Lee Cronin: Controversial Nature Paper on Evolution of Life and Universe | Lex Fridman Podcast #404

Lee Cronin 0:00 ... every star in the sky-

Lex Fridman 0:01 Mm-hmm.

Lee Cronin 0:02 ... probably has planets.

Lex Fridman 0:03 Yep.

Lee Cronin 0:04 And life is probably emerging on these planets. But I think the commentorial space associated with these planets is so different. Our causal cones are never gonna overlap, or not easily. And this is the thing that makes me sad about alien life, why- it's why we have to create alien life in the lab as quickly as possible, because I don't know if we are gonna be able to- be able to build, um, architectures that will intersect with alien intelligence and architectures.

Lex Fridman 0:35 In- in intersect, you- you don't mean in time or space?

Lee Cronin 0:38 Time and the ability to communicate.

Lex Fridman 0:39 So the ability to communicate.

Lee Cronin 0:41 Yeah. My biggest fear, in a way, is that life is everywhere, but we've become infinitely more lonely because of our scaffolding in that commentorial space.

Lex Fridman 0:52 The following is a conversation with Lee Cronin. His third time on this podcast. He is a chemist from University of Glasgow who is one of the most fascinating, brilliant, and fun to talk to scientists I've ever had the pleasure of getting to know. This is a Lex Fridman podcast. To support it, please check out our sponsors in the description. And now, dear friends, here's Lee Cronin.

Lex Fridman 1:16 So your big assembly theory paper was published in Nature.

Lee Cronin 1:19 Yeah.

Lex Fridman 1:19 Congratulations.

Lee Cronin 1:21 Thanks. (laughs)

Lex Fridman 1:21 It created, uh, I think it's fair to say, a lot of controversy, but al- also a lot of interesting discussion. So maybe I can try to summarize assembly theory and you tell me if I'm wrong.

Lee Cronin 1:32 Go for it.

Lex Fridman 1:33 (laughs) So assembly theory says that if we look at any object in the universe, any object, that we can quantify how complex it is by trying to find the number of steps it took to create it, and also we can determine if it was built by a process akin to evolution by looking at how many copies of the object there are.

Lee Cronin 1:55 Yep. That's spot on. Yep.

Lex Fridman 1:56 Spot on?

Lee Cronin 1:57 Spot on.

Lex Fridman 1:58 I was not expecting that. Okay. So le- let- let's go through definitions.

Lee Cronin 2:01 (laughs)

Lex Fridman 2:03 So there's a central equation that I'd love to, uh, talk about, but definition wise, what is an object?

Lee Cronin 2:10 (laughs) Um, yeah. Uh, an object, so from- so if I'm gonna try to be as meticulous as possible, objects need to be finite, um, and they need to be decomposable into sub-units. All human made artifacts are objects. Um, is a planet an object? Probably yes in the- if you scale out. So an object is finite and countable and decomposable, um, I suppose mathematically. But, uh, yeah, I still- I still wake up some days and go- to- think to myself, "Wh- what- what is an object?" Because it's- it's- it's n- a non-trivial, um, question.

Lex Fridman 2:50 "Persists over time..." I'm quoting from the paper here. "An object is finite, is distinguishable."

Lee Cronin 2:57 Mm-hmm.

Lex Fridman 2:57 Sure, that's a weird adjective. Distinguishable. (laughs)

Lee Cronin 3:03 We've had so many people h- help- offering to rewrite the paper after it came out.

Lex Fridman 3:07 Yeah.

Lee Cronin 3:07 You wouldn't believe it. It's so funny. (laughs)

Lex Fridman 3:10 "Persists over time and is breakable such that the set of constraints to construct it from elementary building blocks is quantifiable. Such that the set of constraints to construct it from elementary building blocks is quantifiable."

Lee Cronin 3:25 The history is in the objects. It's kinda cool, right?

Lex Fridman 3:28 So, okay, so what defines the object is its history or memory.

Lee Cronin 3:34 Yeah.

Lex Fridman 3:34 Whichever is the sexier word.

Lee Cronin 3:36 I'm happy with both, depending on the day. (laughs)

Lex Fridman 3:38 Okay. So the set of steps it took to create the object, so there's a sense in which every object in the universe has a history.

Lee Cronin 3:48 Yep.

Lex Fridman 3:49 And that is part of the thing that is used to describe its complexity.

Lee Cronin 3:54 Yeah.

Lex Fridman 3:54 How complicated it is. Okay. What is an assembly index?

Lee Cronin 4:00 So the assembly index, if you're to take the object apart and be super lazy about it or minimal, say what it- 'cause my- you know, it's like you've got a really short term memory, so what you do is you lay all the parts on the path and you find the minimum, um, number of steps you take on the path to add the parts together to-

Lex Fridman 4:20 Yeah.

Lee Cronin 4:21 ... re- to- to reproduce the object and that minimum number is the assembly index. There's a minimum bound. And it was always my intuition that minimum bound in assembly theory was really important and I only worked out why a few weeks ago, which is kind of funny.

Lex Fridman 4:33 Hm.

Lee Cronin 4:33 'Cause I was just like, no this is sacrosanct, I don't know why, it'll come to me one day, and then when I was pushed by a bunch of mathematicians, um, we- we- we came up with the- the correct physical explanation, which I can get to. But it's the minimum and it's really important it's the minimum. And the reason I knew the minimum was right is 'cause we could measure it. So almost before this paper came out, we've- we'd published papers that explained how you can measure the assembly index of molecules.

Lex Fridman 5:00 Okay, so that's not so trivial to figure out. So when you look u- at an object, we could say a molecule but we say object more generally.

Lee Cronin 5:08 Mm-hmm.

Lex Fridman 5:09 To figure out the minimum number of steps it takes to create that object, that doesn't seem like a trivial thing to do.

Lee Cronin 5:17 So with molecules it is- it's not trivial, but it is possible because what you can do... And because I'm- I'm a chemist so I'm kind of like I see the lens of the world through just chemistry, um...

Lex Fridman 5:28 Yeah.

Lee Cronin 5:28 Um, I break the molecule apart and break bonds. And if you break up- if you take a molecule and you break it all apart, you have a bunch of atoms, and then you say, "Okay, I'm going to then form bond- take the atoms and form bonds and go up the- the chain of events to make the molecule." And that's what made me realize... Take a toy example, literally a toy example. Take a Lego object-

Lex Fridman 5:51 Mm-hmm.

Lee Cronin 5:51 ... which is broken up of Lego blocks. So you could do exactly the same thing. In this case, the Lego blocks are naturally the smallest. They're the atoms in the actual composite Lego architecture, but then if you t- maybe take, you know, um, a couple of blocks and put them together in a certain way, maybe they're a- have a- they're offset in some way, that offset is in- on the memory. You can use that offset again with only a penalty of one and you can then make a square, triangle, and keep going, and you remember those motifs on the chain so you can then leap from the- the-... start with all the Lego blocks or atoms just laid out in front of you, and say, "Right, I'll take you, you, you, connect," and do the least amount of work. So it's really like, uh, the- the smallest, um, li- um, steps you can take on the graph to make the object. And so for molecules, it came relatively intuitively, and then we started to apply it to language. We've even started to apply it to mathematical theorems. But I'm so well out of my depth. But it looks like you can take a minimum set of axioms and then start to build up kind of, uh, mathematical architectures in the same way. And then the shortest path to get there is something interesting that I don't yet understand.

Lex Fridman 7:02 So wha- wha- what's the computational complexity of figuring out the shortest path in, um, with molecules, with language, with mathematical theorems? It seems like once you have the fully constructed Lego castle or whatever your favorite Lego world is, figuring out how to get there from the building, basic building blocks, isn't like a... is that an NP-hard problem? It's a hard problem.

Lee Cronin 7:28 It's a hard problem, but actually if you look at it... So the best way to look at it, for... let's take a molecule. So if the molecule has, um, 13 bonds, first of all, take 13 copies of the molecule and just cut all the bonds. So take... cut 12 bonds. And then you just put them in order.

Lex Fridman 7:41 Yeah.

Lee Cronin 7:42 And then that's how it works. So... and you keep looking for symmetry and repo- or, or copies so you can then shorten it as you go down, and that becomes combinatorially quite hard.

Lex Fridman 7:54 Mm-hmm.

Lee Cronin 7:54 Um, for some natural product molecules, um, it becomes very hard. It's not impossible, but we're looking at the bounds on that at the moment. But as the object gets bigger-

Lex Fridman 8:04 Mm-hmm.

Lee Cronin 8:05 ... it becomes really hard. And... but there... that's the bad news. But the good news is there are shortcuts. And we might even be able to physically measure the complexity without computationally calculating it, which is kind of insane.

Lex Fridman 8:18 Wait, wait, how would you do that?

Lee Cronin 8:20 Well, in the case of a molecule, um, let- lo- so if you shine light on a molecule, let's take it infrared, the- the molecule has... each of the bonds absorbs the infrared differently-

Lex Fridman 8:31 Mm-hmm.

Lee Cronin 8:31 ... in what we call the fingerprint region. And so it's a bit like, uh, um... and because it's quantized as well, you have all these discrete kind of absorbances. And my intuition, after we realized we could cut molecules up in mass spec, that was the first go at this.

Lex Fridman 8:46 Mm-hmm.

Lee Cronin 8:46 We did it with using infrared, and the infrared gave an e- us an even better correlation assembly index, and we used another technique as well in addition to infrared called NMR, nuclear magnetic resonance, which tells you about the number of different magnetic environments in a molecule, and that also worked out. So we have three techniques which each of them independently gives us the same or tending towards the same assembly index for a molecule that we can calculate mathematically.

Lex Fridman 9:12 Okay, so these are all methods of mass spectrometry, mass spec. You scan a molecule, it gives you data in the form of a mass spectrum, and you're saying that, uh, the data correlates to the assembly index.

Lee Cronin 9:25 Yeah.

Lex Fridman 9:26 S- how generalizable is that shortcut, first of all, to chemistry, and second of all beyond that? Because that seems like a nice hack and you're extremely knowledgeable about various aspects of chemistry so you can say, "Okay, it kind of correlates." But, you know, the whole idea behind assembly theory paper, and perhaps why it's so controversial, is that it reaches bigger. It reaches for the bigger general theory of objects in the universe.

Lee Cronin 9:58 Yeah, I'd say so. I'd agree. So I've started assembly theory of emoticons with my l- lab, believe it or not. So we take emojis-

Lex Fridman 10:05 Yeah.

Lee Cronin 10:06 ... pixelate them-

Lex Fridman 10:07 Yeah.

Lee Cronin 10:07 ... and work out the assembly index from an emoji.

Lex Fridman 10:09 Yeah.

Lee Cronin 10:09 And then work out wh- how many emojis you can make on the path of emoji. So there's the uber emoji from which all other emoj- emo- emojis emerge.

Lex Fridman 10:17 Yeah.

Lee Cronin 10:18 And then you can... so you can then take a photograph, and by looking at the shortest path on, on... by reproducing the pixels to make the image you want, you can measure that.

Lex Fridman 10:28 Mm-hmm.

Lee Cronin 10:28 So then you start to be able to take, um, spatial data. Now there's some problems there. What is then the definition of the object? How many pixels? Um, how do you break it down? And so we're just learning all this right now.

Lex Fridman 10:42 So how do you compute the as- how would you begin to compute the assembly index of a graphical, like, a set of pixels on a 2D plane that form a thing? Wh-

Lee Cronin 10:54 So you would first of all determine the resolution, so then... wh- what-

Lex Fridman 10:58 Sure.

Lee Cronin 10:59 ... how- how many... what is your XY, and what are the number on the-

Lex Fridman 11:01 Yep.

Lee Cronin 11:01 ... X and Y plane, and then look at the surface area, and then you take all your emojis and make sure they're all looked at the same resolution.

Lex Fridman 11:08 Yes.

Lee Cronin 11:08 And then we would basically then, um, do the... exactly the same thing we would do for cutting the bonds. You'd cut bits out of the emoji on the... and look at the- the... you'd have a bag of pixels, so... um, and you would then add those pixels together to make the overall emoji. (laughs)

Lex Fridman 11:26 Wait, wait a minute. But, like, first of all, not every pixel's... I mean, this is at- at the core sort of machine learning and computer vision, not every pixel is that important, and th- there's like macro features, there's micro features-

Lee Cronin 11:39 Features, yeah.

Lex Fridman 11:39 ... and all that kind of stuff.

Lee Cronin 11:40 Exactly.

Lex Fridman 11:40 Like what... like, uh, you know, the eyes appear in a lot of them. The smile appears in a lot of them.

Lee Cronin 11:47 So in the same way in chemistry we assume the bond is fundamental, what we do in here is we assume the resolution at the scale at which we do it is fundamental. And we're just working that out. And that... you're right, that will change-

Lex Fridman 11:57 Sure.

Lee Cronin 11:57 ... right? Because as you take your lens out a bit, you... it will change dramatically.

Lex Fridman 12:02 Yeah.

Lee Cronin 12:02 But it, but it's just a new way of looking at not just compression, what we do right now in computer science-

Lex Fridman 12:08 Yeah.

Lee Cronin 12:08 ... and data, one big kind of, um, uh, um-... kind of m- misunderstanding as assembly theory is telling you about how compressed the object is. That's not right. It's a, how much information is required on a chain of events. 'Cause the nice thing is if you... When you do compression in computer science, w- we're wandering a bit here but it's kind of worth wondering I think, and you- you, um, assume you have instantaneous a- access to all the information in the memory.

Lex Fridman 12:37 Yeah.

Lee Cronin 12:37 In assembly theory, you say, "No, you don't get access to that memory until you've done the work." And then when you've done access to that memory, you can have access but not to the next one. And this is how, in assembly theory, we talk about the four universes. The assembly universe, the assembly possible, and the assembly contingent, and then the assembly observed. And they're all... all scales in this combinatorial universe.

Lex Fridman 12:58 Yeah. Can you explain each one of them?

Lee Cronin 13:00 Yep. So the assembly universe is like anything goes. Just, it's just combinatorial kind of explosion in everything.

Lex Fridman 13:07 So that's the biggest one?

Lee Cronin 13:08 That's the biggest one. It's massive.

Lex Fridman 13:09 Assembly universe, assembly possible, assembly contingent-

Lee Cronin 13:13 And assembly observed, yeah.

Lex Fridman 13:16 ... assembly observed. And, uh, on the Y-axis is assembly steps in time.

Lee Cronin 13:20 Yeah.

Lex Fridman 13:21 And, you know, on the X-axis as- as the thing expands through time, more and more unique objects appear.

Lee Cronin 13:29 So yeah. So assembly universe, everything goes.

Lex Fridman 13:32 Yep.

Lee Cronin 13:32 Um, assembly possible, laws of physics come in. In this case, in chemistry, bonds.

Lex Fridman 13:36 Mm-hmm.

Lee Cronin 13:37 In assembly... So that means...

Lex Fridman 13:39 Those are actually constraints, I guess?

Lee Cronin 13:40 Yes. And they're the only constraints. They're the constraints at the base. So the way to look at it is you've got all your atoms, they're quantized, you can just bung them together. So then you can become a kind of... So in the way... In computer science-speak, I suppose, the assembly universe is just like no laws of physics, things can fly through mountains, beyond the speed of light. In- in the assembly possible, you have to apply the laws of physics but you can get access to all the motifs instantaneously with no effort. So that means you could make anything.

Lex Fridman 14:09 Mm-hmm.

Lee Cronin 14:10 Then the assembly contingent says, "No, you can't have access to the highly assembled object in the future until you've done the work in the past on the causal chain." And that's really the really interesting shift where you go from assembly, um, possible to assembly contingent. That is really the key thing in assembly theory that says you cannot just have instantaneous access to all those memories, you have to have done the work somehow. The universe has to have somehow built a, um, a system that allows you to select that path, um, rather than other paths. And then the final thing, the assembly observed, is basically just saying, "Oh, these are the things we actually see. We can go backwards now and understand that they have been created by this- this causal process."

Lex Fridman 14:59 W- wait a minute. So when you say the universe has to construct a system that does the work, is that like the environment that al- that- that allows for like selection?

Lee Cronin 15:08 Yeah. Yeah, yeah. So you could...

Lex Fridman 15:09 That's the thing that does the selection.

Lee Cronin 15:10 You could think about it in terms of a Von Neumann constructor versus a selection, a ribosome, a Tesla assem- plant assembling Teslas. You know, the- the difference between the assembly universe in Teslarand and the- the- the Tesla factory is, everyone says, "No, Teslas are just easy. They just spring out, you know how to make them." Well, in a Tesla factory, you have to put things in sequence and out comes a Tesla.

Lex Fridman 15:32 So you're talking about the factory?

Lee Cronin 15:33 Yes. This is- this is really nice. Super important point is that when I talk about the universe having a memory or there's some magic, it's not that. It's that tells you that there must be a process encoded somewhere in physical reality, be it a cell, a Tesla factory or something else, that is making that object. I'm not saying there's some kind of woo-woo memory in the universe, you know, morphic resonance or something. I'm saying that there is an actual causal process that is being directed, constrained in some way, um, so it's not kind of, uh, just making everything.

Lex Fridman 16:10 Yeah. But Lee, what's the factory that made the factory? Uh, so what- what is the... So, uh, first of all, you assume the laws of physics is, uh, just sprung to-

Lee Cronin 16:22 Mm-hmm.

Lex Fridman 16:22 ... existence at the beginning. Those are constraints. But what- what makes the factory the environment that does the selection?

Lee Cronin 16:29 This is the question, or... Well, it's the first interesting question that I want to answer out of four. I think the factory emerges in the envi- the interplay between the environment and the objects that are being built.

Lex Fridman 16:43 Mm-hmm.

Lee Cronin 16:43 And- and here, let me... I'll have a go at explaining to you the- the shortest path. So why is the shortest path important? Imagine you've got, um... I'm gonna have to go chemistry for a moment then abstract it. Um, so imagine you've got, uh, an envi- a given environment that, um, that you have a budget of atoms you're just flinging together.

Lex Fridman 17:03 Yep.

Lee Cronin 17:04 And the- the objective of those atoms that are being flung together, in say molecule A, um, have to make... Th- they have a... They decompose. So molecules decompose over time. So the molecules, um, in this environment, in this magic environment, have to not die, but they do die. There's a... There's a... They have a half-life. So the only way the molecules can get through that environment out the other side, let's p- pretend the environment is a box you can go in and out without dying, and there's a... there's just an infinite supply of atoms coming or f- well, a large supply. The- the molecule gets built, but the molecule that h- is able to template itself being built-

Lex Fridman 17:43 Mm-hmm.

Lee Cronin 17:43 ... um, and survives in the environment, will- will basically reign supreme. Now, let's say that molecule takes 10 steps now, and it, and it's using a finite set of atoms, right? Or, uh, now let's say another molecule, smart-ass molecule we'll call it, comes in-

Lex Fridman 18:01 Yeah.

Lee Cronin 18:01 ... and can survive in that environment and can copy itself, but it only needs five steps. The molecule that only needs five steps, 'cause it's contin- both molecules are being destroyed but they're creating themselves faster they can be destroyed, you can see that the shortest path...... reign supreme.

Lex Fridman 18:20 Mm-hmm.

Lee Cronin 18:20 So the shortest path tells us something super interesting about the minimal amount of, uh, information required to propagate that motif in time and space, um, and it's just like a kind of, it seems to be like some kind of conservation law.

Lex Fridman 18:35 So, one of the intuitions you have is the propagation of motifs, in time, will be done by the things that can construct themselves in- in the shortest t- path.

Lee Cronin 18:47 Yeah.

Lex Fridman 18:47 So like, you're gonna assume that most of the objects in the universe are built in the shortest, in the most efficient way.

Lee Cronin 18:54 The- the- (sighs) so-

Lex Fridman 18:57 Big leap I just took there.

Lee Cronin 18:58 Yeah. No, ye- ye- y- yes and no, because there are other thi- so, in the limit, yes, because you want to tell the difference between things that have required a factory to build them, and just random processes.

Lex Fridman 19:10 Mm-hmm.

Lee Cronin 19:10 Um, but, you can find instances where the shortest path isn't taken for an individual object, a individual function.

Lex Fridman 19:19 Mm-hmm.

Lee Cronin 19:20 Um, and people go, "Ah, that means the shortest path isn't right." And then I say, "Well, I don't know. I think it's right still." Because, so, of course, because there are other driving forces, it's not just one molecule. Now, when you start to, now you start to consider two objects, you have a joint assembly space, and it's not, now it's a compromise between not just making A and B in the shortest path, you wanna be able to make A and B in the shortest path, which might mean that A is slightly longer. You're compromised.

Lex Fridman 19:49 Mm-hmm.

Lee Cronin 19:49 So when you see slightly more nesting in the construction, when you take a given object, that can look longer, but that's because the overall function is the object is still trying to be efficient.

Lex Fridman 20:01 Yeah.

Lee Cronin 20:01 And th- this is still...

Lex Fridman 20:03 Sure.

Lee Cronin 20:03 ... very hand wavy, um, and maybe having (laughing) no leg to stand on.

Lex Fridman 20:07 Yeah.

Lee Cronin 20:07 But we think we're getting somewhere with that.

Lex Fridman 20:09 And there's probably some parallelization?

Lee Cronin 20:11 Yeah.

Lex Fridman 20:12 Right? So this is all, this is not sequential. The building is... I- I- I guess when you-

Lee Cronin 20:17 No, you're right.

Lex Fridman 20:18 ... when you're tr- when you're talking about complex objects, you, you don't have to work sequentially. You can work in parallel. You can get your friends together and they can-

Lee Cronin 20:25 Yeah. These- and the, the, the thing we're working on right now is how to understand these parallel processes. Now there's an in- a new thing we've introduced called assembly depth.

Lex Fridman 20:35 Mm-hmm.

Lee Cronin 20:36 And assemble- assembly depth can be lower than the assembly index for a molecule when they're cooperating together, 'cause exactly this parallel processing is going on.

Lex Fridman 20:47 Mm-hmm.

Lee Cronin 20:47 And my team have been working this out in the last few weeks, because we're looking at what compromises does nature n- need to make when it's making molecules in the cell? And I- I wonder if, you know, I- I'm maybe like, uh, well, I'm always leaping out of, um, my competence (laughs) . But in economics, I'm just wondering if you could apply this in economic processes. It seems like capitalism is very good at finding the shortest path.

Lex Fridman 21:09 Mm-hmm.

Lee Cronin 21:10 You know, every time. And there are ludicrous things that happen because actually the cost function has been minimized. And so I keep seeing parallels everywhere where there are complex, nested systems, where if you give it enough time, and you introduce a bit of heterogeneity, the system readjusts and finds a new shortest path. But the shortest path isn't fixed on just one molecule now, it's in the actual existence of the object over time. And that object could be a city, it could be a cell, it could be a factory. But I think we're going way beyond molecules and- and my competence, (laughs) I probably should go back to molecules, but hey.

Lex Fridman 21:44 All right,

Lex Fridman 21:45 before we get too far, let's talk about the assembly equation. (sighs) Okay. How should we do this? Uh, lemme just even read that part of the paper. "We define assembly as the total amount of selection necessary to produce an ensemble of observed objects, quantified using equation one." The equation basically has A on one side, which is the assembly of the ensemble.

Lee Cronin 22:11 Mm-hmm.

Lex Fridman 22:12 And then, a sum from one to N, where N is the total number of unique objects, and then there is a few variables in there that include the assembly index, the copy number, which we'll talk about. That's an interesting, I don't remember you talking about that. That's an interesting addition and I think a powerful one. Has to do with what? That you can create pretty complex objects randomly.

Lee Cronin 22:39 Mm-hmm.

Lex Fridman 22:40 And in order to know that they're not random, that there's a factory involved, you need to see a bunch of them.

Lee Cronin 22:45 Yep.

Lex Fridman 22:45 That's- that's the intuition there. It's an interesting intuition. And then, uh, some normalization. What else is it? And...

Lee Cronin 22:54 N minus one, just to make sure that more than one object, one object could be a one-off and random.

Lex Fridman 22:59 Yep.

Lee Cronin 22:59 And then you have more than one identical object, that's interesting.

Lex Fridman 23:02 When- when there's- when there's two of a thing.

Lee Cronin 23:05 Two of the thing...

Lex Fridman 23:05 That's interesting.

Lee Cronin 23:05 ... is super important, especially if the ind- index, assembly index is high.

Lex Fridman 23:10 So, uh, we could say, several questions here. One, let's talk about selection.

Lee Cronin 23:14 Mm-hmm.

Lex Fridman 23:15 What is this term selection? What is this term evolution that we're referring to? Which- which aspect of Darwinian evolution are we referring to that's interesting here?

Lee Cronin 23:24 So, yeah, so (laughs) this is probably, what, you know, the paper, we should talk about the paper for a second. The paper did, what it did is it kind of annoyed, um, well it didn't annoy, I mean, it got attention. And obviously, angry people, the angry people were annoyed.

Lex Fridman 23:39 There's angry people in the world, that's good.

Lee Cronin 23:41 So what happened is the evolutionary biologists got angry. We were not expecting that, 'cause we thought evolutionary biologists would be cool. I knew that some, not many, computational complexity people will get angry 'cause I'd kinda been poking them, and maybe I deserved it. But I was trying to poke them in a productive way.

Lex Fridman 23:58 Mm-hmm.

Lee Cronin 23:59 And then, the physicists kinda got grumpy because the initial conditions tell everything. The prebiotic chemists got slightly grumpy because there's not enough chemistry in there. Then finally, when the creationists said it wasn't creationist enough, I was like...

Lex Fridman 24:11 Right.

Lee Cronin 24:12 "I've done my job."

Lex Fridman 24:12 The phys- well, you're saying the physics they say... Because you're basically saying that physics is not enough to tell the story of how biology emerges?

Lee Cronin 24:22 I think so. Classic phy-

Lex Fridman 24:23 And then they said, "A few physics is the beginning and the end of the story."

Lee Cronin 24:28 Yeah.

Lex Fridman 24:29 Okay.

Lee Cronin 24:29 So what happened is, the r- reason why people put the phone down on the call for the paper, if you're, if you're view- reading the paper like a phone call, they got to the abstract.

Lex Fridman 24:37 Yep.

Lee Cronin 24:38 And in the abstract, it-

Lex Fridman 24:39 The first sentence is pretty strong.

Lee Cronin 24:40 The first two sentences caused everybody...

Lex Fridman 24:42 "Scientists have grappled with reconciling biological evolution with the immutable laws of the universe defined by physics."

Lee Cronin 24:51 True. Right? There's nothing wrong with that statement. Totally true.

Lex Fridman 24:55 Yeah.

Lee Cronin 24:56 Second, second one-

Lex Fridman 24:56 "These laws underpin life's origin, evolution, and the development of human culture and technology, yet they do not predict the emergence of these phenomena." Wow. First of all, we should say the title of the paper...

Lee Cronin 25:09 (laughs)

Lex Fridman 25:09 This, this paper was accepted and published in Nature. The title is "Assembly Theory Explains and Quantifies Selection and Evolution." Very humble title. And, and the (laughs) ... The, the entirety of the paper I think, uh, presents interesting ideas but reaches high.

Lee Cronin 25:26 I am not... I would do it all again. This paper was actually on the pre-print server for over a year.

Lex Fridman 25:33 You regret nothing.

Lee Cronin 25:34 Yeah, I, I, I think... Yeah, I don't regret anything.

Lex Fridman 25:37 You and Frank Sinatra did it your way.

Lee Cronin 25:39 What I love about being a scientist is kind of sometimes I'm... 'Cause I'm a bit dim, I'm like... And I don't understand what people are telling me. I wanna get to the point. This paper says, "Hey, laws of physics are really cool. The universe is great. But they don't really ex- it's not intuitive that you just run the standard model and get life out." I think most physicists might go, "Yeah, there's, there's... You know, it's not just, we can't just go back and say that's what happened, 'cause physics can't explain the origin of life yet." That does- doesn't mean it won't or can't, okay? Just to be clear. Sorry, intelligent designers. We are gonna get there. Second point, we say that evolution works, but we don't know how evolution got going. So biological evolution and biological selection. So for me this seems like a simple continuum. So when I mentioned selection and evolution in the title, I think, and in the abstract, we should have maybe prefaced that and said, "Non-biological selection and non-biological evolution."

Lex Fridman 26:38 Sure.

Lee Cronin 26:39 And then that might have made it even more crystal-clear. But I didn't think that biology, evolutionary biology, should be so bold to claim omish- ownership of selection and evolution. And secondly, a lot of evolutionary biologists seem to dismiss the origin of life questions and say it's obvious. And, and that causes a real problem scientifically, 'cause when two different... When the physicists are like, "We own the universe, the universe is good, we, uh, explain all of it, look at us," and the evol- biologists say, "We can explain biology," and the poor chemists are in the mid- in the- in the middle going, "But hang on..." (laughs)

Lex Fridman 27:11 Mm-hmm.

Lee Cronin 27:12 And this paper kind of says, "Hey, there is an interesting, um... disconnect between physics and biology, and that's at the point at which memories get made in chemistry through bonds, and hey, let's look at this closer and see if we can quantify it." So yeah, I mean, I've- I never expected the paper to- to- to kind of get that much interest. And still, I mean, it's only been published just over a month ago now.

Lex Fridman 27:38 So just, uh, to linger on the selection, what is the br- broader sense of what selection means?

Lee Cronin 27:46 Yeah, that's a really... Good. For selection, selection... So I think for selection you need... So this is where, for me, the concept of an object as something that can persist in time, and and not die, but basically it can be broken up.

Lex Fridman 28:01 Mm-hmm.

Lee Cronin 28:02 So f- so if I was gonna kind of bolster the definition of an object... So, so if an- if something can form and persist for a- a- a long period of time, um, under a- a- an existing environment that could destroy other... And I'm gonna use anthropomorphic terms, I apologize, but weaker objects, um, or less robust, um, then the environment could have selected that. So a good chemistry example is if you took some carbon and you made a- a chain of carbon atoms, whereas if you took some, I don't know, some carbon, nitrogen, and oxygen, and made chains from those, you'd start to get different reactions and rearrangements. So a carb- a chain of carbon atoms might be more resistant to falling apart, uh, under acidic or basic conditions, um, versus another set of molecules. So it survives in that environment. So the acid pond, the molecule, the- the molecule, the resistant molecule can get through, and, and then- then that molecule goes into another environment. So that m- environment now maybe being an acid pond, it's a basic pond, or maybe it's an oxidizing pond. And so if you've got carbon, and it goes in an oxidizing pond, maybe the carbon starts to oxidize and break apart. So you go through all these kind of obstacle courses, if you like, given by reality. So selection is the ability f- happens when an object survives in an environment for some time. But, and this is the thing that's super subtle, the object has to be continually being destroyed and made by a process.

Lex Fridman 29:42 Hmm.

Lee Cronin 29:42 So it's not just about the proce- the object now, it's about the process and time that makes it, 'cause a rock could just stand on the mountainside for 4 billion years and nothing happen to it, and that's not necessarily really advanced selection. So for selection to get really interesting, you need to have a turnover in time.

Lex Fridman 29:59 Mm-hmm.

Lee Cronin 29:59 You need to be continually creating objects, producing them, what we call discovery time. So there's a discovery time for an object. When that object is discovered, if it's, say, a molecule that can then act on itself, or the chain of events that caused itself to bolster its formation, then you go from discovery time to production time, and suddenly you have more of it in the universe. So it could be a self-replicating molecule. And the interaction of the molecule in the environment, in the warm little pond, or in the sea, or wherever, in the bubble, could then start to build a proto-factory in the environment. So really, to answer your question-... what the factory is, the factory is the environment, but it's not very autonomous. It's not very redundant. There's lots of things that could go wrong. So once you get high enough up the- the- the hierarchy of networks of interactions, something needs to happen that needs to be compressed into a smaller volume and made resistant and robust. Because in biology, selection and evolution is robust, that you have error correction built in, you have really, you know, th- there's good ways of basically making sure propagation goes on. So really, the difference between inorganic, abiotic selection evolution, and evolution and stuff in biology, is robustness. Um, the ability to- to kind of propagate over- over, uh, in- the- the ability to survive in lots of different environments.

Lex Fridman 31:25 Mm-hmm.

Lee Cronin 31:25 Whereas our poor little inorganic soul molecule, whatever, just dies in lots of different environments. So there's something super special that happens from the inorganic envi- molecule in the environment that kills it, to where you've got evolution and cells can survive everywhere.

Lex Fridman 31:44 How special is that? How do you know those kinds of, uh, evolution factories aren't everywhere in the universe?

Lee Cronin 31:51 I- I don't. And I'm excited, 'cause I think selection isn't special at all. I think what is special is the history of the environments on earth that gave rise to the first cell, that now has, you know, has taken all those environments and is now more autonomous. And I would like to think that... You know, this paper could be very wrong (laughs) but I don't think it's very wrong. I mean, it's certainly wrong, but it's less wrong than some other ideas, I hope.

Lex Fridman 32:25 Mm-hmm.

Lee Cronin 32:26 Right? And if this allow- inspires us to go and look for selection in the universe, 'cause we now have an equation where we can say, we can look for selection going on and say, "Oh, that's interesting. We seem to have a proc- process that's giving- 'cause giving us high copy number objects that also are highly complex, but that doesn't look like life as we know it." And we use that and say, "Oh, there's a hydrothermal vent. Oh, there's a process going on in these molecular networks." Because the assembly equation is not only meant to identify at the higher end advanced selection, what you get, I recall in biology, you super advanced selection, and even, I mean you could use the assembly equation to look for technology and-

Lex Fridman 33:07 Mm-hmm.

Lee Cronin 33:07 ... um, god forbid, we could talk about consciousness and abstraction. But let's keep it primitive molecules and biology. So I think the real power of the assembly equation is to- is to say how much selection is going on in this space.

Lex Fridman 33:20 Mm-hmm.

Lee Cronin 33:20 And there's- there's this really simple thought experiment I could do, is you- you have a little Petri dish, and on that Petri dish you put some simple food-

Lex Fridman 33:27 Mm-hmm.

Lee Cronin 33:28 ... so the assembly index of all the sugars and everything is quite low. So then- and you put a single eco- cell of- E. coli cell.

Lex Fridman 33:35 Yeah.

Lee Cronin 33:36 And then you say, "I'm gonna- I'm gonna measure the assemblient, this amount of assembly in the box." So it's quite low, but the rate of change of assembly, dA/dt, will go voom sigmoidal as it eats all the food, and the number of E. coli cells will re- will replicate because they take all the food, they copy themselves, the assembly index of all the molecules goes up, up, up, and up, until the food is exhausted in the box. So now the- now the E. colis stop, I mean die is probably a strong word, they stop respiring 'cause all the food is gone, but suddenly the amount of assembly in the box has gone up gigantically because of that one E. coli factory has just eaten through-

Lex Fridman 34:16 Mm-hmm.

Lee Cronin 34:17 ... and there were lots of other E. coli factories, run out of food and stopped. And so that, looking at that, so in the initial box, although the amount of assembly was really small, it was able to m- replicate and use all the food and go up. And that's what we're trying to do in the lab actually, is kind of make those kind of experiments and- and see if we can spot the emergence of molecular networks that are producing complexity as we feed in raw materials and we feed a challenge, an environment, you know, we try and kill the molecules. And- and- and really, that's the main kind of idea for the entire paper.

Lex Fridman 34:52 Yeah, and see if you can measure the changes in the assembly index throughout the whole system.

Lee Cronin 34:56 Yeah.

Lex Fridman 34:57 Okay. What- what about if- if I show up to your planet, we'll go to Mars or some other planet from a different solar system, and how do we use assembly index there to discover alien life?

Lee Cronin 35:10 Um, in, very simply actually. If we, let's say we'll go to Mars with a mass spectrometer with a sufficiently high resolution. So what you have to be able to do... So a good thing about mass spec, um, is that you can, um, select a molecule from the mass, and then if it's high enough resolution, you can be more and more sure that you're just seeing, um, identical copies. You can count them, and then you fragment them and you count the number of fragments and look at the molecular weight. And the higher the molecular weight, and the higher the number of fragments, the higher the assembly index. So if you go to Mars and you take a mass spec with a high enough resolution and you can find molecules... And I'll give- a- a gu- a guide on earth. If you could find molecules, say, greater than 350 molecular weight with more than 15 fragments, you have found artifacts that can only be produced, at least on earth, by life. Now you would say, "Oh, well, maybe the geological process," I would argue very vehemently that that is not the case, but we can say, look, if you don't like the cutoff on earth, go up higher, 30, 100.

Lex Fridman 36:16 (laughs)

Lee Cronin 36:17 Right? Because there's gonna be a point where you can find a molecule with so many different parts, the chances of you getting a molecule that has 100 different parts, um, and finding a million identical copies, you know, that's- that's just impossible, that could never happen in an infinite set of universes.

Lex Fridman 36:37 C- can you just linger on this copy number thing? A million different copies?What do you mean by copies, and why is the number of copies important?

Lee Cronin 36:49 Yeah. That- that was so interesting in that, um, I always understood the copy number is really important but I never explained it properly, (laughs) for ages. Um, and it be- I kept having this... It goes back to this, if I give you a, um, a- a- I don't know, a really complicated molecule, and I say "It's complicated," you could say, "Hey, that's really complicated." But is it just really random?

Lex Fridman 37:12 Mm-hmm.

Lee Cronin 37:13 And so, so I realized that ultimate randomness and ultimate complexity are indistinguishable, until you can, um, you can see a structure in the randomness, so you can see copies.

Lex Fridman 37:26 So copies implies structure?

Lee Cronin 37:31 Yeah.

Lex Fridman 37:31 (inhales)

Lee Cronin 37:33 The factory.

Lex Fridman 37:33 I mean, there's a deep, profound thing in there 'cause like if you just have a random, random process, you're going to get a lot of complex, beautiful, sophisticated things.

Lee Cronin 37:46 Mm-hmm.

Lex Fridman 37:47 What makes them complex in the way we think life is complex or, um... Yeah. S- s- something like a, a factory that's operating under a selection processes, there should be copies. Is there, like, some looseness about copies? Like, what does it mean for two objects to be equal?

Lee Cronin 38:06 It- it's- it's all to do with the- the telescope or the microscope you're using. And so at the r- the maximum resolution... So in the nice thing about, the nice thing about chemists is they have this concept of the molecule, and they're all familiar with a molecule. And molecules, you can hold, uh, you know, in your hand, um, lots of them-

Lex Fridman 38:24 Mm-hmm.

Lee Cronin 38:24 ... identical copies. Uh, a molecule is actually a super important thing in chemistry to say, look, you can have a mole of a molecule, so an Avogadro's number of molecules, and they're identical. What does that mean? That means that their molecular composition, the bonding, and so on, the configuration is all... is- is indistinguishable. You can hold them together, you can overlay them. So the way I do it is if I say, "Here's a bag, um, of 10 identical molecules. Let's prove they're identical." You pick one out of the- the- out of the bag and you basically observe it using some technique, and then you put it- you take it away and then you put- take another one out. If you observe it using technique and you see no differences, they're identical. It's really interesting to get right because if you take, say, two molecules, molecules can be in different vibrational and rotational states, they're moving all the time. So with this respect, identical molecules have identical bonding.

Lex Fridman 39:12 Mm-hmm.

Lee Cronin 39:13 In this case, we don't even, uh, um, talk about chirality 'cause we don't have a chirality detector. So two ident- identical molecules in one conception assembly theory basically, um, considers both hands as being the same. Um, but of- but of course they're not, they're different. As soon as you have a chiral d- distinguisher detect- to detect the left and the right hand, they become different. And so it's to do with the detection system that you have and the resolution.

Lex Fridman 39:40 So I wonder if there's an art and science to the which detection system is used when you show up to a new planet.

Lee Cronin 39:48 Yeah, yeah, yeah.

Lex Fridman 39:49 So like you- you're talking about chemistry a lot today. We have kind of standardized detection systems, right? Of how to compare molecules. So when you start to talk about emojis, and language, and, uh, mathematical theorems, and, uh, I don't know, more sophisticated things at- at different scale, at a smaller scale than molecules, at a larger scale than molecules, uh, like what detection... Like if- if we look at the difference between you and me, Lex and Lee, are we the same? Are we different?

Lee Cronin 40:24 Sure. I mean, of course we're different close up. But if you zoom out a little bit-

Lex Fridman 40:28 Yeah.

Lee Cronin 40:28 ... we'll morphologically look the same.

Lex Fridman 40:30 Yeah.

Lee Cronin 40:30 Not- not... Well, you know, height and characteristics, hair length, stuff like that.

Lex Fridman 40:35 Well- well also, like, the species and...

Lee Cronin 40:37 Yeah, yeah, yeah.

Lex Fridman 40:38 And- and also, there's a sense why we're both from Earth.

Lee Cronin 40:42 Yeah. I- I agree. I mean, this is the power of assembly theory in that regard; that you... If- if you... So if everything... So the way to look at it, if you have a box of objects, if they're all i- if they're all indistinguishable, um, then, using your technique, you then- you- what you then do is you then look at the assembly index. Now, if the assembly index of them is really low, right, and they're all i- they're all indistinguishable, then you've- then it's telling you that you have to go to another resolution. So that would be... You know, it's kind of a sliding scale. It's kind of nice.

Lex Fridman 41:15 Got it.

Lee Cronin 41:15 So you-

Lex Fridman 41:15 Got it. So those two kind of, uh, are in tension with each other?

Lee Cronin 41:18 Yeah.

Lex Fridman 41:18 The co- the number of copies and the assembly index?

Lee Cronin 41:20 Yeah.

Lex Fridman 41:22 That's really, really interesting. So okay. So you show up to a new planet, you'll be doing what? (laughs)

Lee Cronin 41:28 I would do mass spec. I would bring in the-

Lex Fridman 41:30 On a sample of what? Like, first of all, like how big of a scoop do you take? Do you just take a scoop? Like what? Like, uh... So we're looking for primitive life.

Lee Cronin 41:41 I would, I would look... Yeah. So if we're just going to Mars, or Titan, or Enceladus, or somewhere, so a number of ways of doing it. So you could take a large scoop, or you could go for the atmosphere and detect stuff. So, and you could make a li- um, a life meter, right? So, um, one of, uh, uh, Sarah's colleagues at ASU, Paul Davies, keeps calling it a life me- (laughs) a life meter, which is quite a nice idea because you think about it, if you've got, um, a living system that's producing these, uh, highly complex molecules, and they drift away, and they're in a highly, um, kind of, um, demanding environment, they could be burnt, right? So they could just be falling apart. So you want to sniff a little bit of complexity and say, "Warmer, warmer, warmer. Oh, we found life."

Lex Fridman 42:27 Yeah.

Lee Cronin 42:27 "We found the alien. We found- we found the alien Elon Musk smoking a joint in the bottom of the cave on Mars." Or Elon himself, whatever, right?

Lex Fridman 42:34 Yeah.

Lee Cronin 42:34 And say, "Okay, found it." So what you can do is a mass spectrometer, um, you could just look for things in the gas phase. Or you go on the surface, drill down, because you want to find molecules that are... Y- y- well, you've- you've either got to find...... the source, living system. Because the problem with just looking for complexity is it gets burnt away. So in a harsh environment on- on- on say, on the Mar- surface of Mars, there's a very low probability that you're gonna find really complex molecules because of all the radiation and so on.

Lex Fridman 43:05 Mm-hmm.

Lee Cronin 43:06 If you drill down a little bit, you could drill down a bit into- into soil that's billions of years old. Then I would put in some solvent, water, alcohol or something, or take a- a scoop, put it in- vo- put it vola- m- m- make it volatile, put it into the mass spectrometer, and just try and detect-

Lex Fridman 43:23 Mm-hmm.

Lee Cronin 43:23 ... high-complexity, high-abundant molecules. And if you get them, hey presto, you can have evidence of life.

Lex Fridman 43:29 Mm-hmm.

Lee Cronin 43:30 Wouldn't that then be great if you could say, "Okay, we've found evidence of life. Now we want to keep s- keep the life meter, keep searching for more and more complexity until you actually find living cells"? You can get those new living cells and then- and then you can bring them back to Earth, or you could try and sequence them. You could see that they have different DNA and proteins.

Lex Fridman 43:48 Go along the gradient of the life meter.

Lee Cronin 43:50 Exactly.

Lex Fridman 43:50 How would you build a life meter? Who- let- let's say we're together starting a new-

Lee Cronin 43:54 Just a mass spectrometer.

Lex Fridman 43:55 ... new company, launching a life meter.

Lee Cronin 43:56 Mass spectrometer would be the first way of doing it. Just take-

Lex Fridman 43:59 No, no, no. But that's- that's, um, that's one of the major components of it. But I'm talking about like-

Lee Cronin 44:03 I would-

Lex Fridman 44:04 ... wha- if it's a device, we gotta, and- and branding logo, we gotta talk through that.

Lee Cronin 44:07 All right.

Lex Fridman 44:08 That's later. But what's the input? What's the, like how do you get to the, um, a- a metered output?

Lee Cronin 44:15 So I would- I would take a life... So my- my life meter, our life meter. There you go.

Lex Fridman 44:21 Thank you.

Lee Cronin 44:21 Yeah, you're welcome. (laughs)

Lex Fridman 44:24 (laughs)

Lee Cronin 44:24 Uh, uh, it would have both infrared and mass spec. So it would have two ports so we could shine a light. Um, and so what it would do is you would have a- a vacuum chamber, and you would have a- an electrostatic analyzer.

Lex Fridman 44:37 Mm-hmm.

Lee Cronin 44:38 And you'd have a monochromator to producing infrared. Um, you'd add the sump. So you'd take a scoop of the sample, put it in the life meter. It would then a- add a solvent or heat up the sample so some volatiles come off. The volatiles would then be put into the- into the mass spectrometer, into the electrostatic trap, and you'd weigh the molecules and fragment them.

Lex Fridman 44:58 Mm-hmm.

Lee Cronin 44:58 Alternatively, you'd shine infrared light on them and you'd count the number of bands. But you'd have to, in that case, do some separation, 'cause you wanna separate increa- And so in mass spec, it's really nice and convenient 'cause you can separate electrostatically, but, um, you need to have that.

Lex Fridman 45:12 Can you do it in real time?

Lee Cronin 45:13 Yeah, pretty much. Uh, pretty much, yeah. So let's go all the way back. So let's, okay, we're really gonna get this-

Lex Fridman 45:18 Yeah, let's go.

Lee Cronin 45:18 ... the- the (laughs) Lex's life meet- Lex and Lee's life meter.

Lex Fridman 45:21 No, no. Lex and Lee.

Lee Cronin 45:22 (laughs)

Lex Fridman 45:23 It's a goo- it's a good- good, uh, good ring to it.

Lee Cronin 45:25 All right. So, um, you have a- you have a vacuum chamber. You have a little nose. The nose would have, um, uh, some, uh, uh, a- a- a packing material. So you would take your s- your sample, add it onto the nose, add a solvent or a gas. It would then be sucked up the nose, and that would be separated using chrome- what we call chromatography. And then as each band comes off the nose, we would then do mass spec in infrared. And in the count- in the- in the case of the infrared, count the number of bands. In the case of the mass spec, count the number of fragments and weigh it. And then the further up in molecular weight range for the mass spec and the number of bands, you go up and up and up from the, you know, dead, interesting, interesting, over the threshold, oh my gosh, Earth life, and then right up to the batshit crazy, this is definitely, um, you know, alien intelligence that's made this life, right? You could almost go all the way there. Same in the infrared. And it's pretty simple. The thing that is really problematical is that for many years, decades, what people have done, and I can't blame them, is they've rather, they've been obsessing about small biomarkers on- that we find on Earth. Amino acids, like single amino acids, or evidence of small molecules and these things, and looking for those rather than looking for complexity. The- well, the bea- if the- beautiful thing about this is you can look for, um, complexity without Earth chemistry bias or Earth biology bias. So, assembly theory is just a way of saying, "Hey, complexity and abundance is evidence of selection. That's how our universal life meter will work."

Lex Fridman 46:59 Complexity and abundance is evidence of selection. Okay. So let's apply our life meter to Earth. So, what... You know, if we were just to apply assembly index measurements to Earth, what do- what- what kind of stuff are going to be get, uh, are going to get? What's impressive-

Lee Cronin 47:26 So-

Lex Fridman 47:26 ... about some of the complexity on Earth?

Lee Cronin 47:28 ... so we did this a few years ago in the, um, when I was trying to convince NASA and colleagues that this technique could work. And honestly, it's so funny because everyone's like, "No, ain't gonna work." (laughs) And I was just like... Because the chemists were saying, "Of course there are complicated molecules out there you can detect that just form randomly." I was like, "Rea- rea- really?" That's like- that was like, you know, that was a bit like a, um, I don't know, someone saying, "Of course Darwin's textbook was just written randomly by some monkeys on a typewriter." And it was just, for me it was like, "Really?" And the- and- and I've pushed a lot on the chemists now, and I think most of them are on board, but not totally. I re- really had some big arguments. But the copy number caught there 'cause I think I confused the chemists by saying one-off, and then when I made clear about the copy number-

Lex Fridman 48:14 Sure.

Lee Cronin 48:14 ... I think that made it a little bit easier.

Lex Fridman 48:16 Just to clarify, yeah, chemists might say that of course out there, outside of Earth, there's complex molecules?

Lee Cronin 48:24 Yes.

Lex Fridman 48:24 Okay. And then you're saying, wait a minute, that's like saying of course there's aliens out there. Like you-

Lee Cronin 48:31 Yeah. Exactly that.

Lex Fridman 48:32 Yeah. Okay.

Lee Cronin 48:32 Exactly.

Lex Fridman 48:33 But you're- you're saying, you clarify that that's actually a very interesting question and we should be looking for complex molecules of which the copy number is two or greater.

Lee Cronin 48:45 Yeah. Exactly. So on Earth, so coming back to Earth, what we did is we...... took a whole bunch of samples, we, eh, and we were running prebiotic chemistry experiments in the lab. Um, we took various inorganic minerals and extracted them, look at the volatile, because m- me- there's a special way of treating minerals and polymers in assembly theory. Where what, in this, in our life machine, we're looking at molecules. We don't care about polymers because they don't, they're not volatile, you can't hold them. They're not i- how, how can you make, if you can't discern that they're iden- identical, then it's very difficult for you to, to, to work out if that's undergone selection or they're just around a mess. Same with some minerals. But we can come back to that. So basically, what you do, w- we got a whole range of samples, inorganic ones.

Lex Fridman 49:32 Mm-hmm.

Lee Cronin 49:33 We got a load of, we got Scotch whiskey, and also got-

Lex Fridman 49:36 Nice.

Lee Cronin 49:36 ... took a Ardbeg, which is one of my favorite whiskeys, which is very peaty, and another whisk-

Lex Fridman 49:41 What does peaty mean?

Lee Cronin 49:42 Is like, um, so the way that on, uh, on, um, in Scotland, in Islay, which is a little island, the, the, the, the, the Scotch, the Scot- the whiskey is let to mature in barrels, and, um, the, the, it's said that the peat, you know, the, the, the, the, the complex molecules in the peat-

Lex Fridman 50:02 Mm-hmm.

Lee Cronin 50:03 ... find their way through into the whiskey, and that's what gives it this intense brown color-

Lex Fridman 50:08 Mm-hmm.

Lee Cronin 50:09 ... and really complex flavor. It's literally molecular complexity that does that.

Lex Fridman 50:12 Mm-hmm.

Lee Cronin 50:13 And so, you know, vodka is the complete opposite, it's just pure, right? With a lot-

Lex Fridman 50:17 So the better the whiskey, the higher the assembly index?

Lee Cronin 50:18 Yes.

Lex Fridman 50:18 Or the high- the higher the assembly index, the better the whiskey.

Lee Cronin 50:20 That's what I mean. I really-

Lex Fridman 50:22 Eh.

Lee Cronin 50:22 ... love deep, peaty Scottish whiskeys. Near my house, there is a, a lo- one of the, the Lowland distilleries called Glengoyne, it's still beautiful whiskey but not as complex. So for fun, I cook- took some Glengoyne (laughs) uh, whiskey and Ardbeg and put them into the mass spec and measured the assembly index. I also got E. coli. So the way we do it, take the E. coli, break the cell apart, look, take it all apart, could, um, and also got some beer. And, and w- people were ridiculing us, saying that, "Oh, beer is evidence of complexity." And one of the, one of the computational, uh, complexity people was just throwing, who, yeah, we w- kind of, kind of he's very vigorous in his disagreement of assembly theory, was just saying, you know, "You don't know what you're doing. Even beer is more complicated than human." What he didn't realize is that wh- it's not beer per se, it's taking the yeast extract, taking the extract, breaking the cells, extracting the molecules, and just looking at the profile of the molecules to see if there's anything over the threshold. And we also put in a really complex molecule, Taxol. So we took all of these, but also NASA gave us, I think, five samples.

Lex Fridman 51:29 Mm-hmm.

Lee Cronin 51:29 And they wouldn't tell us what they are. They said, "No, we don't believe you can get this to work." And they really f- you know, they gave us some super complex samples. And they gave us two fossils, one that was a million years old and one was at 10,000 years old, um, sea, something from Antarctica seabed, and they gave us a Murchison meteorite and a few others. Put them through the system. So I, we, we took all the samples, treated them all identically, put them into mass spec, fragmented them, counted m- and in this case, implicit in the measurement was we, um, you, in mass spec, you only detect, um, peaks when you've got more than, say, let's say 10,000 identical molecules. So the copy number's already baked in, but wasn't quantified, which is super important there. This was in the first paper, because I was like, "It's abundant, of course." Um, and when you then took it all out, we found that the biological samples, um, gave you, um, molecules that had an assembly index greater than 15, and all the abiotic samples were less than 15. And then we took the NASA samples and we looked at the ones that were more than 15 or less than 15, and we gave them back to NASA, and they're like, "Oh, gosh. Yep. Dead, living, dead, living. You got it."

Lex Fridman 52:40 Mm-hmm.

Lee Cronin 52:41 And, um, and that's what we found on Earth. Um...

Lex Fridman 52:44 That's a success.

Lee Cronin 52:45 Yeah. Oh, yeah. Resounding success. Um-

Lex Fridman 52:48 Wait, can, can you, can you, uh, just go back to the beer and the E. coli? So what, what's the assembly index on those?

Lee Cronin 52:54 So what you were able to do is like, the assembly index, um, of, w- we found high assembly index molecules origi- originating from the beer sample-

Lex Fridman 53:06 Mm-hmm.

Lee Cronin 53:06 ... and the E. coli sample. So-

Lex Fridman 53:08 Because of the yeast on the beer?

Lee Cronin 53:09 I mean, there, there, there were, I didn't know which one was higher. We, we didn't really do any detail there because now we are doing that,

Lee Cronin 53:16 because one of the things we've done, um, it's a secret but I can tell you (laughs) .

Lex Fridman 53:22 (laughs)

Lee Cronin 53:22 I think it's a- (laughs) .

Lex Fridman 53:23 Nobody's listening. (laughs)

Lee Cronin 53:25 Well, is that we've just mapped the tree of life using assembly theory.

Lex Fridman 53:29 Mm-hmm.

Lee Cronin 53:29 'Cause everyone said, "Oh, that, you can't do it from biology." And what we were able to do is, so you, I think there's three way- well, two ways of doing tree of life traphi- uh, um, well, three ways actually.

Lex Fridman 53:37 Yeah, what's the tree of life?

Lee Cronin 53:39 So the tree of life is basically, um, tracing back the history of life on Earth, all the different species going back what, who evolved from what, and it all goes all the way back to the first kind of life forms, and they branch off, and like you have plant kingdom, the animal kingdom, the fungi sys- uh, kingdom, you know, and different, and different branches all the way up. Um, and the way this was classically done, and I'm no evolutionary biologist, evolution biologists are very, uh, tell me every day-

Lex Fridman 54:07 (laughs)

Lee Cronin 54:07 ... at least 10 times, um, uh, I wanna be one though. I kinda like biology, it's kinda cool, but-

Lex Fridman 54:12 Yeah, it's very cool.

Lee Cronin 54:13 Um, but basically-

Lex Fridman 54:14 Evolutionary.

Lee Cronin 54:15 ... what, uh (laughs) , what Darwin and Mendeleev and all these people do is just they draw pictures, right? And they collect taxa. They just con- they were able to draw pictures and, and say, and say, "Oh, these look like common classes."

Lex Fridman 54:26 Yeah.

Lee Cronin 54:27 Then... (laughs)

Lex Fridman 54:29 They're artists, really. They're just, you know.

Lee Cronin 54:31 But they're, they're, but they're, they were able to find out a lot, right? In looking at vertebrates, invertebrates, Cambrian explosion, all this stuff. And then, um, then came the genomic revolution, and suddenly everyone used gene sequencing, and Craig Venter's a good example. I think he's gone around the world in his yacht just taking up samples, looking for new species, where he's just found new species of life just from sequencing. It's amazing.... so you have taxonomy, you have sequencing, and then you can also do a little bit of kind of molecular, um, uh, kind of archeology like, you know, measure the samples and- and kind of form some inference. What we did, um, is we were able to fingerprint... So we took a load of random samples from all of biology, and we used mass spectrometry. And what we did now is not just look for individual molecules, but we looked for coexisting molecules where they hadn't looked at their joint assembly space, and where we- we were able to cut them apart and re- and undergo recursion in the mass spec and infer some relationships, and we were able to recapitulate the tree of life using mass spectroscopy. No sequencing and no drawing.

Lex Fridman 55:41 All right. Can you, uh, try to say that again with a little more detail? So recreating, what does it take to recreate the tree of life? What does the reverse engineering process look like here?

Lee Cronin 55:52 So what you do is you take an unknown sample, you bung it into the mass spec, you get a... 'Cause this comes from what you're asking, like what do you see in E. coli.

Lex Fridman 56:00 Mm-hmm.

Lee Cronin 56:00 And so in E. coli, you don't just see, it's not a, it's not a, it's not the- the most sophisticated, um, cells on- on earth make the most sophisticated molecules. It is the coexistence of lots of complex molecules above a threshold.

Lex Fridman 56:13 Mm-hmm.

Lee Cronin 56:13 And so what we realized is you could fingerprint different life forms. So fungi make really complicated molecules. Why? 'Cause they can't move. They have to make everything on site.

Lex Fridman 56:23 Mm-hmm.

Lee Cronin 56:24 Um, whereas, you know, some animals are like lazy, they can just go eat the fungi-

Lex Fridman 56:28 Mm-hmm.

Lee Cronin 56:28 ... and they don't need to- to make very much. And I, um, and so what you do is you look at the... So you take, I don't know, the fingerprint, maybe the top number of high molecular weight molecules you find in the sample, you fragment them to get their assembly indices, and then what you can do is you can af- infer common origins of molecules. You can do a kind of molecular, um, um... When the reverse engineering of the assembly space, you can infer common roots and look at what's called the joint assembly space. Um, but what, let's translate that into the experiment. Take a sample, bung it in the mass spec, take the top, say, 10 molecules, fragment them, and then, and that gives you one fingerprint. Then you do it for another sample, you get another fingerprint. Now the question is, you say, "Hey, are these samples the same or different?" And that's what we've been able to do, and, um, by basically looking at the assembly spaces these molecules create. Without any knowledge of assembly theory, you are unable to do it. With a knowledge of assembly theory, you can cons- reconstruct the tree.

Lex Fridman 57:35 Uh, how does- how does knowing if they're the same or different give you the tree?

Lee Cronin 57:38 Let's go to two leaves on different branches on the tree, right? What you can do, by counting the number of differences, you can estimate how far away their origin was.

Lex Fridman 57:48 Got it.

Lee Cronin 57:49 And that's all we do. And it just works. But when we realized you could even use assembly theory to recapitulate the tree of life with no gene sequencing, we were like, "Huh?"

Lex Fridman 57:58 So this- this is looking at samples that exist today in the world.

Lee Cronin 58:00 Yeah.

Lex Fridman 58:00 What about like things that are no longer exist? I mean, the tree contains information about the past.

Lee Cronin 58:08 I would love-

Lex Fridman 58:09 Some of it is gone, yeah.

Lee Cronin 58:11 Yeah. A- absolutely. I would love to get old fossil samples and apply assembly theory mass spec and see if we can find new forms of life-

Lex Fridman 58:19 Mm-hmm.

Lee Cronin 58:19 ... that have, that are no longer amenable to gene sequencing 'cause the DNA is all gone.

Lex Fridman 58:24 Mm-hmm.

Lee Cronin 58:24 'Cause DNA, DNA and RNA is quite unstable, but some of them are complex molecules, might be there, it might give you a hint of something new, or wouldn't it be great if you-

Lex Fridman 58:32 Interesting.

Lee Cronin 58:33 ... if you find a sample that's worth really persevering and doing, um, you know, doing, uh, the proper extraction to re- to, you know, PCR and so on and then sequence it and then put it together.

Lex Fridman 58:46 So when the thing dies, you can still get some information about its complexity?

Lee Cronin 58:50 Yeah. And we can, and it appears that you can, um, do some dating. Now, there are really good techniques. There's radiocarbon dating, there is, um, longer dating going, looking at radioactive minerals and so on, and you can also, in bone, you can look at the... What happens in, after something dies is the imme- the, you get what's called racemization where the- the- the chirality in the polymers basically changes and you just get, you get decomposition. And the rate of, uh, the deviation from the pure po- um, uh, um, enantiomer to the mixture, you can have a ti- it gives you a time- timescale on it, half-life, so you can date when it died. I wanna use assembly theory to see if I can date, use it, and date death and things, and- and trace the tree of life and also decomposition of molecules. Uh-

Lex Fridman 59:45 Do you think it's possible?

Lee Cronin 59:46 Oh yeah. The, when- without a doubt. It may not be better than what, 'cause like the, I was just at a conference where some brilliant people were looking at isotope enrichment and- and looking at how life en- enriches isotopes and, they're really sophisticated stuff that they're doing. But I think there's some fun to be had there because we, it gives you another dimension of dating, how old is this molecule-

Lex Fridman 1:00:06 Mm-hmm.

Lee Cronin 1:00:07 ... um, in terms of in, or more importantly, how long ago was this molecule produced by life?

Lex Fridman 1:00:13 Mm-hmm.

Lee Cronin 1:00:13 The more complex the molecule, the more prospect for decomposition, oxidation, reorganization, loss of chirality, and all that jazz. But what life also does is it enriches, as you get older, the- the amount of carbon-13 in you goes up-

Lex Fridman 1:00:29 Mm-hmm.

Lee Cronin 1:00:29 ... because of the, because of the way the metabo- because of the way the- the bonding is in- in carbon-13. So it has a slightly different strength, bond strength, and you, it's called the kinetic isotope effect. So you can literally date how old you are, you know, uh, or when you stop metabolizing. So you could date someone's dea- how old they are, I think. I'm making this up. This might be right. (laughs) But I think it's roughly right. The amount of carbon-13 you have in you, you can kind of estimate how- how old you are.

Lex Fridman 1:00:56 How old living orga- humans are, or living organisms?

Lee Cronin 1:00:59 Yeah, yeah. Like, you could say, "Oh, this person is 10 years old and this person's 30 years old." Because they'll be metabolizing more carbon and they've accumulated it.

Lex Fridman 1:01:06 Yeah.

Lee Cronin 1:01:06 That's the basic idea. It's probably completely wrong time scale, but-

Lex Fridman 1:01:10 Signatures of- of chemistry are fascinating.

Lee Cronin 1:01:12 Yeah. (laughs)

Lex Fridman 1:01:12 So, y- you've been saying a lot of chemistry examples for assembly theory. What if we zoom out and look at a bigger scale of an object?

Lee Cronin 1:01:22 Mm-hmm.

Lex Fridman 1:01:24 Ah, you know, like really complex objects, like humans. Or living organisms that are made up of, you know, millions or billions of other organisms. How- how do you try to apply assembly theory to that?

Lee Cronin 1:01:38 At the moment, um, we're- we're thi- we should be able to do this to morphology and cells, so we're looking at cell surfaces. And really, um, try and extend further. It's just that, you know, we worked so hard to get this paper out and people to start discussing the ideas, and I was, and I... (laughs) But- but it's kinda funny because I think the peb- the- the penny is falling on this. So, yeah, so, th-

Lex Fridman 1:02:03 What's that even... What- what- what's it mean for a penny to be fallen?

Lee Cronin 1:02:06 Well, I mean, you know, the- the- the penny's dropped, right? 'Cause a lot of people were like, "It's rubbish, it's rubbish. You've insulted me. It's wrong." And I'm- and I, you know, I mean, the paper got published on the 4th of October.

Lex Fridman 1:02:16 Mm-hmm.

Lee Cronin 1:02:16 It had 2.3 million engagements on Twitter.

Lex Fridman 1:02:19 Mm-hmm.

Lee Cronin 1:02:19 Right? And it's been downloaded over a t- few hundred thousand times. And someone actually said to me, wrote to me and said, "This is an example of really bad writing, and what not to do." And I was like, "If all of my papers got read this much," 'cause that's the objective, if I have a publishing a paper, I want people to read it, "I wanna write that badly again."

Lex Fridman 1:02:37 Yeah. I don't know what's the deep insight here about the negativity in the space. I think it's probably the immune system of the scientific community making sure that there's no bullshit that gets published. That's-

Lee Cronin 1:02:48 Uh...

Lex Fridman 1:02:48 And then it can overfire, it can do a lot of damage, it can shut down conversations in a way that's not productive.

Lee Cronin 1:02:53 We are gonna go back... I mean, I'll answer your question about the hierarchy and assembly, but let's go back to the reception. People saying the paper was badly written, I mean, of course we could improve it. We could always improve for clarity.

Lex Fridman 1:03:04 Let's go there before we go to the hierarchy.

Lee Cronin 1:03:06 Yeah.

Lex Fridman 1:03:06 Um, you know, it has been criticized quite a bit, the paper. Uh, what has been some criticism that you found most powerful? Like, that you can understand and... Can you explain it?

Lee Cronin 1:03:23 The... Yes. The most exciting criticism came from the evolutionary biologists telling me that they thought that- that, uh, it w- origin of life was a solved problem. And I was like, "Whoa, we're really onto something, because it's clearly not." And when you poke them on that, they just said, "No, you don't understand evolution." And I said, "No, no, I don't think you understand that evolution had to occur before biology, and we need... There's a gap."

Lex Fridman 1:03:46 Mm-hmm.

Lee Cronin 1:03:46 That was really, for me, that misunderstanding, and that- that did cause an immune response, which was really interesting. Um, the second thing was the fact that physicists... Well, the physicists were actually really polite, right? Really nice about it. But they just said, "Heh, we're not really sure about the initial conditions thing, but this is a really big debate that we should certainly get into because, you know, the in- the- the- the emergence of life was not encoded in the initial conditions of the universe."

Lex Fridman 1:04:15 Mm-hmm.

Lee Cronin 1:04:16 Um, and it can't, and I think assembly theory shows why it can't be. I'll say-

Lex Fridman 1:04:23 O- okay.

Lee Cronin 1:04:24 ... I'll say that ag-

Lex Fridman 1:04:24 Sure. If you, if you could say that again.

Lee Cronin 1:04:26 I, the- the- the origin of the- the emergence of life was not and cannot, in principle, be encoded in the initial conditions of the universe.

Lex Fridman 1:04:35 Just to clarify what we mean by life is like, what, high assembly index objects?

Lee Cronin 1:04:39 Yeah. And this goes back to your favorite subject.

Lex Fridman 1:04:43 What's that?

Lee Cronin 1:04:43 Time.

Lex Fridman 1:04:44 (laughs)

Lee Cronin 1:04:45 (laughs)

Lex Fridman 1:04:47 Right, so why? So why, wha- what does time have to do with it?

Lee Cronin 1:04:50 We- I mean, probably, we can come back to it later. But I-

Lex Fridman 1:04:53 Okay, all right.

Lee Cronin 1:04:54 ... I think it might be, if we have time.

Lex Fridman 1:04:56 Yeah.

Lee Cronin 1:04:56 (laughs) But, um, I think that I've- I think I now understand how to explain how, um... You know, lots of people got angry with the assembly paper, but also the- the ramifications of this is how time is fundamental in the universe, and- and this notion of combinatorial spaces.

Lex Fridman 1:05:16 Mm-hmm.

Lee Cronin 1:05:16 And there are so many layers on this, but, um, you have to become an intuit- it, I think you have to become an, uh, intuitionist mathematician.

Lex Fridman 1:05:24 Mm-hmm.

Lee Cronin 1:05:25 And you have to abandon platonic mathematics.

Lex Fridman 1:05:27 Mm-hmm.

Lee Cronin 1:05:28 And also, platonic mathematics has left physics astray. But there's a lot (laughs) to unpack there. So we can go to the ass-

Lex Fridman 1:05:34 Platonic mathematic... Okay, wait. There's- there's a- there's a... It's okay. The evolutionary biologists criticize because the origin of life is, uh, understood?

Lee Cronin 1:05:46 The- they-

Lex Fridman 1:05:47 And not... It- it doesn't require an explanation that involves physics.

Lee Cronin 1:05:51 Yeah. They bas-

Lex Fridman 1:05:52 That's their statement.

Lee Cronin 1:05:53 Well, I mean, it w- I thi- they said lots of confusing statements. Basically, I realized the evolutionary biology community that were vocal, and some of them were really rude, really spiteful.

Lex Fridman 1:06:03 Mm-hmm.

Lee Cronin 1:06:04 And needlessly so, right? Because, look, you know, um, it... I- I- I didn't... People mi- misunderstand publication as well. Some of the peoples have said, "How dare this be published in Nature?"

Lex Fridman 1:06:17 Mm-hmm.

Lee Cronin 1:06:17 "This is h- you know, how, what a terrible journal." And- and I th- and it really... And I watched a set of people, look, this is a brand new idea that's not only potentially going to change the way we look at, um, biology, it's gonna change the way we look at the universe. And everyone's like saying "How dare you? How dare you be so grandiose?" I'm like, "No, no, no, this is not hype. We're not m- we're not, like, saying we've invented some, um, I don't know, we've discovered a- alien in a closet somewhere just for hype. We're" ... to genuinely mean this, to genuinely have the impact, or ask the question. And the- the way people jumped on that was a really bad precedent for young people who wanna actually do something new. Because-... this makes a bold claim, and the chances are that it's not correct. But what I wanted to do is a couple of things, is I wanted to make a bold claim that was precise and testable and correctable, not a woolly- another woolly information in biology argument information Turing machine blah, blah, blah, blah, blah, a concrete series of statements that can be falsified-

Lex Fridman 1:07:27 Mm-hmm.

Lee Cronin 1:07:27 ... and explored, and either the theory could be destroyed or built upon.

Lex Fridman 1:07:32 Well, what about the criticism of you're just putting a bunch of sexy names on something that's already obvious?

Lee Cronin 1:07:41 Um, yeah, that's really good. So- so, um, the assembly index of a molecule is not obvious, no one had measured it before, and no one has thought to con- quantify selection, uh, um, complexity and copy number before-

Lex Fridman 1:07:56 Mm.

Lee Cronin 1:07:56 ... in such a primitive pr- um, um, n- um, quantifiable way.

Lex Fridman 1:08:01 Mm-hmm.

Lee Cronin 1:08:02 I think the nice thing about this paper, this paper is- is a tribute to all- well, not... to all the people that understand that- that biology does something very interesting. Some people call it negentropy. Some people call it- think about w- what, you know, organizational principles, that lots of people were not shocked by the paper because they'd done it before. A lot of the- lot of the arguments we got, some people said, "Oh, it's rubbish. Oh, by the way, I had this idea 20 years before."

Lex Fridman 1:08:29 (laughs)

Lee Cronin 1:08:29 I was like, "W- which one?"

Lex Fridman 1:08:32 Right.

Lee Cronin 1:08:32 If- i- is it you're ru- the rubbish part or the really revolutionary part? So this kind of plucked two strings at once. It plucked the, there is something interesting that biology does, we can see around this, but we haven't quantified yet, and what this is, a first stab at quantifying that. So the- the- the- the fact that people said, "Um, this is obvious but it's also..." Um, so if, so if it's obvious, why have you not done it?

Lex Fridman 1:08:59 Sure, but th- uh, there's- there's a few things to say there. One is, you know, this is, um, in part a philo- a philosophical framework because, you know, it's not like you can apply this generally to any object in the universe. It's very chemistry focused.

Lee Cronin 1:09:15 Yeah, well, I think you will be able to, we just haven't got there robustly. So we can say how can we... let's go up a level. So if we go up from a level, we'll go up, let's go up from molecules to cells, 'cause you jumped to people and I jumped to emoticons, and both are good and we'll- and they will be assemblies.

Lex Fridman 1:09:30 Yeah, let's- let's stick with cells, yeah. Good point.

Lee Cronin 1:09:31 So we go from, if we go from... so if we go from, um, molecules to assemblies, and let's take a cellular assembly, a nice thing about a cell is you can tell the difference between a eukaryote and a prokaryote, right? The organelles are specialized differently. We then look at the cell surface, and the cell surface has different glycosylation patterns and these cells all stick together. Now let's go up a level in multicellular creatures. You have cellular differentiation. Now if you think about how embryos develop, you go all the way back, those cells undergo a differentiation in a causal way-

Lex Fridman 1:10:04 Mm-hmm.

Lee Cronin 1:10:04 ... that's biomechanically a feedback between the genetics and biomechanics. I think we can use assembly theory to apply to tissue types. We can even apply it to different cell disease types.

Lex Fridman 1:10:14 Mm-hmm.

Lee Cronin 1:10:15 So that's what we're doing next. But we're trying to walk... you know, the thing is, I'm trying to leap ahead, I want to leap ahead to go, well, we apply it to culture-

Lex Fridman 1:10:23 Mm-hmm.

Lee Cronin 1:10:24 ... but clearly you can apply it to memes and culture, and we've also applied assembly theory (laughs) to, um, CAs.

Lex Fridman 1:10:31 Mm-hmm.

Lee Cronin 1:10:32 And not as you think.

Lex Fridman 1:10:34 Cellular automata, by the way.

Lee Cronin 1:10:35 Yeah, yeah, t- so not just as you think. We're... different CA rules were invented by different people at different times.

Lex Fridman 1:10:41 Mm-hmm.

Lee Cronin 1:10:42 And one of my, uh, um, one of my coworkers, very talented chap, basically was like, "Oh, I can realize that different people had different ideas with different rules," and they copied each other and made slightly different b- b- different cellular automata, um, rules and they, and pub- and looked at them online.

Lex Fridman 1:10:58 Mm-hmm.

Lee Cronin 1:10:58 And so he was able to refer (laughs) an assembly index and copy number of rule whatever doing its thing. But I digress.

Lex Fridman 1:11:04 Mm-hmm.

Lee Cronin 1:11:04 But it does show you can apply it at a higher scale. So what do we need to do to apply assembly theory to things? We need to agree there's a common set of building blocks. So in a cell... well, in a- in a multicellular creature, you need to look back in time.

Lex Fridman 1:11:19 Mm-hmm.

Lee Cronin 1:11:19 So there is the- the initial, um, cell, for which the creature is fertilized and then starts to grow, and then there is cell differentiation, and you have to then make that causal chain both on those. So it requires, um, d- development of the organism in time.

Lex Fridman 1:11:34 Mm-hmm.

Lee Cronin 1:11:35 Um, or if you look at the cell surfaces and the cell types, they've got different, um, um, uh, features on the cell, what fills the walls and inside the cell. So we're building up. But obv- obviously I want to leap to things like emoticons, language, mathematical theorems.

Lex Fridman 1:11:53 No, but that's a v- very large number of steps to get from a molecule to, uh, the human brain.

Lee Cronin 1:12:01 Yeah. Um, and I think they are related, but in hierarchies of emergence, right?

Lex Fridman 1:12:06 Yeah.

Lee Cronin 1:12:06 So you shouldn't compare them. I mean, the assembly index of a human brain, what does that even mean? Well, maybe we can look at the morphology of the human brain, say all human brains have these number of features in common.

Lex Fridman 1:12:17 Mm-hmm.

Lee Cronin 1:12:18 If they have those number of... and then let's look at a brain in- in a- a whale or a dolphin or a chimpanzee or a bird, and say, "Okay, let's look at the assembly indices number of features in these," and now the copy number is just a number of, oh, how many birds are there? How many chimpanzees are there? How many humans are there?

Lex Fridman 1:12:34 But then you have to discover for that the features that you would be looking for.

Lee Cronin 1:12:39 Yeah, and that means you need to have a- you need to have some idea of the anatomy...

Lex Fridman 1:12:43 But is there an automated way to discover features?

Lee Cronin 1:12:46 Um, I- I guess so. I mean, and I think this is g- a good w- way to apply machine learning and image recognition just-

Lex Fridman 1:12:54 Right.

Lee Cronin 1:12:54 ... to basically characterize things.

Lex Fridman 1:12:55 So apply compression to it to see what-

Lee Cronin 1:12:57 Exactly.

Lex Fridman 1:12:57 ... emerges and then use the thing, th- the features used as part of the compression a- as the measurement of, uh, as the thing that is searched for when you're measuring assembly index and copy number.

Lee Cronin 1:13:09 And- and the compression has to be, remember the assembly universe, which is you have to go from assembly...... possible to assembly contingent. And that jump from asse- 'cause assembly possible, all possible brains, all possible features all the time.

Lex Fridman 1:13:22 Yeah.

Lee Cronin 1:13:22 But we know that, e- on the tree of life, and also on the lineage of life, going back to LUCA, the human brain just didn't spring into existence yesterday. It is a long lineage of brains going all the way back.

Lex Fridman 1:13:33 Mm-hmm.

Lee Cronin 1:13:34 And so if we could do assembly theory to understand the development, not just in evolutionary history but in biological development as y- you grow, we are gonna learn something more.

Lex Fridman 1:13:45 What, uh, would be amazing is if you can use assembly theory, this framework, to show the increase in the assembly index, uh, associated with, I don't know, uh, cultures or pieces of text, like language-

Lee Cronin 1:14:02 Yeah.

Lex Fridman 1:14:02 ... or images and so on, and illustrate, w- without knowing the data ahead of time, just kind of like you did with NASA, that you were able to demonstrate that it applies in those other contexts. I mean, and that, you know, probably wouldn't at first, and you have to evolve the theory somehow, you have to change it, you have to expand it, you know, um...

Lee Cronin 1:14:21 I think so.

Lex Fridman 1:14:22 ... uh, uh, but like that, uh, I guess this is, as a paper, a first step in saying, "Okay, can we create a general framework for measuring complexity of objects, for measuring life, the complexity of living organisms?"

Lee Cronin 1:14:39 Yeah.

Lex Fridman 1:14:39 That's- that's what this is reaching for.

Lee Cronin 1:14:41 That is the first step. And also to say, look, we have a way of quantifying selection and evolution-

Lex Fridman 1:14:47 Mm-hmm.

Lee Cronin 1:14:47 ... in a- in a fairly- in a fairly, not- not mundane, but a fairly mechanical way.

Lex Fridman 1:14:52 Yeah.

Lee Cronin 1:14:53 Because before now is, you know, there's- it- it wasn't very, the ground truth for it was very subjective.

Lex Fridman 1:14:59 Mm-hmm.

Lee Cronin 1:15:00 Whereas here, we're talking about clean observables. And there's gonna be layers on that. I mean, we- with collaborators right now, w- we already think we can do assembly theory on language. And not only that, wouldn't it be great if we can pr- so the, if we can figure out how under pressure language is gonna evolve and be more efficient, 'cause you're gonna want to transmit things. And again, it's not just about compression, it is about, um, understanding how you can make the most of the in- the architecture you've already built.

Lex Fridman 1:15:29 Mm-hmm.

Lee Cronin 1:15:30 And I think this is something beautiful that evolution does. We're- we're reusing- reusing those architectures. We can't just abandon our evolutionary history.

Lex Fridman 1:15:37 Mm-hmm.

Lee Cronin 1:15:37 And it's if you don't want to abandon your evolutionary history and you- and you know that evolution has been happening, then assembly theory works. And I think that's- that's a key comment I want to make is that assembly theory is great for understanding where evolution has been used.

Lex Fridman 1:15:51 Mm-hmm.

Lee Cronin 1:15:51 The next jump is when we go to technology. 'Cause of course if you take the M3 processor, um, I want to buy, I haven't bought one yet, I can't justify it but I want to at some point. The M3 processor arguably is, there's quite a lot of features-

Lex Fridman 1:16:05 Mm-hmm.

Lee Cronin 1:16:05 ... a quite large number. The M2 came before it, then the M1, all the way back.

Lex Fridman 1:16:09 Mm-hmm.

Lee Cronin 1:16:09 You can apply assembly theory to microprocessor architecture.

Lex Fridman 1:16:12 Mm-hmm.

Lee Cronin 1:16:13 It doesn't take a huge leap to see that.

Lex Fridman 1:16:15 I'm a Linux guy, by the way. So your examples go way over my head.

Lee Cronin 1:16:18 Yeah, well, whatever-

Lex Fridman 1:16:19 Is that- is that like a- is that a fruit company of some sort? I don't even know.

Lee Cronin 1:16:23 (laughs)

Lex Fridman 1:16:23 Yeah, there's a lot of interesting stuff to ask about language. Like you could look at ... how would that work? You could look at GPT-1, GPT-2, GPT-3, 3.5, 4, and try to analyze the kind of language it produces. I mean, that's almost trying to look at assembly index of int- intelligent systems.

Lee Cronin 1:16:45 Yeah, I mean, I think, um, the thing about large language models, um, and- and this is a whole hobby horse I have at the moment-

Lex Fridman 1:16:53 Mm-hmm.

Lee Cronin 1:16:53 ... um, is that obviously they're- they're all about the- the, uh, the in- the evidence of evolution in the ass- in the- in the large language model comes from all the people that produced all the language. And that's really interesting. And all the corrections in the- in the- in the mechanical turk. Right?

Lex Fridman 1:17:15 Sure.

Lee Cronin 1:17:15 Um, and- and so-

Lex Fridman 1:17:17 But that's part of the history, part of the memory of the system.

Lee Cronin 1:17:20 Exactly. So can you... so- so it would be really interesting to basically use an assembly-based approach to s- to making language in a hierarchy, right?

Lex Fridman 1:17:30 Mm-hmm.

Lee Cronin 1:17:30 I think is- uh, my guess is that you could- we might be able to build a new type of large language model that uses assembly theory, that it has more understanding of the past and how things were created, right? Basically, the thing with LLMs is they're like everything, everywhere, all at once, splat-

Lex Fridman 1:17:51 Mm-hmm.

Lee Cronin 1:17:51 ... and make- make the user happy. So there's not much intelligence in the model. The model is how the human interacts with the model. But wouldn't it be great if we could understand how to embed more intelligence in the- in the system?

Lex Fridman 1:18:03 What do you mean by intelligence there? Like, y- you seem to, uh, associate intelligence with history-

Lee Cronin 1:18:11 Yeah. Well, I-

Lex Fridman 1:18:11 ... or memory.

Lee Cronin 1:18:12 ... I think selection produces intelligence.

Lex Fridman 1:18:15 Wait, what? You're almost implying that selection is intelligence. No?

Lee Cronin 1:18:20 Yeah, kind of. I would go that- I would go out on a limb and say that, but I think it's a little bit more. Human beings have the ability to abstract and they can break beyond selection. And this is what, like Darwinian selection-

Lex Fridman 1:18:31 Mm-hmm.

Lee Cronin 1:18:31 ... um, because the human being doesn't have to basically do trial and error-

Lex Fridman 1:18:35 Yeah.

Lee Cronin 1:18:35 ... but they can think about it and say, "Oh, that's a bad idea, won't do that," and then technologies and so on.

Lex Fridman 1:18:39 So we escaped Darwinian evolution and now we're onto some other kind of evolution, I guess?

Lee Cronin 1:18:44 Yeah.

Lex Fridman 1:18:44 Higher-

Lee Cronin 1:18:45 Yeah.

Lex Fridman 1:18:45 ... higher level evolution?

Lee Cronin 1:18:46 And that- and that we'll- we'll- assembly theory will measure that as well, right?

Lex Fridman 1:18:49 Yeah.

Lee Cronin 1:18:49 Because it's all a lineage.

Lex Fridman 1:18:50 Okay. Another piece of criticism, or by way of question is, how is assembly theory, or maybe assembly index different from Kolmogorov complexity? So for people who don't know Kolmogorov complexity of an object is the length of a shortest computer program that produces the object as output.

Lee Cronin 1:19:10 Yeah, I'm- I- I seem to- there seems to be a disconnect between the computational approach. So yeah, so Kolmogorov measure-... requires a Turing machine.

Lex Fridman 1:19:23 Mm-hmm.

Lee Cronin 1:19:24 Requires a computer, um, and that's one thing. And the other thing is, um, assembly theory is supposed to trace the process by which life evolution emerged, right? That's the main thing there. There are lots of other layers. So, so Kolmogorov complexity, you can, you can approximate Kolmogorov complexity, but it's not really telling you very much about the actual, um, it, it's really telling you about, like, your da- your dataset, compression of your dataset.

Lex Fridman 1:20:00 Sure.

Lee Cronin 1:20:00 And so, that doesn't really help you identify the, the turtle, in this case, is the computer.

Lex Fridman 1:20:07 Mm-hmm.

Lee Cronin 1:20:08 And so what assembly theory does is... I- I'm gonna say, (laughs) it's a trigger warning for anyone listening is, uh, uh, who loves complexity theory, I think that we're gonna show that AIT is a very important subset of assembly theory, because here's what happens. The, um, I