#123 – Manolis Kellis: Origin of Life, Humans, Ideas, Suffering, and Happiness
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The following is a conversation with Manolis Kellis, his second time on the podcast. He's a professor at MIT and head of the MIT Computational Biology Group. He's one of the most brilliant, productive, and kind people I've had the fortune of talking to. A lot of my colleagues at MIT and former MIT faculty and students wrote to me after our first conversation with some version of, Manolis is awesome, isn't he? I'm glad you guys are now friends. I am too.

and I'm happy that he makes time in his insanely busy schedule to sit down and have a chat with me. Quick summary of the sponsors, Public Goods, Magic Spoon, and ExpressVPN. Please check out these sponsors in the description to get a discount and to support this podcast. As a side note, let me say that I just got back from talking to Joe Rogan on his podcast, my fifth time on there. I also got a chance to record a separate conversation with Joe on this podcast.

We talked on both quite a bit about his journey and his advice for mine. One of the things that I think made his show special is that he just had fun and made choices that didn't get in the way of him having fun and loving life. I'm learning to do just that. It's tough since I'm naturally full of self-doubt and anxiety, but I'm learning to let go and have fun, even if my monotone robotic voice sometimes sounds otherwise.

For Joe, that involved talking to his friends, comedians, especially ones that brought out the best in him. Duncan Trussell and the five-hour first episode on Spotify comes to mind as an example of that. Duncan has been a guest probably close to, if not more than 50 times on Joe's podcast. My hope with amazing people like Manolis is to find my Duncan Trussell, my Joey Diaz, and yes, even my Eddie Bravo.

Obviously, Joe and I are very different people, but ultimately both love life when we can interact often with people we love and who inspire us, make us smile, make us think, and make us have fun when we get behind the mic of a podcast, whether anyone is listening or not.

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So secure your online activity by going to expressvpn.com slash relaxpod to get an extra three months free and to support this podcast. And now here's my conversation with Manolis Kallis. What is beautiful about the human epigenome?

Don't get me started. So first of all, as an engineering feat, the human epigenome manages the most compact, the most incredible compaction you could imagine. So every single one of your cells contains two meters worth of DNA. And this is compacted in a radius which is one thousandth of a millimeter. That's six orders of magnitude.

To give you a sense of scale, it's as if a string as tall as the Burj Al Khalifa, which is about a kilometer tall, was compacted into a tiny little ball the size of a millimeter. And if you put it all together, if you stretch the trillions of cells that we have, we have about 30 trillion cells in your body. If you stretch the DNA, the two meters worth of DNA in every one of your trillion cells, you would basically reach all the way to Jupiter a hundred times.

Yeah, it's all curled up in there. It's 30 trillion cells. 30 trillion cells. In a human body. Every one of them, two meters worth of DNA. So all of that is compacted through the epigenome. The epigenome basically has the ability to compact this massive amount of DNA from here to Jupiter 10 times into one human body, into just the nuclei of one human body. And the vast majority of the human body is not even these nuclei.

And that's sort of the structural part. So that's the boring part. That's the structural part. The functional part is way more interesting. So functionally, what the human epigenome allows you to do

It's basically control the activity patterns of thousands of genes. So 20,000 genes in your human body, every one of your cells only needs a few thousand of those, but a different few thousand of those. And the way that your cells remember what their identity is, is basically driven by the epigenome.

So the epigenome is both structural in sort of making this dramatic compaction, and it's also functional in being able to actually control the activity patterns of all your cells. Now, can we draw a definition distinction between the genome and the epigenome? Again, being Greek, epi means on top of. So the genome is the DNA and the epigenome is anything on top of the DNA.

And there's, you know, three types of things on top of the DNA. The first is chemical modifications on the DNA itself. So we like to think of four bases of the DNA, A, C, G, T. C has a methyl form, which is sometimes referred to as the fifth base. So methyl C takes a different meaning.

So in the same way that you have annotations in an orchestra score that basically say whether you should play something softly or loudly or space it out or, you know, interpret basically the score, the human epigenome allows you to modify that primary score. So a modified C basically says, play this one softly. It's basically a sign of repression in a gene regulatory region.

I love how you're talking about the function that emerges from the epigenome as a musical score. It is in many ways. And every single cell plays a different part of that score. It's like having all of human knowledge in 23 volumes, like 23 giant books, which are your chromosomes.

And every single cell has a different profession, a different role. Some cells play the piano and they're looking at chapter seven from chromosome 23 and chapter four from chromosome two and so on and so forth. And each of those pieces are all encoding in the same DNA. But what the epigenome allows you to do is effectively...

conduct the orchestra and sort of coordinate the pieces so that every instrument plays only the things that it needs to play. One thing that kind of blows my mind, maybe you can tell me your thoughts about it, is the way evolution works with natural selection is based on the final sort of the entirety of the orchestra musical performance, right? But there's these

incredibly rich structural things, like each one of them doing their own little job that somehow worked together. Like the evolution selects based on the final result and yet all the individual pieces are doing like infinitely minuscule specific things

How the heck does that work? It's a very good insight. And you can even go beyond that and basically say evolution doesn't select at the level of an organism. It actually selects at the level of whole environments, whole ecosystems. So let me break this down. So you basically have at the very bottom, every single nucleotide being selected.

But then that nucleotides function is selected at the level of, you know, each gene and every, not even each gene, each gene regulatory control element. And then those control elements are basically converging onto the function of the gene. And many genes are converging onto the function of one cell. And many cells are converging onto the function of one tissue or organ. And all of these organs are converging onto the level of nucleotides.

an organism. But now that organism is not in isolation. So if you basically think about why is altruism, for example, a thing, why are people being nice to each other? It was probably selected. And it was probably selected because those species that were just nasty to each other didn't survive as a species. And now if you think about symbiosis of

you know, there's plants, for example, that love CO2, and there's humans that love O2. And we're sort of, you know, trading different types of gases to each other. If you look at ecosystems where one organism was just really nasty, that organism actually died because everyone they were being nasty to was killed off. And then that kind of, you know,

of life is gone. So basically what emerges is selection at so many different layers of benefit, including all of these nucleotides within a body interacting for the emergent functions at the body level. - Yeah, I wonder if it's possible to break it down into levels that's selection even beyond humans, like you said environment, but there's environments that are all different levels too, right?

at the minuscule, at the organ level, at the tissue level, like you said, maybe at the microscopic level. It'd be fascinating if like there's a kind of selection going on at like both the quantum level and like the galaxy level. - Yeah, yeah, yeah. - Right? Of all different forms. - Yeah, let's again sort of break down these different layers. So basically if you think about the environment in which a gene operates,

That gene, of course, the first definition of environment that we think of is pollution or sunlight or heat or cold and so on and so forth. That's the external environment. But every gene also operates at the level of the internal cellular environment that it's in. If I take a gene from, say, an African individual and I put it in a European context, will it perform the same way? Probably not, because there's a cellular context of thousands of other genes that that gene has co-evolved with

you know, in the out of Africa event and, you know, all of this sort of human history of evolution. So basically, if you look at Neanderthal genes, for example, which again happened long after that out of Africa event, there's incompatibilities between Neanderthal genes and modern human genes.

that can lead to diseases. So in the context of the Neanderthal genome, that gene version, that allele was fine. But in the context of the modern human genome, that Neanderthal gene version is actually detrimental. So it's, you know, that cellular environment constitutes the genetics of that gene, but also, of course, all of the epigenomics of that gene. It's fascinating that the gene has a history. I mean, we talked about this a little bit last time, but

And then some of your research goes into that, but the genes as they are today have a story from the beginning of time. And then sometimes their story was like their path was useful for survival for the particular organisms and sometimes not.

That's fascinating. Let me ask a tangent. We kind of started talking offline about Neanderthals. Do you have something interesting genetically, biologically, in terms of difference between Neanderthal and the different branches of human evolution that you find fascinating? Neanderthals are only one of about five branches that we are pretty confident about. One branch of out-of-Africa events.

So basically there's Neanderthals, there's Denisovans. What is the evidence for Denisovans? One tiny little fragment of one pinky from one cave.

- Relatively recently discovered, right? - Less than 10 years ago. - Yeah. And those are like little folks, right? - No, no, no, no, no. That's yet another one, though. Homo florensis. It had the little folks in sort of Indonesia. But then the nissevans are basically another branch that we only know about genetically from that one bone. And eventually we realized that it's one of the three major branches along with Neanderthal, modern human, and the nissevan.

And then that one branch has now resurfaced in many different areas. And we kind of know about the gene flow that happened in between them. So when I was reading my Greek mythology, it was talking about the age of the heroes. These eras of human-like precursors that were wiped out by Zeus or by all kinds of wars and so on and so forth, like the Titans and the, you know, it's ridiculous to sort of read these stories as a kid because you're like, oh yeah, whatever, right?

And then you're growing up and you're like, whoa, layers and layers of human-like ancestors. And who knows if those stories were inspired by bones that they found that kind of looked human-like but were not quite human-like. Who knows if stories of dragons were inspired by bones of dinosaurs. Basically, this archaeological evidence has been there and has probably entered the folk imagination today.

into those stories, but it's not that far, you know, removed from what actually happened of massive wars of wiping out Neanderthals as humans are, modern humans are populating, you know, Europe. Do you think, do you think what killed the Neanderthals and all those other branches is human conflict or is it genetic conflict? So is it us humans being the opposite of altruistic towards each other? Or is it, uh,

some other competition at some other level, like as we're discussing? Yeah. So if you look at a lot of human traits today, they're probably not that far removed from the human traits that got us where we are now. So, you know, this whole tribalism, you know, you're my sports team or you're my, you know, political party or you're my, you know, tiny little village. And therefore, you know, if you're from that other village, I hate you. But as soon as we're both,

in the major city, I can't believe we're from the same region, my friend, come here, my family. And like two neighboring countries fighting. And as soon as they're off in another country, we're like, oh, I can't believe that. So it's kind of funny, like this tribalism is nonsensical in many ways. It's like cognitive incongruent, that basically we like kin and selection for sort of

liking kin is hugely advantageous genetically. Probably across all kinds of organs, across all kinds of life. Yeah. So basically, if you now transport that to the sort of humans arriving in Europe and Neanderthals are everywhere, what are you going to do? You're going to kill them off.

you know, there's this battle for territory and this battle for they're not like us. We have to get rid of them. So basically there's a, you know, very interesting mix there. But, and yet, and yet, when you look at the genetics, there's tons of gene flow between them.

So basically, you know, love, romance between, you know, new species. We have tribes, but love spans the gap between the different tribes. It's Romeo and Juliet across species boundaries. Sneaks away from the village to hang out with the genus. But even before the out of Africa, there's, you know, within Africa selection, which was probably massive battles of larger and larger tribes selecting for our social networking activities.

And savviness and, you know, probably all our conspiracy theory genes are, you know, dating back from then. And, you know, so there's a lot of this mischievousness in the history of human evolution that unfortunately is still present in, you know, many ugly forms today.

but probably contributed to our success as a species in wiping out other species. It just sucks that we don't have neighboring species that are, you know, intelligent like us, but yet very different than us. So we have like, you know, dogs or wolves, I guess, co-evolved. They figured out how to...

neighbor up with humans in a friendly way and collaborate and develop in time? You're describing this as if the wolves made a choice. It's possible that the wolves never had a say, that basically humans were just so overpowering that they had captive wolves and then at every generation killed off eight of the nine pups and only kept the one that was milder. And it only takes a few generations to then sort of have pups that are really mild.

And so the Neanderthals weren't useful in the same way that wolves were. I don't know if it's a question of useful. They were probably super useful. My thinking is that they were scary. That basically something that almost resembles you is something that you try to eliminate first. It's too close. Yeah. And speaking of, you know, species that are intelligent and sort of what's left of evolution,

It is a shame, exactly like you say, that so many different amazing life forms were extinct and the kind of boring ones remained. So if you look at dinosaurs, I mean, the diversity that they had, if you look at sub, you know, like there's just so many different lineages of life that were just abruptly killed.

And yet, out of that death emerged many new kinds of really awesome lineages. Do you think there was, in the history of life on Earth, species...

that may be still alive today that are more intelligent than humans. And we just don't know. So there's a case to be made for dolphins. Like if you look at their brains, if you look at the way that they play, if you look at the way that they learn, you know, I mean, they don't have opposable thumbs and we do. So, you know, that probably made a big difference. It's terrifying to think that like, not terrifying. I don't know how to feel about it, that they're more intelligent than us. It's like the hitchhiker's guide to the future.

I know. But how do you define intelligence? Basically, like I was saying last time, you know, stupid is a stupid does and smart is a smart does. So if the dolphins are basically super smart, figure out the meaning of life and just go around playing with water all day, which is probably the meaning of life. Yeah.

then we wouldn't know because all they're doing is kicking water just like sharks are, and sharks are probably pretty stupid. So basically, it's very difficult to sort of judge a species' intelligence unless they kind of go out of their way to demonstrate it. Yeah, and that's instructive for our understanding of any kind of life form. You know, I recently talked to Sarah Seager looking for life out there on other planets. It'd be fascinating to think if we discover a habitable planet

outside of Earth and one day, maybe many centuries away, I'll be able to travel with a robot there. How would we actually know that this species would probably be able to detect that it's a living being, but how would we know if it's an intelligent being? I mean, it's both exciting and terrifying to come face to face with a life form that's of another world.

Like something that clearly is moving in a, how would you say, like a deliberate way? And to then like ask, well, how do I ask that thing whether it's intelligent? - No, but the question that you're asking is applicable to every species on the earth now. - On earth now, yeah. - Yeah, so basically, you know, dolphins are a great example. We know that they're, you know, clearly capable hardware-wise and behavior-wise of intelligence.

you know, how do we communicate? So basically, if your question is about crossing species boundaries of communication, the way that I want to put it is that humans have achieved a level of sophistication in our behaviors, in our communication, in our language, in our ways of expressing ourselves, that I have no doubt that if we encountered a human-like form of intelligence, we'd figure out their language in a few weeks.

Like, it'd be just fine. As long as, you know, of course, they're both trusting each other and not annihilating each other and not sort of fearing each other and attacking each other. - What about, let me ask, just out of curiosity and into science fiction land a little bit. So clearly you're one of the top scientists in the world. So if we were to discover an alien life form, you would be brought in to study its genetics.

Do you think the epigenome that we talked about, the genome, the code, the digital code that underlies that alien life form would be similar to ours? Like in fundamental ways, maybe not exactly, but in fundamental ways of how it's structured? Yeah. So you're getting to the very definition of life. You're getting to the very definition of what makes life, life and how do we decode that life?

And it's so easy to think that every life form would basically have to, you know, like oxygen,

have to like heat from the sun and rely on sort of being in the habitable zone of, you know, its solar system and so on and so forth. But I think we have to sort of go beyond this sort of, oh, life on another planet must be exactly like life is on earth. Because of course, life on earth happens to rely on the proximity to the sun and benefit from that amount of energy. But we're talking at

the timescales of human life, where we kind of live, I don't know, between, and I'm going to be super wide here, we're going to live between six Earth months and 200 Earth years. So basically, if you look at the timescale that we inhabit on Earth, it is very much dictated by the amount of energy that we receive from the sun. If you look at, I don't know, Europa,

you know, the smallest, the fourth smallest moon of Jupiter, the smallest of the Galilean moons, and also the smallest in its distance from Jupiter. It has an iron core. It has a rock exterior. It has ice all around it. And it has probably massive liquid oceans underneath. And the gravitational pull, the gravitational pull of Jupiter is probably creating all kinds of movement under that ice.

How did life evolve on Earth? Yes, sure, life now, most of life that we above the surface look at has to do with exploiting the solar energy for our daily behavior. But that's not the case everywhere on the planet. If you look at the bottom of the ocean, there are hydrothermal vents. There's both black smokers and white smokers, and they are near these volcanic vents

you know, ducts that basically emanate a massive amount of energy from the core of our planet. What does life need? It needs energy. Does it need energy from the sun? It couldn't care less. Does it need energy from, you know, the earth itself? Yeah, possibly it could use that. And if you look at how did life evolve on, you know, on earth,

There are many theories. I mean, a kind of silly theory is that it came from outer space, that basically there's a meteorite out there that sort of landed on Earth and it brought with it DNA material. I think it's a little silly because it kind of pushes the buck down the road. Basically, the next question is how did it evolve over there? Whereas our planet has basically all of the right ingredients, why wouldn't it evolve here? So basically, let's kind of ignore that one. And now the two other competing hypotheses are from the outside in or from the inside out.

What's that mean? From the outside in means from the surface to the bottom of the ocean. From the inside out means from the bottom of the ocean to the surface. So life on the surface is pretty brutal. Life obviously evolved in the water and then there was an out of water event. But basically before it exited, it was clearly in the water, which is a much nicer and shielded environment. So just to be clear, on the surface...

Are you referring to the... The surface of the sea or the bottom of the sea? Versus the bottom of the sea. And you're saying life on the surface is harsh. Life outside the water is horrible. It takes huge amounts of evolutionary innovations to sustain living outside the water.

That's so interesting. Why is that? So it's easier to, life is easier in the water. Maybe, see, I'm telling dolphins. We are 70% water. No, dolphins went back into the water. Really? Of course. Because dolphins are mammals. Of course. Yeah. Interesting. Well, again, they might be smarter. They went back. They're like, screw this. So if you basically think about the fact that we are 70% water, we're basically transporting the sea with us outside the sea.

You know, if we don't have water for about 24 hours, we're dry. And if you look at life under the sea, I mean, I don't know if you're a diver, but when you go diving, your brain explodes.

Again, when I say the boring life forms is what we see all the time, like tetrapods. I mean, what a stupid, boring body plan. Seriously. Like, just go diving and you'll see that a tiny little minority of the stuff under the sea, under the surface of the sea, is actually tetrapods.

It's like, you know, snails with all kinds of crazy appendages and colors and, you know, round things and five-way symmetric things and, you know, eight-way symmetric things, all kinds of crazy body plans.

And only the tetrapod fish managed to get out. And then they gave rise to all the boring plans we kind of see today of basically, you know, humans with four limbs, birds with four limbs, lizards with four limbs. And, you know, right. It's kind of boring. If you look at by comparison, life underwater is teeming with diversity. So now let's roll back the clock.

and basically say, where did life in the ocean come from? From the surface or from the bottom? Exactly. Those two options you were mentioning. Exactly. So basically, life on the surface is one option. And then the idea there is that there's tides with the moon and the sun sort of causing all this movement. And this movement is basically causing nutrients to sort of coalesce and bounce around, et cetera. That's one option. The second option, massive amount of energy under...

you know, from the core of our planet, basically exploited, leading to these basic ingredients of life forms. And what are these basic ingredients? Metabolism, being able to take energy from the environment and put it as part of yourself.

Metabolism, it basically means transformation, again, in the Greek. It basically means taking stuff from, you know, like nutrients or energy source or anything and then making it your own. The second one is compartmentalization. If there's no notion of self, there can't be evolution. You have to know where your own boundaries end and where the non-self boundaries begin.

And that's basically the lipid bilayer nowadays, which is extremely simple to form. It's basically just a bunch of lipids, and then they eventually just self-organize into a membrane. So that's a very natural way of forming a self. And then the third component is replication. Replication doesn't need to be self-replication. It could be A helps make more of B, B helps make more of C, and C helps make more of A.

Any kind of self-reinforcement is what you need to ignite the process of evolution. After you've ignited that process, you know, I don't want to say all hell breaks loose, but all paradise breaks loose. So basically you then boom, you know, have life going. And the moment you have ABC, some kind of thing looping back onto A, you can make modifications and you can improve. And then you let natural selection work. Is there some element of that that's like, like, uh,

Like some state representation that stores information? Maybe I should say information? Absolutely. Is that a fundamental part of life? We like to think of life as the information propagation, which is DNA, the messenger, which is RNA, and then the action, which is protein. So basically, DNA, we think, is an essential part of life.

That's where the storage is. And therefore, that early life form must have had some kind of storage medium, DNA. If you look at how life actually evolved, DNA was invented much later. Proteins were invented later. And RNA was found by itself, thank you very much, in an RNA world. So the early version of life as we know it today was in fact RNA molecules performing all of the functions.

The RNA molecule itself was the protein actuator by creating three-dimensional folds through self-hybridization. Self what? Self-hybridization. So basically the same way that DNA molecules can hybridize with themselves and basically form this double helix.

The single-stranded RNA molecule can form partial double helices in various places, creating structure as if you had a long string with complementary parts, and you could then sort of design kind of like origami-like structures that will fold onto themselves. And then you can make any shape from that. That early RNA world eventually got to replication, where enzymes encoded in RNA would replicate DNA.

RNA itself. And then that process basically kicked off evolution. And that process of evolution then led to major innovations. The first innovation was translation. So you start with an RNA molecule and you translate it into another kind of form. And that's the first kind of encoding. You're like, well, do you need some kind of code? Yeah, but the code was in fact one thing. It was conflated with the actuators.

The actuators were separated from the code only later on. So you first had the self-replicating code, which was also the actuator. And then you kind of have a functionalization, partitioning of the functionalization, a sub-functionalization of the proteins that are now going to be the workhorse of life, but they're not self-replicating. The code remains the RNA. So the most beautiful and most complex RNA machine known to man is the ribosome.

The ribosome is this massive factory that is able to translate RNA into protein. The ribosome, I mean, if you want, I don't know, divine intervention in the history of life, the ribosome is it. - That's one of the great invention in the history of life. - It's, yeah. But again, you can't think of great inventions as one-time steps. They're basically, you know, the culmination of probably many competing software infrastructures for life preservation.

That won out. And then when the ribosome was so efficient at making proteins, all the other ones basically died out. And then the life forms that were using the modern ribosome were basically the more successful ones because it could make proteins. And now those proteins are much more versatile because RNA only has four bases. Proteins eventually have 20 amino acids, not initially, but eventually.

And then they can form in much more complex shapes and they can create all kinds of additional machines. One of which is reverse transcriptase. So you basically now have RNA. Again, we like to think of transcription as the normal, reverse transcription as the oddball. Well, RNA preceded DNA. So reverse transcription actually was the first invention before transcription itself. So basically RNA invents proteins. RNA and proteins together invent DNA.

So you now have a more stable medium, a more stable backbone with two helices instead of one, two strands instead of one, the double helix. And RNA basically says, listen, I'm tired. I'm going to delegate all information storage to DNA. And I'm going to delegate most actuation to proteins. Proteins. But that's, to you, is not like a...

That's just an efficiency thing. It's not a fundamentally new innovation. That's why when you're asking, is a separate information storage medium a definition of life? I'm like, no. Any kind of self-preservation, self-reinforcement. And it didn't need to be RNA-based initially. It didn't need to be self-replication initially. You just need to have enough RNA molecules randomly arising that reinforce each other that ultimately lead to

the closing of that loop and the ignition of the evolutionary process. - Can we just rewind a little bit? Like if you were to bet all your money on the two options in terms of where life started. - Probably the bottom. - At the bottom of the ocean. I don't know if this is answerable, but how hard is the first step? Or if there's something interesting you can say about that first leap. - Yeah, yeah, yeah. - From not life to life. - Yeah, I think it's inevitable.

On Earth or just... In the universe. I think it's inevitable. If you look at Europa, you know, going back to the moon of Jupiter. It's also a really nice song by Santana. Europa basically has all the ingredients. It has, you know, the core that can emit energy. It has the shielding through the ice sheet, protecting it just like an atmosphere would. It even has a layer of oxygen, probably sufficiently dense to sustain life.

So my guess is that there's probably independently a reason life form already teeming in Europa because as soon as it today. Is that exciting or terrifying to you? It's, I mean, as a scientist, I can't wait to see non-DNA based life forms. I can't wait because we are so born in, you know, sort of,

borné, as I would say in French. But basically we're sort of, you know, we are so narrow-minded in our thinking of what life should look like that I can't wait for all that to just be blown away by the discovery of life elsewhere. Let me bring you into another science fiction scenario. So on that point, if we discover life on Europa and you were brought in,

You seem very excited, but how would you start looking at that life in a way that's useful to you as a scientist, but also not going to kill all of us? So to me, it's a little bit scary, not because it's a malevolent life, like it's a dictator petting a cat, it's evil, but just the way life is,

It seems to be very good at conquering other life. So there's a lot of science fiction movies based on that principle. And that's sort of what causes the public to be so scared. But if you think about sort of would Europa life be scared of humans coming over and taking over? Chances are no, not even like earth bacteria, because earth bacteria would be wiped out in an instant in this foreign world.

Because they don't know how to metabolize energy that doesn't come from the types of energy sources that are here. The levels of acidity may just kill us all off. And at the same way, in the converse way, if you bring life from Europa on Earth, it'll die instantly because it's too hot. Or because it doesn't know how to cope with, I don't know, the sun's radiation so close to this completely inhabitable zone by their standards.

So what we call the habitable zone might actually be the inhabitable zone. Inhabitable for them. So the difference, if the environments are sufficiently different, you think we'll just not be able to even attack each other and the basic... It'll take massive amounts of engineering to create machines that will go there and sample the oceans, basically drill through...

the layers of ice to basically sample and see what life is like there and detecting it will probably be trivial. It definitely won't be DNA based. It's not like we're gonna send a sequencer, but it'll be some other kind of combination of chemicals that will look non-random. - So if you had to bet, if I took that life form we find in Europa and put it on a sandwich that you're eating and eat that sandwich. - It'll taste just fine.

Well, I know about that. Will it taste fine? That's interesting. So the other question is, do we have taste receptors for this? So where does our taste come from? It's basically adaptations to chemical molecules that we are used to seeing. We don't have taste buds for things we don't even know about. So we won't be able to know that this chemical tastes funny. But you think it won't be... It's likely not to be dangerous. Like it won't know how to even...

Do you think our immune system will even detect that something weird is going on? Probably.

And it'll be very easy to detect because it'll be very different from us. - Very weird. - But it won't be able to sort of attack. I mean, the scene from, I don't know, "Independence Day," where like they're communicating with the alien computer and they're like, "Ooh, I'm in." I mean, it's hilarious 'cause like Macs and PCs have trouble communicating. I mean, let alone in alien technology or even alien DNA. - So, okay, now I was talking about you being a scientist on Earth, but say you were a scientist that were shipped over to Europa

to investigate if there's life, what would you look for in terms of signs of life? Life is unmistakable, I would say. The way that life transforms a planet surrounding it is not the kind of thing that you would expect from the physical laws alone. So it's, I would say that as soon as

life arises, it creates this compartmentalization. It starts pushing things away. It starts sort of keeping things inside that are self. And there's a whole...

signature that you can see from that. So when I was organizing my Meaning of Life symposium, my friend who's an astrophysicist, basically we were deciding on what would be the themes for the symposium. And then I said, well, we're going to have biology, we're going to have physics. And she's like, ah, pfft.

come on, biology is just a small part of physics. Everything's a small part of physics. And I mean, in many ways it is, but my immediate answer was, no, no, no, no, wait. Life challenges physics. It supersedes physics. It sort of fights against physics.

And that's what I would look for in Europe. I would basically look for this fight against physics, for anything that sort of signatures of not just entropy at work, not just things diffusing away, not just gravitational pulls, but...

clear signatures of, you remember when I was talking earlier about this whole selection for environments, selection for biospheres, for ecosystems, for these multi-organism form of life. And I think that's sort of the first thing that you can look for, you know, chemical signatures that are not simply predicted from the reactions you would get randomly. Such a beautiful way to look at life. So you're basically leveraging some energy source and

To enable you to resist the physics of the universe. Fighting against physics. But that's the first transformation. If you look at humans, we're way past that. What do you mean by transformation? So basically there's layers. I sort of see life, you know,

When we talk about the meaning of life, life can be construed at many levels. We talked about life in the simplest form of sort of the ignition of evolution. And that's sort of the basic definition that you can check off. Yes, it's alive. But when Alexander the Great was asked, to whom do you owe your life? To your teachers or to your parents? And Alexander the Great answered,

I owe to my parents the zine, the life itself. And I owe to my teachers the F-zine, like euphony. F means good, the opposite of cacophony, which means, you know, bad. So F-zine, in his words, was basically living life.

a human life, a proper life. So basically we can go from the zine to the F-zine. And that transformation has taken several additional leaps. So basically, you know, life on Europa, I'm pretty sure has gotten to the stage of A makes B makes C makes A again. But getting to the F-zine is a whole other level. And that level requires cooperation.

That level requires altruism. That level requires specialization. Remember how we were talking about the RNA specializing into DNA for storage, proteins, and then compartmentalizations. And if you look at prokaryotic life, there's no nucleus. It's all one soup of things intermingling. If you look at

eukaryotic life, again, you for true good, you know, so a eukaryote basically has a nucleus and that's where you compartmentalize further the organization of the information storage from all of the daily activities. If you look at a, you know, human body plan or any animal, you have a compartmentalization of the germline.

You basically have one lineage that will basically be saved for the future generations. And everything outside that lineage is almost superfluous. If you think about it, the rest of your body, all it does is ensure that that lineage will make it to the next generation, that these germ lines will make it to the next generation. The rest is packaging. I'm sorry to be so blunt. And if you look at nutrition, you know, we're deuterostomes. What does deuterostome mean? Deutero means second generation.

where this is the second mouth. The first mouth is actually down here, it's the esophagus. So, deuterostomes have evolved a second layer of eating, kind of like alien with the two mouths. So, you can think of us as alien where the first mouth is up here and then the second mouth is down there. And of course- Is the first mouth just the physical manipulation of the food to make it more consumable? Correct, correct. And basically, again, if you look at a worm,

It's an extremely simple life form. It basically has a mouth. It has an anus. And it has, you know, just some organs in between that consume the food and just spit out poo. Humans are basically a fancy form of that. So you basically have the mouth. You have the digestive tract. And then you have limbs to get better at getting food. You have eyesight, hearing, et cetera, to get better at getting food. And then you have, of course, the germline. And all of this food part, it's just auxiliary to the germline.

So you basically have layers of addition, of compartmentalization, of specialization on top of this zine to get all the way to the earth zine. Yeah, so like the worm is like Windows 95, very few features, very basic. And then us humans are like...

Windows Vista, Windows 10, whatever it is. - Well, a few innovations beyond that, but yeah. - Beyond that, all right. - Where, I don't know. - Where Windows 2000, at least put it that way. - So, okay, that's such a fascinating way to look at life as a set of transformations. - Exactly. - So like, is there some interesting transformations through our history here on earth

that like appealed to you? - Of course. - And what are the most brilliant innovations and transformations? - Yeah, yeah, yeah. I mean, this is such a fascinating question. Of course, like, you know, we're talking about basic, basic life forms, and we're talking about eukaryotic life forms. And then the next big transformation is multicellular life forms.

where the specialization separates the germline from everything else that accompanies it and sort of carries it. And then that specialization then sort of has this massive new innovation, like above the second mouth, which is this massive brain,

And this massive brain is basically something that arises much, much later on. Basically, you know, notochords, like having the first spinal cord, this whole concept that along with these very simple layers, you basically now have a coordinating agent. And this coordinating agent is starting to make decisions.

And remember when we were talking about free will? I mean, you know, as a worm is hunting for food, oh, it has plenty of free will. It can choose to, you know, follow chemotaxis to the left or chemotaxis to the right. And maybe that's free will because it's unpredictable beyond a certain level. So you basically now have...

more and more decision-making and coordination of all of these different body parts and organs by a central operating system, a central machine that basically will control the rest of the body. And the other thing that I love talking about is the different timescales at which things happen. You know, we're talking about the human epigenome before. The human epigenome is basically able to find what genes should be expressed in response to environmental stimuli

in the order of minutes, and basically receive a stimulus, transfer all that data through this humongously long string of searching, and then sort of find what genes to turn on, and then create all that. All of that is happening in the timescale of minutes. Basically, you know, three minutes to half an hour. That's the expression response. But our daily life doesn't happen on the order of three minutes to half an hour. It happens on the order of milliseconds. Like I throw a ball at you, you catch it right away.

No gene expression changes there. You just don't have time to do that. So you basically have a layer of control built on a hardware that supports it, but that hardware itself lives in a different timescale than the controlling machine on top of that. Is that an accident, by the way? Is that like a feature? Was it possible for life to have evolved where...

The daily life of the organism as it interacts with its environment was on a timescale similar to the way our internals work. If you look at trees, they look kind of boring and stupid. You're like looking at a tree like stupid. If you speed up the movie of a tree from spring until October, you'll be like, oh my God, it's intelligent.

And the reason for that is that at that timescale, the tree is basically saying, oh, I'm looking for a, you know, a thing to catch onto. Ooh, I just caught onto that. I'm going to grow more here. I'm going to spawn there, et cetera. Like I can see the trees in my garden just growing and sort of, you know, looping around. And it's all a matter of timescale. And if you look at the human timescale,

Remember, we were talking about neoteny the last time around, the whole fact that our young are pretty useless until, you know, maybe, you know, a few months of age, if not a few years of age, if not, I don't know, getting out of college. And then we basically hold them, enabling their brain to continue being malleable and infusing it with knowledge and, you know, thoughts as, you know, that period of neoteny increases and expands.

If you fast forward, I don't know, another million years. So humans have only been around, you know, different from apes for about that long. Jump another unit of that, another human-chimp divergence. What could happen? From an evolutionary timescale, a lot. One of the things that's happening already is expansion of human lifespan.

We have longer and longer periods before we mature, and we have longer and longer periods before we have babies. So intergenerational distance is, you know, grown from, I don't know, 16 years to 40 years. You're saying that's in the genetics? No, no, not necessarily. But it's sort of an environmental tendency that's happening. But as we medically expand human lifespan...

the generations might actually be pushed instead of 40 years to 60 years, to 100 years. Like if we look at the long arc of the evolutionary history. Exactly. So as we start thinking about intergalactic travel now...

Sorry, that's a heck of a transition. Yeah, so let's talk about... No, no, no, no, no. As we as a species start thinking about... I'm talking about these transitions that are happening, right? That's awesome. So continue along these transitions, what does the future hold in the next million years? So the concept of us going to another planet and that taking three human lifetimes might be a joke if the human lifetime starts being 400 years.

Or 800 years. So imagine... It's all timescale. It's all timescale. Just different timescales. You ask me offline whether I would like to live forever. I mean, my answer is absolutely. And there's many different types of forevers. One forever is, do I want to live forever?

kind of like Groundhog Day? And the answer is absolutely. The stuff that I want to learn today will probably take a lifetime just to learn, you know, basically to clear my to-do list for the day. - You mean like relive the day? - Relive the day. - And then pick up different things from the richness of the experience that they're all in today. - Exactly. There's just so much happening in the world every single day. So much knowledge that has happened already that just to catch up on that will probably take me around forever.

On that point, I would just love to see you in the Groundhog movie just...

because you're so naturally as a scientist, but just the way your mind works beautifully, just all the richness of the experiences that you will pick up from that. It's a beautiful visual. - I try to live each day as if it was Groundhog Day. I'm basically every single day waking up and saying, all right, how would Bill Murray get out of that one? - Well, you know what? On a funny tangent,

I got a chance to go to a Neuralink demonstration event. I'm not sure if you're familiar with Neuralink. And I talked to Elon for a while, and one of the funny things he said on his Groundhog Day thing is, you know, it's a beautiful dream to eventually be able to replay our memories. So we're kind of these recording machines. Our brain is kind of maybe a noisy recording machine of memories.

And it would be beautiful if we can someday in the future, maybe far into the future, be able to, like in the Groundhog Day situation, replay that. And the funny comment that stuck with me is he said that maybe this, our conversation now, is a replay of a previous memory. And that stuck with me because

it would probably be my replay. Who the hell am I? I'm just some idiot guy. But Elon Musk is probably, because of SpaceX and so on, is probably going to be remembered as a special person, one of our special apes in history. So if I wanted to replay a memory, it would probably be that one, talking to Elon for a while. That's an interesting possibility from a... If we think about time scales, if we think about

richness of the experience through time that we humans take and be able to replace some aspects of that, of that biology. That's super interesting. But anyway, sorry for the tangent. You were talking about timescales and the expansion of the

human lifetime and the idea of intergalactic travel. Yeah. No, but you're laughing about it. Yeah, no, for sure. That is the future. You're talking about this. You're talking about exploring alien worlds and going to other planets. I mean, you know, when Sarah was here, she was talking about sort of going to other planets when we find these life. I mean, I'm just very naturally...

given the topics that we've approached, talking about the timescale at which this will happen. So you think eventually we will, human or life, life will expand out into the universe. The point that I'm trying to make is that an intergalactic species will probably find ways to engineer its biology in order to

expand the way that we experience time, expand the timescale that we experience. And going back to this whole concept of, you know, would I like to live forever? Yes, I'd like to live forever. Even if it was, even if I was stuck on the same day, I'd love to live forever because I would finally have time to do all these things that I want to do. But

If living forever actually comes with a perk of watching the whole world evolve forever, I mean, that's a huge perk. And I would, you know, just, it'll never get boring, just a never changing world. And then the mind, you know, sort of experiment that I want you to do is to also ask, what if I wanted to live forever one day at a time every year or one day at a time every decade? Would you choose that?

where you would wake up and the world would be 10 years later every single day you wake up. It's the opposite of Groundhog Day, where basically you always wake up and it's always 10 years later. So you're saying that's such a powerful, interesting concept that

Life is more interesting if you're, of all the life forms on earth, that you're the slowest one. Exactly. Like trees have it right. Like trees have it right. Olive trees. Like, you know, they've been there since the Minoan civilization. Yeah. And, you know, that takes us back to the question you asked about sort of the transformations that have happened in humanity. The Minoan civilization is one of them.

You know, there's this paper that was published just a couple of years ago by one of my friends that basically looked at the genetic makeup of the Minoans and the Mycenaeans in ancient Greece and how they relate to modern Greeks. And they found that indeed there was very little gene flow

from, you know, the outside. And, you know, it's fantastic to sort of think about these amazing civilizations that transformed the way that human thought happens, that basically looked for rules in nature, that looked for principles, that looked for the standard of beauty, not human beauty, but beauty in the natural world.

This whole concept that the world must be elegant and there must be deeper ways of understanding that world. To me, that's a massive transformation of our species, similar to, you know, the earlier transformation that we were talking about of even involving a brain. Of, you know, learning how to communicate language or the evolution of eyesight, right?

If you look at sort of, you know, we're talking about these worms crawling around and then sensing which direction are the chemicals more abundant, you know, chemotaxis. So eventually they grow a nose. Eventually they grow a, I mean, when I say nose, I mean ways of sensing chemicals. That's probably one of the earliest senses. You know, we always talk about how deep rooted it is in our brain.

That's one of the earliest senses. If you look at hearing, that's a much later sense. If you look at eyesight, that's an intermediate sense where you're basically sensing where the light direction comes from. That's probably something that life didn't need until it got, you know, into the surface and so on and so forth. So there's a lot of

you know, milestones. And I was talking about the latest milestone, which is LIGO last time of being able to detect gravitational waves and sort of being able to sort of have a sense that humans haven't had before. So you see that as a yet another transformation. It gives us an extra little sense. Of course. And now if you go back to this history of ancient Greece, I mean, this, this transformation that happened, I mean, of course the Egyptians had this incredible, you know, civilization for thousands of years, but,

But what happened in Greece was this whole concept of let's break things down and understand the natural world. Let's break things down and understand physics. Let's basically build rules around architecture, around elegance, around statues and tragedy. I mean, another question that you asked me in passing was this whole concept of embracing the good and the bad, embracing the full range of human emotions. And if you look at Greek tragedy,

It's the definition of that. It's, I mean, drama. I mean, again, it's a Greek word, but the whole concept of drama

Some problems that are just so vast and large that dying is the easy way out. That death, oh, that's the easy solution. So I want to touch a little bit on that point and sort of talk about this concept that life supersedes physics and that the brain supersedes life.

That basically we have a brain that can decide to not follow evolution's path. We can decide to not have children. We can decide to not eat. We can decide to suicide. We can decide to sort of abolish communication with the outside world. I mean, all the things that make us human, we can basically decide not to do that.

And that is basically when the brain itself is basically superseding what evolution program is for. So, okay. So one of the, it's okay. My mind was already blown at the beautiful formulation of the idea that life is a system that resists physics. Yeah. And our brain or perhaps the content of it or whatever,

However, maybe functionally, our brain is a thing that resists life. Yes, yes. You're so...

- You're so brilliant. - But I want you to see all of that as continuum. Basically, you're sort of talking about the sort of individual transformations, but it's a path that humanity has been taking. - It's a transformation. - It's a path of transformation. And then I want us to think about what it truly means to become human, like the F zine. And you asked me about what motivated my Meaning of Life Symposium. What motivated it in part

I mean, of course, it was an inside joke of turning 42. But what motivated him in part was actually a midlife crisis.

So the joke that I always like to say is Christos Papadimitriou, a famous Greek professor who was previously at MIT, at Harvard, at Stanford, at Berkeley, everywhere. Brilliant, brilliant person. Actually, Costis' advisor. Advisor, yeah. So Christos Papadimitriou likes to say that when you're an undergrad, you work like a rat to get into grad school. And when you're a grad student, you work like a rat to get your PhD. And when you're a postdoc, you work like a rat.

to get your assistant professor's job. And when you're an assistant professor, you work like a rat to become a full professor. And then when you're a full professor, well, by then you're basically a rat. So basically what happened to me is that I arrived at the end of the rat race. You know, life is a rat race. You constantly have hurdles to jump over. You constantly have tunnels and secret pathways. And I figured it all out. And eventually, as I was turning 42, I looked back and I was like,

"Wow, that was an awesome rat race, but I'm not a rat." I basically got out of the labyrinth and I was like, "I'm not a rat," turns out. - Is that the first moment where you saw that you were in a rat race? - No, no, no. I've known that I'm in a rat race for a long time. It's so easy to be in a rat race. It's so easy to be an undergrad because you have problem sets.

And you know, we're all smart people. You know, Promset, it has a solution. Somebody made it for you. You can just solve it. Everything was made as a test. And you keep passing those tests and tests and tests and tests. And you have tasks that are well-defined. The PhD is a little different because it's more open-ended. But yet you have an advisor who's guiding you. And then you become a professor. And tenure is a well-defined set of tasks. And you do all that. And at 42, I basically had bought a house.

Three kids, beautiful wife, tenure, awesome students, tons of grants. Life was basically laid out for me. And that's when I had my main life crisis. That's when people usually buy a Harley Davidson. And they basically say, oh, I need something new. I need something different. I need to be young myself, et cetera. But basically that was my realization that it's not a rat race. That there's no rat race. It's over. That...

I have to basically think, how do I fully instantiate myself? How do I complete my transformation into an actual human being? Because it's very easy to sort of forget all the intangibles of life. It's very hard to just sort of think about the next task and the next task, and it's all metrics. And, you know, what is the number of viewers I have? What is the number of, you know, publications I have? What is the number of citations, the number of talks, the number of grants? It's very easy to quantify everything. And then at some point you're like,

This is real life. It's not a test anymore. And that's something that I told my wife early on. I was like, no, no, no. Our life is not going to be, let's put the kids through college. And that, you know, maybe that's when I escaped the rat race. Maybe it continued being a rat race. Maybe the next step would have been, all right, how do I make sure that my kid is first in class? How do I make sure that they're, you know, into the greatest college? And then, you know, they're into college.

And then you're like 60. So how do you escape? Is there a light at the end of the tunnel of a midlife crisis? So you should watch that symposium because the videos were transformative to me and to many others. So basically, the advice that I received from all of my friends was so meaningful. There's some advice that basically says...

You have to constantly maintain unachievable goals, goals that you can make progress towards, but you can never be fully done with. And I think that's almost playing into the sort of rat race thing. Like basically make sure that there's more obstacles for your little rat persona to jump through.

So that's one possibility. So first of all, watch. Is it available somewhere? It's on YouTube. Just Google meaning of life symposium. I should have known this. You should have told me this. This is awesome. Okay. This is great. And also, seeing rat race is, if we look at Ratatouille, I mean, that's a beautiful...

That's a beautiful thing of challenges and overcoming challenges. That could be fundamentally the meaning of life is to see life as a set of challenges and to fully engage in the overcoming of those challenges. I would say that that's embracing the rat race view of life.

So a joke that we like to have with my wife all the time is we basically say, we pretend that we're in this all-inclusive resort, that we've basically hired all these people to go on the esplanade and play games because we enjoy watching people playing on the esplanade. And we enjoy sort of laying and looking at life and all the people biking and rollerblading and all of that.

And then we've paid all these people in this all-inclusive resort that we live in. And then what are we going to do today? I'm like, oh, I've signed up for professor activities. It's going to be awesome. They lined up a bunch of super smart MIT students for me to meet with. I'm going to have a grant writing meeting afterwards. It's going to be

awesome. And then she signed up for a bunch of consulting activities. It's going to be great. And then in the evening, we just get back together and say, hey, how was your consulting today? So in a way, that's another view of life of basically, wait a minute, if I was a gazillionaire, what would I choose to do? I would probably pay an awesome university to give me an office there and just

pay a bunch of super smart people to work with me, even though they don't really want to, et cetera, et cetera, et cetera. In fact, I would have exactly the life that I have now working my butt off every single day because it's so freaking fulfilling. Well, that's, so let's clarify. It's just a beautiful way. It's almost like a video game view of life that is a set of, I mean, again, game is not perhaps a positive term, but it's a, it's a, it is a beautiful term. So you,

Do you or do you not like the rat race view of life? No. Because it is fulfilling in some fundamental way. The rat race is about the goal. My view of life is about the path. So again, quoting Greece. Those folks have come up with some good stuff. So this Ovisseus Elitis basically wrote this beautiful poem about sort of going through life saying, as you go through your journey,

impersonating Ulysses of his voyage. He says, wish that the path is long and arduous because when you get to Ithaca, you might realize that it was all about the path, not the destination. So the rat race view of life makes it all about the destination. It's like, how do I get through the maze to get there? But the all-inclusive resort view of life is about the path.

It's about, wow, today I couldn't wish for a better set of activities all programmed for me to enjoy having my brain, having my body, having my senses and, you know, the life that I have. So it's a very different kind of view. It's focused on the journey, not on the destination. So you mentioned kind of the ups and downs of life and the midlife crisis, right?

And right now you said focusing kind of on the journey. But what the journey involves is ups and downs. Is there advice or any kind of thoughts you can elucidate about the downs in your life? Yeah. The hard parts.

parts of your life and how you got out or maybe not? Or is there, how do you see the dark parts of life? So I'm so glad you're asking this question because it's something that our society does a terrible job at preparing us for. Every Hollywood movie has to have a happy ending. It is ridiculous. You can count on your 10 fingers, the number of bad ending movies that you've ever watched, and you probably wouldn't need all 10 fingers.

We strive to tell everyone, yes, you can succeed. Yes, you're a millionaire, just temporarily disabled. And yes, you know, the prince will eventually figure out his princess and they will have a happily ever after ending. And yes, the hero will be beaten and beaten and beaten. But you know that at the end of the movie, the good guys will win.

We need more movies where the bad guys win. We need more movies where just everybody dies. Where just, you know, MacGyver doesn't figure out how to disable the bomb and just explodes. You just need more movies that are more realistic about the fact that life kind of sucks sometimes and it's okay. So again, growing up in Greece, I have been exposed to songs that are not just sad, but they're miserable. Yeah.

- Miserable. So one of them comes to mind. And it's basically talking about this woman who's lamenting in the early morning about losing the joyful kid, the joyful young man who basically died in the civil war in the arms of our own fellow citizens.

And she's like, if only he had died fighting the foreign forces, if only he had died at the, you know, sides of the, you know, general, if only he had died with honor, I would be proud to have lost.

The Joyful Kid. I mean, it's devastating, right? It's like he didn't just die. He died without honor. And my friend who was with me was listening to the song and she's like, this is depressing.

I'm like, whoa, whoa, whoa, you have to listen to another one. It's not as sad. And she's like, what, this one died with honor? So that's one example. It's a kind of a celebration of misery. No, no, no, no, no, no, no. So let me give you a couple more examples and then I'll answer that question. So another example is I picked up this book that I had from my childhood and I started reading stories to my kids.

And the first story is about these two children. One is really poor living on the street and the other one is really rich living in the house in the bright light above. And the poor one is wishing, looking at that window and wishing that he could have that house. And the other one is at the window wishing that he was free, that he wasn't sick all the time, that he could escape outside. It's only four pages long. And at the end, both children die. One of them dies from cold. The other one dies from illness.

And you're like, how is that even a children's story? The next story, I'm like, okay, that's fine. Let's skip this one. So I read this to my kids and then I read the next one. And the next one is about this woman whose brother is at war against the Turks and he is going to die. And she prays to the Virgin, please don't let him die. And the Virgin appears and she's like, no problem. Tell me who to kill instead.

And she's like, anyone, anyone. No, no, no, no. Choose one. How about this Turk? This one has two kids, a beautiful family waiting for him at home. She's like, no, not this one. Choose another one. And then she goes through all the life stories of the others. And she's like, no, no, just don't take anyone. She's like, I can't do that. You can choose to bring your brother back and he will be depressed for the rest of his life because he didn't fight at war, because he didn't go to that battle.

And he will live without honor. And in the end, the woman decides to have her brother killed instead because he dies without honor. I mean, this is insane. So why am I giving you these examples? It's not a glorification of misery. It's expanding your emotional range. It's teaching you that. And when I read these stories, I'm not a jerk. I'm crying out loud. I have tears. And my face becomes red.

from the pain that I'm experiencing through these stories. It's just so deeply touching to embrace the suffering, not because of an accident, but because of a choice, the sacrifice to embrace the fact that not everything is cute and rosy and always ending well.

And I think that we don't do a good enough job of teaching our kids that just life sucks and life is unfair sometimes. And that's okay. And sometimes I read a story to my kids. I read a story every night.

And sometimes the story is horrible. And sometimes the story is good and sort of friendly and happy. And my kids always ask, what's the moral of the story? And sometimes there's a moral and it's like, oh, you should be good or you should be nice. You should be helping each other, et cetera. And sometimes there's just no moral. And I tell my kids, you know what? Sometimes just life doesn't make sense and it's okay. And you can't comprehend everything.

And I think this concept of how do you deal with the bad days comes from the fact that we're taught, we're brainwashed into thinking that every day should be a happy day. And we're not ready to cope with misery. And the other thing that crying through these stories teaches you is that you don't have it nearly half as bad as you think.

Do you see what I mean? Basically, it tells you that, I mean, my mom would always tell me about how she was transformed as a teenager when she volunteered in the hospital. And she saw all these people at the brink of death, clinging for life and helping them out to best she could and crying her heart out when they were dying. And just sort of how that taught her the appreciation for what we have every day.

Waking up every morning and saying, my life doesn't suck. My life is not nearly half as bad as it could be. And sort of embracing the joy that we have of living where we live in the moment we live. And I'm going to go further. If you look at the arc of human life, you know, human existence through the centuries, there's no better way to be alive than now.

I mean, we're complaining about every single little thing, but life expectancy is at an all-time high. Sickness, all-time low. Poorness, misery, all-time low. There's no better time to be alive globally across all of human existence, number one. Number two, here in Boston, there's no better place to be alive.

If you think about the amalgamation of science, engineering, technology, the ridiculously awesome people you're bringing every week to your podcast, I mean, it's

This is the ancient Greece of modern society. But the weather still sucks. No, let me put it this way. The weather gives us a range of emotions. The full range of human weather patterns. There's such a fascinating thing about human psychology. I often reread this book. I'm not sure if you're familiar with it. It's Man's Search for Meaning by Viktor Frankl. And he talks about, you know,

his living through the Holocaust and the concentration camps. And even there where there's like human misery is at its highest. Even there, he discovers these moments by observing the suffering, by accepting the suffering. He, uh,

He observes moments of true joy of how great his life is relative to others at the camp.

uh, who have it worse. Yeah. So, so it's, it's a dangerous slippery slope to think that way because it's basically being better than Jones's. And if, you know, if the house next door has a giant car, then you want to get a bigger car or something like that. It's not comparative misery. I think the way that I see it is slightly different. It's, and it's not even thinking about all the worst possible outcomes that could have happened, but didn't.

The example, as you were talking about the concentration camps, the most horrible, I mean, one of the most horrible moments of human existence. I was thinking about pictures that I was seeing of kids in Syria, in war-torn zones. And you're looking at these kids. And again, I cried out loud, imagining my own son in the van,

after a bomb explosion, watching his father die or his siblings die or losing his friends. It's something that we are not capable of fathoming. But if you actually put a seven-year-old in that situation, the look that I saw in these kids' eyes basically said, it is what it is. It was...

And I've experienced that with my own kid. When he gets, like, my three-year-old last, like, two years ago, who's now my five-year-old, she was burned really badly with, like, hot chocolate and coffee that just peeled off her skin. So you could actually see just her fragile skin had just peeled off. And she was the happiest little kid.

She was just going along with the punches. It is what it is. It is what it is. She accepted it. So it's quite dramatic to sort of realize that children don't say, oh, I could have it better. They sort of embrace the moment, not embrace, but sort of accept the moment. And then they can have moments of pure joy in a horrendous war-torn country.

And, you know, like so many people from, you know, these war-torn countries basically say, oh, you think you Americans are going to just come and just send us a bunch of aid and food, et cetera? Yeah, sure. That's helpful. But what do we dream of? What do we struggle for? We struggle for love. We struggle for meaning. We struggle for, you know, emotions and friendships. We struggle for the same things you guys struggle for.

We're not just like every day waking up and saying, oh, I wish I had more food. No, that's just the given. I just don't have enough food. But what we struggle with

are basically everything else. And that sort of gives you some perspective on life. It basically says, you know, and another story that my mom told me when I was a kid is this story about sort of this man who's basically, you know, he sees the Christ appear in front of him. He says, oh Christ, I'm carrying all these problems. I'm carrying this big bag. Can you please take it from me? And he's like, sure, let me just give you any other bag.

And basically, and of course the person in the end accepts his own bag. So acceptance, ultimately, the path you recommend is acceptance. Every single other bag is probably worse. It's the evil you don't know versus the evil you know. Like we all struggle with our own problems, but if you look at the bigger picture, it's just your path through life. And if you embrace it, the good and the bad, every single day, it's just joy and

elation, sadness, misery. If you don't have both, you're not a complete human being. You know, you can't, I mean, the last example I'm going to give is the movie Inside Out by Pixar. Beautiful movie. Which one is that? The one with the little characters controlling the frame. Oh, the emotions. Yeah. So you basically have joy and sadness and fear and disgust, et cetera. And the moral of the story, if you remember the movie, the moral of the story is that in the end,

Joy is basically trying to fix everything to make everything happy. And she's failing miserably and everything else is like crumbling and falling apart. And the little girl basically becomes emotionless because all she knows how to do is fake happiness.

And I think it's a very good analogy for our everyday society where we're always saying, are you happy? Are you happy? My mom calls me and she's like, Manolis, are you happy? I'm like, mom, stop asking this stupid question. No, I'm not happy. What you should be asking is if I'm fulfilled. And that's a very different thing. I don't go around being happy.

- I would love it if your mom called and said, "Manolis, are you suffering beautifully?" Or something like that. - That's exactly right. That's what she should be asking. Are you struggling to achieve something great? That's the question that mom should be asking. - Hear that mom call me about the suffering, not about how good are you doing? - So what I tell her is that life is not about maximizing happiness. Life is about accomplishing something meaningful.

And accomplishing that meaningful thing cannot come from a series of joyful moments. It comes from a series of struggles, of successes and failures, of people being nasty to you and people being nice to you and embracing the full thing. And if you supersede that constant need for gratification, if you supersede that constant need for kindness, you suddenly know who you are.

And what I like to say to my kid, and my son the other day was telling me, oh, so-and-so called me such and such. And I'm like, are you such and such? He's like, no. I'm like, ha-ha, see, they were wrong. And what I tell him is, if you know who you are, what other people say about you only teaches you about them. Yeah. So it has no influence on your self-esteem. If you know where you stand, you embrace the good, but you also embrace the bad.

I have plenty of bad and I'm embracing it. I'm a procrastinator. How do I deal with that? I trick myself into procrastinating about mindless, stupid little day-to-day things. And in that procrastination time, doing important things for the future. So accepting who you are. Accepting your flaws. Accepting the whole of it. Accepting the struggle. Accepting the sleeplessness. Accepting the fact that the journey is what matters.

hoping that your path to Ithaca is full of troubles because those troubles are the life you will lead. Accepting that life will not start after the next milestone, that life has already started a long time ago. And what you're experiencing now is the life. This is it. It's not some kind of future thing that you work yourself hard to get to. And then after that, you live happily ever after. To me, the happily ever after, that's the end of the story. Nothing happens after that.

They struggled and they struggled and they struggled is much more interesting story than they lived happily ever after. So I think we have to embrace that as a society, that it's not just about the happy ending, that our kids are brainwashed into expecting that things will be happy and rosy and it's okay if they're not. And they should keep struggling because the struggle is the journey and the journey is the meaning of life. It's not the end, it's the journey.

- What about accepting one of the harder things? We talked a little bit about immortality. What about accepting that life ends? So do you, Manolis, think about your own mortality? How, we talked about accepting that there's ups and downs to life. What about the ultimate down, which is the finality of it? Do you think about that? Do you fear it? - You also asked me if I'm afraid of getting older.

Yes. And that's on the path to mortality. So let me talk about that first step and then the last step. The last step. Literally the last step.

So getting older, what does that mean? When I was 18, when I was 20, my brain, I felt, was at my maximum. I was like, nothing is impossible. I can solve anything. I could take any math puzzle, any logic puzzle, any programming puzzle and just solve it in milliseconds. I just saw the answer through problems. I was like feeling invincible. I would show up at lecture with my newspaper, lift up my head every now and then, point to errors,

Just brat, complete brat. I would raise my hand and correct my professor from the whole classroom. Total brat. I have some of those in my class now and it's awesome. It's like very- I used to be you. Teaches you humility. So I felt invincible and I was like, this is it. This is awesome. I'm living the life. 10 years later, my brain didn't work the same way. I wasn't as good at the tiny little puzzles, but it worked in different ways.

And right now, 20 years later, it works in yet different ways. And oh gosh, I love the journey. Can you maybe give some hints of the interesting different ways that your brain works as it aged? Yeah. I went from the phase of sheer speed and hardcore quantitative thinking to sort of stepping back, being able to sort of make more connections.

Being able to sort of say, yeah, but let's use that thing. Sort of a huge new creativity being unleashed. Basically, when you're young, you're sort of thinking about that one problem. You can sort of reconfigure all the variables combinatorially in your head and just...

wipe it all out. When you're, you know, just a little older, you start getting more creative. You start bringing in things from different fields and different contexts and sort of stepping outside the box. Basically, it's like being in the rat race and saying, there's a ceiling. Why are we trying to get through that? So it's sort of, you know, thinking outside the box. And then at 40,

What I'm going through now is this whole sort of embracing the path of life. And when I say life has started already, it's not a test anymore. This is basically embracing the finality, embracing that the journey is what it's at. So what I like to say is live every day as if it's your last one and make plans as if you'll never die. I always have the long-term goal.

that I'm sort of planning out for that will eventually become the short term. And I always have the sort of short term. And I think this ability to sort of look at life in the past and look at life in the future

jointly and sort of embrace the continuity both of life in the universe and on our planet, as well as life as a human being from the beginning to the end, just as a path, as a journey, and just embracing every aspect of that. I mean, I was talking about parenthood the other day and how amazingly fulfilling it is to sort of relive childhood through the eyes of my kids, but with the perspective of a parent.

So the sheer, you know, arrogance of youth. Watching this in my kid, I can see myself when I was 18 correcting my professor. I felt so proud. Little did I know that my professor was working on so much more interesting things than the three little things he was putting on the board that day. And I was like, I'm invincible. But in fact, no, just a little brat.

And basically right now, I sort of can see the sort of journey with a little more humility. I can sort of look at my own students with their unbelievable abilities, being able to do things that I'm no longer able to do better than I probably was ever able to do. But yet being able to guide them and shape their thinking and blow their minds with new ideas and new directions through my perspective.

And I know when something is solvable because I've been there, but I'm not going to even bother. It's not that I can't do it. I'm sure I could if I tried. I just, I'm not interested in that anymore. So what I'm embracing this journey of aging is how my brain is changing and how I'm constantly trying to figure out the niches, the evolutionary niches that I'm best adapted for, for the tasks that I'm best at while hiring and recruiting people

both assistants and research scientists and students and postdocs, and that will be the best at those tasks. But someone still has to see the big picture. And I love being in that role. So you're at the timescale of a human lifespan, you're doing the same thing that the worm does

did at the evolutionary time scale of growing arms, of the specialization, the compartmentalization he talks about. I mean, it's fascinating to think of what 80-year-old Manolis would look back at the man that's sitting here today.

And laugh at the arrogance. I was like, no little thing. You didn't figure out anything. I mean, ultimately, it seems that if you're introspective about life, it leads to a kind of acceptance, a deeper and deeper acceptance of the whole of it.

Again, I want to be cautious about acceptance because it almost says that you can't change it. It's sort of embracing the struggle and embracing the journey is the way that I would put it. So you ultimately feel the journey isn't just something that happens to you. Of course. You shape it. You shape it. Remember how I was saying that Boston is the best place and the best time to live in right now, you know, in the history of humanity? Yeah.

I'm exaggerating a little bit, but the way that I think about this is that if you look at the whole of cosmos, where would you rather be? If you're just a bunch of molecules, roughly your biomass, where would you rather be? Would you rather be a rock on Mars? Probably not. Would you rather be in a black hole? Probably not. Would you rather be in an exploding supernova? Maybe, that might be interesting.

But being on Earth is an awesome solar system, an awesome planetary system, an awesome place to be in. Across all of space-time, it's a pretty good place to be in as a bunch of molecules. If you are a bunch of molecules on Earth today, being an animal with some kind of awareness of the stuff around you is wonderful. Being a human among all animals is amazing because you have all this introspection and

And being a human who's young, fit, athletic, smart, et cetera. I mean, you know, you have so much to be happy for. Beyond that, being surrounded by a bunch of awesome people that you interact with all the time. I mean, I feel blessed to interact with the people I know, with the friends I have, the dinners that I have, all of this. Students that I interact with. I'm so blessed. And the last little blip in this awesomeness of local maximum, the last little blip,

It comes from being kind, being grateful and being kind. I don't know if you remember that little prayer that I described last time of thank you for all the good you've given me and give me strength to give unto others with the same love that you've given to me. And the whole point of that is being grateful and being kind. What does that do? From a purely egoistic perspective, it makes the people around you happier.

And it takes that little maximum a little bit further because you'll be surrounded by happy people by being kind. That's the purely egoistic view. And the purely altruistic view, or maybe it's egoistic as well, is that it just is good to give. It feels good to give. Like basically watching somebody who's touched by what you said, watching somebody who's like appreciating a rapid response or a generous offer or just...

Random acts of kindness is so fulfilling. So evolutionarily, we were selected for that. There's just such a good feeling that comes from that. You know, it's fascinating to think you said Boston is the best place and talking about kindness that the very thought that Boston is the best place in the universe is almost, it's a kind of a gravitational field, uh,

Your thought and your very life in itself is a kind of field that makes that real. Yeah. The self-fulfilling prophecy. Yeah. By claiming it's the best and thinking it's the best, it becomes the best. And you make others...

It's not a force that just applies to your own cognition. Exactly. It applies to the others around you. And then suddenly you live in an even better place. Yeah. Because it creates the reality, the actual reality, the social reality. Exactly. And it molds the environment. Exactly. What's one of the coolest things about you, I think, is you represent the best of MIT, like the spirit of MIT. Yeah.

I'm so glad that I'm fortunate enough to be able to talk to you because there's a kind of cynicism about academia in parts that I think is undeserved and that there's this MIT, of course, but academic institutions,

is a sacred place where ideas can flourish and just in the same very way that you're talking about is both kindness and curiosity and that like that weird thing that happens when a bunch of curious descendants of apes get together and just like get excited and this this ripple effect that happens I mean that's the most beautiful aspect of MIT people might think like

competition and grants and like position, like you said, the rat race, but like underneath it all is, is these curious human beings inspiring younger human beings. And there's this ripple effect that happens. And I'm so glad that,

I mean, I'm glad that I get a chance to record this because it inspires so many other students and so many other people to do the same, to embrace the inner curious creature that it's not about the race. - So let's talk about the negative. Let's talk about, no, no, no, I'm serious, I'm serious. You know, you have to embrace the good and the bad. So let's talk about the negative. - As the grief comes out. - Let's address it. So why do people want positions of power?

Why do people want, you know, more money, more power, more this, more that? Remember the part where I was saying, if you know who you are, what other people think about you, it makes no difference to you. It only teaches you about them. Many people feel defined themselves. They feel instantiated through the eyes of others. So being in a position of power makes them feel better about themselves.

Who knows what other kind of struggles they might have that creates that need to feel better about themselves. But they have a bunch of struggles and everybody has a bunch of struggles. And every time I see somebody behaving poorly, I'm basically thinking, well, they're in a tough spot right now and it's okay. You know, I can kind of see how I would behave badly in other circumstances as well. So I think...

If you take away that sort of having to prove yourself in the eyes of others, life becomes so much easier. So when I first became a professor at MIT,

I started wearing adult clothes. I had my like, you know, I mean, before- - You became a serious person, quote, unquote. - I basically had, you know, I would always like go around in my roller blazer and my shorts and a t-shirt. And eventually I was a professional, like, ooh, I bought all these khaki pants and, you know, these nice like, you know, shirts with like, you know, whatever they call it, the patterns.

And I was like, you know, dressing with my nice belt every day, showing up. And then a few months later, I was like, I can't stand it. And I just went back to my rollerblades and my t-shirts and my shorts. And it was this struggle of sort of not feeling that I fit in. I was so intimidated by all of my colleagues, like just watching their incredible achievements, like persons next to me and the person, you know, the floor below me. I was like,

oh my God, like they clearly made a mistake. What the heck am I doing here? How will I ever live up to these people's standards? And eventually you grow up to realize that the way that I grew up to realize that the way that other people perceived my work was very similar to the way that I perceived other people's work as flawless, right?

I knew all of the flaws in my work. I knew the limitations. I knew what I hadn't managed to achieve. And what I saw was maybe a third of the way of what I was trying to achieve. And I saw everything as flawed. What they saw, what I had achieved, they didn't see what I hadn't achieved. They only saw the one third down, which was pretty good in their eyes. So they all respected me. And I was feeling miserable about myself. I was like, I'm not worthy.

And I think that this is a cognitive problem that we have. We kind of...

It's kind of like when we're talking about artificial general intelligence, HEI, of sort of, we kind of have this definition that anything that machines can do is not intelligent and anything that they can't do is intelligent. Therefore, we narrow, narrow, narrow, narrow the field of what intelligence truly means. And as soon as machines achieve something, it's not intelligent anymore. I feel like I was doing the same thing with myself. As soon as I could solve something, it was the kind of thing that a kid like me could solve. And therefore it was kind of easy. But to the others, it seemed hard. Yeah.

But to me, it seemed easy. So it was this kind of thing that everything that my colleagues were doing seemed impossible to me, but everything that I was doing seemed impossible to them. So it was that realization that sort of made me mature into sort of a, not more confident, but more comfortable human being. Can you actually linger on that a little bit? I mean, you mentioned Minsky. I remember you said something in an interview where he said the secret to his, um,

Like the way he approached life was to never be happy with anything he did. So there's something powerful as a motivator to doing exactly what you're saying, which is everything you've achieved to see that as easy and unimpressive.

What do you do with that? Because clearly that's a useful thing. I think I've kind of matured past that. And I think the maturity past that is to sort of accept what it is and accept that it has helped others build onto it and therefore advance human knowledge. So it's very easy to sort of fall into the trap of, oh, everything I've done is crap.

What I told you last time is that I always tell my students that our best work is ahead of us. And I think that's more of my mindset. That's a beautiful way to put it. Exactly. What we've done is strong. It's great. It's great for the time. And it'll become obsolete in 30 years. Not we can't, we are doing even better. We're doing even better. Exactly. So basically our next work will just strive. And again, you can't let the perfect be the enemy of the good.

At some point you have to wrap. I was having a meeting with my student yesterday and it was like, listen, we know this is not perfect, but it's way better than anything that's ever been done before. You know how to improve it, but if you try to, your paper is never going to get published. So, so it, you know, there's this balance of we're already at the top of the field, get it out. And then you work on the next improvement.

And in my experience, this has never happened. We've never actually worked on the next improvement. And that's okay. It didn't make a difference. Because you're basically putting a new stepping stone that others will be able to step on and surpass you. My advisor in grad school would basically tell me, Manolis, let others write the second paper in that field. Just write the first one, move on. Move on to the next field. You don't want to be writing the second and the third and the fourth and the fifth paper in the same field. Just write.

And it's very shocking to a student to hear that because I was like, I was at the top of my game. I was owning that field and I published the first paper. I'm like, I'm ready for two and three and four. He's like, move on, just let it be. And I was like, whoa. And it's so liberating to sort of not have to surpass everyone, but just put your little stepping stone out there and others will step on it and put their own stones further and eventually cross a bigger river and

than if you try to sort of make a giant leap all at once. So you need both. - Beautifully put. So the funny thing is, I believe I closed the previous episode with a Darwin quote about the power of poetry and music in life. - I think your quote, and again, I only heard it once, was Darwin basically saying, "If I were to live life again, next time, I would read more poetry and something about art every week," or something like that. - Yeah. - Yeah.

It's so interesting for somebody who studied life at a very cold, I would say, genetic level to say that, yeah, the highest form of living is the art. But on that, which made me realize that you write poetry and I forced you or maybe convinced you somehow to maybe share if it's possible, if it's okay, some of...

the poetry you've written yourself in your life? - So again, being Greek, a lot of my poems have been pretty miserable. And I always like to say that it's very hard for me to write a poem when I'm happy.

And I just have to be in a state of deep despair in order to write poems. But the first poem I ever wrote was in English class. I'm Greek, I grew up in Greece, but I was in a French high school and I was taking English as a foreign language. So the English teacher basically asked us to write a poem in English.

So this is basically what I'm going to embarrass myself and read from my 16-year-old self many, many years ago. Can you give a little bit more context about who you were in this moment? So here's what's really interesting. In terms of growing up, how do we grow up? Yeah.

It's very difficult to grow up if you're in the same school going from one class to the other and all your friends know you inside out. It's very difficult to change. It's very difficult to grow up because they have a certain set of expectations for who you are and for how you're going to behave. So in many ways, we kind of tend to get set in our ways and not change very much.

I think something that helped me grow up is that when I was 11 years old, I was a kid in Greece in primary school. When I was 12 years old, I was a kid in Greece in a first year of high school. When I was 13, I was in France. So basically moved countries and schools. The next year, I moved schools again because it was a transition in the French educational system from one school to the next. The next year after that, my family moved to New York.

in a French high school there. And the next year after that, I'm moving to MIT. So basically between 11 and 19, every single year, I actually had the opportunity to grow. I was not held by people who knew me and I could reinvent myself or reshape myself or reshape my, you know, sort of personality, my emotions, my, you know, as I was growing up, especially in such a transformative time of a kid's life.

from 11 to 17. - Okay, first of all, it's so powerful that you think of it that way. Did you think of it that way at the moment? 'Cause it's kind of a source, you said an opportunity to grow, but it's kind of suffering. I mean, you're being torn away from the thing you know into a thing you don't know. - So when we moved from South France to New York, I was pissed.

I was pissed. I was taking these long bike rides in the countryside, jumping in French swimming pools. And I had all these wonderful friendships going downtown and just staying by the fountains in the dim lit streets.

streets of Aix-en-Provence in the south of France. It was magical. And suddenly I moved to New York City, a city of cement, of ugliness, like trash in the streets and every corner. It's horrible. Snow everywhere. Having never seen snow or like real snow in my life.

I moved from Athens to South France to Southern New York. So I was pissed. But whether I saw it as an opportunity for growth, I don't think so. I don't think that I was that self-reflective. It was just how it happened. Only now do you see it this way. I saw it like that probably pretty early on, but not during those transitions. So basically during those transitions, I was just a kid being a kid, you know, and, um,

Maybe the time that I started seeing it that way was maybe when I decided to stay at MIT as a professor after having been there as a student. And I kind of saw the struggle of getting professors to not see you as a kid when they're your peers. And I was very flattered when one of my friends basically told me, oh, I remember you in recitation. When you first asked me a question, I said, wow, this kid...

I'll pay attention. One day you'll be a peer. So it's, you know, certainly my perception was that many of them could not see me as anything but a kid. But it turns out that some of them saw me as something different than a kid even before I was actually their colleague. So it's kind of an interesting place because what I like to say about MIT is that people treat you as equal no matter what stage. And they respect you for what you say, not for who you are when you're saying it.

And if I'm wrong, my students will tell me. They will have no reservation to just be bluntly, you know, sorry, I don't agree with that. Yeah, I mean, the beautiful thing about you, sorry to put it this way, is, you know, maybe people who weren't familiar with your work beforehand might think, like, you

might not realize that you're a world-class scientist who leads a large group and so on. Because there's a youthful nature to you that it's, I mean, you talk like an undergrad, you know, with the excitement and the fresh eyes and the sort of excitement about the world. And that's, first of all, super contagious and beautiful. You know, it's easy to sort of fall into behaving seriously because then people kind of,

start putting you on a pedestal more into a position of power, you want to sort of

act like you're in a position of power as opposed to allowing yourself to be lost in the, just the curiosity, the, the childish view of the world, which is just this open-eyed love of knowledge. And that was the transition that I was describing when I decided to go back to my rollerblades and t-shirt and baseball cap. Basically, you know, when I, when I, when I met my first postdoc,

It was basically, you know, he was interviewing for postdocs at MIT. He already had several first author papers to his name in top journals. And my friend, Yulia, basically introduced me to Alex Stark, who basically was interviewing at the time with Rick Young and with Eric Lander, just like these massive names in the field. And I was just a first year faculty person with, you know, zero credibility, basically.

And she basically says, oh, there's this friend of mine, Alex, who's visiting. He's also German. You know, he wanted to meet you. I'm like, oh, sounds great. I'd love to talk science. I show up, we sit at the amphitheater in Stata. Uh, you know, I basically arrive in my rollerblades, you

jump a few steps, sit down, wearing my blades, we're having these awesome conversation about science and about gene regulation and how the whole thing works and sort of my perspective and his perspective, and we're just bouncing ideas for 30 minutes.

And then I just dash off to my next meeting. And he basically emails me afterwards. And I was giving him advice about how to interview with Eric Lander, how to interview with Rick Young and how to sort of get a position with them. And then after a while, he emails me saying, I would love to become a postdoc in your group. I'm like,

What? Are you kidding me? So he basically didn't care that I wear rollerblades and t-shirt. All he cared about was my ideas and sort of embracing the me with the childhood excitement about science was basically what attracted him.

It wasn't the, wow, this guy runs a big lab or this and that. It was just like, I like his ideas. I want to work with him. That, by the way, folks, is the best of MIT. That's what MIT stands for. So that's a beautiful story. But take me back to the poem. And where did this poem come from? Where's your mindset? So who is the 17, 16-year-old kid,

Manolis. So again, I've just seen snow for the first time and I'm in New York. So I'm, you know, maybe that's where the sadness in the poem comes from. But anyway, we're asked in class to write an assignment. This is my third language. I'm not very good at it. So pardon me, but here's what I wrote.

Children dance now all in row, children laughing at the snow, but in time's endless flow, children sooner or later grow. Men are mortal, we go by, if we know it, we may cry, but I thought a love so sweet was immortal, was so deep. There I told you, darling sweet, that forever love would keep. Blossomed spring and summer shined, then blue autumn, winter died. One year passed, but the clouds,

Still remember all our vows. Never faked and never lied. All we did was stare and smile. All alone, sitting down, to the snow we made our vow. But you told me you were right. Birds who love are birds who cry. Now with laughter children play. Yet the sky is so grey. Even if the snow seems bright, without you have lost their light.

Sun that sang and moon that smiled. All the stars have ceased to shine. All of nature drew its grace, found its light within your face. Now you're gone and won't return. Let the snow and my heart burn. There's a Greek. That's beautiful. That's beautiful, by the way. And the rhyming, the musicality, there's both a simplicity...

I'm 16. And a musicality too. No, no, no. But like, so I really enjoy like Robert Frost poems. I don't mean simplicity in a bad way, in a negative way at all. Again, it's very weird to analyze your own poem, but I think it captures the simplicity of youth and the way that it kind of starts with children dance, lonely low. It basically, and it kind of shows that snow can be interpreted first in the first verse as a happy thing. And then in the end, you know,

Now with Laughter Children Play, I'm like, now I've grown, basically. It's this transformation that we're actually talking about. This whole men are mortal, we go by.

i'm sort of you know you're saying are you comfortable with growing old i'm like duh i was i was since i was 16. yeah and what's really interesting is that you know again when i was 12 years old in our summer house in greece i remember sort of telling my sister my outlook that i would have as a father for how to bring up my own kids so it's very weird that i've always sort of seen the full path

From, you know, a kid. From when you were young. Yeah. I don't know if you like this Johnny Mitchell song. I've looked at clouds from both sides now, from up and down, and still somehow it snows illusions I recall. It's clouds illusions I recall. I really don't know clouds at all.

So it's really beautiful. So I think the Johnny Mitchell song, which again, I heard for the first time much, much after this, and I wouldn't even compare this to that. But what Johnny Mitchell is saying in that song is that you can see life from two perspectives. You can see the good or the bad in both, you know, in everything you see. And I think that's the allegory of snow right now. You can see snow as this bright, white, wonderful thing, or you can see snow as this miserable, you know, gray thing.

thing. So that sort of, and what I like about the last verse now with the laughter children play is that it's a recall to the first one where I was the kid

enjoying careless life and eventually was making promises that something would be forever. And I think part of that is also the loss of my friendships in France, of being in New York now and sort of everything's gray. And, you know, even though the snow seems bright, without you have lost their light, sun that sang and moon that smiled. So it's this concept that if you lose your love, the same thing can be perceived in a very different way.

Let me ask you this, because somebody wrote me this long email, and I think you're the perfect person to ask this. You mentioned love. From a genetic perspective, what is it? What do you make of love? Why do we humans fall in love? In your own life, why did you fall in love?

The email that was written to me was, you always talk about mortality and fear of mortality, but you don't ask about love. I don't know if there's some thoughts you could give about the role of love in your own life.

or the role of love in human life in general? - I think love in many ways defines my life. It's basically, I like to say that I'm a human first and a professor second.

And I think this passion for life, this passion for, you know, everything around us. I mean, the only way to describe that is love. It's basically, you know, embracing your, you know, emotional self, embracing the, you know, the non-brainiac in you, embracing the sort of intangible, the...

not very well defined. And even in my own research, I'm just very passionate about everything I do. You know, there's a certain passion that comes through. And what, I'm sorry, again, being Greek, the etymology of the word passion. What was passion? Passion is suffering. The etymology, when we talk about the passion of the Christ, it's the suffering. And in the Greek version of that word, pathos, like pathology,

Pathos is deep suffering. It's the concept of someone who's sympathetic. Sympathetic means suffering together.

experiencing emotions together. So it's funny that you asked me about love and I respond with passion, passion for life, passion for research, passion for my family, for my children, for, you know. So there's a certain passion that defines me and everything else follows rather than the other way around. I'm not first thinking with my brain

what is the most impactful fable we could write and then going after that, I'm thinking with my heart, what am I passionate about? What drives me, what just makes me tick?

And that's a beautiful way to live, but I love it how the Greek part of you just kind of connects it to the suffering. So if you could remove the suffering. No, no, no, no, no, no. When I say suffering, I don't mean suffering as in being miserable. I mean suffering as in being emotionally invested in something. Remember, I mean, again, if you look at this poem, what is it saying? It's saying birds who love are birds who cry. Right?

Right? Yeah. That's the very definition of love. Yeah. Exposing your fragility. Yeah. If you're not afraid of suffering, you don't fall in love. As soon as you hold back, you protect, you shield your heart, no love can enter. So there's this Simon and Garfunkel song. I am a rock. I am an island. And a rock feels no pain. And an island never cries.

So again, there's some aspects of that into this poem. The, you know, the fact that, you know, but you told me, you know, there I told you, darling sweet, that forever love would keep is this intermediate thing. And then there's a recall, but you told me you were right. Birds will love or birds will cry. So it basically says that love is the fragility that you're willing to give to another person. It's opening up your vulnerable spots. It's sort of accepting that love

There's no safety net. You're just giving yourself fully and you're ready to be hurt. So you've already been way too kind with your time, but I'm going to force you to stay here just a few minutes longer as we're talking about goodbyes. You have a really nice other poem here about goodbyes. Can I force you to read it as well? Oh, twist my arm, twist my arm. So the next poem was written specifically for our high school yearbook.

So another poem written on demand. The rest of them are just so miserable written by pure, you know, sadness and melancholy. But this one was also written on demand. And it was basically saying goodbye, as is appropriate right now, to my friends and sort of, again, reflecting this whole journey and transformation through life.

And also, I think showing a little bit of introspection about how we kind of had it easy in high school and we're about to go into rougher waters. So the title is actually The Tidewaters and it's an analogy on that. So here it goes. All this was another lake where some rest we sailors take. Waters calm and full of fish. We'll find there what we wish. Some seek fruit and others feast. Some of us just look for peace.

Some find fresh ships, other love, some seek both, and neither have. We were different when we came, each his own story and fame. Different people had we been, different cultures had we seen, different nature, different face, each unlike all in this place. We had faced success, defeat, that in one lake came to meet. There, the orders that we followed and the pride that we swallowed made us one but not the same.

Joined us strangers who there came. Sooner, later, groups were made. Tribes where differences will fade. Some attached, more or less. Others fought and made a mess. But again we have to go. What for? Where to? We don't know. Still we know it. We will try. There to rush, to flee, to fly. There'll be some who wish to stay, but they'll carry on away. We'll continue on our journey as we came here, strong yet lonely.

From the lake a river flows, from the river many goals. On that river we will race. Each will try to find his pace. In that scene, the sailors face their first fear, defeat, disgrace. Here and there comes out a face that the waters soon embrace. Some get lucky, find their way. Others sink beneath the waves.

In this race we will part. Some will settle near the start. Some set goals beyond the stars. 'Cause the river carries far. You should know in what we've done, the hard part is still to come. So I'll have to say goodbye. Don't you worry, I won't cry. Neither will they, those who try, till the end, to keep their pride. But please know, dearest friends, who are always there to mend.

I will always need your hand. I will miss you till the end. I don't think there's a better way to end it.

Manolis, like I said last time, you're one of the most special people at MIT, one of the most special people in Boston, and whatever mental force field that you're applying in saying that Boston is the best city in the world, MIT the best university in the world, you're actually making it happen. So thank you so much for talking to me. It's a huge honor. Thank you so much. It's been a pleasure.

Thanks for listening to this conversation with Manolis Kellis, and thank you to our sponsors, Public Goods, Magic Spoon, and ExpressVPN. Please check out these sponsors in the description to get a discount and to support this podcast. If you enjoy this thing, subscribe on YouTube, review it with five stars on Apple Podcasts, follow on Spotify, support on Patreon, or connect with me on Twitter at Lex Friedman.

And now, let me leave you with some words from another well-known Greek, Alexander III of Macedonia, commonly known as Alexander the Great. There is nothing impossible to him who will try. Thank you for listening, and hope to see you next time.