm obsessed with moss.

[490] I love growing moss.

[491] And moss is a very peculiar creature because if you try to grow moss, it will not grow.

[492] It's a little bit like a child.

[493] If you try to tell a child to go left, he or she will go right.

[494] And so if you try to make moss grow, it won't grow.

[495] And exactly when you're looking away and places that you don't want moss to grow, it'll thrive and flourish.

[496] And this is for my own garden.

[497] I've been trying to solve for a long time is why?

[498] Why is it that I put buttermilk and whatever else moss experts tell you and the moss will die in like three days?

[499] Whereas in places where I don't, it thrives.

[500] And bit by bit following advice from other people, I've started piecing things together.

[501] So someone said, plant oak saplings.

[502] Because oak saplings have a symbiotic relationship with moss, and they allow the moss to grow.

[503] And sure enough, I planted some oak saplings, and the moss started growing around them.

[504] And so bit by bit by bit by bit, this holistic idea of the human body, like moss, we'll have to solve.

[505] That's the secret to understanding ourselves.

[506] But we're not there yet.

[507] We're actually one step still behind.

[508] And the one step still behind is, before we understand the song of the ecosystem, we have to understand the song of the cell, which is to figure out just, by yourself, not in relationship with the large environment that you're living in, how one piece is talking to another piece.

[509] And that's what our lab has started to do.

[510] We've started to explore things like, how does metabolism affect cancer?

[511] That's one of the biggest projects that we have.

[512] Another project is, how does a neighboring cell affect a cancer cell?

[513] How does the cancer create a home for itself?

[514] So that's another song.

[515] It's a malignant song.

[516] Yeah.

[517] How does bone sustain itself?

[518] How do bones grow?

[519] when you have a fracture, how do they repair themselves?

[520] When you get a bone marrow transplant, how do all the cells know to start growing and repopulate your blood system?

[521] And then why is it that, you know, everyone with bone marrow transplant doesn't have cancer and they, you know, explode with blood?

[522] Because they know how to stop growing and because they're sending signals to each other to start and stop growing.

[523] So that's the intermediate level that we're still struggling to understand we'll slowly crack that open and then comes your question, which is how does this organism then fit into the bigger environment?

[524] Don't we think we know how cells communicate?

[525] We think they're talking chemically, yeah?

[526] We know that they're talking chemically.

[527] We also know that they're talking physically in the sense that, you know, there are now lots and lots of experiments that show that there's physics behind this too in the sense that when they touch each other, their forces, their share forces.

[528] We know that.

[529] That's a general idea.

[530] We need to know exactly what chemical, under what circumstances, what physical circumstances, et cetera, in order to cure diseases.

[531] And can we ask, too, like, who's orchestrating it?

[532] That's my great curiosity.

[533] It's like even if you find the mechanism by which they're all communicating with one another, like the beehive or something, where's the master plan coming from?

[534] The DNA?

[535] But is that complete?

[536] You could say it's coming from DNA.

[537] But the master plan is, to some extent, that when cells accumulate with each other, they form a system that has evolutionary advantage.

[538] It's a natural selection process.

[539] Cells learn to communicate with each other, not because there's a brain behind it or because there's God sitting there saying, you've got to talk to him or her.

[540] It's because the only way the organism could survive was if one white cell talk to another white cell.

[541] In an organism where two white cells could communicate with each other, that organism is a much better defended organism against a pathogen and will survive.

[542] So the master plan really is the playing out of evolution by natural selection.

[543] And there's no other master plan.

[544] And that's what's amazing about it.

[545] It's a distributive plan.

[546] Like no one said that this is how you have to behave, but that's how cells behave.

[547] Right.

[548] And so that general principle is known.

[549] But the details are very important now.

[550] A cancer cell, which has metastasized to your bone, what exactly is it doing to make a home for itself?

[551] When I say exactly, I mean, what chemical is it secreting so that the bone thinks that it's perfectly fine to have a breast cancer cell sitting inside bone?

[552] That's not normal.

[553] Why would your lung cells say, oh, okay, it's perfectly fine this morning for a breast cancer cell to come and sit in the lung?

[554] Why would it say that?

[555] Yeah.

[556] And why does the spleen not ever say it's okay?

[557] This question comes to us from the 1890s.

[558] The spleen and the liver are their same size.

[559] The spleen almost never has metastases.

[560] The liver is one of the most frequent sites of metastases.

[561] Why?

[562] And they're next to each other.

[563] So somehow or the other, there's something in the spleen or something about the cells of the spleen that won't allow or won't be permissive to a breast cancer cell coming and setting up shop there, where there's something in the liver which says, come be my guest.

[564] Why?

[565] The answer has to be that the pancreatic cancer cell makes some factor, a chemical factor, which then makes it a permissive cell.

[566] It becomes what the biologist Ruslan Mesasov calls a client cell.

[567] It obtains a client permission to live inside the liver.

[568] And what's more is that it also allows that cell not to be scanned by the immune system.

[569] Right.

[570] Does it become invisible or a recognized client?

[571] We now know that some of them become invisible, invisible in the sense that the immune system thinks of those cells as part of the normal repertoire of that organ.

[572] Since it doesn't attack the organ, it doesn't attack the cancer cell that's resonant in the organ.

[573] But now we've discovered more.

[574] So not only does the cell make this cloak of invisibility around itself, it also makes a house of invisibility around itself.

[575] So in other words, it attracts other cells to form a kind of shell around it.

[576] But what we need to know, if we want to solve all these problems, is how is it making that camouflage?

[577] What chemical?

[578] It's not enough to say a chemical.

[579] We need to know exactly what chemical.

[580] Can that chemical be inactivated?

[581] Can that chemical be targeted?

[582] This is what my lab has taken on.

[583] So I often say I missed the genomic and genetic revolution.

[584] It passed by me. And in some ways, I'm thankful for it because genomics and genetics is very seductive.

[585] You can sequence the Morse code, but if you read the Morse code, you cannot from that code understand exactly the questions that I asked you.

[586] Nothing in reading human DNA will tell you that a spleen is not a site of metastases while the liver is a frequent set of metastases.

[587] You can read the genome backwards, upwards, sideways, and nothing will tell you why this fact is true.

[588] You have to look at the cells.

[589] You have to look at cell biology.

[590] Is it feasible that in 100 million years we will evolve for every organ to behave like the spleen?

[591] Yes, I think it's feasible.

[592] I suspect that there will be some common themes and they're already becoming clear.

[593] There are some common themes that allow metastatic cancer cells to set up shop in various organs.

[594] The factors that they use to set up shop are actually not infinite.

[595] They're finite.

[596] And in fact, many of them are shared between organs.

[597] So I think it is possible that in the future we'd have some kind of way of preventing that.

[598] We just have to figure out if you can do it in a manner that doesn't have toxicity in the entire body.

[599] We would have to intervene though, right?

[600] Like for it to happen on an evolutionary scale, that's why cancer is so present is that you can reproduce long before you ever deal with cancer.

[601] That's what makes it so lethal is you're getting it in your 40s, 50s, you've already passed your genes on.

[602] And so for there to be any mutation that would cure you from that, it's not going to make you more advantageous to other people that don't have the gene because everyone's going to reproduce before cancer age, mostly.

[603] Yeah, that's, of course, a big conundrum.

[604] Most diseases that happen after reproductive age, it's difficult for natural selection to work on those diseases because you've already reproduced unless they're genetically passed down.

[605] And cancer, although it's a genetic disease, it's a disease that happens in older age, typically, not always, but it happens because something changes the genes, a copying error or a carcinogen changes the code.

[606] But natural selection can't act on that because you haven't passed that code down to your children.

[607] Your children have gotten the intact code.

[608] Now, that's not completely true.

[609] You and I know that there are some familial cancers where the genes are passed down.

[610] And in those cases, if you get the cancer early enough in your life, there's adverse selection against that.

[611] And that's why most cancers are not acted upon by standard natural selection.

[612] Now, there are people who study biology and evolution and talk about sort of kin selection in the sense that you need families and you need a protective environment, et cetera, et cetera.

[613] There is a way for natural selection to act beyond reproductive age.

[614] But that's a different story.

[615] It's somewhat a minor story.

[616] Okay, I just want to comment on one thing, and then I want to try to ensnare you in something you probably don't want to talk about.

[617] But really quickly, the fact that the genomic revolution passed you by could be this huge asset to you, right?

[618] Because just like CRISPR and these other technologies and what we did with the COVID RNA vaccine, that happened as a result of a great scientist being forced out of the DNA exploration, having to focus on RNA, which no one wanted to study, right?

[619] RNA has been fascinating to scientists for a long time.

[620] It's harder to study for various reasons.

[621] Its biology is more complex.

[622] every cell doesn't have the same RNA, bar a few sperm and egg cells and your immune cells which are slightly different from each other, and some mutations that occur in individual cells.

[623] So with those exceptions aside, for the most part, every cell in your body has the same DNA.

[624] And so it's much easier to study that.

[625] Every cell in your body, on the other hand, does not have the same RNA.

[626] RNA is made from DNA.

[627] It's a soft copy.

[628] And your brain cell has a completely different set of RNA molecules than and your liver cell.

[629] And so RNA has been a great problem to study.

[630] Studying it has won dozens of Nobel Prizes, has had really quite a impact on human biology.

[631] And you're absolutely right.

[632] There were lots of people in that time studying DNA and very few people studying RNA.

[633] And in fact, it's the study of RNA that led to the creation of the new vaccines.

[634] Okay.

[635] I got to say one more time, for anyone who's not normally drawn to a scientific book or a book on biology, I have to say that your writing really transcends the topic.

[636] I've recommended the emperor to a bunch of people that I don't have a ton of interest in it and everyone found it to be that same weird, romantic, historic, noir experience.

[637] There's something really broadly appealing about the way you write, and I think everyone would really enjoy the song of the cell.

[638] And I think it asks some bigger questions, which is we're so caught up in the pieces and not necessarily the whole.

[639] hole that everything adds up to.

[640] We're kind of missing a lot because of that myopic view of everything.

[641] Perfectly right.

[642] I just want to ask you, and again, you probably want to talk about this, but I'm reading a book called Behave right now.

[643] I don't know if you've heard of it, but it's fantastic.

[644] I have.

[645] I can't believe how much I love it.

[646] But, of course, in it, it's going through how there's kind of a resurgence in Lamarckian inheritance.

[647] When you're in your entry biology class and they're teaching you evolution, the wrong theory was that a giraffe could stretch its neck and make its neck longer pass it onto its kid.

[648] He became a punchline in the mark.

[649] Now as we learn a lot more about all the different things that are reading the DNA, transferring, turning jeans on, turning them off, it seems much more complicated.

[650] In reading Behave, I'm like, could you just say that DNA is every single ingredient in a pantry, every single food product that could ever exist, and that really it takes a chef to then make you a dish with all these ingredients, like between the RNA and the epigenome, turning on and turning off genes.

[651] It just seems like maybe an endless pantry and that there's great variability with all these ingredients and that perhaps maybe some co -view of it could exist.

[652] I'm wondering if from when you wrote your paper in the New Yorker in 2016, you got some backlash, if even from 2016 to 2022, has it inch close?

[653] to maybe a view of evolution that maybe involves both elements?

[654] The 2016 paper, first of all, was an extract from a massive book.

[655] Yes, the gene.

[656] And standard mechanisms of gene regulation, there are four chapters on it.

[657] The extract happened to be from a chapter which talks about what I would call non -standard or newer ways by which we are exploring the way genes are regulated.

[658] And a certain group of scientists who are very touchy about standard ways of gene regulation started saying, no, no, no, no, this is all new.

[659] Of course it's new.

[660] That's why it's in the New Yorker.

[661] If it was a standard textbook explanation, it wouldn't be.

[662] Now, over time, I think people are realizing that there's more to gene regulation than we originally knew because the code is the code, right?

[663] There's a master code.

[664] That code has to be regulated so that your neuron doesn't.

[665] have the same RNA and proteins than your white blood cell.

[666] The standard model, which is a very classical model, and is absolutely correct, is that there are factors called transcription factors, master regulators, you can call them whatever you want.

[667] They turn genes on and off.

[668] Absolutely correct.

[669] Discovered by Jacob and Mono in the 1950s and 60s and elaborated on extensively.

[670] What's interesting is that standard model now is being refined.

[671] And we are realizing that there are more.

[672] more and more elements to that standard model that need to be added.

[673] And this indignance about not thinking that there are more things that need to be added is just to me absurd.

[674] I'll give you some classical examples.

[675] The cancer that I study, acute myelogynous leukemia, AML, the most common mutations are mutations in the very genes that don't fit into the standard model.

[676] In other words, these are genes that attach chemical signals to DNA, not transcript.

[677] factors.

[678] Here's a totally dysregulated cell whose genome has been totally dysregulated.

[679] Typically, not always, does not have alterations or the alterations are rare in those very factors that, you know, are considered the classical ways that genes are regulated.

[680] And I cannot seem to convince people that we need to think a little bit more deeply about genetic regulation.

[681] It's more complex.

[682] Now, the second part of the question that you ask is about Lamarckian evolution.

[683] The article was very clear.

[684] There are some examples in smaller animals of intergenerational Lamarckian evolution.

[685] But those examples are fewer and far between.

[686] We know the mechanisms of some of them, whether they last across multiple generations of a question mark.

[687] But also, this is a strange thing about the blogosphere.

[688] Someone will pick up something from the blog and say, you know, Siddhartha Mukherjee is a proponent of Lamarck in evolution.

[689] Whereas in fact, I'm exactly the opposite.

[690] And can I be clear?

[691] I don't believe in Lamarck in that you can stretch your neck and pass it.

[692] I guess the component of it that they're probably wrongly labeling Lamarckian seems to be your environment is in the mix.

[693] It's not just your genes that you pass down.

[694] You might have an enormous spectrum of outcomes, phenotypical spectrum of outcomes based on your DNA, that the environment can actually go inward and activate.

[695] Yes, and there are some examples, and they're increasing numbers of examples of that, mostly in smaller animals.

[696] I don't think that there's been any definitive example in humans.

[697] So the question is, can this happen in humans?

[698] There has been a lot of controversy about it.

[699] I've acknowledged the controversy.

[700] The book, the article, everything I've written, talks about this as speculative, controversial, and unlikely to have evidence in humans.

[701] I can't say any more than that.

[702] Yeah, yeah.

[703] But you're absolutely right.

[704] The environment impinges on genetic regulation.

[705] The way we understand gene regulation is incomplete.

[706] still.

[707] We need a lot more understanding.

[708] And the classical model of gene regulation in which factors attach themselves to the genome, activates certain genes, and then there's a positive feedback of these works, but it doesn't work completely.

[709] It doesn't explain certain things.

[710] You have to invoke some different ways of gene regulation.

[711] And the fact that people don't accept that is absurd.

[712] It's looking away from the problem.

[713] Well, I think it gets done to the very most fundamental flaw we all humans cannot resist, which is we want a definitive statement.

[714] We're so uncomfortable if we don't have a definitive statement.

[715] Either Newtonian physics works or no, oh, it doesn't work in this situation.

[716] Oh, no, now we need to incorporate.

[717] There's such discomfort with the notion that multiple things may be working at once and not at all times and sometimes at other times.

[718] But I think when we get anchored into these binary, I just feel like you're bound to miss so much.

[719] It's like confirmation bias.

[720] You can't see the contradictory facts because you're now just trying to defend Newtonian physics or that nothing goes faster than the speed of lighter.

[721] Any one of these things, it's just funny to me that it feels present in biology as it is in politics and everywhere else.

[722] All absolutely correct.

[723] I mean, I think that gene environment interactions are not fully understood yet.

[724] Gene regulation is not fully understood yet.

[725] There's a group of what I would call old school classical biologists who believe that they had solved the problem, then dusted their hands off, and indeed they'd solved the most major part of the problem, which is, yes, it's absolutely true that the reason your neuron is a neuron or your nerve cell is a nerve cell and your white cell is a white cell is because there are factors in it, there are proteins in those cells that bind to DNA, activate or repress certain other genes, and thereby make certain proteins express in the nerve cell and not in the white blood cells.

[726] that's absolutely true.

[727] But that explanation of gene regulation is still incomplete.

[728] It does not explain certain things that we're finding out about cancer, for instance.

[729] It doesn't explain certain things that we're finding out about gene environment interactions.

[730] It does not explain certain things about how some of these signals can maintain their permanence when the cell divides.

[731] It did not explain why calico cats are calico.

[732] They have patches of different colors in their skin.

[733] So there were things about the classical model, which is absolutely correct, but does not fully capture the complexities of gene environment interactions.

[734] And I wish someone would just be able to say that without being smacked on the head by old school classical biologists, because there have been dozens, hundreds, thousands of papers now written about new forms of gene regulation.

[735] There have been prizes, including at least one Nobel Prize, awarded for these new findings about gene regulation.

[736] And there will be many more Nobel Prizes, two breakthrough prizes awarded for this, multiple major papers written about all of this.

[737] And it says it this entire field of non -classical gene regulation did not exist.

[738] And then the defense is, oh, you're being Lamarckian.

[739] Right, because we know that's wrong.

[740] If I hang that on you, then debate over.

[741] And I keep saying, no, no, you don't understand.

[742] You can think about gene regulation without being a Lamarckian.

[743] So it's not like I'm digging up his grave and bringing up his ghost and saying, oh, gosh, you know, Lamarck was right and Darwin was wrong.

[744] How many times do I have to say that?

[745] No, Darwin's clearly right.

[746] And some other people might be right.

[747] Not Lamarck, per se, but some other people might be right in addition.

[748] Exactly.

[749] Well, I just want to thank you.

[750] Besides your incredible gift for writing, which again, I hope everyone experiences in their life.

[751] It's so beautiful and tragic and inspiring.

[752] Additionally, I would say, I love you as a disruptor, someone who's not afraid to flip a model on its head, to use metaphor in a way that helps us break out of these patterns.

[753] I think anyone who's a catalyst for always challenging the models we're stuck in is a wonderful force for good.

[754] dig you, and you do look like the kick -ass scientists from Jurassic Park.

[755] You're a creative motherfucker.

[756] Let's put it that way.

[757] You're an artistic biologist, and it's really cool.

[758] I love your podcast, so kudos back to both you guys.

[759] I want everyone to buy and read the song of the cell and exploration of medicine and the new human.

[760] Out October 25th.

[761] Be well.

[762] Thank you so much for your time.

[763] I know it's valuable.

[764] I hope I get to see you again in person.

[765] I'm going to pick up my style game if I know that's eminent because I want to also be compared to something while we're together.

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

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

[768] Okay, well, we have a special gas.

[769] Hi.

[770] Welcome to the show.

[771] Prairie.

[772] I'm from Lomaxlico, Colorado, U .S .A. Who is this one for, Mani?

[773] Siddhartha Mukherty.

[774] Oh, man. Right out.

[775] Intimidating.

[776] Did you listen to it?

[777] Yes.

[778] That's not what I meant.

[779] I know you added them.

[780] I didn't know if you were there yet.

[781] I don't know.

[782] Of course you are.

[783] I have to be by the time I do this with you.

[784] Of course.

[785] I wasn't saying anything.

[786] I just meant you did hear it.

[787] I was pretty critical after that one.

[788] I was not proud of my performance in that one.

[789] I remember being in a bad mood after that.

[790] Why?

[791] I try my hardest to maybe condense what I think I understand about their thing into like a simple analogy or simple delivery of this thing.

[792] And I just didn't have those skills that day is what I thought.

[793] And then I was like, I think I failed at that.

[794] And then I think he thinks I'm dumb.

[795] This is what I thought at the end of all of it.

[796] How do you work through that?

[797] I can't work through something I've done 15 years Like if I feel like I did something Yeah I had to go Yeah Some of them you're not gonna think you nailed it And some you're gonna And there'll be more Yeah like I get hung up on a cameo Something as simple as that And then when I hit Oh God And I'll think of it for three days Wow Yes I will tell you it was good and interesting and it didn't feel like you weren't talking enough or you weren't doing it felt like you were doing the perfect amount well I also the other reason I was upset was that I and I apologize to you afterwards was very sweet was it was like there's only a handful of these and there's really no predicting why I'm going to be insecure I can't pinpoint it right like I weirdly it was more fine talking to Bill Gates than I was him yeah there was something about him that had same with jared diamond like i gotta be perfect on my end and what he knows is so dense that i've got to like figure i got to crack this thing anyways all that anxiety resulted in me not leaving the door open at all for you to talk and i knew it was happening and i was panicked that i wasn't getting to this other thing we need to know about his book whatever i was very stressed about it.

[798] And then in my worst way of dealing with that is I just, you know, I'm trying to control the whole thing.

[799] And then afterwards, I was very regretful that I didn't leave more space for you.

[800] You know what part of it was?

[801] We have a certain guess where I think we're, I guess it's almost like we're not entitled to their time.

[802] But you are entitled to their time.

[803] No, I'm saying us, this show doesn't warrant their time.

[804] He's running five companies and he's got a lab he's breaking through the stuff and he's writing these impossibly beautiful books there's no way he wants to talk to strangers for an hour sometimes i start with that i think oh god this guy is like what a waste of time this is yeah i have that assessment occasionally about guess and then i'm in a bad i'm off kilter yeah i get that i get that yeah i just felt like sometimes like oh my god i'm wasting this guy's time but we have the time right so like yes whether or not he wants to be there doesn't want to be there i guess i could choose to hear that i'm not going to but i could choose to hear that as we only have so much time with this incredibly smart person so it should be oh my god i i could have never guessed that would be a takeaway of what i was just saying really oh my god yeah i accept it i can understand now that you paint it that way how that's how that sounds to you i wasn't saying that in reference to me railroading and not letting you in that wasn't a comment on that i was saying sometimes there's a handful of people that i'm insecure going into interviews with having nothing to do with you yeah or even considering whether i'm going to talk too much or make space for you that aside yeah yeah yeah there's a handful of people that I'm too stressed out about when we start.

[805] It's like I got to somehow talk about his whole cancer book and the can in the cell and all that stuff.

[806] And I think he might be doing us a favor through Adam Grant.

[807] I don't know if he wants to be here.

[808] I mean, yes.

[809] And I'm just going to get like, it's not a favor.

[810] It's a, it's a great place to promote a book.

[811] Exactly.

[812] Yes.

[813] Thank God it only happens once in a blue moon.

[814] Yeah.

[815] But it does happen.

[816] And he was one of them.

[817] and I thought I did a terrible job and I also in my panic did not leave any room for you to talk which absolutely sucked but when I say we don't deserve their time I don't mean so therefore I should take all the time at all I don't think I just want you to not be worried about it it went great it went great that's a good episode he's fascinating but for the record I've never in my life made an analysis this is worthy of Monica participating or not.

[818] My worry would be that it's not conscious, but that's in the mix.

[819] But I...

[820] There are certain people that I'm afraid if I don't lay out with the architecture I've come up with two hours before the interview.

[821] If I don't lay this roadmap out, we'll never get to the thing.

[822] There are times I have that panic.

[823] Of course.

[824] And I know it's trickier with our experts, obviously.

[825] But it is like what we learned episode six, which is don't be so married to the thing because our best episodes are what we are not doing that different with experts i will say but yeah like we're talking about the work they've kind of we are but we are talking to our audience yeah it's a tricky thing to navigate yeah like part of me like Hillary Clinton that's easy we know and love Hillary Clinton so if we hear about the fact that bill won't get rid of his video collection that to me is an awesome detour yeah and I'm delighted to let it go and let the show be that.

[826] Yeah.

[827] But if like Jared Diamond's on and he proved how civilizations ended up being advantaged over others, I feel like my job's to lay that out, not let people know about Jared Diamond's wife's video collection.

[828] It feels different.

[829] That's interesting because to me it doesn't.

[830] To me like when people comment on like the Obama episode or something, they're excited about the stupid stuff, not the stuff that.

[831] Definitely Obama and definitely Hillary Clinton because you already know what they are.

[832] Right.

[833] It's like when Jared Diamond's on.

[834] I don't think the average person knows Jared Diamond or has read guns, germs, and steel.

[835] And my hope is that we can distill that book into an episode.

[836] Yeah.

[837] I have that book in the trunk of my car right now.

[838] Funny enough, someone gave it to me yesterday, or two days ago.

[839] What?

[840] At a soccer game.

[841] Oh.

[842] Really?

[843] And said, have you ever read this?

[844] And I said, I know.

[845] And I thought in my head I know you guys were talking about it And I was like, yeah, this might be a toughie for me Yeah, it's a thick one Yeah Oh, that's him Okay, so Aaron just arrived from his home land Native land.

[846] Native land Beverly Hills.

[847] Beverly Hills, Michigan Beverly Hills, Michigan this morning Five -day trip Slept like a baby Went right to sleep on the plane in my pajamas So now, update, Aaron sleeps quiet as a church mouse with his apnea machine.

[848] Right.

[849] How do you think on the airplane you sound?

[850] I'm assuming really loud, according to the people next to me. Did anyone say like, oh, you're a realese?

[851] Nope.

[852] No, but I felt it.

[853] You felt judge when you woke up.

[854] Yeah.

[855] The thing is about that machine, it doesn't cure you.

[856] You have to use it.

[857] Right.

[858] When I decided not to, it's exactly like it was last year.

[859] Oh, my God.

[860] Will you tell really quick, your decision to not take it a couple weekends ago?

[861] I never related more to a story.

[862] Oh, no. Okay.

[863] Okay, I went on a retreat, a weekend retreat, men's retreat, AA.

[864] Right.

[865] So a sober weekend in northern Michigan with 14 guys.

[866] Wow.

[867] Big nice cabin on the river, the whole thing.

[868] So it's, I had never done this.

[869] And when I was asked to do it in the spring, I was like, when, September?

[870] Oh, yeah, count me in.

[871] And, you know, just tell me when you need the money.

[872] And that's something I should do as a sober person.

[873] And then it crept up.

[874] And I was like, oh, fuck.

[875] I'm like, who's going?

[876] I don't know anybody except my one friend.

[877] And it turned out I did know some people, but I didn't want to go.

[878] I finally decided to go.

[879] Wow.

[880] I'm proud of you.

[881] I'm impressed.

[882] But when I was packing, Ruthie said, oh, aren't you going to pack your machine?

[883] And I said, no. Because I'm more than likely going to be turning right around.

[884] Oh.

[885] And I'm not going to stay.

[886] You're going to like make good on your commitment.

[887] and then also not go.

[888] Yeah, so I was like, I need an out, and I don't bring the machine.

[889] Built an out.

[890] And I also turned down a ride.

[891] Okay, smart.

[892] Yep.

[893] Because, you know, you don't want to be stuck.

[894] No. Mm -hmm.

[895] And I didn't even want to go, let alone be stuck.

[896] Yeah.

[897] So I didn't bring the machine, and I was in a room with three of us, three guys and three little beds.

[898] My buddy has a machine.

[899] What a middle -aged camping trip this.

[900] Oh, the other half of the guys were on the floor one because they were so fucking old.

[901] They couldn't get up the stairs.

[902] Oh, wow.

[903] So he had a machine.

[904] I admitted to what I was thinking.

[905] When I got there, I was like, listen, I'm going to be real honest.

[906] I had this feeling.

[907] And I'm really stubborn and really defiant.

[908] And I'm going to show you guys by not bringing my machine and driving by myself.

[909] and, you know, just in my own head.

[910] But you admitted that out loud?

[911] I did.

[912] Wow.

[913] This is the great dichotomy of Aaron Winkle.

[914] This is impressive.

[915] I'm impressed.

[916] Okay, so the third guy, neither of us had met.

[917] I told him, hey, buddy, I'm sorry.

[918] But I should have a machine, too.

[919] And he's like, great.

[920] Right.

[921] Like, great.

[922] Understandably.

[923] Sure.

[924] So the first nine.

[925] happened in the books and I got up and my friend said well I can tell you this he listens the podcast so he said Dex was right you need a machine and I think the other guy didn't get a wink of sleep that night so I went to the storm button some ear plugs for the because I stayed the entire trip then he liked it and then it wasn't I had a great time.

[926] You had a great time.

[927] Oh, yeah.

[928] Oh, my God.

[929] Spiritual meetings.

[930] It was great.

[931] Yeah.

[932] I fought it.

[933] Contrary action, they say.

[934] You're doing things you don't think you should do.

[935] But I can so relate to like packing and not even as like, like even a nice compromise would have been like, I'm going to bring the machine and say I didn't.

[936] Right?

[937] Oh, shit.

[938] My wife told me she stuck it in there.

[939] Like there'll be all these ways where you could get out of it.

[940] but even in your mind you're like no not bringing nope and you know ruthie she was like do you not remember six months ago or whatever however long it was you might have a stroke in your sleep that's how bad your apnea is yeah so who are you doing this to you make punishing all these people by killing yourself because they invited you on a trip yeah um so you were afraid you'd feel awkward at yeah so you know I don't know if I have a, you know, want to be a martyr.

[941] I don't know.

[942] Well, I also get the feeling.

[943] It's like, I can't stay the night.

[944] Like, you're, like, blocked yourself in.

[945] Like, you're like, I don't want to go.

[946] And so I'm not going.

[947] And so I definitely am not going because I'm not bringing the machine.

[948] I guess how far was it from the house?

[949] It was three and a half hour drive.

[950] Okay.

[951] I was going to say maybe the next day, go get it.

[952] Well, you would have had it Uber like your Volvo.

[953] Yeah, you have stuff Uber like you're proud of suspenders.

[954] I should have.

[955] I ended up spending money because I left everything else there.

[956] I left Ruthie's new headphones under the bed.

[957] I left.

[958] I left like three.

[959] I only brought four things.

[960] I left three of them.

[961] And I had to have them send it back to me. So I did end up paying for a delivery back to my house.

[962] Oh, wow.

[963] Yeah.

[964] Well, I'm proud that you stay.

[965] I'm sorry for that person Because less we forget I've experienced You without your machine Oh yeah In the car In the RV That's a tough sitch And Monica's very protective of you And loves you And you even angered her But I didn't think that could happen But definitely you and Laura When I woke up I felt a chill in the air that morning You didn't anger me But I was upset.

[966] I couldn't believe what I had experienced.

[967] I couldn't believe it.

[968] Some people, you just can't believe it.

[969] Yeah.

[970] You got to kind of witness it.

[971] It's kind of like Eric's sneeze.

[972] We could talk about it forever, but you've got to experience it.

[973] Yes.

[974] Because I had headphones in with white noise, and it didn't matter.

[975] And it was like, wait, how is this not mattering?

[976] The reason it's impossible to ignore is that there is no, pattern to it.

[977] And there's long periods of zero breathing.

[978] So you actually, as someone who loves Aaron, you're considering waking up and starting mouth to mouth.

[979] Like a couple hundred times a night you think, oh, I got to go nudge him and see if I can get him started back up.

[980] I think I actually, now that you're, I think I do have a little PTSD because my dad snored or snores.

[981] I assume he still snores.

[982] So if we went on vacation.

[983] Oh, this just happened.

[984] You guys went on a family vacation in New York, six years ago, five years ago.

[985] Yeah, a long time ago at this point.

[986] But yeah, we went on a family.

[987] All of my life, we go on family vacations.

[988] We have one hotel room, obviously.

[989] And so my mom and dad have a bed, and then me and my brother have a bed.

[990] And my dad would snore, and then, yeah, it would stop.

[991] And I would be like, he's dead.

[992] And I always thought my dad was dead.

[993] So, like, more reason to think he's dead.

[994] So anyway, yes, I think I just got a little PTSD.

[995] Yes.

[996] So back to the air.

[997] plane to date.

[998] You can't, I guess you can't take it on a plane.

[999] It's too big, right?

[1000] No, I had it with me. You actually can, it's not even counted as carry on because it's a medical device.

[1001] So, yeah, I had it.

[1002] I guess it's never occurred to me to fucking plug it in.

[1003] Oh, my God, that's so great.

[1004] You're like, you know, the guy's like using it to charge his laptop to do his spreadsheet.

[1005] You're like, I'm so sorry, can I take this power?

[1006] I want to take a nap.

[1007] All the lights go out.

[1008] Trip the brake.

[1009] But we spent two weeks together in the motorhome And I didn't hear him at all But you didn't hear him that night So I have no trust in your ability to know the sound I had the machine in the motorhome You did, yeah, yeah, yeah It was like a little church mouse with the other mice In fact, the mice were louder than Aaron That's when I heard him is in the middle of the night That is wild because you're right I can sleep through it for the most part I just have been 30, 30 years of sleeping in the same room with them.

[1010] And it's crazy, but I got there.

[1011] The fact that I do have hearing good enough that I heard mice in the middle of the night.

[1012] It tells me my hearing is good while I'm asleep.

[1013] Unless the mouse was ripe by your ear.

[1014] No, it was like, I think I told you this.

[1015] I thought Aaron was up eating chips.

[1016] Right.

[1017] I was like, God damn.

[1018] He's gotten into the ruffles.

[1019] The mouse was eating the chips next to me. Not even close to Dex, no. But you heard the bag crinkled.

[1020] I heard the bag being opened and crunchy crunch and I thought Aaron's tearing into those ruffles in the middle of the night.

[1021] We're going to have to talk about that in the morning.

[1022] Hungry, hungry.

[1023] So hungry.

[1024] Did you see how delicately Aaron was handling those mice on Instagram when we caught them?

[1025] I thought it was so nice.

[1026] He had a tender side of him.

[1027] It's so sweet.

[1028] All right.

[1029] Oh, I know an update that I have to give.

[1030] Okay.

[1031] Because Monday's episode, we came out that I had been in a motorcycle race and I was just had the singular goal of not finishing last.

[1032] Yep.

[1033] And I achieved that goal.

[1034] Yes.

[1035] Yes.

[1036] And I just, I guess that's an update that's worth saying.

[1037] And did you have fun?

[1038] That was the mail.

[1039] I had a blast.

[1040] I was telling Aaron about it today when we were working out.

[1041] Got down there and I missed the first practice.

[1042] Anyways, we had two like heats.

[1043] and you got time to see if you'd make it to the main race.

[1044] And we kept making it through our heats.

[1045] The race was supposed to start at 140.

[1046] They had been running late all day.

[1047] So we got down to the track from the pits, which is a bit of a ride.

[1048] So I had Kristen and Delta on my motorcycle.

[1049] DeCastro had Lincoln on his motorcycle.

[1050] We ride to the track.

[1051] We're putting them over the fence so they can watch.

[1052] It's 1 .30.

[1053] We're 10 minutes early.

[1054] And we look, our race is happening.

[1055] Oh, God.

[1056] It's happening.

[1057] There's like 10 different classes, and our class is racing.

[1058] And I have this moment where I'm like, no, we've driven all the way to Huntington Beach.

[1059] Now my family's here to watch, and there's the race.

[1060] I'm not in it.

[1061] That's it.

[1062] So I, in a moment of panic, I just enter the track mid -race.

[1063] and then by the blessings of Thor and Valar of Ovala, there was a bad enough crash right as I entered that they had to do a total restart of the race.

[1064] So then DeCastro followed me out.

[1065] We got on the line, everyone else had already had a lap, restarted the race, and we made it in time for the race.

[1066] It was assholes and elbows.

[1067] People were crashing, left and right, and there were 17 of us, and we finished 6 and 7.

[1068] The 7th, DeCastro beat me. Great.

[1069] Sounds perfect.

[1070] Sounds like a perfect, grace.

[1071] I did see a little video.

[1072] Yeah.

[1073] Kristen made fun of it pretty good.

[1074] She already tell you about it.

[1075] She showed me the video.

[1076] Oh, yeah, yeah.

[1077] The video's cute, good.

[1078] It just was fat.

[1079] It was over fast.

[1080] Well, she also missed a lot.

[1081] So two things.

[1082] She's right, and there's a lot of stuff missing from that video.

[1083] She doesn't have my passes.

[1084] I got two guys on.

[1085] one turn.

[1086] It was so exciting.

[1087] Oh, yeah.

[1088] No, no. I think she was more laughing at that it was very quick.

[1089] Yes, it was only six laps.

[1090] Right.

[1091] Yes, on a short track.

[1092] So I was telling her this.

[1093] Let's get to the meat of this.

[1094] Because I was very quick to admit it to Aaron, so I should admit it to everyone.

[1095] This really parallels an experience.

[1096] Oh, that's a ding, ding ding, ding Brie.

[1097] You met Bree.

[1098] Oh, we have to talk about that.

[1099] Yes.

[1100] Okay.

[1101] So one time after Brie hearing all these fight stories all these years we were at a bar in santa monica del's it was new year's eve these two gang bangers came in and picked literally picked a fight with three dudes who all backed down then they pushed scottie at one point next thing you know scotty and i aren't a fight with these two guys the fight again probably last 45 seconds you know in my mind it was a six -minute ordeal it was probably 45 seconds and you take that 45 seconds if you're a boy and then you talk about it for nine hours.

[1102] Nine years.

[1103] Years, yeah.

[1104] You're right, even better.

[1105] Talking about it today.

[1106] Yep.

[1107] 20 years ago.

[1108] So we're at Scotty's house after the whole event and we're by the campfire and now where everyone's talking about.

[1109] Dean was there, buddy from Detroit.

[1110] Everyone just re -every element of this scuffle is being retold.

[1111] And Reed just ran, maybe because she was drunk, she just hit me with the truth.

[1112] She's like, I don't know.

[1113] I thought it'd look cooler.

[1114] Wait, she saw a video?

[1115] No, she was there.

[1116] She was watching me fight this guy.

[1117] Oh, I see.

[1118] And she's like, you know, your arms are so long and he was far.

[1119] I just thought it would look cooler.

[1120] Like maybe I don't know, like a movie or something.

[1121] But it was so deflating.

[1122] And I just all of a sudden I could maybe see it from her point of view.

[1123] And I'm like, I bet it didn't look that cool.

[1124] Like in my mind, it looked like Rocky.

[1125] Yes.

[1126] But she was like, yeah, I just didn't look that cool.

[1127] It's really funny.

[1128] It was a reality -shattering.

[1129] To let Kristen off the, she was not saying it wasn't cool.

[1130] No, no, I know.

[1131] But so the race finishes and we're back in the pits, and it, mind you, now I have some self -awareness.

[1132] So we get back to the pits and I notice Steve and I are on minute seven of rehashing the race because this guy crashed in front of him, then two guys crashed in front of me, then I almost said, you know, and I pass those two guys, and I was in, and I look at Kristen and I said this is the debrief this is the five second fight that you talk about for hours right she goes no it was a great great 30 second race she said all that happened huh wow lot to talk about it was a 30 second race I was just like oh my it was so demoralizing that's for you guys you did it in the video The whole video...

[1133] Let it rip.

[1134] No. No, I was like, oh, cool.

[1135] But it was like, it was...

[1136] But she was stopping filming between laps for some reason.

[1137] Right, sure.

[1138] Well, probably for...

[1139] To conserve.

[1140] Because it wasn't worth the footage.

[1141] Well, she stopped between laps...

[1142] No, she got you doing your laps.

[1143] A few.

[1144] Okay, okay, a few.

[1145] She didn't get them all, and she missed the pass.

[1146] Okay, okay, okay.

[1147] And then, but...

[1148] Some of the more spectacular crashes.

[1149] Okay, I believe that that happened.

[1150] And then, but in the video, Delta, you just see her turn around to the camera, she's like, where's dad?

[1151] And like, you had just like.

[1152] I wish they hadn't come as soon as they were in position.

[1153] I was like, this isn't worth them having come down for this.

[1154] I regretted it.

[1155] And then she hit me with it was 30 seconds.

[1156] Well, I guess, you know what I don't like about this?

[1157] Last fact check, I was like, I wish I was invited.

[1158] to this like you should have invited me I want to be invited and now you're definitely not going to invite me to anything well I told you this is exactly why I don't want anyone to see anything I do so yeah it had been better for me that just no one saw it and it could have been my own experience and no one was reminding me it was 30 seconds and it would have been but you knew it was gonna be fat like it's not like you were like oh fuck I had no idea what it was Monica I got there and was like what are we doing tell her about the guy who was ex -champion that raced in yours okay yes yes so Robbie Maddow he's the Jordan of cool motorcycle stuff he's the one who wrote his motorcycle on the ocean he wrote it at the Olympic park and jumped the down ski he makes these incredible Red Bull videos they're insane he's a legend he was in the class before us one of the best motorcycle riders in the world it's the practice and he goes into turn one some guy comes flying into him and smash it to his hand and when he came back into the pits his fucking finger was almost torn up he goes this is the worst injury I've gotten right to motorcycle in a decade.

[1159] It was this stupid flat track race that's 30 seconds long.

[1160] Oh, my God.

[1161] I'm glad you made it.

[1162] I was just delighted I didn't go down.

[1163] Half the people in this race crashed.

[1164] Ew.

[1165] Yeah.

[1166] I will say this.

[1167] I wanted a hundred more laps.

[1168] Like, I was just finding my rhythm on lap six.

[1169] I was like, get in the field of track and I had passed a couple guys and I'm like, you give me a hundred more laps.

[1170] I'm going to be up there.

[1171] I'm going to at least get to Castro.

[1172] Didn't get those laps.

[1173] You didn't have enough time.

[1174] Just didn't have enough time to settle in.

[1175] You only had 30 seconds.

[1176] That's crazy.

[1177] Okay.

[1178] Now, Bree.

[1179] Bree.

[1180] Yes, I met Bree.

[1181] What?

[1182] Yes.

[1183] Never had met her.

[1184] I get a text from Bree yesterday saying, I'm at Houston's and I see Monica.

[1185] Oh.

[1186] Yeah, and then Dax texts to me. Bree's going to come say hi.

[1187] And I said, what are you talking about?

[1188] I'm at Houston's.

[1189] You're assuming I don't even know where you're at.

[1190] Yeah.

[1191] But I know everything.

[1192] Yeah, you knew.

[1193] You have eyes everywhere.

[1194] That's right.

[1195] Don't ever think you can double cross me because I know what's going on.

[1196] But no, she was at Houston's.

[1197] I was at Houston's and she came and said hi.

[1198] I know, introduced herself.

[1199] She was so sweet.

[1200] I was so nervous to meet her.

[1201] Wow.

[1202] And she was nervous to meet you, which is adorable.

[1203] Does Bree live in L .A.?

[1204] She lives in Pasadena.

[1205] She does.

[1206] Right by that Houston's.

[1207] You know, I put olive oil in my coffee.

[1208] I'm always trying to get people to try it.

[1209] and I just had a huge sip of my very sharp olive oil and now I don't know what happened And now you're crying Now I'm fucked up Okay so she came up to the table Take it to earn up real water Oh boy Okay I'm back You're back that was scary for me Okay were you eating by yourself Okay I was eating by yourself I go to sometimes I go to see Jess on Sundays Sunday is tomato soup and grilled cheese day at Houston's very limited edition, very special day.

[1210] So I'll go and sit in just a section by myself.

[1211] And so that is what I was doing.

[1212] But I was really nervous and I was like, I didn't dress, right?

[1213] You know, I didn't dress appropriately.

[1214] Did you get insecure that you were by yourself?

[1215] I did a little bit after, but I didn't have time.

[1216] You know, it was all happening so fast.

[1217] Yeah, you got a text and all this is she was right at the table.

[1218] Oh, my God.

[1219] And she looked so cute.

[1220] She was dressed for an appearance.

[1221] For a meat cute?

[1222] Yeah.

[1223] And we hugged and then.

[1224] Oh, you started right with a hug.

[1225] Yeah.

[1226] Was that too strong?

[1227] I love that.

[1228] That's what I would want for both of you because I like you guys so much.

[1229] I mean, I feel like I know her so well, which is crazy.

[1230] And she probably knows you much better than you would imagine.

[1231] I assume she feels somewhat similar to that.

[1232] But anyway, I felt like I was meeting a movie star.

[1233] And she did too She said those exact words Talked for a second And then she just like You're doing great You know Dax No I said Oh Dax just told me you were gonna come by And she said oh good And then I think I said All right then I do you want to go on a men's A campy trip in 10 months No I think I said Oh do you live in the neighborhood And she said yes She said where do you live And I answered but she didn't hear me. I hate when that happens and I had to repeat it.

[1234] And then we talked about Houston's and then she said...

[1235] Yeah, she said, yeah, I love it here and I love Jess and talked a little bit more about the experience and then she was like have a good meal or whatever and she started walking off and then her and Jess saw each other and hug hug hug hug, hug, chat, chat, chat.

[1236] And then, but then I did get a little nervous because Jess was like...

[1237] I liked her more.

[1238] Probably, I'm sure.

[1239] I'm sure he does.

[1240] No, he was clearing the table next to mine and he was going to try to get very quickly.

[1241] Oh, he wanted to help her.

[1242] She wasn't already seated.

[1243] Oh, okay, that's a totally different dynamic than she was mid -meal and came over to say hi.

[1244] I think she was waiting.

[1245] She was waiting for a seat.

[1246] I would have not wanted to sit next to her.

[1247] Well, right.

[1248] So then Jess was starting to clean it and he was like, is it weird?

[1249] I said no. I was like, no, get her, seat her.

[1250] But then as soon as I saw that, I was like, no, I don't want that.

[1251] You know you have to keep, like, making eye contact and smiling and waving, but not joining each other.

[1252] And then I really felt by myself.

[1253] Yeah.

[1254] Because I was like, oh, fuck, I'm sitting by myself.

[1255] And if she sits next to me, then it's, because if I have a friend, I can just talk to my friend.

[1256] That's right.

[1257] But I didn't have a friend.

[1258] No, it could have been really awkward.

[1259] But it also would have been fine.

[1260] It would have been fine, but it would have been nerve.

[1261] I would have, that would, I, yeah, I mean.

[1262] oh my god yes i love that yes oh he speaks so high of you okay great enjoy your meal and then i see them for the next hour one foot away from me oh my god you'd have to well then i'd say well don't ever look up at that table because you don't want to make eye contact i would just be on my phone and then i'd be insecure the whole time like they're thinking what is he looking at if they glanced over i'm just staring at my plate i guess no no phone this is why we have phones now you can always be looking at your phone.

[1263] Anywho, that didn't work out.

[1264] She sat somewhere else.

[1265] Okay.

[1266] By the grace of God.

[1267] No, it was really nice to meet her.

[1268] And then on the way out, she came and they said goodbye, and I met her husband and her children.

[1269] Oh, good.

[1270] She was there with the whole gang.

[1271] Yeah, it was really cute.

[1272] Do you see her little girl, Mazzy?

[1273] I saw the girl and the boy.

[1274] Yeah, yeah, yeah.

[1275] They were really cute.

[1276] I like the little girl because she's got the same ears that stick out like Brie.

[1277] I didn't notice that.

[1278] Yeah.

[1279] So then you text me, my god she's so pretty and i felt like she was a celebrity and then so i immediately sent that to brie i knew it i knew it would make her feel really happy because i want her to feel happy and she wrote back oh my god i just said the identical thing to jess and she was nervous that she was meeting a celebrity i thought this was so sweet on both ends anyhow it was really nice to meet her i should have told her that she was built like a brick shit house.

[1280] How about this?

[1281] Even better compliment than built like a brick shit house is the time she had all the right stuff.

[1282] All the right shit.

[1283] Shit.

[1284] You remember that story here?

[1285] She and I were two being on the San Marcos River in Austin.

[1286] Oh, I do.

[1287] Yeah, yeah, yeah.

[1288] And this awesome hillbilly came out.

[1289] He's like coming off the bridge his cigarette out of his mouth, cut off jean shorts.

[1290] And he saw that I was with her.

[1291] So it's not like he was hitting on her.

[1292] And he just goes, damn, girl, you got all the right shit.

[1293] She said, I like that.

[1294] I felt like I had time traveled or something.

[1295] Yes.

[1296] Because I met this person from your life.

[1297] You know so much about her.

[1298] So I know so much about her from you.

[1299] And she's a real person in this world who goes to Houston.

[1300] Yeah.

[1301] When you sent the text that she was going to come say hi, I was like, but that's Beyonce.

[1302] Like, Beyonce isn't real.

[1303] Right.

[1304] Right, right, right.

[1305] She's just like a person people talk about.

[1306] She's not real.

[1307] Then also I was like sad.

[1308] Yeah.

[1309] That we didn't make it.

[1310] Well, kind of.

[1311] Like, it made me sad, but, like, you can have this intense, very deep, meaningful relationship with a person.

[1312] And then now they're at dinner with their husband and two children.

[1313] And it's just, like, life is sad, kind of.

[1314] I don't know.

[1315] It's also beautiful.

[1316] Yeah.

[1317] Like, she and I had some life together in Santa Monica.

[1318] Yeah, I know.

[1319] And now she has this beautiful life with Brad and her beautiful kids.

[1320] This is fun for the listener I don't know if we've ever said this Oh you should say this This is incredible At some point we hang out with Brie and I don't know how this all becomes unveiled But the point is is Kristen had met Brie like I think one time that Kristen came over We first started dating My mom was in town So Brie was visiting to hang with my mom Yeah And she came over and we all like ate dinner together And then Brie left and she was like Not conventional To have dinner with your ex girl's friend on like an eighth date, you know?

[1321] And I was like, I guess, yeah, but now she's just a good friend of mine, blah, blah, blah.

[1322] Yeah.

[1323] Anyways, her husband, Brad, who I've talked about, he's a genius, Brad Winterbrom.

[1324] He is a motherfucker at Marvel.

[1325] He's a creative genius.

[1326] He seemed cool.

[1327] He's super cool.

[1328] I love Brad.

[1329] Kristen went on a fucking date with Brad in New York City when she went to NYU.

[1330] Like, she was like, wait, Bree's new boyfriend is who?

[1331] Oh, Brad, Winterbaum.

[1332] Oh, my God, I know.

[1333] I went on a date with, I was like, what are the odds of this?

[1334] So crazy.

[1335] No way.

[1336] They also said it immediately also then.

[1337] So they like that.

[1338] Oh, yeah.

[1339] What could be more fun.

[1340] Yeah.

[1341] It is really fun.

[1342] Unfortunately, they didn't bang.

[1343] That would be much better for them.

[1344] It would be more tit for tat.

[1345] Right.

[1346] Everyone's banged everyone.

[1347] Yeah.

[1348] Everyone here is fucked.

[1349] So let's just get on with it.

[1350] I like when I realize that in a room.

[1351] In our friendship group, though, was just a given.

[1352] I don't think anyone had not slept with anyone in our core group.

[1353] You're right.

[1354] It is beautiful.

[1355] But it's sad and beautiful.

[1356] I guess that's what life is all about.

[1357] Bittersweet.

[1358] But what's beautiful and neat about it is, in so many ways, life is short, but also life's long.

[1359] You can have a lot of lives.

[1360] And you can have, like, beautiful chapters in your life.

[1361] And because the end don't mean they weren't worth your time or beautiful or memorable and meaningful.

[1362] And yet there's other chapters.

[1363] Yeah, exactly.

[1364] Well, said.

[1365] Do you ever think that, Aaron?

[1366] I do.

[1367] I don't want to put you in a position, but I know this just happened.

[1368] Like, Aaron was just at his kid's soccer game, and he's with his ex -wife, and it's just harmony, right?

[1369] It's just like, you're looking at this beautiful boy you guys created.

[1370] Yeah.

[1371] He's such a sweetie pie, and he's huge and gorgeous, and he's an athlete, and they're sitting there in harmony, right?

[1372] Yeah, and it's taken a while to think like that.

[1373] that but I definitely do and I think there's chapters that are definitely worth it I think if people can be grown up about it it feels dishonorable to pretend that's the thing for me is like how could you have spent a decade with Adrian and pretend you didn't but Aaron and I have this in common you're friends with all of your exes yeah even the shorter relationships I know that you and I had a lot of when we're younger that we continue to be friends yeah yeah that's nice Anyway, okay, well, that was really a fun Sunday for me to get to meet a celebrity.

[1374] I met a celebrity yesterday.

[1375] So I met a lot of your ex -girlfriends.

[1376] So there's one left that you are refusing to.

[1377] Well, there's more than one left.

[1378] There's one left that I care about.

[1379] Yeah, yeah.

[1380] I'd like to meet Carrie.

[1381] Oh, you'd love Carrie.

[1382] Yeah.

[1383] She's wild.

[1384] Yeah.

[1385] And Trici.

[1386] You want to meet Tricia?

[1387] Oh, sure.

[1388] Yeah.

[1389] Let's bring Trishy into the mess.

[1390] Did you see the picture I posted of Gary and Tracy?

[1391] I did.

[1392] It's so cute.

[1393] Oh, my God.

[1394] Well, part of it for me is, you know, because I'm just like jealous a lot.

[1395] Yeah, yeah, yeah, yeah.

[1396] Of everything.

[1397] You know, sometimes I have this with people in my life where I'm like, it's a little uncomfortable that somebody knew you when I didn't know you.

[1398] Uh -huh.

[1399] I have this with a lot of people.

[1400] Right.

[1401] And of course, that's just how life was.

[1402] goes.

[1403] It's normal.

[1404] But it's weird.

[1405] It's weird when you think you know someone so well.

[1406] And then you realize, oh my God, they had a huge whole life.

[1407] I mean, I met you and you were, and you're older than me. I had to say that.

[1408] But really?

[1409] Like, yeah, when I was, I was already 40.

[1410] No, you were, were 49.

[1411] You were on the verge.

[1412] You were on the verge.

[1413] You were on the verge.

[1414] Delta was born when I was one week before my 40th birthday, I guess.

[1415] Yeah.

[1416] And I was doing so.

[1417] Light City, or like it in a little bit.

[1418] Anyway.

[1419] Yeah, still older than me though.

[1420] So a whole life.

[1421] Yeah.

[1422] I get that.

[1423] I was thinking about this a lot the other day in reference to something else we've been chatting about it.

[1424] I guess like the thing I occurred to me that just I think fundamentally you and I have a different perspective on is you have kind of a zero -sum view of things.

[1425] And I kind of have an infinite view of things.

[1426] So it's like if someone's attention goes to someone else, That's attention you're not getting or focus you're not getting or love.

[1427] Sometimes that's real, especially with attention.

[1428] Love, I think you're right, is more amorphous, but.

[1429] Yeah.

[1430] I mean, if it was really like, if you could say it was black and white, like, I want plans with you on Thursday.

[1431] No, I'm picking to go out with Joe.

[1432] Sorry, Rob.

[1433] Did that trigger you about the David thing?

[1434] Well.

[1435] We have some internal caution.

[1436] conflict, Aaron.

[1437] Is that what's going on?

[1438] Rob wasn't invited to one thing.

[1439] It turns out everyone wants Ferrier's attention.

[1440] God bless him.

[1441] I know.

[1442] I just started wanting it.

[1443] We've never met in person, but I'm a...

[1444] I think about him often.

[1445] Get in line, Aaron.

[1446] It's a long -ass line.

[1447] So I guess if I had that experience where it's like I wanted to hang with someone and I couldn't because that person chose to hang with someone else, I could understand that.

[1448] Yeah.

[1449] That just hasn't been in practice my experience in life.

[1450] I also think, like, my formative friendships, like, Aaron and I were best friends with Jack.

[1451] Like, all three of us were best friends.

[1452] It never occurred to me, like, if Aaron was spending the night at Jacks and I wasn't, it just started out as a sharing best friendship.

[1453] Aaron and Aaron and I were best friends, and Aaron and Aaron and Dean and I were, you know.

[1454] Yeah.

[1455] Yeah, we have a lot of.

[1456] Yeah, there's always, like, you and I and some other folks.

[1457] Right, but you probably feel safe because there's always you two and then there's a third coming in and out at all times.

[1458] This sounds like I'll be pat myself on the back because a lot of these friends I introduced Aaron to.

[1459] So like I introduced Aaron to my friend Kurt.

[1460] He and Kurt moved to fucking Georgia together.

[1461] Like I didn't live with Aaron.

[1462] He didn't come to live in California with me. Yeah.

[1463] But I genuinely was like, I'm so glad Aaron's having fun with Kurt.

[1464] And he's not alone.

[1465] Like I just was like, Well, Aaron and I have a, we have a cellular love for each other and I'm not worried.

[1466] Have you ever been jealous of any of my friends?

[1467] I was just trying to, I think I'd be lying if I said I wasn't, not when we were young, but later in life, yeah, I think maybe once in a while when I'd come out here, I knew you had been having so much fun with like Nate Tuck and I was in a funk in my life.

[1468] And I think, yeah, I think those were maybe sometimes I felt.

[1469] a little jealousy.

[1470] Yeah.

[1471] That makes sense.

[1472] It makes sense.

[1473] Especially if you're observing me have something with someone that's similar to what you and I have when we're in business.

[1474] Yeah.

[1475] Right.

[1476] And I'd say Nate is the person that I was most in business with.

[1477] Nate and Scotty were the only two people that I ever felt like that in business with.

[1478] Yeah.

[1479] And I am 100 % I'm bored with Nate and Scotty.

[1480] And you being in a business with them.

[1481] No, but it's human.

[1482] I guess that's what, like, because sometimes I think I like that you're saying that, Aaron.

[1483] One, it's very vulnerable.

[1484] And two, I think it's more common to be on this side of those feelings than on your side of that.

[1485] I mean, yours is very commendable.

[1486] But you really are working against some.

[1487] Some natural, primitive, primal humans.

[1488] Security stuff.

[1489] I'm not complimenting myself.

[1490] I'm not working at this.

[1491] I just happen to be wired in this way.

[1492] I know.

[1493] I'm happy when you guys are on your road trips.

[1494] You are.

[1495] Yeah.

[1496] But sometimes I want to join for a little bit.

[1497] Sure.

[1498] Until the snoring starts.

[1499] For like a day.

[1500] Yeah.

[1501] So the machine breaks.

[1502] Yeah, exactly.

[1503] Just for like a day.

[1504] Okay.

[1505] We didn't do any facts.

[1506] But there aren't that many because he knows stuff.

[1507] Is beyond reproach?

[1508] Exactly.

[1509] The only thing I will correct is, so you reference the George Mambiot episode.

[1510] and you said that there's 20 ,000 kinds of fungi phyla.

[1511] Right.

[1512] I went back and listened.

[1513] Hard to find the exact moment.

[1514] God bless you.

[1515] I did it.

[1516] That was laborious, I'm sure.

[1517] It kind of was.

[1518] Yeah.

[1519] But I found it.

[1520] I found it.

[1521] 1 ,000 phyla major groups of bacteria in the world.

[1522] Okay.

[1523] And then all human gut are in four phyla.

[1524] And those are the same four phyla that are in the rhizosphere of the soil.

[1525] Yeah.

[1526] So 1 ,000 versus 20.

[1527] Not bad, 20x error.

[1528] Yeah, not that.

[1529] Not bad.

[1530] And then I guess I just thought it was interesting.

[1531] I didn't realize how rare spleen cancer, like how rarely it metastasizes in the spleen.

[1532] Very interesting, right?

[1533] I didn't know that.

[1534] I didn't know that.

[1535] All the secrets must lie within the spleen.

[1536] Do you know this, Aaron?

[1537] The spleen and the liver are identical in shape, yet the liver gets cancer all the time.

[1538] and the spleen won't get it virtually.

[1539] Almost never gets like metast.

[1540] Yeah.

[1541] E is traveling all through the body.

[1542] The spleen is like, no, you can't stop here.

[1543] Well, it can happen, but it's so rare.

[1544] So it's 2 % of all lymphomas.

[1545] But comparatively, it's very hard to metastasize in there.

[1546] They don't know why.

[1547] It's a very encouraging thing to know.

[1548] I think so.

[1549] Yeah, because you think if you could recreate the microbiome or whatever, the microcosm, the microcosm, The cell.

[1550] Whatever's happening in that spleen if you could recreate it in other organs it'd be nearly impervious to cancer.

[1551] I know.

[1552] Or can you just pull the cancerous cells out of everywhere else in your body and put it into your...

[1553] To get it munched up.

[1554] Ew.

[1555] Like a garbage disposal.

[1556] Munched up.

[1557] Yeah, that would also be good if it detected any abnormalities to scent.

[1558] I mean, that's what the immune system's supposed to do and then it just gets thwarted.

[1559] It gets thwarted.

[1560] It's a great word.

[1561] All right.

[1562] That was the only thing.

[1563] things well there was one more but it started like two more but well one was that you said that psychedelics and ecstasy are prevalent in carola but were you just saying that i was not saying that okay i had a friend who relapsed and it was on a spiritual sojourn to carola oh and they told me well you know everything is available there everywhere and it's all very high grade just in carola really yes and that it's very because it's a big meditation retreat area, I think.

[1564] It's a pocket of like where people go to take retreats, I think.

[1565] This person was like it started with, you know, kind of a TM -ish trip.

[1566] And then it was, oh, this is all available.

[1567] Oh, psilocybin, that seems medicinal and great.

[1568] And then it was everything.

[1569] Yeah, of course.

[1570] And he came home and was drinking again.

[1571] Sure.

[1572] Yeah, yeah, yeah, yeah.

[1573] Sucks.

[1574] But according to him, there's one human's account of what he found.

[1575] Yeah.

[1576] I don't know.

[1577] I'd certainly like to go find out.

[1578] You can double check, cross those teams and dot those eyes.

[1579] Yeah.

[1580] Ask some people.

[1581] For science.

[1582] I can't get ecstasy from you, right?

[1583] This isn't prevalent here, is it?

[1584] You don't have Molly, do you?

[1585] You're not allowed.

[1586] I'm going to tell them.

[1587] Those are my people.

[1588] See, if you see a big honky.

[1589] Don't you dare.

[1590] Too many tattoos.

[1591] You'll see them.

[1592] Oh, you'll see them.

[1593] He'll be bragging about a 30 -second race.

[1594] He just finished.

[1595] seventh in he'll talk to you for an hour seventh is good seventh is good yeah listen it's way above what I was expecting yeah it's great all right I love you I love Aaron yeah guys order a cameo from Aaron as you heard he'll be fucked up over he doesn't send you a good one he cares so much that he thinks about it days after that says a lot it really does I'm glad you feel that way about it to be honest I'm glad that you're glad because I was embarrassed to say it really sweet Anything you do, you should fucking care about doing it or don't do it.

[1596] I agree.

[1597] I agree.

[1598] All right.

[1599] All right.

[1600] Love you guys.

[1601] Love you.

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