Manolis Kellis: Origin of Life, Humans, Ideas, Suffering, and Happiness | Lex Fridman Podcast #123

Lex Fridman 0:00 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. (laughs) 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. If you enjoy this thing, subscribe on YouTube, review it with five stars on Apple Podcast, follow on Spotify, support on Patreon, or connect with me on Twitter @lexfridman. I also this time put a link in the description to a survey for this podcast on how I can improve and also an option if you like, I don't know why you would like to, but if you like to join an inner circle of people that help guide the direction of this podcast via email or occasional video chats. If you have a few minutes, please fill it out. As usual, I'll do a few minutes of ads now and no ads in the middle. I try to make these interesting, but I give you timestamps so you can skip. But still, please do check out the sponsors by clicking the links in the description. It's the best way, honestly, to support this podcast. This show is sponsored by Public Goods, an online store for basic health and household stuff. Their products have a minimalist black and white design that I find to be just clean, elegant, and beautiful. It goes nicely, at least I think so, with the design of Crew Dragon and the recent SpaceX NASA mission that sent two humans into space. To me, very few things are as inspiring as us humans reaching out into the unknown, the harsh challenges of space. Colonizing Mars may not have obvious near-term benefits, but I believe it will challenge our scientists and our engineers to create technologies whose impact will be immeasurable for us humans here on Earth, or those of us who, uh, choose to stay here on Earth. Personally, I'm kind of a longtime big fan of this planet. (laughs) Anyway, visit, uh, publicgoods.com/lex and use code LEX at checkout to get 15 bucks off your first order. This episode is also supported by Magic Spoon, low-carb, keto-friendly cereal. You might have heard on other videos that I eat keto mostly these days, so Magic Spoon is a delicious healthy treat on a hard workout day that fits into that crazy diet. Also, they're a sponsor of Episode 100 with my dad and got my dad to buy this cereal, and he now loves it, honestly just loves it. It's kind of funny actually. The deep heartfelt nature of that conversation and the silliness of the cereal captures my dad perfectly. Much of the hardship in his life he dealt with using wit and humor. His favorite flavor happens to be cocoa. Mine is too. He hasn't bought the Eight Sleep mattress yet, though my mom wants to, but he's all about this Magic Spoon cereal. I think it's his actually favorite sponsor of this podcast, probably because they chose to sponsor the episode he's on. Anyway, click the magic spoon.com/lex link in the description and use code LEX at checkout for free shipping, to let them know I sent you, and also indirectly to make my dad happy. This show is also sponsored by ExpressVPN. Get it at expressvpn.com/lexpod. They gave me a suggested opening line of, "Using the internet without ExpressVPN is like going to the bathroom and not closing the door." This is like GPT-3 suggesting to me how to be more human-like, and I'll honestly take all the help I can get. By way of life advice, let me tell you that you need a VPN to protect you from Russians like me. In fact, this podcast is a kind of hack of your biological network where I use my monotone, low-energy voice to convince you to buy a kind of expensive cereal as a way to influence the stability of the US economy. I use ExpressVPN on both Windows and Linux to protect myself if I ever do shady things on the internet, which of course I never do and never will.So, secure your online activity by going to expressvpn.com/lexpod to get a extra three months free, and to support this podcast. And now, here's my conversation with Manolis Kellis.

Lex Fridman 6:21 What is beautiful about the human epigenome?

Manolis Kellis 6:24 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 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...

Lex Fridman 7:24 (laughs)

Manolis Kellis 7:24 ... a hundred times.

Lex Fridman 7:26 Yeah. It's all curled up in there.

Manolis Kellis 7:28 It's all-

Lex Fridman 7:28 You said 30 trillion cells...

Manolis Kellis 7:31 30 trillion cells.

Lex Fridman 7:31 ... in the human body.

Manolis Kellis 7:32 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's not even nee- these nuclei. And that's sort of the structural part. So, so, 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 is 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.

Lex Fridman 8:37 Now, can we draw a loo- a definition distinction between the genome and the epigenome?

Manolis Kellis 8:43 Again, being Greek, epi means on top of.

Lex Fridman 8:46 Mm-hmm.

Manolis Kellis 8:47 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, uh, you have annotations in a orchestra score that basically say whether you should play something softly, or loudly, or space it out, or you know, uh, 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-

Lex Fridman 9:36 Yeah.

Manolis Kellis 9:36 ... sign of repression in a gene regulatory region.

Lex Fridman 9:39 (laughs) I, I love how you're talking about the, the function that, uh, emerges from the epigenome as a, as a musical score.

Manolis Kellis 9:48 (laughs)

Lex Fridman 9:48 It's a-

Manolis Kellis 9:48 It is in many ways. And, uh, 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 7 from chromosome 23, and chapter 4 from chromosome 2, and so on and so forth. And each of those, uh, pieces are all encoded 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

Manolis Kellis 10:28 to play.

Lex Fridman 10:29 One thing that kind of blows my mind, maybe you can tell me your thoughts about it, is the, the way evolution works with natural selection is, uh, based on the final sort of, the entirety of the orchestra musical performance, right? And then, but there's these incredibly rich structural things, like each one of them doing their own little job, that somehow work to get, like the evolution selects based on the final result, and yet the, all the individual pieces are doing like infinitely minuscule, specific things. How the heck-

Manolis Kellis 11:06 It's a very-

Lex Fridman 11:06 ... does that work? Like-

Manolis Kellis 11:07 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 nucleotide's function is selected at the level of, you know, each gene, and every, uh, 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 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, um, symbiosis of, you know, uh, there's plants, for example, that love CO2, and there's humans that love O2, and we're sort of, you know, trading, um, different types of, uh, gases to each other. If you look at, um, ecosystems where one organism which is really nasty, that organism actually died, because everyone they were being nasty to was killed off. And then that kind of, you know, universe of life is gone.

Lex Fridman 12:53 Mm-hmm.

Manolis Kellis 12:53 So basically what emerges is selection at so many different layers of benefit, including, you know, all of these nucleotides within a body interacting for the emergent functions at the body level.

Lex Fridman 13:10 Yeah, I wonder, I wonder if it's possible to break it down into levels, that selection even beyond humans. Like, you said environment, but there's environments at all different levels too, right? Uh, 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, the galaxy level.

Manolis Kellis 13:35 Yeah, yeah, yeah.

Lex Fridman 13:36 Right?

Manolis Kellis 13:36 So, so, um-

Lex Fridman 13:37 Of all different forms.

Manolis Kellis 13:38 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, uh, sort of human history of evolution. So basically if you look at neanderthal genes, for example, which again happened long after that, uh, 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, it's, you know, that cellular environment constitutes the genetics of that gene, but also, of course, all of the epigenomics of that gene.

Lex Fridman 14:57 Yeah, it's fascinating that the, the gene has a history. I mean, we talked about this a little bit last time, but to th- and, and then s- some of your research goes into that, but the, the genes as they are today have, have a story from the beginning o- of time, and then somet- sometimes their story was, like, their path was useful for survival for the particular organisms and sometimes not. That's fascinating. Let me ask, as a tangent,

Lex Fridman 15:26 we kind of started talking offline about neanderthals. Uh, do you have something interesting genetically, biologically, in terms of difference between, uh, neanderthal and, like, the different branches of human evolution that, uh, you find fascinating?

Manolis Kellis 15:42 Neanderthals are only one of about five branches that we are pretty confident about. One branch-

Lex Fridman 15:49 Branches of?

Manolis Kellis 15:50 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 in Siberia.

Lex Fridman 16:05 (laughs) Recent, so relatively recently discovered, right?

Manolis Kellis 16:08 Less than 10 years ago.

Lex Fridman 16:09 Yeah.

Manolis Kellis 16:09 So-

Lex Fridman 16:09 And those are, like, little folks, right? I- Were they-

Manolis Kellis 16:11 No, no, no, no, no. That's yet another one.

Lex Fridman 16:13 (laughs)

Manolis Kellis 16:13 Homo floresiensis. Yeah, the little folks-

Lex Fridman 16:16 Yeah.

Manolis Kellis 16:16 ... in sort of Indonesia. But then, uh, denisovans 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 denisovan. 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, you know, precursors that were wiped out by Zeus or by all kinds of wars and so on and so forth, like the Titans and the, the, you know. It's, it's ridiculous to sort of read these stories as a kid because you're like, "Oh, yeah, whatever." 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? And basically this archeological evidence has been there and has probably entered the folk imagination, migrated into those stories, but it's not that far re- you know, removed from what actually happened, of massive wars, of wiping out neanderthals as humans are, modern humans were populating, um, you know, Europe.

Lex Fridman 17:37 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, uh, us humans being the opposite of altruistic towards each other? Or is it, uh, some other, uh, uh, competition at some other level, like as we're discussing?

Manolis Kellis 17:58 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!"

Lex Fridman 18:26 (laughs) Yeah.

Manolis Kellis 18:26 "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."

Lex Fridman 18:32 Right.

Manolis Kellis 18:32 So, it's, it's kind of funny, like, the, this tribalism is nonsensical in many ways. It's like, con- cognitive incongruent, that basically we like kin, and selection for, for sort of liking kin is hugely advantageous genetically.

Lex Fridman 18:49 Probably across all kinds of organ-

Manolis Kellis 18:50 Of course.

Lex Fridman 18:50 All, all, across all kinds of life.

Manolis Kellis 18:52 Of course, yeah. So, so basically if you now transport that to the sort of humans arriving in Europe and Neanderthals are everywhere, what are you gonna do? You're gonna kill them off. Uh, 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, um, 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-

Lex Fridman 19:23 (laughs)

Manolis Kellis 19:23 ... between, you know-

Lex Fridman 19:24 Yeah, it's funny.

Manolis Kellis 19:24 ... new species.

Lex Fridman 19:24 We have tribes but love, uh, uh, spans, uh, uh, the gap between the different tribes.

Manolis Kellis 19:30 It's-

Lex Fridman 19:30 Somebody sneak-

Manolis Kellis 19:31 It's Romeo and Juliet across species boundaries. (laughs)

Lex Fridman 19:33 (laughs) It sneaks away from the village to, uh, hang out with the Genoese.

Manolis Kellis 19:34 But, but, but even before, 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 and savviness and, uh, you know, probably all our conspiracy theory genes are, you know-

Lex Fridman 19:55 (laughs)

Manolis Kellis 19:55 ... dating back from then. And, you know, so, 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.

Lex Fridman 20:14 It just sucks that, uh, we don't have neighboring species that are, you know, intelligent like us, uh, that, but yet very different than us. So we have like, you know, dogs or wolves, I guess, uh, co-evolved. They figured out how to, uh, neighbor up with humans in a friendly way and collaborate and, uh, de- develop in time.

Manolis Kellis 20:40 You're describing this as if the wolves made a choice.

Lex Fridman 20:43 Um, yeah.

Manolis Kellis 20:44 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.

Lex Fridman 20:56 Ah, humans.

Manolis Kellis 20:57 And it only takes a few generations to then sort of have pups that are really mild.

Lex Fridman 21:02 And so the Neanderthals weren't useful... (laughs) in the same way that wolves were.

Manolis Kellis 21:07 Um, I don't know if it's a question of useful. They were probably super useful. My thinking is that they were, um, scary, that basically something that almost resembles you-

Lex Fridman 21:18 Yeah.

Manolis Kellis 21:18 ... is something that you'd try to eliminate first.

Lex Fridman 21:21 It's too close.

Manolis Kellis 21:22 Yeah.

Lex Fridman 21:22 It's too close.

Manolis Kellis 21:22 And, uh, speaking of, um, 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. (laughs) So if you look at dinosaurs, I mean, the diversity that they had. If you look at some, you know, uh, like there's just so many different lineages of life that were just abruptly killed, and yet out of that death emerged, you know, many new kinds of really awesome lineages.

Lex Fridman 22:00 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?

Manolis Kellis 22:09 So there's-

Lex Fridman 22:09 Like dolphins?

Manolis Kellis 22:09 ... a case could 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, uh, you know. I mean, they don't have opposable thumbs and we do, so, you know, that probably made a big difference.

Lex Fridman 22:22 It's terrifying to think that, like, not terrifying, I don't know how to feel about it, that they're in- more intelligent than us. It's like The Hitchhiker's Guide to... (laughs)

Manolis Kellis 22:30 So... I know. But how do you define intelligence? Basically, like I was saying last time, you know, stupid is as stupid does, and smart is as smart does. So-

Lex Fridman 22:38 Yeah.

Manolis Kellis 22:38 ... if the dolphins are basically super smart, figured out the meaning of life, and just go around playing with water all day, which is probably the meaning of life... (laughs)

Lex Fridman 22:49 Yeah. (laughs)

Manolis Kellis 22:49 ... then we wouldn't know, because all they're doing is kicking water just like sharks are, and sharks are probably pretty stupid. So, (laughs) so basically it's very difficult to sort of judge a species' intelligence unless y- they kind of go out of their way to demonstrate it.

Lex Fridman 23:02 Yeah, and that's instructive for our understanding of any kind of life form. Uh, you know, I'd recently talked to Sara Seager looking for life out there on other planets. It'd be fascinating to think if we discover a habitable planet out-, you know, o- outside of Earth in one day, maybe many centuries away, or be able to travel with, like, a robot there. How would we actually know that this species... We'd probably be able to detect that it's a living being, but how would we know if it's an intelligent being? I mean, uh, it's both exciting and terrifying to sort of come face to face with a life form that's of another world. Like, something that clearly is moving in a, um, how would you say? Like, a deliberate way. (laughs) And to then, like, ask, well, how do I ask that thing whethe- whether it's intelligent?

Manolis Kellis 24:02 No, but the question that you're asking is, um, applicable to every species on, on the Earth now.

Lex Fridman 24:07 On Earth now, yeah.

Manolis Kellis 24:08 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 in communication-Um, (sighs) the way that I wanna put it is that, uh, humans have achieved a level of sophistication in our behaviors, in our communication, in our language, in our ways of expressing ourselves that w- I have no doubt that if we encountered a human-like form of intelligence, we'd figure out their language in a few weeks.

Lex Fridman 24:48 Mm-hmm.

Manolis Kellis 24:48 Like, it'd be just fine, as long as, you know, of course, they're both trusting each other, not annihilating each other, and not sort of fearing each other and attacking each other.

Lex Fridman 24:57 What about, uh ... Let me ask, like, just out of curiosity, into science-fiction land a little bit, if ... so, uh, clearly, you're one of the top scientists in the world, so if we were to discover an alien life form, uh, you would be brought in to study its genetics.

Manolis Kellis 25:15 (laughs)

Lex Fridman 25:15 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 the, in, um, in fundamental ways, maybe not exactly, but in fundamental ways-

Manolis Kellis 25:31 The-

Lex Fridman 25:31 ... how it's structured?

Manolis Kellis 25:32 Yeah, so, so you're getting to the very definition of life. You're getting to the very definition of what- what makes life, life, and how do we decode that life. And, um, it's so easy to think that every life form would basically have to, you know, like oxygen, has- have to like heat from the sun, uh, 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 timescales of human-

Lex Fridman 26:18 Mm.

Manolis Kellis 26:18 ... life, where we kind of live, I don't know, between ... And- and I'm gonna be super wide here. I'm gonna ... We- we're gonna live between six Earth months and, you know, 200 Earth month- Er- Er- Earth months. Uh, or 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 gravitation of pull, the gravitational pull of Jupiter is probably creating all kinds of movement under that ice.

Manolis Kellis 27:16 How did life evolve on Earth? Yes, sure, life now, most of life that we above the surface look at, has to do with ex- exploiting the solar energy for, you know, 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, uh, 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, uh, 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 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-

Lex Fridman 28:23 (laughs)

Manolis Kellis 28:23 ... question is, how did it evolve over there?

Lex Fridman 28:24 Yeah, exactly.

Manolis Kellis 28:25 Uh, whereas our planet has basically all of the right ingredients. Why would it evolve here? So basically, let's kind of ignore that one. And now the- the two other competing hypotheses are from the outside in or from the inside out.

Lex Fridman 28:36 What's that mean?

Manolis Kellis 28:36 From the outside in means from the surface to the bottom of the ocean.

Lex Fridman 28:40 Ah.

Manolis Kellis 28:41 From the inside out means from the bottom of the ocean to the surface.

Lex Fridman 28:44 (laughs)

Manolis Kellis 28:46 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.

Lex Fridman 29:05 So just to be clear, on the surface, are- are you referring to the ...

Manolis Kellis 29:10 The surface of the sea or the bottom of the sea.

Lex Fridman 29:12 Uh, versus the bottom, uh, of the sea.

Manolis Kellis 29:15 Of the ocean.

Lex Fridman 29:15 And you're saying life on the surface is, uh, is harsh chemically.

Manolis Kellis 29:19 Life outside the ... Li- life outside the water is horrible. It takes huge amounts of evolutionary innovations to sustain living outside the water.

Lex Fridman 29:30 Why? Yeah, that's so interesting.

Manolis Kellis 29:32 (laughs)

Lex Fridman 29:32 Why- why is that? So it's easier to ... Life is easier in- in the water. Maybe ... See? I'm telling you dolphins are-

Manolis Kellis 29:37 We are- we are 70% water.

Lex Fridman 29:39 ... onto something.

Manolis Kellis 29:39 No, dolphins went back into the water.

Lex Fridman 29:42 Really? Oh-

Manolis Kellis 29:42 Of course.

Lex Fridman 29:42 ... 'cause dolphins are mammals.

Manolis Kellis 29:44 Of course. Yeah.

Lex Fridman 29:45 Interesting. Well, again, they might be smarter. They went back.

Manolis Kellis 29:48 (laughs)

Lex Fridman 29:48 They're like, "Screw this."

Manolis Kellis 29:49 So- so if you, if you basically think about, uh, the fact that we are 70% water, we're basically transporting the sea with us outside the sea.

Lex Fridman 30:01 (laughs)

Manolis Kellis 30:01 You know, if we- if we-

Lex Fridman 30:02 That's fascinating.

Manolis Kellis 30:02 ... don't have water for about a- a- a, you know, 24 hours-

Lex Fridman 30:05 That's

Narrator 30:05 (laughs) I'm kidding.

Manolis Kellis 30:05 ... we're dry.

Lex Fridman 30:06 Yeah.

Manolis Kellis 30:07 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 li- the- the boring life forms is what we see all the time, like tetrapods. I mean, what a stupid, boring body plan.

Lex Fridman 30:22 (laughs)

Manolis Kellis 30:22 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, uh, humans with four limbs, birds with four limbs, lizards with four limbs and, you know... (laughs) 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?"

Lex Fridman 31:12 The three-

Manolis Kellis 31:12 From the surface-

Lex Fridman 31:13 H- hold on a second.

Manolis Kellis 31:13 ... or from the bottom?

Lex Fridman 31:14 Exactly. Those two options that you were mentioning.

Manolis Kellis 31:16 Yeah, 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, you know, coalesce and, you know, bounce around, et cetera. That's one option. The second option, massive amount of energy under, you know, from, from, from our, the core of our planet, basically, uh, 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. (laughs) Um, 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, 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.

Lex Fridman 33:02 (laughs)

Manolis Kellis 33:02 So basically, you then, boom, you know, have life going, and the moment you have A, B, C, some kind of thing looping back onto A, you can make modifications, and you can improve, and then you let natural selection work.

Lex Fridman 33:17 Is there some element of that that's like co- like, uh, like some state representation that stores information? Like, I, maybe I should say information?

Manolis Kellis 33:27 Yeah, no. Absolutely.

Lex Fridman 33:27 Is that a fundamental part of life?

Manolis Kellis 33:28 So- so 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.

Lex Fridman 33:40 Mm-hmm.

Manolis Kellis 33:41 So basically, DNA, we think is an essential part of life. That's where the storage is, and therefore, that early life forms 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.

Lex Fridman 34:27 Self- what?

Manolis Kellis 34:28 Self-hybridization. So basically, the same way that DNA molecules can hybridize with themselves-

Lex Fridman 34:33 Mm-hmm.

Manolis Kellis 34:33 ... and basically form this double helix, the single-stranded RNA molecule-

Lex Fridman 34:37 (laughs)

Manolis Kellis 34:37 ... can form partial double helixes 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 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 gonna 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, if you want, I don't know, divine intervention in the history of life, the ribosome is it. (laughs)

Lex Fridman 36:19 That's one of the great invention in the history of life, is the ribosome?

Manolis Kellis 36:21 It's- 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 they 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, we, 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, uh, 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 gonna delegate all information storage to DNA, and I'm gonna get- delegate most actuation to proteins."

Lex Fridman 37:56 Proteins. But that's, to you, is not like a... that- that's just an efficiency thing, it's not a fundamentally-

Manolis Kellis 38:03 Correct.

Lex Fridman 38:04 ... new-

Manolis Kellis 38:04 Correct.

Lex Fridman 38:05 ... innovation.

Manolis Kellis 38:05 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, 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, you know, the closing of that loop and the ignition of the evolutionary process.

Lex Fridman 38:35 Can we just rewind a l- a little bit? Like, if you were to bet all your money on the two options in terms of where life started...

Manolis Kellis 38:41 Probably the bottom.

Lex Fridman 38:42 The, at- at the bottom dose? 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-

Manolis Kellis 38:53 Yeah. Yeah, yeah. So-

Lex Fridman 38:54 ... about from not, from not life to life?

Manolis Kellis 38:57 Yeah. I think it's inevitable.

Lex Fridman 39:00 On Earth or just... (laughs)

Manolis Kellis 39:02 In the universe.

Lex Fridman 39:02 (laughs)

Manolis Kellis 39:03 I think it's inevitable. If you look at Europa, you know, going back-

Lex Fridman 39:08 Which is?

Manolis Kellis 39:08 The, the, the moon of Jupiter.

Lex Fridman 39:10 It's also a really nice song by Santana.

Manolis Kellis 39:12 (laughs)

Lex Fridman 39:12 Yeah.

Manolis Kellis 39:13 Europa basically has all the ingredients. It has, you know, the core that can emit energy. It, 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 a independently arisen life form already teeming in Europa, because as soon as it-

Lex Fridman 39:45 Today?

Manolis Kellis 39:47 Today.

Lex Fridman 39:47 Is that exciting or terrifying to you? (laughs)

Manolis Kellis 39:51 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, uh, in, in, you know, sort of, uh, ɔr nɛ, as I would say in French. But basically we're sort of, you know, we, we, 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-

Lex Fridman 40:19 Whoa.

Manolis Kellis 40:19 ... the discovery of life elsewhere.

Lex Fridman 40:21 L- let me bring you into another science fiction, uh, uh, sc- scenario. So on that point, if we discover life on Europa, and you were brought in, you seem very excited, but, um, 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? (laughs) So like, the... to me, it's a little bit scary, because not, not because it's malevolent life, like it's a, it's a dictator petting like a cat, it's evil. But just the way life is, it seems to be very good at conquering other life.

Manolis Kellis 41:04 So there's a lot of science fiction movies based on that principle.

Lex Fridman 41:07 Yeah.

Manolis Kellis 41:08 And, uh, 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's bacteria, because Earth's 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 s- in the converse way, if you bring life from Europa on Earth, it'll die instantly, because it's too hot or (laughs) because it doesn't need to know how to cope with, I don't know, the sun's radiation so close to this completely inhabitable zone by their standards. (laughs)

Lex Fridman 41:53 So-

Manolis Kellis 41:53 So what we call the habitable zone might actually be the inhabitable zone for them.

Lex Fridman 41:56 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 on, on a basic, uh-

Manolis Kellis 42:06 It'll take massive-

Lex Fridman 42:07 ... biological-

Manolis Kellis 42:07 ... amounts of engineering to create machines that will go there and sample the, you know, 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, you know, some other kind of combination of chemicals that will look non-random.

Lex Fridman 42:36 So if you had to bet, if I took that life form we find on, uh, Europa and, like, put it on a sandwich that you're eating and, like, eat that sandwich-

Manolis Kellis 42:45 It'll taste just fine.

Lex Fridman 42:47 And you'll be... well, I... that... we know about that.

Manolis Kellis 42:49 (laughs)

Lex Fridman 42:50 I don't know, actually-

Manolis Kellis 42:50 And it won't kill you.

Lex Fridman 42:51 ... will it taste fine? That's interesting though.

Manolis Kellis 42:52 So the, the other question is, do we have taste receptors for this?

Lex Fridman 42:56 Do you underst-

Manolis Kellis 42:56 So where, where does our taste come from?

Lex Fridman 42:58 Well, with the chemistry.

Manolis Kellis 42:58 It's basically adaptations to chemical molecules that we are used to seeing.

Lex Fridman 43:03 So you think even the chemistry of that life-

Manolis Kellis 43:03 We don't have taste buds for things we don't even know about.

Lex Fridman 43:06 Wow.

Manolis Kellis 43:06 So we won't, yeah, we won't be able to know that this chemical tastes funny.

Lex Fridman 43:09 But you think it won't be...... it's likely not to be dangerous. Like, it- it won't know how to even intere- do you think our immune system will- will even detect that something weird is- is going on?

Manolis Kellis 43:20 Probably.

Lex Fridman 43:22 (laughs)

Manolis Kellis 43:22 And it'll be very easy to detect, because it'll be, it'll be very different from us.

Lex Fridman 43:25 Very weird.

Manolis Kellis 43:25 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." (laughs)

Lex Fridman 43:34 (laughs)

Manolis Kellis 43:34 I mean, it's hilarious-

Lex Fridman 43:35 Yeah.

Manolis Kellis 43:35 ... because like Macs and PCs have trouble communicating. (laughs)

Lex Fridman 43:40 (laughs) That's funny.

Manolis Kellis 43:40 I mean, let alone an alien technology or even alien DNA.

Lex Fridman 43:43 So okay,

Lex Fridman 43:44 uh, now I was talking about you being a scientist on Earth, but say you were a scientist, uh, that were shipped over to Europa to investigate if there's life. What would you look for in terms of signs of life?

Manolis Kellis 43:57 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, uh, uh, 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, uh, my- my friend who's an astrophysicist, um, basically, uh, we were- we were deciding on what would be the themes for the- for the symposium, and then, uh, I said, "Well, we're gonna have biology. We're gonna have physics." And she's like, "Ah, psh, come on. Biology's just a small part of physics." (laughs)

Lex Fridman 44:47 (laughs) Everything's a small part of physics, right? (laughs)

Manolis Kellis 44:50 And, uh, I mean, in- in- in many ways it is.

Lex Fridman 44:53 (laughs)

Manolis Kellis 44:53 But my immediate answer was, "No, no, no, no. Wait. Life challenges physics. It supersedes physics. It- it sort of f- fights against physics." And that's what I would look for in Europa. I would basically look for this fight against physics, for anything that's 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 environment, selection for biospheres, for ecosystems, for these multi-organism form of life? And I think that's sort of the- the first thing that you can look for. You know, chemical signatures that are not simply predicted from the reactions you would get randomly.

Lex Fridman 45:38 That's such a beautiful way to look at life. So you're basically leveraging some energy source to enable you to resist the physics of the universe? (laughs)

Manolis Kellis 45:48 Fighting against physics.

Lex Fridman 45:49 (laughs)

Manolis Kellis 45:50 But that's- that's the first transformation. If you look at humans, we're way past that.

Lex Fridman 45:54 What do you mean by transformation?

Manolis Kellis 45:55 So- so basically there's- there's layers. I sort of see life, you know... When- 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, (laughs) "To whom do you owe your life, to your teachers or to your parents?" And Alexander the Great, uh, answered, "I owe to my parents the zene, the life itself, and I owe to my teachers the euphzene." Like euphony, euph means good, the opposite of cacophony, which means, you know, bad. So, euphzene, in his, uh, words, was basically living a human life, a proper life. So basically we can go from the zene (laughs) to the euphzene. 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 euphzene is a whole other, um, 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 eu- 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 germ line. 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. (laughs) I'm- I'm sorry to be so blunt.

Lex Fridman 48:27 Yeah.

Manolis Kellis 48:27 And if you look at nutrition, you know, we're deuterostomes. What does deuterostome mean? Deutero means second. We're the- this is the second mouth. The first mouth is actually down here. It's the esophagus.

Lex Fridman 48:39 Mm-hmm.

Manolis Kellis 48:39 So deuterostomes have evolved a second layer of eating, kinda like alien with the two mouths. (laughs)

Lex Fridman 48:45 Yeah. (laughs)

Manolis Kellis 48:46 (laughs) 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-

Lex Fridman 48:52 Is- is- is the first mouth just the- the physical manipulation of the food to make it more consumable?

Manolis Kellis 48:56 Correct. Correct. Correct. And basically, again, you know, if you look at-

Lex Fridman 48:59 So weird.

Manolis Kellis 48:59 ... if you look at a worm-

Lex Fridman 49:01 Yeah. (laughs)

Manolis Kellis 49:01 ... it's an extremely simple life form.

Lex Fridman 49:02 Yeah.

Manolis Kellis 49:02 Basically has a mouth, it has an anus-

Lex Fridman 49:05 Yeah.

Manolis Kellis 49:05 ... and it has, you know, just some organs in between that consume the food and just spit- spit out poop.

Lex Fridman 49:09 Yeah.

Manolis Kellis 49:10 Um, 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 foo- food.

Lex Fridman 49:24 Yeah.

Manolis Kellis 49:25 And then you have, of course, the germ line, and all of this food part, it's just auxiliary to the germ line. So, you basically have layers of addition, of compartmentalization, of specialization on top of this xene to get all the way to the euxene.

Lex Fridman 49:39 Yeah, so like, the worm is, like, Windows 95, very few features, very basic, and then us humans are like Windows Vista or Windows 10, whatever it is.

Manolis Kellis 49:49 Well, a- a few- a few innovations beyond that, but yeah-

Lex Fridman 49:51 Beyond that, or where, I don't know-

Manolis Kellis 49:53 Windows 3000, let's put it that way. (laughs)

Lex Fridman 49:56 So, okay, uh, th- that's such a fascinating way to look at life as a set of transformations.

Manolis Kellis 50:01 Exactly.

Lex Fridman 50:02 So, like, is there some interesting transformations through our history here on Earth-

Manolis Kellis 50:07 Of course.

Lex Fridman 50:07 ... that, like-

Manolis Kellis 50:07 Of course.

Lex Fridman 50:07 ... appeal to you?

Manolis Kellis 50:08 Of course. So-

Lex Fridman 50:09 I mean, what are the most brilliant innovations and transformations you can say?

Manolis Kellis 50:12 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 germ line from everything else that accompanies it and- 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 the- 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, uh, free will?

Lex Fridman 51:04 Mm-hmm.

Manolis Kellis 51:04 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.

Lex Fridman 51:13 Yeah.

Manolis Kellis 51:13 And maybe that's free will because it's unpredictable beyond a certain level. So, um, 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

Manolis Kellis 51:35 the other thing that I love talking about is the different timescales at which things happen. You know, we were 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 an h- to half an hour. That's the expression response. But our daily life doesn't happen on the order of three minutes to an h- 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.

Lex Fridman 52:37 Is that an accident, by the way? Is that, like, a feature? Is it- was it possible for life to have evolved where the- our d- the daily life of the organism as it interacts with its environment was on a timescale similar to, uh, the- the way our internals work?

Manolis Kellis 52:54 If you look at trees, they look kind of boring and stupid. You're, like, looking at a tree, you're like, "Stupid." If you speed up the movie of a tree-

Lex Fridman 53:02 Yeah.

Manolis Kellis 53:02 ... 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- a, you know, a thing to catch onto. Ooh, I just caught onto that. I'm gonna grow more here, I'm gonna spawn out there," et cetera. Like, I can see the trees in my garden just growing and sort of, you know, looping around, and, um, 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. Um, and then we- 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 gain- 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 because before we have babies. So, intergenerational dif- distance is s- you know, grown from, I don't know, 16 years to 40 years.

Lex Fridman 54:36 You're saying that's in the genetics, like-

Manolis Kellis 54:38 No, no, not necessarily, but- but it's- 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.

Lex Fridman 54:57 Like, if we look at the long arc of the-

Manolis Kellis 54:59 The- exactly.

Lex Fridman 54:59 ... evolutionary history.

Manolis Kellis 55:00 Exactly. So, as we start thinking-

Lex Fridman 55:03 Yeah.

Manolis Kellis 55:03 ... about intergalactic travel now ...

Lex Fridman 55:05 (laughs) Sorry. That- (laughs) that's- that's a heck of a transition. Uh, yeah, so let's talk about intergalactic travel.

Manolis Kellis 55:12 No, no, no, no, no, no.

Lex Fridman 55:13 Yeah.

Manolis Kellis 55:13 As- as we as a species start thinking about... I b- I'm- I'm talking about these transitions that are happening, right?

Lex Fridman 55:18 Oh, that's- that's- that's awesome.

Manolis Kellis 55:19 So, continuing 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-

Lex Fridman 55:37 It's all timescale.

Manolis Kellis 55:38 It's all timescale, just different timescales.

Lex Fridman 55:40 Yeah.

Manolis Kellis 55:41 Y- you asked 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 today forever? Kind of like Groundhog Day. And the answer is absolutely. The stuff that I wanna learn today will probably take a lifetime just to learn, you know, (laughs) basically to clear my to-do list for the day.

Lex Fridman 56:06 You mean, like, relive the day-

Manolis Kellis 56:07 Relive the day.

Lex Fridman 56:08 ... and then, and then pick up different things from the richness of the experiences-

Manolis Kellis 56:11 Exactly.

Lex Fridman 56:11 ... they're all in today?

Manolis Kellis 56:12 Uh, 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.

Lex Fridman 56:20 (laughs) O- on that, on that point, um, just, I would just love to see you in a groundhog movie just (laughs) 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. Uh, uh, uh, it's a beautiful visual. But you say-

Manolis Kellis 56:38 I try to live each day as if it was Groundhog Day.

Lex Fridman 56:40 Groundhog Day.

Manolis Kellis 56:41 I- I- I'm basically every single day waking up and saying, "All right, how would Bill Murray g- get out of that one?" (laughs)

Lex Fridman 56:46 Well, you know what? On a, on a funny tangent, I, I got a chance to, uh, go to a Neuralink demonstration event.

Manolis Kellis 56:55 Yeah, yeah, yeah.

Lex Fridman 56:56 I'm not if you're familiar with Neuralink.

Manolis Kellis 56:57 I read about that.

Lex Fridman 56:58 And, uh, I talked to Elon for a while, uh, and one of the funny things he said on this 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, um, maybe a noisy recording machine of memories, and it'll be beautiful if we can s- some day 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 memor- of a previous memory.

Manolis Kellis 57:39 That's true.

Lex Fridman 57:40 And that stuck with me because it would probably be my replay. You know, um-

Manolis Kellis 57:44 Mm-hmm.

Lex Fridman 57:44 ... who the hell am I? I'm just some idiot guy, but like-

Manolis Kellis 57:47 (laughs)

Lex Fridman 57:47 ... Elon Musk is a, you know, uh, uh, probably because of SpaceX and so on is probably going to be remembered as a special person-

Manolis Kellis 57:54 Yeah.

Lex Fridman 57:55 ... one of our-

Manolis Kellis 57:55 Yeah.

Lex Fridman 57:55 ... special apes-

Manolis Kellis 57:56 Yeah.

Lex Fridman 57:57 ... in, in history. So if I wanted to replay a memory, probably be that one, you know, talking to Elon-

Manolis Kellis 58:02 Yeah, yeah.

Lex Fridman 58:02 ... for a while.

Manolis Kellis 58:02 Yeah. That's awesome.

Lex Fridman 58:03 And that's an interesting, uh, possibility from a ... if we think about timescales, if we think about the richness of the experience through time that we humans take and being able to replay some aspects of that, of that biology. That's-

Manolis Kellis 58:22 Yeah.

Lex Fridman 58:22 ... super interesting. But anyway, (laughs) sorry for, sorry for the tangent. Let's ... yeah, you were talking about timescales and the expansion of the human lifetime and, uh, the-

Manolis Kellis 58:33 So- so-

Lex Fridman 58:34 ... idea of intergalactic travel. (laughs)

Manolis Kellis 58:35 Yeah. No, but, but you're laughing about it, so

Narrator 58:37 (laughs)

Manolis Kellis 58:38 ... what are you laughing about?

Lex Fridman 58:38 For sure, that is the future.

Manolis Kellis 58:39 You're talking about this. You're talking-

Lex Fridman 58:40 Yeah.

Manolis Kellis 58:40 ... about exploring alien worlds-

Lex Fridman 58:42 Yeah.

Manolis Kellis 58:42 ... and going to other planets. I mean, you know, when Sara was here, she was talking about sort of going to other planets when we find this life. I mean, I'm, I'm just very naturally, given the topics that we've approached, talking about the, the timescale at which this will happen. And basically-

Lex Fridman 58:56 So you think eventually we will ... human, or life, life will expand out into the universe?

Manolis Kellis 59:03 The, 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.

Lex Fridman 59:16 Yeah.

Manolis Kellis 59:17 Expand the, the, the timescales 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 t- forever, even if it was, even if it 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 wanna 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, uh, you know, sort of, uh, experiment that I want you to, 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?

Lex Fridman 59:59 Mm-hmm.

Manolis Kellis 59:59 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.

Lex Fridman 1:00:11 So, 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.

Manolis Kellis 1:00:24 Exactly. Exactly.

Lex Fridman 1:00:25 (laughs) Like trees have it right. (laughs)

Manolis Kellis 1:00:26 Like trees have it right, olive trees. Like, you know, they've been there since the Minoan civilization.

Lex Fridman 1:00:31 Yeah.

Manolis Kellis 1:00:32 And, you know, that takes us back to the, the question you, you asked about sort of the transformations that have happened in humanity.

Lex Fridman 1:00:37 Yeah.

Manolis Kellis 1:00:37 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, um, that basically looked at the, uh, genetic makeup of the Minoans and the Mycenaeans in ancient Greek, in ancient Greece and how they, they're, 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, 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 standards 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 evolving a brain. (laughs) Of, you know, learning how to communicate, language, or the evolution of eyesight. If you look at sort of, you know, we were 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... Yeah, I mean, when I say nose, I mean ways of sensing chemicals. That's probably one of the earliest senses. You- 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 o- 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, uh, 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.

Lex Fridman 1:02:39 (laughs) So, you see that as a j- yet another transformation-

Manolis Kellis 1:02:41 Of course.

Lex Fridman 1:02:41 ... that gives us an extra little sense?

Manolis Kellis 1:02:43 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 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, about, around elegance, around, you know, statues and tragedy." I mean, a- a- an- another question that you asked me in passing was this whole concept of embracing the good and the bad, embracing your, 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. (laughs) But- but the whole concept of some problems that are just so vast and large that dying is the easy way out.

Lex Fridman 1:03:40 (laughs)

Manolis Kellis 1:03:42 (laughs) That death-

Lex Fridman 1:03:42 Yeah.

Manolis Kellis 1:03:42 ... "Oh, that's the easy solution." You know, so- so I wanna touch a little bit on that point, and- and, um, 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- that is basically when-

Lex Fridman 1:04:27 Yeah. (laughs)

Manolis Kellis 1:04:27 ... the brain itself-

Lex Fridman 1:04:28 So brilliant.

Manolis Kellis 1:04:28 ... is basically superseding what evolution programmed us for. Pow. (laughs)

Lex Fridman 1:04:34 So, uh, so I, okay, j- so one of the, it's, okay, I will, my mind was already blown at the beautiful formulation of the idea that life is, uh, is a system that resists physics.

Manolis Kellis 1:04:49 Yeah.

Lex Fridman 1:04:50 And our brain, or perhaps the content of it, or however it may be functionally our brain is a thing that resists life.

Manolis Kellis 1:05:00 Yes. Yes.

Lex Fridman 1:05:03 You're- you're so f-

Manolis Kellis 1:05:05 (laughs)

Lex Fridman 1:05:05 You're so brilliant. (laughs)

Manolis Kellis 1:05:07 But- but- but- but- but, uh, I want you to see all of that as a continuum. Basically, you're sort of talking about the sort of individual transformations, but it's a path...

Lex Fridman 1:05:16 Yeah.

Manolis Kellis 1:05:16 ... that- that humanity has been taking.

Lex Fridman 1:05:17 It's a transformation.

Manolis Kellis 1:05:18 It's a path

Manolis Kellis 1:05:19 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.

Lex Fridman 1:05:30 Mm-hmm.

Manolis Kellis 1:05:30 What motivated it, in part, I mean, of course, it was an inside joke of turning 42-

Lex Fridman 1:05:35 (laughs) Yeah.

Manolis Kellis 1:05:36 ... but what motivated it 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, Berkeley, everywhere, uh, brilliant, brilliant person, as, actually Costis' advisor.

Lex Fridman 1:05:53 Advisor, yeah, yeah.

Manolis Kellis 1:05:54 Uh, so- 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 post-doc, you work like a rat to get your assistant professorship.

Lex Fridman 1:06:08 Yeah.

Manolis Kellis 1:06:09 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. (laughs)

Lex Fridman 1:06:18 (laughs) Ah, that's brilliant.

Manolis Kellis 1:06:19 So- so basically, what happened to me is that I arrived at the end of the rat race.

Lex Fridman 1:06:24 Yeah.

Manolis Kellis 1:06:25 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- I'm not a rat, it turns out." (laughs)

Lex Fridman 1:06:47 Is that the first moment where you saw that it's, that you weren't in a rat race?

Manolis Kellis 1:06:53 It- it, no, no, no. I've known that I'm in a rat race for a long time, and it's so easy to be in a rat race. It's so easy to be an undergrad-

Lex Fridman 1:06:58 Day-to-day?

Manolis Kellis 1:06:58 ... 'cause you have problem sets. And-

Lex Fridman 1:07:00 (laughs) Problem sets.

Manolis Kellis 1:07:00 ... you- you know, we're all smart people. You know, problem set, it has a solution. Somebody made it for you, you can just solve it.

Lex Fridman 1:07:06 Yeah.

Manolis Kellis 1:07:06 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 again, you have an advisor who's guiding you. And then you become a professor, and tenure is a well set, defined set of tasks, and you do all that. And at 42, I basically had bought a house, three kids, beautiful wife, tenure-

Lex Fridman 1:07:34 Yeah.

Manolis Kellis 1:07:36 ... awesome students, tons of grants.Life was basically laid out for me.

Lex Fridman 1:07:40 Yeah.

Manolis Kellis 1:07:41 And that's when I had my ... midlife crisis. That's when people usually buy a Harley-Davidson. (laughs)

Lex Fridman 1:07:46 (laughs)

Manolis Kellis 1:07:47 And they basically say, "Oh, I need something new, I need something different, I need to be young myself," etc. 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?" 'Cause 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, then 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, w- I was like, "No, no, no, our life is not gonna 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?"

Lex Fridman 1:08:45 Right.

Manolis Kellis 1:08:46 How do I make sure that they're-

Lex Fridman 1:08:47 Exactly.

Manolis Kellis 1:08:47 ... you know, into the grea- greatest college? And then, you know, they're into college, and then you're, like, 60. (laughs)

Lex Fridman 1:08:55 So how do you, how do you escape? What is the, um... Is, is there a light at the end of the tunnel of a midlife crisis?

Manolis Kellis 1:09:03 So, 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. This, you know ... There's some- 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 there's more obstacles for your little rat persona to jump through.

Lex Fridman 1:09:41 Y-

Manolis Kellis 1:09:41 So, that's one possibility.

Lex Fridman 1:09:42 So, fir- uh, first of all, watch, is it available somewhere?

Manolis Kellis 1:09:46 It's on YouTube. Just Google-

Lex Fridman 1:09:47 What? Really?

Manolis Kellis 1:09:48 ... Google Meaning of Life Symposium. (laughs)

Lex Fridman 1:09:49 I should have known this. I mean, you should have told me this. I... This is awesome. Okay.

Manolis Kellis 1:09:53 Yes.

Lex Fridman 1:09:53 This is great. But, a- and also, like, you know, saying rat race is, uh ... you know, if we look at Ratatouille, it- it's not ... (laughs) I mean, that's a beautiful, that's a beautiful thing, uh, of- of challenges and overcoming challenges. That could be fundamentally the meaning of life, is, um, to see life as a set of challenges, and to, uh, fully engage in the overcoming of those challenges.

Manolis Kellis 1:10:24 I would say that that's embracing the rat race view of life. So, so a- a joke that we like to have with my wife all the time is, um, we basically say, uh, we- we- 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, 'cause 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, uh, "What are we gonna do today?" I'm like, "Oh, I've signed up for professor activities."

Lex Fridman 1:10:56 (laughs)

Manolis Kellis 1:10:56 "It's gonna be awesome. They- they- they lined up a bunch of super smart MIT students for me to meet with. I'm gonna have a grant-writing meeting afterwards. It's gonna be awesome. And then she signed up for a bunch of consulting activities. It's gonna be great." And then in the evening, we just get back together and say, "Hey, how was your consulting today?"

Lex Fridman 1:11:11 Yeah. (laughs)

Manolis Kellis 1:11:12 Oh, you know ... (laughs) 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-

Lex Fridman 1:11:29 (laughs)

Manolis Kellis 1:11:30 ... (laughs) et cetera, et cetera, et cetera.

Lex Fridman 1:11:32 Yeah.

Manolis Kellis 1:11:32 In fact, I would have exactly the life that I have now, working my butt off every single day-

Lex Fridman 1:11:37 Yeah.

Manolis Kellis 1:11:38 ... because it's so freaking fulfilling.

Lex Fridman 1:11:40 Well, that's ... Uh-

Manolis Kellis 1:11:42 (laughs)

Lex Fridman 1:11:42 So, so let- let's clarify. Uh, this is a beautiful way, it's almost like a video game view of life, that just a set of ... I mean, again, game is not, perhaps, a positive term-

Manolis Kellis 1:11:51 Yeah.

Lex Fridman 1:11:51 ... but it's a, it's a ... It is a beautiful term. So, you (laughs) ... You ... Do, do you or do you not like the rat race view of life?

Manolis Kellis 1:12:01 No. Hm. Because-

Lex Fridman 1:12:02 Because it is fulfilling-

Manolis Kellis 1:12:02 Because-

Lex Fridman 1:12:02 ... in some fundamental way.

Manolis Kellis 1:12:04 ... the rat race is about the goal. My view of life is about the path, so again, quoting Greece. (laughs)

Lex Fridman 1:12:12 Those folks have come up-

Manolis Kellis 1:12:13 So-

Lex Fridman 1:12:13 ... with some good stuff.

Manolis Kellis 1:12:14 So, this, um, Odysseus Elytis basically wrote this, uh, beautiful poem about sort of going through, uh, 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."

Lex Fridman 1:12:46 And-

Manolis Kellis 1:12:46 So, the- 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.

Lex Fridman 1:13:18 So, we ... You mentioned kind of the ups and downs of life, and the midlife crisis, and right now, you said focusing kind of on the journey.

Manolis Kellis 1:13:28 Mm-hmm.

Lex Fridman 1:13:29 But what the journey involves is ups and downs.

Manolis Kellis 1:13:33 Mm-hmm.

Lex Fridman 1:13:34 Is there, uh, advice or any kind of thoughts that you can elucidate about the downs in your life-

Manolis Kellis 1:13:44 Yeah.

Lex Fridman 1:13:44 ... the hard ...... parts of your life and how you got out, or maybe not, or is there... Yeah, how do you see the dark parts-

Manolis Kellis 1:13:54 Yeah.

Lex Fridman 1:13:54 ... of life?

Manolis Kellis 1:13:55 So, I, 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.

Lex Fridman 1:14:15 (laughs) Yeah.

Manolis Kellis 1:14:16 We strive to tell everyone, "Yes, you can succeed. Yes, you're a millionaire, just temporarily disabled. And yes," you know, uh, "the prince will f- eventually figure out his princess and they will have a l- 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.

Lex Fridman 1:14:46 (laughs)

Manolis Kellis 1:14:47 (laughs) Where, where just, you know, MacGyver doesn't figure out how to disable the bomb and it just explodes. (laughs) You just, 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, I, uh, have been exposed to songs that are not just sad, but they're miserable.

Lex Fridman 1:15:11 (laughs)

Manolis Kellis 1:15:11 Miserable. So-

Lex Fridman 1:15:14 So they-

Manolis Kellis 1:15:14 ... so one of them, one of them comes to mind.

Lex Fridman 1:15:17 (laughs)

Manolis Kellis 1:15:17 And, and it's, 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, uh, general. If only he had died with honor-

Lex Fridman 1:15:52 Yeah.

Manolis Kellis 1:15:52 ... I would be proud to have lost the joyful kid." I mean, it's devastating, right?

Lex Fridman 1:15:58 (laughs)

Manolis Kellis 1:15:59 It's like, he didn't just die-

Lex Fridman 1:16:01 (laughs)

Manolis Kellis 1:16:02 ... he died without honor.

Lex Fridman 1:16:03 Yeah.

Manolis Kellis 1:16:04 And, and, uh, uh, my friend who was with me was listening to this 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."

Lex Fridman 1:16:12 (laughs)

Manolis Kellis 1:16:12 And she's like, "What? This one died with honor?" (laughs)

Lex Fridman 1:16:14 (laughs)

Manolis Kellis 1:16:15 So, so that- that's one example.

Lex Fridman 1:16:17 It's a kind of a celebration of, uh, misery. And-

Manolis Kellis 1:16:21 No. No, no, no, no, no, no. No. So let me give you a couple more examples and, and then I'll answer that question. So another example is I- 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, r- living in a house in the bright light above. And the poor one is wishing, looking out the 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?"

Lex Fridman 1:17:02 (laughs)

Manolis Kellis 1:17:02 The next story, I'm like, "Okay, that's fine. Let's skip this one. Let's..." You know, so I read these to my kids and then I, I read the next one. And the next one is about this, this woman whose brother is at war against the Turks and he is gonna 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."

Lex Fridman 1:17:27 (laughs)

Manolis Kellis 1:17:29 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- the life stories of the others and she's like, "No, no. Just don't, don't take anyone." She's like, "I can't do that. I can ch- you can choose to bring your bro- 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." She's like... And in the end, the woman decides to have her brother killed instead 'cause he dies without... I mean, this is-

Lex Fridman 1:18:04 Ah, that's kind of brilliant.

Manolis Kellis 1:18:04 ... this is insane. So, so-

Lex Fridman 1:18:06 Yeah.

Manolis Kellis 1:18:06 ... why am I giving you these examples? It's not a glorification of misery. It's, uh, it's expanding your emotional range. It's teaching you that... And, and when I read these stories, I'm not, I'm not a jerk. I'm crying out loud. I- I have tears and I... like, my face becomes red from the, the, the, 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, 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's good and, 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 or 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.

Lex Fridman 1:19:42 Mm-hmm.

Manolis Kellis 1:19:43 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- do you see what I mean?

Lex Fridman 1:19:55 Yeah. Yeah.

Manolis Kellis 1:19:56 Basically, it- it tells you that ... I mean, my- 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 the best she could and crying her whol- 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- and sort of embracing the joy that we have of living where we live in the moment we live, and I'm gonna go further. If you look at the arc of human, um, life, the- 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- 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, this is the ancient Greece of modern society.

Lex Fridman 1:21:31 But the weather still sucks.

Manolis Kellis 1:21:32 (laughs)

Lex Fridman 1:21:32 Because ...

Manolis Kellis 1:21:33 No! Let me put it this way.

Lex Fridman 1:21:35 (laughs)

Manolis Kellis 1:21:35 The weather gives us a range of emotion.

Lex Fridman 1:21:38 (laughs)

Manolis Kellis 1:21:39 (laughs) The full range-

Lex Fridman 1:21:40 The full scenic range.

Manolis Kellis 1:21:41 ... of human weather patterns.

Lex Fridman 1:21:42 That's such a fascinating thing about human psychology of ... 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.

Manolis Kellis 1:21:50 Mm-hmm.

Lex Fridman 1:21:51 And, uh, he talks about, you know, his, uh, living through the Holocaust and- and the concentration camps, and even there where there's, like, human misery e- is at its, uh, highest. I- even there he discovers these moments ... By observing the suffering, by accepting the suffering, he, uh, he observes moments of true joy, of, uh, how great his life is relative to others at the camp, uh, who have it worse.

Manolis Kellis 1:22:31 Yeah. So- so it's a- it's a dangerous slippery slope to think that way, because it's basically being better than the Joneses, and if-

Lex Fridman 1:22:39 (laughs)

Manolis Kellis 1:22:39 ... you know, if the- the house next door has a giant car then you wanna get a bigger car or something like that. It's not comparative misery. I think w- uh, 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- the example, as you were talking about the concentration camps, uh, the most horrible, I mean, one of the most horrible moments of human existence. Um, 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, you know, 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- it was ... Uh, and- and- and I've experienced that with my own kid when he gets ... Like, my- my- my three-year-old last, like two years ago, w- who's now my five-year-old, um, she was burned really badly with, like, hot chocolate and coffee that just peeled off her skin.

Lex Fridman 1:24:01 Mm-hmm.

Manolis Kellis 1:24:01 So you could actually see, it just ... her fragile skin had just peeled off, and she was the happiest little kid. She was just going along with the punches.

Lex Fridman 1:24:11 It is what it is. (laughs)

Manolis Kellis 1:24:12 It is what it-

Lex Fridman 1:24:13 She accepted it.

Manolis Kellis 1:24:14 So- so- so it-

Lex Fridman 1:24:15 Oh, man.

Manolis Kellis 1:24:15 ... it's- it's quite-

Lex Fridman 1:24:16 That's profound.

Manolis Kellis 1:24:16 ... quite dramatic to sort of realize that children don't say, "Oh, I could have it better." They- they sort of embrace the moment. Not embrace, but sort of accept the moment.

Lex Fridman 1:24:31 Accept. Yeah.

Manolis Kellis 1:24:32 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 gonna 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 a 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- 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 ... See, he sees the Christ appear in front of him and he says, "Oh, Christ, I have ... 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."

Lex Fridman 1:25:42 (laughs)

Manolis Kellis 1:25:43 And basically ... (laughs)

Lex Fridman 1:25:46 (laughs) Yeah.

Manolis Kellis 1:25:46 And of course, the person in the end accepts his own bag.

Lex Fridman 1:25:49 So acceptance ultimately-

Manolis Kellis 1:25:51 Basically every single-

Lex Fridman 1:25:51 ... the path you recommend is acceptance.

Manolis Kellis 1:25:53 Every single other bag is probably worse.

Lex Fridman 1:25:56 (laughs)

Manolis Kellis 1:25:56 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, 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 gonna give is the movie, um, Inside Out, by Pixar. Beautiful movie.

Lex Fridman 1:26:32 Which one is that?

Manolis Kellis 1:26:33 The one with the little characters controlling what's inside his brain.

Lex Fridman 1:26:35 Oh, the emotions. Oh, great movie. Yeah.

Manolis Kellis 1:26:37 Yeah. So you basically have joy and sadness and fear and disgust, etc. 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