264 - Lee Cronin: The Chemistry of Life

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0:35Lee Cronin:At Blinds.com, we've spent 30 years making it surprisingly simple to get exactly what your home needs. We've covered over 25 million windows and have 50 ,000 five-star reviews to prove we deliver. Whether you DIY it or want a pro to handle everything from measure to install, we have you covered. Real design professionals. Free samples. Zero pressure. Right now, get up to 50 % off with minimum purchase. Plus, get a free professional measure at Blinds.com. Rules and restrictions apply. and it's the hardest question that a being can ask themselves right why do i exist it's easy for me to pick up an object and say why does that exist but why do i exist life is about persistence from existence so you produce a thing that exists great well done but then it has to persist long enough to be effective to do something else we have been totally misunderstanding how reality works.

1:27I want to discover what selection is in the same way that Newton discovered what gravity is. I don't really care about the origin of life. I think the origin of life is a boring problem, but not inconsequential. I think the problem is what is the process that gives rise to life in the universe full stop?

1:54Lee Cronin:your thinking covers a lot of subjects from artificial intelligence to to chemistry to aliens and i'm wondering what ties all of these things together for you and how it all got started yeah i the problem is i keep remaking the question right i um um but i think that the the the most faithful answer i can give is i'm really confused about why we're here if i think about myself as an entity in the world i remember when i was a kid looking at the shoots coming out of the ground and i was growing vegetables or the sun coming through the trees it was like what on earth is going on i didn't know i was allowed to ask questions about science and so when i realized that everyone else is in that delusion as well i i felt a little bit better but i mean life is kind of wacky right so i i i guess um so i started up like that and i'm obviously um i wanted to code stuff the computers were coming i would grew up in a time where all my colleagues my friends had computers and so i started to kind of play around with these and i had a kind of some kind of idea of how i could manipulate i suppose a calculator in a more than a boring way um and and i was just fascinated by biology it's like why do things grow why am i here why do i think what is what is the how is it that I have options because physics I got given this book um that told me about physics and physics told me I didn't have options but suddenly I realized I had options and that was seemed to be completely counter to physics and that was very confusing to me that I had options and physics said no when you say that you're confused about why we're here I just want to clarify what you mean by that is it more a question like uh what is the purpose of life like what is your purpose in existing here or more a question about what is it about how the universe is put together that has allowed for us to exist or made it if you want to put it this way inevitable that we've come to exist oh oh that's so um no i mean i think i'm kind of like um i'm a simpleton when it comes to that and i'm just like why do i exist like i'm an egotistical simpleton i mean i exist look at me i can go around and just create mayhem and then i create mayhem i was like well how did i create mayhem um i i mean i've been a longer i've been around long enough now to discuss with people about their views of the universe and their ideas and i i mean that's so far beyond my paycheck i just prefer to say what's going on here but what i found in the last i guess the last 10 years or so is that my simple approach basically met the people with the large paychecks in the middle because my questions their questions seem to be the same thing which i found very exciting and also a little bit depressing because i thought you know i'm i have no um you know if you take the kind of like the idea of what gravity is or electromagnetism and the thing about the history of it i mean what i'm asking right now is why am i here not in a oh you know in a kind of um a kind of metaphorical sense i'm asking why does biology exists i'm a chemist i'm a chemistry professor and i'm trying to understand why does biology with all its chemistry exist from the chemistry i know and the gap is so big i found very interesting and that's one of the reasons why i've kind of dedicated my life i guess to some degree because i'm so confused to ask that very simple question is what turns sand into cells I really like the way that you put that and it sounds like the question and that most interest you is what is the origin of life from a chemistry standpoint is that accurate but not just the origin because I think the origin is quite boring because it's quite you know um circumstantial I view it if you if you imagine that we have gone few a few billion years we look come in the sky and we see no stars just black and we see the sun and we say oh what was the origin of the sun but then we imagine we say oh what we see the sun but you see all the stars and so when people ask about the origin of life i don't really care about the origin of life i think the origin of life is a boring problem but not inconsequential inconsequential i think the problem is what is the process that gives rise to life in the universe full stop and if you look up in this and i'm just imagining if you look up in the in this night sky while i'm having here we're in my workshop just now this out there is a big little kind of dip where it gets really good light and i did a lot of astrophotography during the pandemic and it was really fascinating because you could look up in the sky and go okay these stars if i look up in any one night if i get lucky well we i never saw this but i can imagine a star dying and a star igniting because right now we're just asking where did how what gave rise to the sun to life but we're not recognizing the fact that light that stars are born and die every day in the universe and what i want to know is not just the original life i want to understand the actual process that gives rise to biology every single day in the universe and that's kind of a radical statement because i'm like assuming that biology is everywhere and i think that's uh i mean probably that's not correct but but that's kind of my starting point if you like okay no interesting so just again for my own understanding you find the the question of the origin of life on earth to be boring because it's just something that maybe happened once but what's more interesting is what is the general principle that or what are the general principles of chemistry that allow for life to come into existence across the universe yeah absolutely that's it i mean that's for me you know for as long as i can remember i was like complete confused i mean um i times i dissect this a lot when I'm talking to people about why am I doing what I'm doing.

8:49And I am remarkably confused about why we are here. And I have been that confused since as long as I can remember. And I think that's the question. What is the physical process? The physical process gives rise to life. In the same way, what is the physical process that gives rise to the sun? The process I know that gives rise to the sun is nuclear fusion and gravity. so hydrogen falls together gravity increases energy the temperature increases there'll be a point where the the temperature is such that you can break this the strong nuclear force a fusion occurs the thing explodes there's so much gravity it doesn't fall apart you've got this kind of like this two things working together you have a sun so i want to know life is about seemingly doing lots of chemistry lots of possibilities and not like running out of material so why how do these things balance together and i'm very inspired by that because i think it's uh the answer or at least a plausible mechanism where right now we're not asking mechanisms we're almost being and i hesitate to say this because i hate that the notion that chemists and original life people being pseudo-religious in their oh it was this thing worked backwards i'm like no no no that doesn't make sense as a scientist i have to ask myself and it's the hardest question that a being can ask themselves right why do i exist it's easy for me to pick up an object and say why does that exist but why do i exist and i think that that's something that I'm maybe a bit of a kind of just want to get beaten up over because that you know I get so many arguments over this well I'm glad that we've taken the time to sort of had this

10:45Lee Cronin:introductory discussion because it helps me think of a roadmap for this conversation because there are two things that I really want to get to which are artificial intelligence and aliens and they're not at least obviously connected to chemistry. But I think an interesting way to go about getting to those topics is discussing, one, what were the maybe dominant theories, if there were any, about these general origin of life processes before you started working, what the problems were with them, and then how your work in chemistry sort of intervened. and the path you're on now but so let's start with that that first one what were or are the the dominant theories on how life can come into existence across the origin across the universe yeah so i think most people i think there's a number of different approaches the first is that people say that life is absolutely unique to earth there is no life elsewhere um which is like i can i can accept that that's a um a a reasonable suggestion because we don't know of any life elsewhere and then but let's let's just park that for a second say well why why is life here well there's evolution and there's chemical evolution and there's a need for certain um processes to occur for evolution to break the barrier but from kind of sand to kind of genetics and so i think what predominantly people would think about say like you know the the the the the genetic world or the the the um the peptide world or the kind of and then the the metabolic world so you've got these kind of different worlds going on and maybe the i would induce another world which i think is not used enough because i think it's interesting which is the self world now never used that before in any i don't think exists so you have kind of like um metabolism genetics proteins and self now the self people will be about cells but i think it goes more than that because self the the when matter has a self matter can become alive so yes i think this self is very interesting and i'm not really sure um that anyone else has thought about in chemistry and i feel a bit lonely because chemists seem to have been put in a box where you just need to do chemistry and you have the philosophers that can think and you have the physicists that can compute and the computer scientists that can tell you're all basically not going to be alive and and the poor chemists have to make drugs so you don't die which is kind of depressing actually so bottom my role is to be a rat is to be a radical and just say actually the origin of life is because of chemistry everything you have is because of chemistry and am i a chemical egotist oh yeah so then how do you formulate or go about considering how chemistry or the principles of chemistry should function in this theory for how life begins across the universe yeah so i think it's very simple actually um i think if you imagine the universe at the beginning where everything was very simple and you had some energy and then energy and matter would combine and i and i i'm be told about this when i collaborate a lot particularly um um sarah walker i've been working with in arizona arizona state university because we kind of came at this at the same time where when i met sarah she kind of she blew my mind because she said stuff and i didn't understand any words he said semantically but it's like i was like hearing a melody which i understood instinctively right it's kind of weird when you meet someone who's like because that's what happens when you have the cross disciplines i spend a lot of my time being clueless and oh oh, that sounds really cool.

14:57I think I get it, but I don't understand the words, but I kind of get it. And the origin of life is a bit like that because what is life is a really important question because, you know, I can pick some. I'm in my workshop just now, so my favorite things I've just 3D printed, like this grid. I'm making a chemical brain on this grid. You can see all the holes in it. This is like a 3D object. I just printed it. It's kind of cool, but it's not alive. It's dead. But it's a living artifact. This artifact doesn't exist anywhere else in the universe that required a you know a stereographic 3d printer required me to actually write the code so when you're coming what to life is chemically i think it's about molecules that can survive or networks of molecules that survive over a period of time that can actually affect their past if you like or affect the ecosystem that produced them so that they then create more um um possibilities survive in the environment because the environment is the enemy the environment is the leveler the environment will kill you unless you understand how the environment is going to change you will die and human beings good examples right a friend of mine i was talking to about it it's like it's actually it's not it's become a friend over many years he's a physicist he's like if i leave oxford and i'm not you know i don't have not equipped i'll just get dissolved by the atmosphere you know run out of fuel and stuff and i was like david that's kind of like that's a bit ridiculous because you go to the hospitals but there were no hospitals and then you know so so i think molecules that can assemble and form networks that replicate themselves or do something to propagate themselves in the future that resist death in the environment is what life is and there's two words i'll say there life is about persistence from existence so you bridge you produce a thing that exists great well done but then it has to persist long enough to be effective to do something else and i think that's really actually the answer to

17:12Lee Cronin:what life is in a way so first just a terminological question you said that this grid that you displayed a moment ago was a living artifact and i don't think that you're i think your use of words is probably careful so i want to ask about it you think of this thing as it's not alive but it to me I would want to say it's an artifact of life rather than a living artifact. So I just want to understand why you chose to describe it that way. No, I would actually say that your terminology is correct. This is an artifact of life. It's not living because I created it. And so you're absolutely right. But if you think about it, if I was to freeze every molecule, sorry, if I was to say, okay, Robinson, freeze.

18:06and i and i was looking at you and i rotate you around and be like this yeah there's like right so so you're absolutely right and this artifact is a product of living technology is not alive in itself but it's a part of a living system and one of the biggest mysteries we're facing is what is the difference between molecules that are taking part in living systems and the products of living systems and are they related and i guess my what i was doing as a shortcut saying yeah this is as live as my you know my hair is right and but but this is not autonomous my hair is autonomous because my body has hair follicles and hair grows this requires me to go to my 3d printer put in the stl file and print it and so i think you're quite right to point that out and there's a continuum of um you know a biogenesis life and then technology which this is and this is not um standalone technology is intrinsically connected to life by this process

19:10Lee Cronin:so i think that's a very nice way of putting it so thanks well another question then maybe this is a good way to help me understand a bit more what you mean by matter comes alive when it has a self and what's the difference or where do you locate the self in the hair follicle that's not there in the grid oh my gosh i think the self in the hair follicle is 4.3 billion years old and i think actually the grid here this is also 4.3 billion years old you just can't tell by looking at it right if you were to say oh this doesn't look like this 4.3 billion years old it's a grid few bits it's not that complicated whereas we looked at the hair follicle and the genetics and what was going on you would require this lineage going backwards and this is the biggest mystery of life in a way that we are still grappling with this understanding of you know if you look around you i mean if i'm in my workshop just now there's there's crazy things everywhere these things are the most um improbable things in the universe in a way and so these improbable things are created by humans or living systems um as a technology and so in a way the way i look at it is you have this kind of inorganic dead matter biology or the origin of life then single cellularity and then going all the way up to memes and technology and none the meme cannot exist without the biology which is kind of wild because people are there's this meme but it's all layers this grid although it looks simple could not exist without 4.3 billion years of evolution that's radical like that really can't exist people say always an argument it can but it can't i mean it requires me to make it in my 3d printer i i think sarah and i disagreed a bit about this and it sounds like you might too that i mean i think it can exist without life at least if our theories of physics are correct in the form of like a a boltzman grid something to that effect um no i i mean i i think your discussion with sarah was really inspiring because i think you got to a lot of the the the nuances of what this what physics can do what chemistry can do what biology can do i really thought it was fascinating um and so i don't i think that we have a blind spot right now is that we do not we have all this stuff around us like i have so many interesting objects i can pick up around me like oh yes my favorite thing here i've got now i found this is this cartridge called open drop i it's a microfluidic programmable device i can just put droplets around sure a boltzman brain could come up with that but it really required a human being to design it and the back has got a see-through back look at the technology in the back all those microprocessors in the back there that they don't appear from nowhere and so whilst i i'm really sympathetic to your view that things can spring in what i realized in my work with sarah is like that's impossible and i think the that we have been totally misunderstanding how reality works probably since the renaissance or maybe actually no back to aristotle um which is kind of a wild claim and given i'm a chemistry professor who doesn't have any philosophy um and is arguably quite poorly trained in all things i i'm i i'm kind of hesitant but what i would say is that um what controls that so if you go back to the grid this is super simple it looks like a simple grid you can do an xyz here right it's a grid it can make a cube great fine who wrote the grid where did the material come from how is it fabricated and what time and energy to have available and then when she did that what technology gave rise to that and what technology gave rise to that and what technology gave rise to that and you end up back at the stone age And so my argument is that these technologies are contingent upon prior technologies, and we are totally, or the vast majority of people looking at them, are unaware that technologies we use today are the product of not just evolution biologically, but technological development over time.

24:03If you woke up tomorrow and every lithographic, every fabrication facility that gave rise to silicon chips was erased, and someone's just taking them away, say, sorry, Lee, sorry, Robinson, no more chips. Cope with the chips you have. But you're allowed to come up with a new process to make chips whilst these chips are alive. that would be amazing because humans would go oh my god we've got to basically redo all this technology you know it's like and so we do not understand or correctly quantify the lineage of technology that goes from one stage to another and that for me is totally wild as a chemist it blew my mind when i realized the dependence of one chemistry set on another was this thing about how time and contingency work together, if that makes any sense to you.

24:59Lee Cronin:Well, I don't want this conversation to depend too much on Sarah's, but one other thing that comes to mind, since you brought up memes, we've been talking about the self, and then your story of sort of replication and persistence, it reminds me of the selfish gene hypothesis, hypothesis uh which sarah thought was a good narrative but didn't have too much experimentation really to back it up if i recall correctly i don't want to put words into her mouth but it does sound somewhat like it resonates with your own theory of what life is so i'm i'm wondering if you think that's fair or if you think it's wrong in some significant way um is the selfish drone gene wrong in some significant way no i don't think it's wrong but i think it's very much a collapse of a high dimensional problem into a low one um and i think there is so much more going on um so what i mean is that matter has to make this transition from this maelstrom of gray goo if you like or just atoms and energy i mean if you think about it go back to the origin of the universe there's hydrogen where the air would go both matters plasma gluons suddenly you have hydrogen and if you adopt that that approach you have the the hydrogen produced after the big bang the hydrogen collapses produces stars the stars burn through their fuel and explode and produce higher elements those higher elements do something something something that is the biggest transformation in the universe ever they bring in combinatorial diversity because you can make lots of different bonds that transition when the first stars exploded and dumped combinatorial stuff into the universe the universe suddenly became big we all thought the universe is small it's big in space but actually we don't understand space correctly no one i know does i understand space i think probably not as wild as some crazy professors out there but i think the universe in terms of causal space is small it's only when it made chemical bonds and matter and elements that we suddenly were able to make stuff happen and so the selfish gene is really very late in that process the selfish gene does not correctly capture the um uh the other things that had to happen to get there but it does correctly capture this nuance that matter wants to persist in time so i don't think it's wrong i just think it's super well defined for a particular part in its timeline i remember talking to risha dawkins about this and i was like that's really great like you nailed it but what happened before and he's like i don't know so so it's very it's very fuzzy it's toward as you put it toward the end of the timeline and it kind of jumps over this step from primordial soup to replicators and you're interested in the chemistry that that arises when you have this big combinatorial space, but you don't have the replicators yet.

28:24Lee Cronin:And you're wondering what facets of chemistry lead from soup to replicators. Yeah, I mean, if I was to put money on it, I would say that the emergence of life or the emergence of complexity associated with life or selection, whichever word you want to give, because life is extreme um actually because biologists say aliens everywhere i don't think necessarily but the fact is that stars are all over the universe and i think the selection wherever there's energy and matter there's selection and so what i'm beginning to realize is selection is everywhere and you just need an you just need matter and energy and you're going to get evolution in the end for me that's radical but obvious um and it allows us to remove this afro-morphization that we have on earth and our local solar system and we need to start looking in our universe for evidence of selection beyond what we expect for the you know the m class star and with james webb and other things we're going to do that and i think it's fascinating but i do think we are the precipice of i mean we understand the chemistry sorry we are the precipice of understanding that gravity operates in the entire universe i don't think a single physicist using this will go no i think we're going to be not that far away from understanding chemistry and biology or the chemistry gives rise to biology is present everywhere in the universe there's biology everywhere and this idea that aliens exist great yes or no it's like it's kind of a bizarre question i argue with people about this a lot it's like we accept that black holes exist and we've never seen one we are life and we basically go as life exists and now you're looking at it wrong does heterogeneity and matter exist does selection exist if those two things exist together you will have life whether it's complex whether it produces tiktok or whatever meme you want or youtube i don't know it'll be different but the fact is with these features you will have life in the universe it is not optional it just is what the universe does i'm i'm with you i mean it i think it will it depends i mean it's an empirical question that will depend on how big the universe is.

31:00Lee Cronin:But I'm with you that it seems much more likely than not that there is going to be lots of life out there. A lot of it might depend on if we're going to be really parochial with regard to what we define life as. Does it have to be carbon-based or something else? But before we talk about those questions about aliens, I want to go back to this fuzzy part of the selfish gene theory. And I want to ask, so in the lab, you have access to this primordial ooze. You have a bunch of chemicals that you can synthesize or collect. But we haven't, as far as I'm aware, created something that everybody would agree is artificial life in a lab.

31:46Lee Cronin:So what I'm wondering is what the current status of experimentation and theorization is in this field and where your work is fitting into it and bridging this gap. Yeah, I mean, I never wanted to work in Origin of Life, actually. It's kind of weird, right? I wanted to solve life. I think it's one of the reasons I started collaborating with Sarah, actually. is like i found the origin of life extremely hard work because you had all these practitioners who had these requirements and i was like i didn't know anything i was like why don't i just basically put a load of chemistry in a pot heat it up and see what happens so i think the major issue of the origin of life is that people have preconceived ideas in and if you say to someone say well well what look for the origin of life they're great okay what is life and if they can't adequately give you an answer it's like if you can't give me an answer to what life is how can you look at the origin of it so they might say okay well look i'm gonna just take what i know on earth for i just take dna rna proteins whatever cells i want to look at those i'm like how would you know that it's like it's a bit like me saying i want to look at the origin of music but look at sony minidisc i'm not sure if your your listeners viewers will ever know what i mean just is right or a or a vinyl record or spotify but everyone knows music when they hear it and so i found that really quite them founding and as a chemist you know it's like what are you what what are you what what what is i guess it comes down to this can we just find what life is rather than obsessing about what we think life is because we see it now um and and i think that's um something we're starting to crack so i i that's one of the reasons i'm not an origin of life researcher i'm characterized origin of life researcher i've debated with um you know religious creationists calls me an origin of life research research researcher i beg your pardon i i'm just a chemist who wants to know how sand turns into cells and i want and i believe and it and it's becoming beyond the belief because for me belief is something i do not have proof for i'm not you know as i i have a lot of religious friends i talk to and they're like and people i talk to are not religious they say how dare you debate religious people i'm like no no no science is here religion is here they do this they never touch but they're very close together and that getting close together is actually quite useful um so i think that people do not understand what life is they are too amper they amper for more too much they put too much weight on what they know and they don't think generally enough and i think that is very frustrating and ever since i was like as long as i can remember i didn't care about any of the the fluff i just want to know what is the mechanism by which sand becomes cells You can discuss the other stuff, Byron, you know, whatever, Halloween, Christmas, whatever, cultural manifestations.

35:03What is the process that turns dead stuff into living stuff?

35:09Lee Cronin:But what have you come up with in investigating this process or asking this question, how does sand turn into matter to cells? it's obviously matter already how does it turn into yeah yeah so i think sand turns into cells via process of continual um uh death if you like of the material and rebirth so you have this finite amount of stuff the way i think about it is let's make a sandbox for life so we know we got this box we've got this sand in there we're going to put an energy in a selection pressure so the material aggregates and it creates objects but then the environment is harsh and it destroys most of the objects the most objects are gone and they're returned back to the norm sad right but the entropy has increased universe has increased but some objects survive and those objects that survive are lucky or whatever happens but if those objects that survive can actually act in the environment to cause more of them survive then you get more complexity and then just imagine it happens again and again and again you have this hierarchy of complexity on complexity on complexity and you know what the cell the biological cell which is one of the meat the most complicated things we know in the universe that people say is impossible to have formed without intervention is merely or fantastically for me i'm in awe of it the process of matter randomly forming aggregates being killed by the environment and the the stuff that isn't killed gets propagated to the next day and it can somehow act in the environment to create more of itself by replication or whatever a network and that basically process of creation destruction survival propagation is the core of turning sand into cells and happens everywhere in the universe and it's completely obvious if matter wants to become more complicated and we see on earth i mean look at us we're so complicated we have you know elon coming up with memes we have the people in china coming up with memes we we have humans creating stuff language culture technology you know competing you know whose electric car is the best whose chemical is the best it's fascinating to watch and so i i think that we are actually discovering the physical processes that give rise to biology and our own technology competing with our resources on earth because although earth is big and there's lots of resources is we have to somehow cooperate together you know whether it's like china saying well you're not going to let rare earths go to us and us goes okay we will invent new materials that have rare earth-like properties using carbon they might do right so there's this kind of interplay between this supply and demand this action and inaction which means that life is not special it's just a a very general phenomena of selection.

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39:28Lee Cronin:As you've said a few times throughout our conversation, this chemical combinatorial space is absolutely huge. So what is it that in your lab you're trying to characterize about this process? process is it the the types of bonds or structures that facilitate this process of making matter more suitable to persistence and replication because i'm sure you're not coming up with a a list of chemicals um that that are more like well maybe i'm wrong that are that we're more likely to find on on earth that will reproduce in in this early stage yeah so i mean what we're trying to do is literally come up with like chemical reactors that will mix and match chemicals change the environment and then see how things survive over time to capture selection for me the the the process gives rise to life is very similar to the process gives rise to a star not because well certainly in terms of analogy because you think about it if someone says to you are there stars in the universe wow how do they form you can say well hydrogen gravity detonation no explosion you know equilibrium so i'll say how's life exist well matter heterogeneity energy survival and reproduction and those are the only things you really need so what i'm trying to create in the lab is those processes working together now to be clear we are on a path where i think it's working but i'm do not think i have the answer i think i'm observing in the lab thanks to the collaborations i have and the team i'm working with evidence that this is that indeed the process that gives rise to biology but i mean you know i've been wrong more than i'm right but if i well oh i was going to say let's just say that you you live for 10 000 years a million years and you can continue running and iterating upon this series of experiments you've been doing in your research program, would the ultimate goal be sort of refining until you have this recipe for creating an existence proof that you've figured out the sort of process?

41:53Yeah, I don't know. Actually, that's a really good point. I mean, so sadly, I think I want to live for a long time, but I think I have to make a better fist of it than that. But yeah, right now in my lab, we're designing experiments that will reveal selection. And the evidence of selection, how it works, almost like evidence that... I think what I'm trying to do is invent gravity, right? It seems a bit weird. In the same way as Newton did. and it goes sounds really weird oh god i'm getting people tell me off but anyway i i mean just for god i want to discover what selection is in the same way that newton discover what gravity is and although newton did not see a star form i don't think anyone's going to argue with him then or now that the way that gravity that the stars are formed by gravity collapsing material causing nucleation so he can do something like that would be good um i don't think we need 10 ,000 years or a million years i think we need a bit longer one of my interesting questions is how long do we need to show chemistry becoming complicated before everyone we talk to even the strongest skeptic will go oh yeah that is correct that is the right way it would work and for me that's more of a dialogue with society and other skeptics right because one of the things i love about being a scientist is that i'm constantly arguing with colleagues about what are we looking for what is the experiment what do they care about and so i have an idea but it's almost certainly wrong but i i'm going to try as long as i can so i mean i actually if i was going to be really brave i think we are right now today as in what's the date we're talking about october uh 2025 i think we're doing experiments right now that have proven that life can emerge from sand now i don't think anyone's gonna understand that for maybe 10 or 20 years and indeed that process is required right because who am i i'm just some random chemist shoveling like sand into a well look at that but i think i think that the processes the physical processes are we can understand on our time scale we don't need we don't need 10 000 years or 100 ,000 years but but in the same way um it took a bit of time when Einstein came up with oh did it again right Einstein came up with relativity everyone would have gone so what but when we started throwing satellites into orbit they started frame dragging and losing their time just imagine if we started throwing satellites into space with no idea relativity and everyone's like why is the time drifting and everyone went I had to go oh phenomenologically there's something wrong with gravity and it required relativity so in a way we've got this similar problem in life and and i think that we just haven't been looking at it correctly i could be wrong but that's my view so ask your question very long i don't think we need 10 000 years i think we just need people to be willing to um um kind of get behind the question but right now there's really weird reasons why chemists aren't getting right in the question sociological reasons right i never saw physicists arguing about whether it was an interesting question to ask how stars form in chemistry we seem to have chemists go arguing about whether the origin of life is a reasonable question or not which is wild to me of course it's reasonable there are two sort of directions

45:42Lee Cronin:in which I'd like to head right now. I'm not sure. Maybe they're the same direction. But I want to ask where two things fit into what we've been discussing. One is assembly theory, which I discussed a bit with, well, more than a bit, but with Sarah in the last episode. But another thing is you started the conversation by talking a bit about an interest in programming. And that brings to mind computation, Camputation, which is a word I've never said out loud, perhaps a word you coined. I'm not sure. But where do these two things figure into what we've been discussing? Oh, yeah, that's so I mean, that's pretty deep.

46:25Yeah. So computation is a word I coined. And actually, it's kind of embarrassing where I coined it, because you like I coined this word. And then I realized it was a thing. and i got talking to david deutsch who was like yeah yeah of course exists i was like okay you now have to write the theory i was like thanks david the david deutsch is a physicist who believes in um is building a language of physics called constructor theories about transformations exist that can make stuff happen and if there's a transformation something happen happens and you know i've been talking for date to david a lot about this and david doesn't want to talk about assembly theory but sociological reasons will about computation is so funny um so let's go back so yeah because i mean dave is a super he's a brilliant scientist and a brilliant philosopher and a brilliant thinker but like everybody he's human right so you know he does he will not he will accept a challenge but some things doesn't recharge them not because he doesn't agree like that's 100 wrong it's just like he only wants to put his effort into a thing that he thinks is important which is which is fine i'm the same right we all have egos our egos push ourselves in certain ways but coming to assembly theory um assembly theory is a very simple theory that makes lots of people kind of like happy because it's so obvious and lots of other people angry because it's so obvious that it can't possibly write and all assembly theory says at this core is to say hey causation is fundamental that's it it doesn't say anything else and what it says is like when you see a complex object on its own you don't know anything about its history like you just say let's say you get beamed into alpha centauri let's just say you're in star trek robinson and you're like there and captain kirk says just go down to the surface of the planet you're like okay and some you go down and someone gives you a complex object you're like oh that's cool and there's a thousand of them you're like oh was this made by a life form or was it randomly created by the laws of physics and if the number of different parts in the object is high enough such that random chance can put them together and the number is large enough then you know for sure that it was created by evolution or technology and that's all assembly theory does and when sarah and i kind of propagated invented this theory we put it out there the entire universe kind of fell out with us as it were all the humans and they're like you know complexity exists i was like really what complexity and people have been misunderstanding complexity evolution and assembly for the last hundred years before freeman dyson died i wrote to freeman actually and told him about some stuff i was working on with metal oxides and self-replication he loved it and i then oh i start off with conversation freeman that's cool he's a hero so i wrote back to him i've got this new idea for complexity and he wrote back dr conan do not try and work on complexity it is not worth working on for the last 50 years people be working on complexity and all they've found out is that there is no complexity it's just people being silly or something to that extent and i was like a bit sad because actually i don't think freeman is indeed correct what assembly just says is like look if i give you an object can you somehow interrogate that object to work out how long it took to make it in a in a kind of like in a in a in a kind of no technology environment just randomly and number two how many of those objects can you find your surroundings because even though if let's take this if you take this object we've got this microprocessor here i can take the part out i'll do it i'll take the bias this is the cartridge i've taken out of this thing right to plug in it's really quite intricate there's lots of things that clearly been manufactured um that didn't randomly form right but the average physicist would say hey there's a probability this could form randomly and i was told the average physicist the probability of this forming randomly is precisely zero not small zero and assembly theory just basically explains that and we really are then able to build a new understanding of what is going on in our physical universe rather than being deluded by

51:07Lee Cronin:probability in physics which is not correct so just to understand this this number zero Even if the universe were infinite in spatial extent and in mass, you would still think the probability is zero? If it was infinite in spatial extent and mass and time, sure. You'd have loads of them. Great. But that's not true, right? And we know the universe, and infinite is a big number. um so the problem is the human mind has the ability to think of infinite where it doesn't have the ability to deliver infinite and so um and i've i've mentioned this right some physicists like there's some great physicists out there like sean carroll and you know frank wilczek and um carlo revelli that think about these things and timelessness but i think they're wrong because time is a finite resource because if the infinite universe is all that required we would have far more interesting things existing than we have now and i think that the fact that we have interesting things exist at all is a testament to physical reality and selection um so i think infinite is a very very hard word and it never exists the only thing that's infinite in the universe is our ability to take a given environment interrogate it in an infinite different ways because of the commentorial complexity but no there is not infinite mass there's not infinite energy which means we don't have infinite opportunities and getting that in our heads and kind of conveying that to people is i think it's quite sobering because there is a big universe and sarah and i have calculated the the possibility of of developing things in a in the universe we have now.

53:11And it's really small, quite humbling, actually. We could be wrong because there could be an infinite universe hiding behind the finite universe. But it means that we've seen no evidence of an infinite universe and infinite time. We've seen evidence of a finite universe and finite time.

53:30Lee Cronin:Well, getting into the very basic nuts and bolts of assembly theory, what constitutes a step in assembly yeah that's great um the assembly in assembly theory an assembly theory is something that i invented um i mean i invented it in a many years ago um running up some steps in japan running back because long before i would talk to people about it thinking about what is a step and i thought i was maybe wrong but a step is like what is the minimum amount of information you can specify to connect two objects together in a way and even then i'm not sure that's an adequate explanation but i have a series of letters or numbers or things i labels a step would be me deciding to take two of those things and combine them together in a binary fashion so let me take the letter l and the letter e to make my name lee i'm going to make le so step would be the combination of l and e and then a second step would be the combination of e and le to make lee and so that would be a that would be a kind of a way we we look at it in terms of a step a step would be a thing where you actually create some constraint to create an object from a uh from the background but even then if you ask me some days i mean i wake up some days i go i have no clue what assembly theory is who invented it it's a silly idea and i'm confused and i would talk to sarah about she's like relax it's okay it's just hard i've got this view you have this view it's we bring it together but it is a non-intuitive um idea at the at the core but suddenly becomes really intuitive that everyone seems to be understanding so the axioms of assembly theory are objects can be broken down into parts that they are composed of number one number two we can take the objects of the base and combine them together in binary steps and only binary steps and number three the object has the shortest path for being produced by the shortest number of those steps together a great way of looking at is the word abracadabra because you say i can take the letters of the base i'm going to combine them together on a graph there's 11 letters in abracadabra but actually if i combine them from the graph with reuse i can do it in seven steps because you have abracadabra and the bra was already made earlier when you put them together so you get a reuse for free or just one unit and so it's a bit like about that information that exists by in the universe the memory it creates so assembly theory says hey you So causation is fundamental, number one.

56:33Number two, copy number of the object, the number of objects you can make, indicates the selections occurred. And number three, there is a causal process at a higher level that allows it to exist in time and exists in the environment, which happens to be the selection process that goes there. and that's kind of where the assembly theory came from at the beginning.

57:01Lee Cronin:No one goes to Hank's for his spreadsheets. They go for a darn good pizza. Lately though, the shop's been quiet so Hank decides to bring back the$1 slice. He asks Copilot in Microsoft Excel to look at his sales and costs to help him see if he can afford it. Copilot shows Hank where the money's going and which little extras make the dollar slice work. Now Hank's has a line out the door. Hank makes the pizza. Copilot handles the spreadsheets. Learn more at m365copilot.com slash work. Marvel Television's Wonder Man. An eight-episode series. Now streaming on Disney+. A superhero remake. Not exactly what we'd expect from an Oscar-winning director.

57:40Lee Cronin:Action! Simon Williams audition for Wonder Man. I'm gonna need you to sign this. Assuming you don't have superpowers. I'll never work again if anyone found out. My lips are sealed.

58:02Lee Cronin:What constitutes an object in assembly theory? I think the example that comes to mind is, would you consider a chess set, so the board and all the pieces, an object above and beyond just the individual pieces and the board? yeah so i think this is the critical question i i think we're going to keep refining over time but if you were to push me on it now an object is a thing that i can measure with a technique number one chessboard would work and equally if i can also imagine how to dissect that object into the parts that would be um very important number two because a molecule is an object and the thing is like you know this is why i said to you at the beginning i wish i was a philosopher because i came up with the idea molecules as objects i'm like it's like what's an object i don't know i just made it up but it seems right but what i'm doing now is like trying to understand where it's like it is a fundamental problem like like um and and actually sarah is writing the philosophy of this right now she's nailed it she's great um but an object needs to be distinguishable and it needs to be kind of uh it can be broken into parts into atoms um and it needs to be finite and there and that that was just what i saw and the more we applied it more it works the chest set is a good example a chest set is an object is correct is composed of a board of all the parts on the board i can take them off and i can put them together and understand they're constructed and i have a path to do that same way say a molecule of dna or a computer chip so so an object is a thing that can be interrogated by observation at the correct level to understand how that thing was assembled and i think that and that and that's what my definition of object is right now but but it needs to be much tighter than that philosophically right i mean you know my way better than me that getting these definitions correct is critical for the next set?

1:00:16Lee Cronin:I mean, there are just a lot of fascinating questions here to me. And on the one hand, I want to say, sure, in our everyday speech, I want to say that a chess set is an object. But in the sense that chemistry or physics wants to get at the world in a mind independent sort of way if you take all of the pieces of a chessboard and scatter them across the the world sure i might still think of it as a connect as an object not a necessarily a connected object but it wouldn't really make that much sense to think of it as an object independent of the human mind since these things are also spatially disparate i don't know yeah so that yeah yeah no that's perfect right because objects are things that can be selected on and so if you took the chess set and scattered it over the world it'd no longer be an object unless you have a super intelligent alien in light chess they'll pick up the board and pick up the piece and say no we're going to play right and so i think that if if the ensemble of atoms can be a selected upon and then it's an object.

1:01:36So I think selection really saves us in that regard. And so for me, I'm completely happy. You know, the invention of assembly theory was an invention that came from, initially from me. It's not very good. Spoke to one of my students, got a bit better. Spoke to Sarah. She's like, no, let's do it again. Made it better as well. and so the the the the conception was to understand the amount of causation required to make things over time that could also cause things themselves so if you took your object and spread it out so it couldn't do much the causal power would go down and so i think there is an argument which you were just invented because you asked me the question i haven't thought about this way is that objects have to have causal power in a new way as well.

1:02:29And that may figure in the definition, which is kind of exciting. But, you know, I mean, I must admit that this week, I wouldn't say I'm depressed on assembly theory. I would just say I don't understand it this week. And that's not for you. It's just like I invent lots of theories all the time. And at times I zoom in and out and I wake up and go, what on earth was I talking about? And then you have the entire internet telling you, yes, Lee, this is complete nonsense. What are you talking about? And what I did, I actually, yesterday, as I was talking to one of my team members and said, well, what do I mean?

1:03:07And I'm like, no, no, relax. You're like, assembly theory is about causation. It's about the number of different parts in your object. I'm like, yeah, I remember that. It's about the number of objects you encounter. I was like, yeah, cool. I can remember that. And then it's about the causal, about how you observe it in the environment, how selection builds them. and they can then create networks of things that act on themselves to create bigger combatorial spaces where you have selection. I was like, ah, that's kind of cool. But for me, you know, the, I would say for me, I'm so not equipped to be doing theory because I am so out of my comfort zone.

1:03:49It's not that I don't feel confident in it. It's just like, I just don't know what I'm talking about some days.

1:03:58Lee Cronin:Yeah, okay. Well, I'm finding this very interesting, even if you feel like you don't know what you're talking about on some days or in some area. I mean, the reason that I asked, I mean, there are many reasons why I asked what a step is in assembly is that I just also had some similar sort of philosophical questions. For instance, I don't know how I told you my last chemistry class was in high school and I don't know if if water is formed when two hydrogen atoms bond to an oxygen atom or how exactly it works but um if a step is just some sort of chemical connection that seems very clear cut something is or isn't a step but if it's mere like spatial like things move closer to each other then it's kind of going to be vague like how close do the l and the le and the e have to be together before they become an object uh so that was just another question i was wondering no no that's perfect i think you'll really hit the nail on the head because i don't understand it and you do what i mean is that the chemical bond is a chemical attraction between two things there is a you have to put energy in to break that bond so yes the bond is the most important thing in molecular assembly because it does create an association between two things it's not it's not discretionary it happens it's defined by quantum mechanics so in the in the water it was quite good because if you have o2 and h2 and yes it is h2 it's not h dot so you have hydrogen molecules h2 and you have o2 so you have to bring in one o2 together and two h2s and then you make h2o because each one you have one oxygen molecule one and so two hydrogens and so the chemical bond and this is why i'm i need to learn philosophy because I'm a chemist who's realized that the origin of life, consciousness, and technology is defined by the bond coming from atoms, producing these ensembles, producing matter.

1:06:20And there's no body doing philosophy and chemistry. We're doing philosophy and physics and computer science till the cows come home. And I'm stuck here literally holding the bonds, like holding the baby going, but but what do i do with this an assembly theory is merely an effort to say ah these things become connected there's an entity that associates in the chemical bond they're not going to fall apart so they're not kind of like you know a happenstance they really exist in space and we can build objects on them build really elaborate things complex molecules ultimately computers human beings animals whatever stars and and it's based on the chemical bond and it's fascinating so an object if you want to go dig dig deeper would be a made of atoms connected by bonds with a finite lifetime that wouldn't break but i could break them into atoms so if i'm being a chemical chauvinist i would say an object from my view it's a collection of atoms atoms bonded together by the chemical bond and i could basically measure and determine really existed it wasn't ethereal i could hold it i could literally give it to you in a glass vial you know if it was you know i don't know caffeine or you know sugar or something right it's like here you go robinson here's my object there's a molecule in a vial and there's a number of copies and i think your clarification there is really important because the object isn't a weak association of objects there has to be an energy that's put them together and you can't just break them apart arbitrarily you need energy to break them apart and that's exactly the definition of a molecule okay very good very interesting one

1:08:09Lee Cronin:one last question that i've been wondering with regard wondering about assembly so just as a i I mean, a prototypical biological molecule, ATP. Do you happen to know off the top of your head its assembly index? It is 21. Okay, perfect. And just also helpful, what are some of the steps in the assembly of an ATP molecule? So ATP contains carbon, nitrogen, oxygen, and phosphorus. and so if you were to take the entire molecule and break it apart um there's lots of ways you could break it apart but there's just a there is a shortest way to get there so you go to the base the base of the tree you would have phosphorus nitrogen um oxygen carbon right and you combine them together and so you could do it in lots of different ways uh you get to the actual object But if you think about it, oxygen, phosphorus atom, another oxygen, dimer making the diphosphate, carbon make the ring, make the other ring, add the nitrogen and then have the sugar in there.

1:09:26And so that would be the way you look at it. You could make a graph taking all those atoms and combine them together. Now, that graph is somewhat arbitrary because you don't know the actual process that built it. all you know is that there was a process that built it because it has 21 steps and so that

1:09:46Lee Cronin:does that make some sense it does make some sense it does make sense and the reason that i was asking is i i think of there are plenty of naturally occurring molecules that have many many steps So, for instance, I think of a massive crystal in a geode as it's just very large. There are many steps. And what I'm wondering is, is there a rule in assembly theory that it only constitutes a new step if it's not repetition? Or a snowflake, for instance, might have many, many steps. It's a large molecule. So what is it that distinguishes the two in terms of assembly theory? yeah so i this allows me to uniquely bring in the assembly equation so in assembly theory we define two parameters we define the assembly index which is a number of steps to make the molecule and its copy number and then we then quantify those together to be a big a so a is about assembly and to this day i'm yet to really adequately explain what a is and again it's going to sound rather hubristic because i'm like a is like a is like it's like gravity right it's like this is the amount of selection per unit object per unit time and so um what i the way i look at that is to say look um when we talk about the the crystal or the snowflake you can get really high assembly index but actually unless you have a more than one copy identical it doesn't count so the assembly equation says is basically a is equal to the sum of yeah um e to the ai times ni minus one over nt so ni is a copy number minus one so it means say oh so ni minus one so if you don't have more than one together at zero over nt the collapse the equation collapses so what that means is if you have an object that has an assembly index of a thousand say you've got this very interesting diamond you've written all this stuff into but you only have one object then that doesn't count to causation that's just a random happenstance and so when i built the equation i actually built the equation looking at this and then inferred the equation from trying to understand physical reality and for me this is hard because i'm not a physicist i don't build a question physicists don't build equation well so chemists don't build equations i was like shit i think there's this new feature reality i need to build it looks like this and looks like this this is how reality is i'm gonna make i'm gonna make some math that fits my reality because i think a lot of people think that math creates reality and i'm like no and this is why i love listening to your podcast actually because you listen to lots of people out there like like tim maudlin is like no no no the actual reality is what you observe then you then capture that into mathematics and go back and there's it's not just tim but lots of people i think that gave me some heart because i'm like okay right way to look at it so when you're looking your geode and whatever if you don't if you unless you have identical objects they do not count and so the assembly equation just collapses so it's not about now the number of parts on the graph it's about the copy number because there is this um you know the thing um if you know you can have a lightning strike that strikes some gluttons and sand and makes a shape my favorite cup here is a very nice intricate cup you know let's just say a lightning strike produced something that looked like this is that an object from design though a lightning strike happened to basically you know produce an object well if i if lightning strikes could produce 100 of these those lightning strikes are no longer random they are some alien fabricating my cup right and so then you are oh the copy number is high the assembly index is high then we go up the assembly equation the assembly equation is the thing that measures selection in reality in the same way that the group the equation of gravity measures the force between objects in space-time that realization may be super happy is there a principled reason so so we haven't on earth like found a mine of coffee cups like yours but is there a principled reason why some other planet elsewhere in the universe with different chemical composition can't naturally have some sort of process that produces a very complicated structure abundantly?