302 | Chris Kempes on the Biophysics of Evolution

Randomness plays an important role in the evolution of life (as my evil twin https://www.preposterousuniverse.com/podcast/2020/10/05/117-sean-b-carroll-on-randomness-and-the-course-of-evolution/ will tell you). But random doesn't mean arbitrary. Biological organisms are physical objects, after all, and subject to the same laws of physics as non-biological matter is. Those laws place constraints on how organisms can fulfill their basic functions of metabolism, reproduction, motility, and so on. Easy to say, but how can we turn this into quantitative understanding of actual organisms? Today I talk with physical biologist Chris Kempes about how physics can help us understand the size of organisms, their metabolisms, and features of major transitions in evolution. Support Mindscape on Patreon https://www.patreon.com/seanmcarroll. Blog post with transcript: https://www.preposterousuniverse.com/podcast/2025/01/20/302-chris-kempes-on-the-biophysics-of-evolution/ Chris Kempes received his Ph. D. in physical biology from the Massachusetts Institute of Technology. He is currently Professor and a member of the Science Steering Committee at the Santa Fe Institute. His research involves the origin of life and the constraints placed by physics on biological function and evolution. Web site http://chriskempes.com/Chris_Kempes/Home.html Santa Fe Institute web page https://www.santafe.edu/people/profile/chris-kempes Google Scholar publications https://scholar.google.com/scholar?hl=en&as_sdt=0%2C21&q=chris+kempes&btnG=&oq=chris+ Origins of Life online course https://www.complexityexplorer.org/courses/170-origins-of-life

Speaker names marked ? are inferred from speaking time and the show’s known hosts — they are not voice-verified.

• 0:00Speaker 00

  Most women have been there. Something feels off. You don't feel like yourself, yet your doctor says everything looks fine. Spoiler: it's your hormones. Midi is a virtual care platform built for women by women and offers specialized hormone care from trained clinicians. Plus, it's covered by most major insurances. Getting started is easy. You can book your first visit with a clinician right away. It's not you, it's your hormones. Visit joinmidi.com to book your first visit. That's join M-I-D-I dot com. Insurance coverage varies. Check with your plan for coverage. Shipping, billing, admin, payroll, marketing. You're managing all the things, so why waste time sending important documents the old fashioned way? Mail and ship when you want, how you want with stamps.com.

• 0:43Speaker 00

  Print postage on demand 24/7 and schedule pickups from your office or home. Save up to 90% with automated rate shopping. That's why over 1 million small businesses trust stamps.com. Go to stamps.com and use code PODCAST to try stamps.com risk-free for 60 days.

• 1:00Sean Carroll?

  Hello, everyone. Welcome to the Mindscape Podcast. I'm your host, Sean Carroll. Have you all heard about the centimeter-long bacterium? I had not heard about this until this podcast, as you will discover, but just a couple of years ago, scientists found a kind of bacterium called Thiomargarita magnifica, which can grow up to a centimeter in length. Okay? It's a tiny little tube-like thing, so it's not a spherical centimeter-long thing, but that's very creepy to me. I don't want any centimeter-long bacteria climbing around anywhere near where I am. And I bring this up because I did, Chris Kempis, today's guest, introduced me to the possibility during this podcast. I had never heard about it, but it shows sort of two sides of a certain coin for a

• 1:44Sean Carroll?

  bacterium that is about the size of a coin. One is, what we will be talking about in the podcast are the existence and usefulness of physical constraints on biological organisms and their evolution. So biological organisms are embedded in the physical world. They obey the laws of physics and therefore they need to use good old sensible, allowed, physical mechanisms to survive, to metabolize, to eat, to move, all of these things. It should be unsurprising that the existence of the laws of physics will provide constraints

• 2:23Sean Carroll?

  on what kind of architectures and morphologies and sizes are allowed in the realm of living organisms. And of course, you can apply this idea, you can actually do it quite quantitatively and specifically, to simple organisms like bacteria. And under some very reasonable assumptions, you can derive the smallest size of a bacterium possible and the largest size of a bacterium possible. And these Thiomargarita guys are way larger than the largest size possible. Of course, that turns out because they violate some of the assumptions you made. They're actually not like one big blob. They're almost like sausage links, kinds of things glued together to make a long tube to grow to that centimeter size.

• 3:06Sean Carroll?

  But it's both an illustration to me of the power of physical constraints in biology, because you can't do anything, you gotta obey the laws of physics, but also the cleverness of biology in figuring out ways around what you thought were physical constraints. So in today's conversation, we're talking to Chris Kempes, who's a faculty member at the Santa Fe Institute, a biophysicist, I think that's safe to say, or a physical biologist, maybe. And the theme running through Chris's work is applying these physical constraints to life in all of its forms. So, starting from viruses to bacteria, but we will also be talking about the transition from prokaryotes to eukaryotes, right?

• 3:48Sean Carroll?

  The existence of nuclei and other substructures in cells that are characteristic of eukaryotic life. And then the transition to multicellularity, and even a little bit about larger macroscopic animals and their constraints. We live in a world governed by the laws of physics, don't forget that, and those laws of physics will matter for, even for biology. Occasional reminder, here at Mindscape, we have a Patreon community that you are welcome to join. Just go to patreon.com/shawnmcarroll, and you can leave.

• 4:20Sean Carroll?

  Oh, actually, we're changing, yeah, we're changing the the funding mechanism. I'm not changing it. Apple is forcing Patreon to do it. So anyway, there's gonna be a monthly subscription fee to Mindscape if you want to be a supporter, but it's not gonna be that much money. I gotta, I actually gotta do that updating now. And then you can be the kind of person who asks questions for the Ask Me Anything episodes, and you get ad-free versions of the podcast and a feeling of belonging that is useful to everyone in our troubled times. So with that, let's go.

• 5:06Sean Carroll?

  Chris Kempes, welcome to the Mindscape Podcast.

• 5:08Speaker 02

  Thanks, Sean. Really glad to be here.

• 5:10Sean Carroll?

  So you know, you're a faculty at the Santa Fe Institute, where I'm fractal faculty. So I guess my my boundary area might be larger compared to my volume than you as just a regular faculty member, since I'm fractal. But in both cases, we're supposed to be thinking about complexity. And it seems to me that even though SFI studies lots of different things, life, living organisms, are kind of the paradigmatic example of a complex system, right? Like, much of what I hear people talking about when they talk about complexity, like, clearly, they're either thinking about life or inspired by living beings. Is that, is that a fair kind of thing?

• 5:51Speaker 02

  I think that's incredibly fair. People often say complex adaptive systems to define complex systems or complexity. And so the adaptive part really matters to many people, right? And so life is the quintessential adaptive system. And what we mean by that typically is that for an organism, just to survive, just to persist, It has to deal with this constantly changing set of environments. It has to respond to all sorts of new predators, new cooperators, new ecologies. And to do that, it has to constantly mutate and evolve and adapt. And so that's one way to really define complexity, which is systems that have to continually find new solutions to an ever-changing world.

• 6:36Sean Carroll?

  It's an interesting perspective because, of course, there's many ways of defining this. I kind of don't care what the definition is, obviously. What matters is what the things do. But that's a very kind of interactionist perspective you just gave. Like, it's about how the system adapts to the world rather than a sort of completely internal definition in terms of hierarchy and organization and parts and holes and things.

• 7:00Speaker 02

  Yeah, I think that's a great point. I mean, I think for me, I really focused on that hierarchy and internal structure and all the ways that organisms come to find solutions. To me, that's all a consequence of needing to adapt. So, you know, I like to say if there's one environment out there with only one limiting resource and it never changes, you only need one very simple organism to survive in that. And in fact, it has no benefit in becoming more complex, in gaining higher levels of structure and developing all these wonderful fractals on the inside like we do with our vascular systems. And so if you have that really boring environment, you don't need adaptation.

• 7:45Speaker 02

  You just need to find one solution and stay there forever. In fact, all mutations are bad. So any, and for us, some mutations are good. And so I think that's, you know, that is why I would sort of say you need that change, you need some external motivation to get all the richness that we see in living organisms.

• 8:08Sean Carroll?

  Good. Okay, so to get down to business, I noticed that you opened a paper you wrote a few years ago with the provocative statement that, quote, "Organisms are subject to the laws of physics." These are bold words, Chris.

• 8:25Sean Carroll?

  Does everyone agree with this? Is this going to be a major constraint?

• 8:29Speaker 02

  Yeah, well, it's interesting, right? Because it's a blatantly obvious statement, as you're alluding to. And yet, it's something we take for granted.

• 8:38Sean Carroll?

  Yeah.

• 8:39Speaker 02

  Right? So, you know, we were handed, in the modern world, this rich set of organisms, this vast diversity that we see in all these different ecosystems that we go into, and amazing creatures that have toxins and weird ways of moving around and all sorts of different intelligences. And so, we look at that world, and we sort of start to, and biology has classically started to try to tell stories about those organisms or explanations focused on the richness of their features. And I think we often forget this very simple fact, which is, those organisms are situated in a physical environment.

• 9:14Sean Carroll?

  Right.

• 9:14Speaker 02

  They're situated in the laws of physics, they're situated in the laws of chemistry. And so, a lot of what I do is to try and use the other end of the spectrum of thinking to say, if all we focused on was the fact that there are these physical laws that organisms live in, how much can we say about biology? How much of all of that richness and amazing variation can we explain from just focusing on the laws of physics or laws of chemistry?

• 9:39Sean Carroll?

  And I guess-

• 9:40Speaker 02

  Now, that's not every project. There are some places where you can't say very much about organisms from that perspective. But a lot of the game we play is to move into that space and say, how much can we explain from this simple perspective?

• 9:51Sean Carroll?

  I'm unsurprisingly going to be sympathetic to this perspective, but I guess I can see why one might not bother with that perspective. I mean, the variety of living organisms is so incredibly large. When you think about what evolution has accomplished with all the species, et cetera, it seems it could do anything. And here you are saying, but yes, you know, the center of mass of the organism will follow Newton's laws of gravitation or something like that. And I guess a typical biologist might say, so what? Like, that's not much of a constraint.

• 10:22Speaker 02

  Exactly, and so I think, you know, you could say, well, imagine I'm in some sort of game theory situation with another organism where it's trying to eat me and I'm trying to build up these defenses, you know, so let's say I keep building this longer and longer spine on the outside of a very hard shell and I do that so that it's harder and more painful for me to fit in something else's mouth. This is the story of different phases of evolution in the history of life. Now, if I keep doing that, though, eventually I start to get a spine that is so long that the leverage on it means it's really easy to break. And so either I can't grow the spine any longer, or I have to make it much

• 11:05Speaker 02

  wider, or I have to use a different material to make that spine, right? So this is a place where you'd say, well, the evolutionary dynamic is really about this predator-prey evolutionary chase where one's trying to eat the other and the other's trying to build up defenses. But at some point, and probably at every point, those decisions run up against the laws of physics, right? So to build a great defense, which you'd say defense is only in the context of a predator, but still to build up a great defense, I have to do so in a way that is also optimizing certain physical constraints. And that's the key. And so it's that every time I'm making evolutionary consideration, I'm also making a physical one. And actually, Galileo was the first person to point this out, as he did with

• 11:49Speaker 02

  sort of his drawings of bones and explaining how as organisms got bigger, their bones had to get much wider just so that it wouldn't break. And so I think this is something, again, we often take for granted.

• 12:02Sean Carroll?

  And the good news here is that by the laws of physics, we really don't need to worry that much about quantum field theory, et cetera, right? It's more or less classical Newtonian stuff.

• 12:11Speaker 02

  Well, there is interesting quantum mechanics in systems like photosynthesis. I don't work so much on those. I'm mostly concerned with packages of biological stuff. So I sort of think You know, the viruses are sort of as small as I get, so I don't go quite to the quantum mechanical scale. But yeah, you can use a lot of classical physics to describe much of what we see in organisms. Now, where that gets complicated is where those classical physics interface with complicated, say, mathematical geometries. So a lot of the work that's been done at the Santa Fe Institute, Jeffrey West and Brian Enquist and Jim Brown did this work in the late 90s, was to show that when you start to think about optimizing

• 12:53Speaker 02

  even classical physical constraints, the best way to do that is with a fractal geometry. And so then, that, the mathematics of that geometry become more complicated, but the constraints you're optimizing are still classical physics constraints.

• 13:08Sean Carroll?

  And just so, I think maybe people might get this mixed up a little bit. I mean, the constraints we're talking about are not necessarily external constraints, like being fit into a box or something like that, right? I mean, there's sort of constraints on what you can do. I don't know. I should always, I always start in these podcasts by like, making statements and then saying, is that right? I should phrase them as questions. Should we think about being fit into a box? Or is there some, or do you mean something slightly different by the words "physical constraints"?

• 13:40Speaker 02

  Yeah. And so what I, what I mean by physical constraint is really, there's a physical law. And as you know well, physical laws often apply at certain length scales or certain amounts of mass, or you know, that, that sort of thing. But over some range of sizes, there are certain physical laws that are present, and those inform sort of how all the physics at that scale operates. And that's what I mean by constraint. So gravity is really, you know, it's a law of physics, but we could think about that also as a constraint in the sense that if I get taller, I have to deal with different forces of braking that owe to gravitational forces on our planet. So it's, it's really that

• 14:25Speaker 02

  sort of thing. Now, you can have more abstract constraints. Some of which emerge in time, I mean, in over evolutionary time. So as organisms evolve and become more complicated, you can get new sorts of constraints. For example, well, I already put the brain here. And so if I'm going to put an eyeball somewhere, where should I put it?

• 14:46Sean Carroll?

  Mm hmm.

• 14:47Speaker 02

  And that's, that's a constraint that's related to an evolutionary decision that was made in the past. And we often call those sort of emergent constraints or physiological constraints. But often when I'm saying physical constraints, I just mean the laws of physics, diffusion, gravity, fluid flow, electricity and magnetism. These are the sorts of things that we're thinking about.

• 15:11Sean Carroll?

  And is this pointing in the direction of explaining examples of convergent evolution? Like dolphins look more or less like fish because given what they're trying to do and the constraints of the laws of physics, that's what an efficiently swimming thing is going to look like.

• 15:26Speaker 02

  Yeah, that's a, that's a great way to put it. And I often like to say that, you know, evolution according to physical constraints is sort of the ultimate convergence. It's the thing you can most rely on, you know, it's, it's the thing most likely to happen. And, and we wrote a paper where we said, you know, you'll get optimization of traits if those traits depend on a very dominant physical constraint. And what I mean is, to your point about quantum mechanics, you know, quantum mechanics certainly apply at the scale of entire trees. They're not a dominant constraint.

• 16:01Sean Carroll?

  Yeah.

• 16:02Speaker 02

  So many of the quantum mechanical effects have been averaged out over all of these different particles that I don't really need to use, say, the Heisenberg uncertainty principle to understand what's happening for a vascular plant or a large tree. However, that constraint is still there. But gravity is a dominant constraint. And so if traits are connected to a dominant physical constraint, evolution will be able to see that and will, will get traits that, that look optimized according to those physics. And then those traits have to be independent enough of other traits. So there are many cases in biology where you would like to optimize something, but you can't for other reasons. So a great example is our optic nerve that connects our eyeball to our brain is longer than it should be.

• 16:45Speaker 02

  And many people have talked about this optic nerve seems much longer than you would want in some optimal case. And part of that is likely due to the fact that you had brain structure and you developed this eye, and then it's really hard to remodel the brain. It's really hard to move around different modules of the brain. And so you deal with a slightly longer optical nerve because it's just too hard to change everything else. And so that's what we mean by traits have to be independent enough of other traits in order for these physical constraints to be something that evolution can see.

• 17:17Speaker 03

  Boot season's back, which means football season is back. And Tacovus has the denim for game day. Handcrafted in three timeless cuts, every style is made to look great with boots. And with multiple washes and colors, they might be the last jeans you ever buy. Find your new favorite denim at tacovus.com or stop by your local Tacovus store. Either way, you'll be showing up on game day. Tacovus denim, it's made for boots.

• 17:47Speaker 04

  OnDeck is built to back small businesses like yours. Whether you're buying equipment, expanding your team, or bridging cash flow gaps, OnDeck's loans up to $400,000 help make it happen fast. Rated A+ by the Better Business Bureau and earning thousands of five-star TrustPilot reviews, OnDeck delivers funding you can count on. Apply in minutes at ondeck.com. Depending on certain loan attributes, your business loan may be issued by OnDeck or Celtic Bank. OnDeck does not lend in North Dakota. All loans and amounts subject to lender approval.

• 18:17Sean Carroll?

  I mean, that might be a good example of, I had a recent podcast with our mutual friend Brandon Abunu, and we were talking about fitness landscapes and seascapes and so forth. The fitness landscape changes over time, so, you know, at one point, the direction to go in was to build a brain, and only later that you'd need to make an optic nerve. And so you're stuck kind of in a little valley where only certain things are possible.

• 18:42Speaker 02

  Exactly. Yeah, exactly. And so what we often, in that same language, what we would say about some of these physical constraints is they create these huge valleys that are impossible to miss.

• 18:53Sean Carroll?

  Yeah, good.

• 18:54Speaker 02

  And so even though there's roughness on the surface, it's really like a...

• 19:00Speaker 02

  Gently undulating grassy hill that is all part of one big valley, one big watershed, where everything rolls to the bottom. And that's just because the physics is so strong, the physical constraints are so strong, you can't help but wind up in the bottom of the valley.

• 19:14Sean Carroll?

  And while-

• 19:15Speaker 02

  But there could be emergent constraints that create local valleys that you can't get out of, as you were mentioning, and so forth.

• 19:22Sean Carroll?

  While we're at this very high level of abstraction, we'll get our hands dirtier in just a second. But the other thing that I liked very much in one of the papers that I've read of yours, the idea of competing constraints, right? Like, there's one constraint that makes you want to grow bigger, another one that makes you want to stay small, and you can almost quantitatively predict what is the smallest kind of organism you could get, what is the largest kind, what is the optimum size.

• 19:49Speaker 02

  Exactly. And there's a lot to say about that. So one really interesting thing is that often the only way to explain what you see in organism structure or function is from a consideration of multiple constraints. And so what you do is you say, we find some way to write down what in some fields would be called a global cost function, where we put all of the terms of different constraints in that same cost function, and maybe one trait interfaces with multiple different constraints, and then we just optimize over the whole thing and find some global optimum under multiple constraints. This is an old idea in engineering. And that often is the best way to explain complicated structures.

• 20:30Speaker 02

  So for vascular plants, which I was mentioning, the original work on that showed it wasn't just about gravity, it's also about fluid flow through the vessels of the plant. And it's about trying to fill space with all the endpoints of the network so that you can either distribute leaves in space to uptake, atmospheric space to uptake sunlight, or to distribute cells in the body and feed them all with this vascular network. So that's a place where you sort of have three main constraints that you're optimizing over.

• 21:02Sean Carroll?

  This is more like an end of the podcast kind of question, but does this mean that if we discover advanced interstellar life, alien life, that we shouldn't be too surprised if there's some commonality of forms in the morphology?

• 21:19Speaker 02

  Absolutely. So I think we wouldn't, I'm willing to make bets about that, actually.

• 21:25Sean Carroll?

  Okay.

• 21:25Speaker 02

  That if you get large multicellular organisms, they will have fractal-like vascular networks with a certain, very specific fractal structure that have been outlined in the whole thread of work that I was discussing before. And so we have some evidence for that in that, you know, the vascular system in plants evolved independently of the vascular system in mammals, and yet they share a huge amount of the same structures. So that's convergent evolution with a huge evolutionary divergence in time. One organism is motile, the other organism isn't. One is, you know, uses sunlight for energy, the other eats things that use sunlight for energy, one's warm-blooded, one's not.

• 22:09Speaker 02

  And yet, the vascular systems we find share certain commonalities because they are roughly the same size and obeying the same physics.

• 22:18Sean Carroll?

  Good. Okay.

• 22:20Speaker 02

  So I think, yeah, I think these are sort of the ultimate astrobiological convergence.

• 22:24Sean Carroll?

  That's, it makes the Star Trek budget help under control, right? All you need is to slap some prosthesis on a human being and you get an alien. You know, physicists, of course, like to look at toy models and spherical cows and so forth to put their theories to the test. So let's think about bacteria. They seem to be simple unicellular organisms that we can really do some math on, perhaps. Well, tell the, tell the audience about bacteria. Like, one amazing thing is the range of sizes that we get in bacteria. This always knocks my socks off.

• 22:59Speaker 02

  Yeah, so bacteria, we think of them as these tiny sacks of stuff, which in some ways they are. But even, as Sean was just saying, even then, we get a factor of 10,000 in cell size, right? So that's four orders of magnitude from the smallest cell to the largest cell. And the smallest cell and the largest cell don't look like each other in lots of different ways that we can get into. And so, you know, people, people often just say bacteria. As the small stuff, not realizing that there's an entire world in bacteria of diversity and different cell sizes and trade offs and lifestyles and environments.

• 23:40Speaker 02

  And so even there, we're talking about half the range of body size differences that we see in mammals in terms of orders of magnitude. And so a factor of 10,000 is definitely nothing to sneeze at.

• 23:55Sean Carroll?

  And just to get, again, our non biologically literate audience up to speed, bacteria don't have nuclei, they're eukaryotes, and they're friends with the archaea, which are the other kinds of prokaryotes, right?

• 24:12Speaker 02

  Exactly, yeah. So bacteria are prokaryotes. They have some amount of internal structure, and this is something we've learned a lot more about recently, but in general, you can think of them as some sort of membrane, and sometimes that's two layers of membrane. And then inside that membrane is a bunch of more or less free-floating stuff. That includes a free-floating genome that's not packaged in a nucleus. It includes a bunch of large molecular machines, often called macromolecules, all of the enzymes and proteins of the cell. And mostly, this stuff just diffuses around and interacts in a very complicated but messy

• 24:55Speaker 02

  network to do all of the functions that a cell needs to do, to metabolize, to synthesize new parts, and eventually to divide, to import and export material from the cell, and for larger cells to swim around and follow nutrients and make some decisions about their environment. But yes, they lack a lot of the internal structure that we see even for other unicellular organisms. So there are other single-cell organisms that have more internal structure. Bacteria tend to be these very simple things. Not quite the simplest life, because I'm a viruses are life too sort of person. And we could get into why I think that's the case.

• 25:38Speaker 02

  So I would count viruses as the smallest life and the simplest example of really an enclosure and some genetic material inside that enclosure. Bacteria then have, you know, this active goopy stuff inside.

• 25:52Sean Carroll?

  But the DNA, they're just like wandering around, you know, bouncing back and forth inside the bacterium.

• 25:58Speaker 02

  Exactly. The DNA is just, so it's actually a circular chromosome in many cells. So it's a DNA that forms this entire loop. And that loop is not a rigid loop, you know, it's malleable and moving in time. And so think about sort of a circular chain inside a cell that's jostling around and sort of moving all over the place while interacting with a bunch of molecules that read off the genetic information and copy the genetic information when the cell divides. And so it's in some ways sort of amazing that without much structure and in such a messy environment, we get such reliable organisms, right?

• 26:38Sean Carroll?

  Yeah.

• 26:39Speaker 02

  There's a sort of unbelievable number of prokaryotes on the planet and they evolve very quickly. They live in every environment you can imagine. They divide reliably. They're just quite amazing creatures.

• 26:53Sean Carroll?

  And so despite the fact that four orders magnitude in size, that is to say a factor of 10 to the four, that's, that's pretty big. It's a, it's a large range, but there is a lower limit and an upper limit. And, and this is where you're going to earn your keep, right? Telling us why the physical constraints help us understand those limits.

• 27:10Speaker 02

  Yeah. So, so something we like to say is that if you have a dominant physical constraint, it will also tell you where there's a wall, where something becomes asymptotically limiting. And what I mean by asymptotically is just something goes off to infinity and you can't keep up with it, or something goes to zero and then it, it does you no good. And so often if you're writing down some optimization equation and it has physical constraints in it, you should expect to see a limit at some scale. And so we see these in lots of different groups of organisms, but particularly in bacteria, we've have pretty well worked out what the lower limit and the upper limit are.

• 27:52Speaker 02

  And so if you think about the smallest bacteria, they have this membrane that is shrinking down. If you imagine a spherical cow, and here we really can't imagine a spherical cow because the small bacteria are little spheres. Yeah. So imagine the small spherical bacterium. And as it shrinks down, you know, it's the membrane has its own finite thickness. And so imagine, you know, you have a really thick tire and you shrink down that tire. Eventually, the rubber is touching the rubber on all sides. And you don't have a tire anymore with something in the middle. You have just a hockey puck. The same thing is happening for cells. So they have this membrane that

• 28:37Speaker 02

  is very thin until you get to really small sizes, and then it starts to represent a large fraction of the cell size. And then you still have to, inside of that, in the remaining volume, fit all of the stuff. So you have to put the DNA in there. You have to put a few functional proteins to actually run the metabolism. And you have to put in this amazing molecular device known as the ribosome, which is sort of this generic tape reading device that takes information from the DNA and turns it into functional proteins. And so in these small cells, the DNA starts to take up roughly half the cell volume. And so you're running into all of these space constraints where you almost can't fit in

• 29:18Speaker 02

  just the information of what the cell is. You know, you think about how strange that is. The storage system for information becomes sort of half the cell volume. And you get to a point where every single gene that you would eliminate kills the cell. So every gene knockout, as we call it, is fatal. And so you can't eliminate any more genes. You're stuck with this minimal genome. And so the smallest cell is defined by this point where you have a minimal genome, a handful of ribosomes, and the functional proteins that do all the other metabolic and physiological aspects of the cell.

• 29:56Speaker 02

  What's amazing is that we write down energetic models of the cell and we think about what's the energy budget of the cell, what it has for running biosynthesis, the production of new stuff, and what it has for maintenance, which is just repairing and the repair and upkeep of existing stuff. Then, at these tiny cell sizes, the maintenance starts to take over the entire metabolism. So you start to look more and more like a cell that can only repair itself. It actually can barely grow any new stuff for replication. And this space constraint and this maintenance constraint, where maintenance metabolism becomes the whole metabolism, both happen at basically the same tiny cell size.

• 30:39Speaker 02

  And so we think it's this dual constraint that sets the smallest possible bacteria. Amazingly, those predictions have agreed with all of the world record holders for smallest bacteria. And so we, and it's where you transition to seeing tiny viruses that crop up at these really small cell sizes. So we think this is, this physical constraint tells you the smallest possible bacterium.

• 31:05Sean Carroll?

  Knowing that our audience is raised on watching movies like Ant-Man and so forth, we have to say, like, why can't you just make the cell wall smaller?

• 31:15Speaker 02

  And you could. And that's, I mean, and that's a really great question, Sean, because that's a game, especially in an astrobiological context, we like to think about a lot, which is, well, but the DNA takes up a certain volume and we've, you know, we're committed to a certain chemistry there. So what if you change that a little bit? And, you know, the membrane is made up of this lipid bilayer, and what if you used a smaller molecule than lipids? And so one can really absolutely start to play that. And this is a place, actually, where we're separating the contingencies of evolution from what might be truly universal. So, yeah, if you could find a smaller enclosure that does all the same things that our membrane

• 31:56Speaker 02

  does, in terms of it's flexible enough, it is, you know, keeps the inside separate from the outside, it has the right sort of hydrophobicity, all those sorts of things, yeah, there's certainly molecules that would be thinner in a layer. And then, yeah, you probably could get a little bit smaller. So I think this is a case where...

• 32:16Speaker 02

  We think we understand the constraints that matter, why the smallest cells on Earth are the smallest they can be, and then we could play a little bit of games with chemistry to say, how much could you push that lower limit in size? In fact, that game was played a bit because the Allan Hills meteorite, which was this meteorite from Mars, where under a microscope, people thought they were seeing structures that really looked like cells, or the remnants of cells, or some sort of precipitate from a cell. And this is famous in the astrobiology community because Bill Clinton gave a press conference saying, you know, you might have potentially found life on Mars, or evidence of life on Mars.

• 32:58Sean Carroll?

  I think infamous is the word you're looking for, not famous.

• 33:01Speaker 02

  You're right, I forgot my prefix. But this, because of how big a news story this was and the implications, the National Academy's put together one of these National Research Council reports, where they gathered experts from paleontology and biophysics and biochemistry to try and say, are these things too small? So that, and one of the, you know, initial sort of critiques was, yeah, but these structures are really small. They're smaller than the smallest cells we see. Are we actually talking about fossils here? And so in this report, which is really wonderful, people work through all these different angles to say, yeah, this is probably too small.

• 33:44Speaker 02

  So people work through, okay, what's the, what's the most curvature you could get from some polymer, some sort of molecule? And are these things below the curvature radius for that molecule, such that we don't think you could actually encapsulate with molecules at this scale? And then, and then people, and then there's all sorts of other rich material in that report. And basically, every paper in this report says, these are too small. But this is exactly the game that we have to play to try and understand what we might be looking at somewhere else.

• 34:20Speaker 05

  Host Thanksgiving with industry-leading quality standards from Whole Foods Market. There are no antibiotics in their meat department, ever, so carve up turkey and spiral-cut ham with peace of mind. Shop organic sides like stuffing mix and cranberry sauce from 365 brand. And guess what? All their delectable pies are made with no high-fructose corn syrup. Gourmet Thanksgiving flavors with the quality you want, only at Whole Foods Market.

• 34:49Sean Carroll?

  But aside from the possibility of novel molecular structures, we are running up against -- so I'm going to have to take back what I said earlier. We're running up against quantum mechanics, because it's the size of the atoms that ultimately sets what we can do here, right?

• 35:04Speaker 02

  That's a great point, yeah. I mean, you could even play a -- I don't know if we have an astrobiology for other universes yet. But you could play that game. You could say, imagine you were in a universe where the atoms were smaller.

• 35:20Sean Carroll?

  Change the mass of the electron, yeah.

• 35:22Speaker 02

  Yeah, exactly. Assuming all the other physics -- you can still get all the other physics you need, what's the smallest possible cell in such a universe? And I think that's -- yeah.

• 35:30Sean Carroll?

  Yeah, people have done that in the context of the anthropic principle. Maybe not exactly that, but they've definitely asked whether that you could have the chemistry. So, okay, I guess that makes perfect sense. To get an organism at all, an organism that has its own DNA and can be produced by itself, there's probably a minimal size you can get away with. There's certain ingredients you can't do without, but why is there a maximum size to bacteria?

• 35:56Speaker 02

  Yeah, so the maximum size is really interesting. That actually concerned us for a long time. So when we first started uncovering what we think was limiting the smallest bacteria, we then had nice laws for how things like growth rate would change with increasing cell volume. And so we thought we understood the trends in bacteria as well as the small limit. But then we had this huge puzzle about why is it that you don't just keep being bigger and bigger bacteria? Right? So what's happening? You know, the biggest bacteria are growing really fast per unit volume. In fact, growth per unit volume is increasing as bacteria get bigger.

• 36:39Speaker 02

  You have lots of metabolic power. Everything seems great for the biggest bacteria. Why, why do you have this major evolutionary transition to unicellulare, which we can get into in a bit, where everything shifts and growth rate decreases and all of that? Why, why is there a motivation for that? Why not just, why aren't we all just giant sacks of bacterial stuff? You know, walking around and building cities and talking on podcasts? And what we proposed as a hypothesis in one of those early papers was it's likely that as growth rate gets faster and faster, eventually the basic biochemistry just can't keep up. Right? So if I have some chemical reaction that can only go at some maximum rate,

• 37:23Speaker 02

  or I have some molecular device that can only work at some maximum rate, eventually it can't keep up with my overall growth rates.

• 37:31Speaker 02

  So it just can't keep up with how fast I'm trying to move. I could pump more and more energy into it and it just can't turn over quickly enough. And we were very used to thinking about that with macroscopic machines, where they all have a, you know, an upper threshold where you're just trying to push them too quickly. And so we said, let's look at all of now the detailed biochemistry, all of the macromolecules, all of these different components of the cell, and ask how they change as cells scale up from very small sizes to very large sizes. And as we do that, we see, uh oh, there's this one component, the ribosome, which again is, is this device that's sort of the center of biosynthesis. It's turning genetic information into functional proteins. It's actually building the functional proteins.

• 38:16Speaker 02

  And we realized for it to keep up with this runaway growth rate. Eventually, you would need more of that device than you have cell. So you would need to pack more. You need more of this machine that can actually fit inside the cell. We call this the ribosome catastrophe. And it sets the largest possible cell size. What's really happening there is that the ribosome is making more ribosomes. So it actually makes some of its own components. And so you reach, it has its own replication rate. So it's a machine that replicates itself with one rate. And eventually, the cell growth rate starts to push up against that ribosome replication rate, and that is an impossibility. And so that's where you get one of these, something goes off to infinity.

• 39:01Speaker 02

  You need infinitely many ribosomes. That can't happen. You overpack the cell. And so we think there's this upper size limit there.

• 39:10Sean Carroll?

  Well, this sounds like something that you could calculate mathematically. And then as scientists, you're going to go compare with the data.

• 39:17Speaker 02

  Exactly. And so we did that. So we said, OK, we know where this asthmatoide is. And let's look at the data. And so interestingly, what you see is that you get less and less species, less and less known species of bacteria as you get closer and closer to this wall. And then we said, well, what's the world record holder bacteria? And I want to be clear here that I'm not talking about these recent world record holders for the longest bacteria. So there are these, you know, almost centimeter long bacteria.

• 39:46Sean Carroll?

  Oh, my God.

• 39:48Speaker 02

  Right?

• 39:48Sean Carroll?

  I'm going to lose sleep now.

• 39:50Speaker 02

  Yeah, exactly. But the key thing to note about those is they're actually filaments. And so they're, they're sort of like a colony of many little rod shaped bacteria like E. coli stuck end to end. And so while they form these very long filaments, there's many copies of the DNA. And, and their dimension in the other radial dimension is like an E. coli. It's a, it's a small bacterium. So they get very long, but they don't get volumetrically big. And that's really what we're talking about when we say size in this case. So anyway, we look for the world record holder volumetric organism, something that's roughly a sphere. And there we find an organism that's about 100 times bigger than our upper bound.

• 40:34Sean Carroll?

  Okay.

• 40:35Speaker 02

  So we thought, okay, this is interesting. Why, how is this thing 100 times bigger than our prediction? Especially since we'd been so pleased by our lower bound predictions. And there's two things to note. One is this organism has these huge internal storage vacuoles. So it has these big internal membranes that it uses to just store inorganic stuff, likely to be able to grow fast later. Right? So it sort of hoards rare stuff and then uses it later. If you remove all of that and you say, let's just talk about the active sort of metabolic portion of the cell, you're still bigger than our limit. Not by as much, but still a little bit bigger. And here then, the other crucial thing to note is that this organism lives in a really resource poor environment.

• 41:20Speaker 02

  So it lives in these ocean, deep ocean sediments, running a metabolism that we know is a really poor metabolism. It just doesn't give you much energy. And so they grow very, very slowly. In fact, they're really hard to study and grow in the lab and you have to do so in sort of environmental settings. And so what that tells us is that this upper bound that we were describing really was a speed limit. Right? It said, no, there's a, there's a fastest growth rate. There's a fastest replication rate. If you want to get bigger than this wall, you just have to grow more slowly. And so that's actually what the next branch of life, the unicellular eukaryotes does is they grow more slowly.

• 42:02Speaker 02

  And that's also what large bacteria that break this rule do is they just stay away from that fast growth limit, that speed limit.

• 42:09Sean Carroll?

  It's very much, I love that example of how science works. Right? Like you have a theory, compare it with the data, you realize I could have had a better theory or a different theory all along, but I'm learning something by looking at what nature actually does.

• 42:22Speaker 02

  Exactly. Yeah. And it made, it made us realize, to your point, exactly what we were talking about in our, in our theory, what our assumptions were is it was about maximum growth rate. And so we're confident in maximum growth rate, but there's ways to break that law. You can, you can just dial down your metabolism and be a slow growing organism.

• 42:38Sean Carroll?

  Is there any relationship between Jeremy England's work on the statistical mechanics of self replication? I've had him on the podcast years ago.

• 42:47Speaker 02

  Yeah, so, you know, there's lots of interesting ideas there. And I think where it interfaces, what we're doing is just to ask questions about what are the fundamental bounds on how efficient you can be, how much energy you need to perform a process and so forth. And we've done a little bit of statistical mechanics on the energetics of different cellular machines. So a bunch of us, including David Wolpert, a few years ago, worked out sort of what we thought the optimal efficiency of something like the ribosome would be, and then compared it to the efficiency of the ribosome that we have. And so if you abstract the ribosome, what it really is, is a device for writing strings,

• 43:31Speaker 02

  for taking a random set of letters that are unorganized and writing those into exactly one string. That string folds up into a functional protein. And so we could compare that thermodynamically to any device that writes strings. And we find that gives us an ultimate efficiency, the best any device in the universe could do at this abstract process. And we found that the ribosome is at most 20 times worse than that limit. And I say 20 times off the limit, that seems really inefficient.

• 43:59Sean Carroll?

  Yeah.

• 43:59Speaker 02

  But for reference, but for reference, our computers, as we talk now,

• 44:04Sean Carroll?

  Right.

• 44:05Speaker 02

  are writing strings at 100 million times worse than the limit. So the ribosome compared to our computers is like many, many, many orders of magnitude more efficient than our than our computers at this string-writing process.

• 44:19Sean Carroll?

  It's bumping up against the limit in some real sense, even though it's 20, factor of 20 way, yeah.

• 44:24Speaker 02

  Exactly. It's feeling the ultimate physical limit.

• 44:27Sean Carroll?

  Interesting. Okay, good. But this doesn't sound like we're done yet. It doesn't sound like this field is completely I's dotted and T's crossed.

• 44:38Speaker 02

  No, definitely not. I think there's, you know, I think the statistical mechanics of cells is something people are working on in lots of interesting ways. As I mentioned earlier, I said, you know, bacteria sort of mostly don't have structure. There's been this whole revolution really in the last 15 years around phase separation in cells, in bacteria, and realizing that different types of stuff are actually forming separated phases. Think liquid in water and how you could have a little bit of, sorry, think of oil in water and how you could have a little oil droplet floating around in water. They're both liquids, but they're sort of separated in an interesting way. And that's happening inside of cells, and that has chemical consequences, that has structural

• 45:20Speaker 02

  consequences. And so I think there's a lot to uncover there. There's a lot of really fundamental statistical mechanics and thermodynamics to do within cells. And then I should say that recently we've worked out other limits at the large end of bacteria where we have come to realize how fundamental constraints of diffusion start to set an upper bound for bacteria, where you need to add internal structure just to make things move around more quickly. And so there's a, there's a sort of diffusive boundary that you start to run into, and then you have to add transport structures to sort of get around that. And that occurs also roughly at the same size that you're seeing this ribosome catastrophe.

• 46:02Speaker 02

  So just like the small end of bacteria, we're seeing a large end where multiple constraints seem to be limiting cells at pretty much exactly the same size.

• 46:09Sean Carroll?

  Well, this is good because it's definitely nudging us in a certain direction. That other overly sized bacterium you talked about before, you mentioned that it has these storage vacuoles inside. It seems as if when you get big, it begins to become helpful to become complex, at least have more structure inside you than the ordinary bacterium does. And of course, we know famously, eventually we're going to make eukaryotes. We're going to make cells by marrying, or I don't know, shotgun marriage of the archaea and the bacteria to get cells with nuclei in them. So is that something, that's a, that seems like an

• 46:50Sean Carroll?

  out of context problem. It's like you're changing all the rules once you make a eukaryote because it's a transition to a whole nother kind of thing.

• 46:58Speaker 02

  Yeah, it's a great point. And you know, I think what's interesting is that we would say, once you get one of these walls, one of these sort of hard limits coming from physical constraints, it tells you you need to shift something about your architecture to get over that constraint, if you're going to get bigger. Now, there's lots of cases where you can imagine evolution never discovers anything that helps you get bigger. But if you see something that gets bigger, it certainly has found some new architecture. And so, you know, one of the great challenges of modern biology is thinking through how and why we

• 47:37Speaker 02

  got eukaryotes. And so, eukaryotes are, as Sean said, a byproduct of what we call an endosymbiotic event, where one cell started living inside the other cell. And so, you, in this case, have a bacteria likely living inside of an archaea. And the bacteria inside the archaea becomes this metabolic structure known as the mitochondria, which many people sort of associate with how life gets big and why life gets big, and how organisms like us can produce so much energy. There's lots of other reasons that you might want a mitochondria. It distributes many copies of the metabolic genome throughout the cell.

• 48:21Speaker 02

  Nick Lane has written really nicely about that. It distributes certain sorts of metabolic processes throughout the cell in a structured way. All of this is sort of really beneficial. And we understand that it must be getting over limits that we saw out of bacteria. I think our perspective would be, the main limits that you start to see are about transport, right? And so, I would almost say, you likely need to solve transport before you solve these other packaging problems around different sorts of genomes, and having lots of internal metabolism and so forth. I think it's actually, you just can't get substrates, the stuff

• 49:05Speaker 02

  that you use, products, the waste. In and out of the cell fast enough with diffusion alone for large bacteria to make the metabolism function. So you have to start adding active transport inside the cell, ways to stir the cytoplasm, ways to move packages around in the cytoplasm, just to overcome the sort of challenges of diffusion. And I think you probably need to do that before you start to get things like the mitochondria and other sort of endosymbiotic events.

• 49:36Sean Carroll?

  This is good because it's not like teleological. It's not like something is making it more complex. It's that the cell, given what it wants to do, is being faced with a problem, and extra layers of structure are going to help it solve that problem.

• 49:50Speaker 02

  Exactly. And you could think of it as, you know, you can think of it as a drift process or a random walk process in evolution. And so if there is one of these walls, I think you expect in evolutionary time for a very long period of time, things just keep hitting that wall and be stuck in a certain size range. And then it's, you're waiting for a chance event where some fairly big change to architecture happens for one reason or another, and that gets you just on the other side of the wall, and then you're off to the races in this other evolutionary trajectory. And then, then all of the physics of that region become a target for evolution, and then you may need to solve a bunch of problems successively. But, you know, many people would say it was harder to get the

• 50:34Speaker 02

  eukaryote than it was to get cellular life in the first place.

• 50:37Sean Carroll?

  Took longer.

• 50:38Speaker 02

  And it took longer, right? And, and I find that really interesting and surprising, right? And I also, I also don't necessarily agree with that because I think there's other factors involved. But, but that sort of thinking, I think, is really important to say you can just stall out at one level of complexity for a long time. Nothing wants you to get more complex. It's just if you stumble upon the right solution that gets you over that hump, then you're into this new valley with no competitors. You've got a new niche, and we know it happens there. Things diversify and, and go in every direction, and you get lots of new solutions. But you have to wait for that chance event to get you over the hump.

• 51:18Speaker 06

  Cash flow crunch? OnDeck's small business line of credit gives your business immediate access to funds, up to $200,000, right when you need it. Cover seasonal dips, manage payroll, restock inventory, or tackle unexpected expenses without missing a beat. With flexible draws, transparent pricing, and control over repayment, get funded quickly and confidently. Apply today at ondeck.com. Funds could be available as soon as tomorrow. Depending on certain loan attributes, your business loan may be issued by OnDeck or Celtic Bank. OnDeck does not lend in North Dakota. All loans and amounts subject to lender approval.

• 51:48Speaker 07

  When you send a business gift, you're doing more than saying thank you. You're recognizing a moment, expressing appreciation, and making a statement about your brand. With Forimprint, that message lands with certainty. With thousands of customizable products, from premium apparel and branded drinkware, to smart tech bags and thoughtfully chosen office items, Forimprint helps your brand show up with the kind of care people remember. You can tailor every detail: your logo, your message, your look. And with thousands without a setup fee, it's easy to create meaningful moments without added cost. You'll also get expert support, dependable service, and their 360-degree guarantee, so

• 52:29Speaker 07

  you can be Forimprint certain your gifts arrive exactly as intended, on time and on brand. Because in a season built around appreciation, the right gift should say it all with confidence, care, and attention to detail. Explore gifting with certainty at forimprint.com. Forimprint, for certain.

• 52:49Sean Carroll?

  And this might actually help push me in the direction of greater understanding towards something that's puzzled me ever since I realized that even though the bacteria got embedded in the archaea to make eukaryotes, and eukaryotes have nuclei, it's not the bacteria that are the nuclei. The nuclei are a whole separate thing. But if it's because it's pressing up against some limit at its current level of complexity and it needs to become more complex, maybe it's not surprising that it's becoming more complex in multiple ways. It's getting a nucleus and it's getting mitochondria.

• 53:25Speaker 02

  Exactly, and I think, and I think one of the reasons for that is, once you move into this new space, you see a bunch of new challenges that you never had to deal with before. And likely, each of those challenges needs its own solution, and so it's not then surprising that you get a bunch of complexity all at once. And maybe you don't get it all at once evolutionarily, but from our, looking back, from our current vantage of all of these well-adapted organisms a billion years later, we would say, oh, wow, you know, all of these, there's many innovations, they're all really optimized, and they all go together. Now, you know, one of the biggest debates in how eukaryotes came to be is the ordering of events. I mean, it's countless papers written about what was first.

• 54:10Speaker 02

  I mean, it's even gotten to the point where we say, well, is that a, you know, mitochondria first argument? Is that a thalactocytosis first argument? And, and so people really are, are trying to work through the ordering and have big debates about the ordering. And we don't have any fossils to tell us, because these things are goopy and don't preserve well. And so, whereas that debate gets resolved in dinosaurs about what happened first, it doesn't get resolved for the eukaryotes yet.

• 54:38Sean Carroll?

  And, and we're still in this realm of what we say eukaryotes, they're much more complex in some way than the prokaryotes, but they're still unicellular organisms, so we can compare them, right? I mean, one of the things you did was say, what kind of scaling remains true as you go from prokaryotes to eukaryotes, and then what things kind of break down and become different?

• 55:01Speaker 02

  Exactly, yeah. So, one, one thing that we found was, the way in which protein concentration scales with cell volume is preserved from bacteria into eukaryotes. And we think there's, there's one optimization related to diffusion that really drives, drives that uniformity in, in this one scaling relationship. However, metabolic power scaling shifts between prokaryotes and eukaryotes, the growth rate scaling shifts.

• 55:38Speaker 02

  Do eukaryotes pick up a bunch of scalings that you obviously don't have in bacteria? Like, how many mitochondria do they have? Jordan Okey has a really wonderful paper showing how many mitochondria you get as a function of cell volume. And so, there's, you know, lots of things are changing and then some things are staying the same. And both of those angles help us understand if we're on to the right theory, if we're on to the right constraints. So, for example, if we think a dominant constraint comes with a limit that should imply a major shift at one scale, and we look at prokaryotes on one side, eukaryotes on the other side, and they have exactly the same scaling, then we were wrong about the constraint. Luckily, that hasn't happened to us.

• 56:21Speaker 02

  But that's a nice way to say, we could easily falsify our theory if we'd picked the wrong constraints, because there are certain things we would predict that just wouldn't hold up. You would move across transitions and either see shifts that you didn't expect, or not see shifts that you did expect, and we think that's a sort of secondary test of these theories.

• 56:41Sean Carroll?

  So, when you say words like, just to be nice to the audience, metabolic power scaling shifts from prokaryotes to eukaryotes, what would that mean? What are some synonyms for that?

• 56:52Speaker 02

  Yeah, that's great. So, what I mean by metabolic power is just the total energy available to a cell. So, this is how, be like the total food that you and I ate. For cells, it's the same. If they use sunlight, it's the total sunlight they're able to capture. If they eat other things, it's how much of that that they're able to eat per unit time. So, that's the sort of total energy budget the cell is, is the metabolic power. And then, scaling is just this idea that if you look across orders of magnitude in one feature, you get a linear relationship in orders of magnitude of another feature.

• 57:34Speaker 02

  And those could have different exponents, which would be the slopes of those different curves in that log-log, order of magnitude, order of magnitude space. And so, when we say there's a shift in a scaling relationship of metabolic power, what I'm really saying is that as you go across this evolutionary divide, you see a change in the exponent from one class to the other. Specifically, in prokaryotes, the exponent is greater than 1, meaning-

• 58:02Speaker 02

  If you double in cell volume, you more than double the total metabolic power. If you go up by a power of 10 in cell volume, you go up by more than a power of 10 in metabolic power. In unicellular eukaryotes, the exponent is sublinear, meaning that if you go up by an order of magnitude in cell volume, you go up by less than an order of magnitude in metabolic power. So, the power per unit volume is increasing in prokaryotes and decreasing in unicellular eukaryotes. And that's a really fundamental difference that drives all sorts of downstream things that we can observe, like the growth rates, like the requirements for the number of ribosomes in the cell, all sorts of different features.

• 58:43Sean Carroll?

  So in a eukaryote, you still need more power when you're bigger, but you need less than your extra bigness.

• 58:51Speaker 02

  Exactly, exactly. You still need more power, but in a sort of gained efficiency way.

• 58:57Sean Carroll?

  Is there a simple way to connect that to the existence of a nucleus in some mitochondria?

• 59:04Speaker 02

  Yeah, so it looks like, the nucleus is a more complicated story, because I think, you know, the nucleus is mostly about regulation and separating out certain parts of the genome from each other and protecting the genome from reactive parts of the cell. But the mitochondria seem to just come along for the ride of that. So there, I think, there's a big debate about causality. People would say, well, the number of mitochondria have the same scaling as the metabolic power. So, are they driving the metabolic power? And I would say, we don't quite know yet. We don't know what's being optimized, because it could be that the number of mitochondria

• 59:45Speaker 02

  you have are just optimized according to some other constraint, and that constraint is what's driving metabolic power, and mitochondria come along for the ride. Or it could be some fundamental constraint about the mitochondria that require the metabolic scaling to be what we observe. But yeah, I mean, in general, that's exactly the sort of connection we try to draw. We say, we have a physical constraint, maybe it predicts something like total metabolism, and then, once we know total metabolism, we can write down a cell model. You know, we can write down a model of cell physiology and ask, what other components should scale in what way according to this metabolism? And in bacteria, that gives us a whole host of predictions, and the same in unicellular eukaryotes.

• 1:00:32Sean Carroll?

  I can't help but mention as a slight aside that there's a lot of really cool work being done on artificial life, like simulated life in a computer, origin of life, or you know, evolution and things like that. And generally, the word metabolism is not there at all, right? These are just running programs and they have all the food that they want. But clearly, if we're going to find some more ultimate end game understanding, the constraints of metabolism in the real world are kind of going to be a big deal.

• 1:01:00Speaker 02

  Absolutely. Yeah, and I think, you know, I think that's something we're starting to run up against more and more recently. I mean, it's interesting that, you know, in early, the early days of computer science, a lot of the considerations were really about, well, how much resources will this need as we scale up? Right? So how, you know, how much time, how many CPUs, what's our, you know, how will this scale up in a resource constraint? And then we got to a point where we were mostly interested in, well, just artificial life in the computer. We had enough resources, so then it's all just about how do you get the right sort of evolutionary dynamic? How do you get open-ended evolution? How do you get things that build up higher layers of structure and function?

• 1:01:44Speaker 02

  And, and there's a really wonderful bit of, of artificial life that was done there. And now with the emergence of AI and LLMs, I think we're back to really wondering about scale and constraints, right? I mean, there's a, there's a huge debate there about what will happen if we make the neural nets 10 times as big? And how many data centers does that take? And so I think we're back to thinking very clearly about scale and about ultimately the physical resources that you need to support artificial intelligence or artificial life or really sophisticated computer programs.

• 1:02:18Sean Carroll?

  Good. That was just an aside. I don't want to get sidetracked by that. Like every, every modern podcast ends up talking about AI at some point. So like, it's an attractor, it's a constraint.

• 1:02:29Speaker 02

  We did it. We checked the box.

• 1:02:31Sean Carroll?

  We did it, yeah. But we have looming in front of us the next big evolutionary major transition, right? From unicellular organisms to multicellular organisms. Let me just first ask, how clear is it what qualifies as a major evolutionary transition? Is it just that you know when you see it? Is there a theory of major evolutionary transitions? Or is it just like, well, we look at the data and we have to explain what we see?

• 1:02:58Speaker 02

  It's a great question. So recently, they've been called for some of those reasons that you're mentioning, Sean, in terms of the problems that raises. Recently, these transitions have started to become major transitions in individuality, right, rather than major evolutionary transitions. I haven't heard that one. That's good. I like it. Yeah. Now, I think individuality is also a complicated concept. And so then we're into talking about, well, what is an individual and how do you define that? And people like David Krakow at SFI work on, you know, entire theories of individuality and that's a frontier area in and of itself. Right. So I think that reframing doesn't quite solve all the problems with how do you know

• 1:03:42Speaker 02

  one? How do you spot one? What's the right metric? I think generally what people are thinking about is you have extra layers of architecture or hierarchy where you've packaged together more lower level things into some higher level thing and where that higher level thing in an evolutionary sense operates as a whole. So the selection that matters to it, the evolution that matters to it, is really on the whole. Now, many of the transitions are really murky, where we have, for multicellular organisms, for example, we have lots of organisms that happily live as a single cell and then come together in multicellular assemblages and even have their own physiology and set of responses and behaviors in that

• 1:04:27Speaker 02

  multicellular assemblage. And then when life shifts, they go back into the unicellular level. That even happens in bacteria. Bacteria going in and out of these biofilms and making complicated choices about whether to form a biofilm and stay in a biofilm. And so multicellularity is a great example of a really murky idea. I think many people would point to a major evolutionary transition. In individuality, as multicellular where it's not so easy to go back and forth between the unicellular and the multicellular phase, and where the multicellular really is being selected, the genomes of the multicellular are really being selected as a whole.

• 1:05:08Speaker 02

  So in our case, you know, all of the features that, you know, we do, everything we do in our life, if we're going to have children, results in a single copy, half a copy, for each human, being combined with another half a copy to form a new organism. So eventually, everything goes through one copy of the genome to go through development and form an entire other multicellular organism. So it doesn't matter that, I mean, my finger only matters in the sense that it eventually interfaces with that one copy of the genome. So if I lose a finger, maybe I die because of that. Hopefully, I don't lose a finger.

• 1:05:47Speaker 02

  But, you know, it's that little bit of tissue is, its entire sort of connection is to this one genome, and it's hard for my finger to decide, actually, I don't really want to hang out with this guy anymore. I'm going to go do my own multi, you know, single cell thing and try and make my own living in the environment. That's, it's sort of, we're, you know, all the cells in my body are committed to each other in a way that's very hard for, for any of us to defect.

• 1:06:16Sean Carroll?

  Right. Good. Okay, that makes perfect sense as to why a theory of individuality would be extremely relevant here. That's good. So, okay, multicellularity itself, one might have guessed, if one were completely ignorant of these things, that maybe eukaryotes that have more complexity inside were more willing or able to become multicellularity because they sort of had more degrees of freedom. But my impression that actually in the data, either one is possible, it's just that the eukaryotes kind of won out empirically.

• 1:06:55Speaker 02

  Yeah, and I think it's, you know, there's a whole debate there about what the eukaryotes have that makes them special for forming multicellular assemblages. People argue that it's the regulatory capacities that those cells have built up to, say, regulate all of these mitochondria. So mitochondria are great, but a bad mitochondria is just a parasite living inside of you as a unicellular eukaryote. So, you know, you have to regulate its metabolism, you have to make sure it doesn't eat your resources. This is why many people think the mitochondria has such a stripped-down genome and actually requires the nucleus to make things for it that get exported and imported into the mitochondria to regulate it and so forth. They're oppressed.

• 1:07:39Speaker 02

  And so that's, you know, there's a huge... Exactly. And so there's a huge amount of regulatory machinery built up in eukaryotes, and some people think that's what's really essential for forming multicellular assemblages where you can then differentiate and regulate cells of different types. In that same sort of vein, there's unique developmental capacities in eukaryotes, unicellular eukaryotes, that people think is maybe important. And so there it may be, in this case, you know, there is a wall at the upper end of eukaryotes, but in this case, it may be that it's not as hard to jump over the wall because

• 1:08:22Speaker 02

  the things that you're forced to do as a eukaryote actually make this multicellular step really easy. And in fact, we see many origins, many unique and separate origins of multicellularity in the history of life. And so that tells us something. It tells us that it's potentially a much easier step than other things, maybe because all the stuff you build up as a eukaryote is exactly what you need to make the next transition in hierarchy. That may have been less true for prokaryotes or eukaryotes.

• 1:08:52Sean Carroll?

  Well, we did have a podcast with Will Ratcliffe. I don't know if you know his work, but he's doing...

• 1:08:57Speaker 02

  I know Will very well, yeah.

• 1:08:58Sean Carroll?

  Good. I mean, he's doing the experiment where he's, you know, stressing these yeasts and they decide that becoming multicellular is a good life-survival strategy.

• 1:09:08Speaker 02

  Exactly, and I think that's just a really wonderful example of they set up a certain sort of physical selection and that selection is sinking or not sinking. And then because of that, you get organisms, the snowflake yeast, that build up more surface area to sink more slowly and they're the ones that get selected on in this environment. But yeah, I think the other, that's sort of two stories. One is, you know, physical constraints matter and the other is, seems pretty easy for lots of single cell eukaryotes to form multicellular organisms and then to start doing, I mean, I think in some of, lots of Will's recent work, they're showing, you know, pretty sophisticated cell differentiation,

• 1:09:53Speaker 02

  right? That you're actually starting to get cells performing different types of functions throughout the colony and that's, that's really exciting.

• 1:10:01Sean Carroll?

  And that does seem like something that a eukaryote would pull off more readily than a prokaryote.

• 1:10:07Speaker 02

  Yes, yes, I think so.

• 1:10:09Sean Carroll?

  Good.

• 1:10:11Speaker 02

  Now, it is tricky. Bactrial biofilms do have lots of really interesting responses within them and there's been debates about all sorts of higher order functions that they might be performing that look like cell differentiation. So I think there, yeah, so there is, there is some trickiness there, but maybe staying in that aggregate or getting irreversibly committed to that aggregate maybe is the hard part. Maybe once you get big and complex and differentiated, there's no way to regulate it in prokaryotes. You know, I think that would be a, a leading idea, but yeah, I think it's, that's still a frontier in my opinion.

• 1:10:56Sean Carroll?

  No, that's good. I don't want to be eukaryocentric. I want to give the prokaryotes their props. It's too easy to be in the situation that we're in. But that, the callback to Radcliffe's work in the multi, what is it called? Multi, right? Multi cellular evolutionary, long-term evolution experiment.

• 1:11:18Speaker 02

  Yes.

• 1:11:19Sean Carroll?

  Like, like we said, they, they kind of put constraints, right? There's a new physical external thing and that's very analogous to what you say was going on in the actual origin of multicellularity back in the snowball Earth times.

• 1:11:34Speaker 02

  Yeah, exactly. And so, yeah, so we, you know, sort of running with this idea of how physical constraints might set up an evolutionary transition, we worked with some paleontologists who were very focused on the fact that one of the huge expansions of multicellularity seems to happen just after Snowball Earth. And so, Snowball Earth was this phase of Earth history where the Earth was mostly covered in snow and ice, including the oceans. So, you know, the glaciers come, even the ocean glaciers, sea ice, come all the way down to the equator. And then people debate about whether this is a hard snowball or

• 1:12:18Speaker 02

  a soft snowball with some amount of open equator and some amount of open patches of water around the planet. But the point is, it's mostly covered in ice and snow. And as an aside, the way that you get out of that is volcanic activity, which keeps pumping CO2 into the atmosphere with no way to take that CO2 up into the ocean and into life. And so then you re-warm the planet through a greenhouse effect, and that pulls you out of Snowball Earth. Otherwise, with no volcanoes, you just get stuck there, which is a sad end to an interesting planet up to that point. So, we said, well, you get

• 1:12:58Speaker 02

  this huge explosion of multicellular organisms just after Snowball. That doesn't seem coincidental. And so, can we take our models of the biophysics for unicellular organisms, say eukaryotes, and simple multicellular organisms, and ask what would happen to those as the world cools down, as you go into one of these snowballs? And so, we sort of invented a sort of toy model organism to represent the multicellular, which is this swimming spherical shell of cells. Now, we see multicellular in the modern world that look quite a lot like this. And so, we said, that seems like a good model. It's hollow on the inside. It's these single-cell

• 1:13:42Speaker 02

  aggregates that could decide to go back to being single cells if they wanted to, but they also can swim around and collectively feed and that sort of thing. And so, then we said, and then you also have large single cells. And so, now what happens as the world freezes? Well, temperature starts to go down first. So, you first get this cooling ocean temperatures.

• 1:14:04Speaker 02

  And then eventually you start to form more and more ice. And when that happens, sunlight and what we call primary productivity, which is just how much sunlight is being captured and turned into biomass and producing sugars and carbon, fixed carbon in the ocean, that then starts to go down as the ice covers the ocean. So in this cooling phase where only temperature is changing, two things are sort of happening. The metabolic rate, that metabolic power that we were talking about, is getting slower and slower because it depends on temperature. And as temperature cools, that rate goes down.

• 1:14:42Sean Carroll?

  Okay.

• 1:14:43Speaker 02

  And what's interesting is that pushes single cell organisms to get bigger and it pushes these spherical multicellular organisms to get smaller.

• 1:14:54Sean Carroll?

  Wait a minute, you have to explain that.

• 1:14:56Speaker 02

  Yeah, so what's happening is the metabolic rate is decreasing. And so it allows these single cell organisms to live the same lifestyle at sort of a larger size because they sort of don't have as much metabolic demand because everything is slower. And then these spherical organisms, as temperature decreases, they're facing increased viscosity. And so their life is a little harder for hunting. And so that's sort of pushing them to be smaller. But then as the nutrients plummet, as the sort of total biomass starts going down, this pushes the multicellular organisms to get bigger and the single cell organisms to get smaller.

• 1:15:39Speaker 02

  And that's mostly a hunting effect, of sort of gathering resources effect for the large spherical things. And so we think this snowball pushes your multicellular organisms to get much bigger. And as you start to get much bigger, you start to run into other physical constraints that would induce sort of more complicated geometries. And as you start to develop these complicated geometries, you start to discover things like sponges, we think. And then you find this multicellular architecture that's really stable and really beneficial. And when the world thaws out, you keep it. You keep, you keep these multicellular around.

• 1:16:21Sean Carroll?

  So it's all because life got hard.

• 1:16:25Speaker 02

  Exactly. Yes, absolutely. Yeah.

• 1:16:27Sean Carroll?

  Life got hard and multicellularity was the solution. But of course, we had to get to the point where we were pushing the boundaries of what the single cell things could do before that became... You know, we had to develop our single cell technology well enough so that we were able to take advantage of a new modality in the multicellular world.

• 1:16:46Speaker 02

  Exactly. Yeah, exactly. Yeah.

• 1:16:49Sean Carroll?

  And then, okay, I presume, I can just sort of imagine that all sorts of new options open up once you become multicellular. I guess the differentiation is key, right? Different cells serving different purposes. On the one hand, you can't have that if you're unicellular. On the other hand, you don't need to have that if you're multicellular. So like, that had to be a new innovation also.

• 1:17:13Speaker 02

  Exactly. I think that's a new innovation. And you can imagine, in a simple way, why differentiation? What the calculus is of whether that's beneficial? So imagine I'm a sponge, and I say, "Well, I have some reproductive cells, and they sort of do the reproductive bit of me. And I have to grow, and then I need things to feed that growth." Okay, so now imagine I'm building a bigger, bigger internal sponge volume. And I just ask the question, if I add a little differentiated cell that has cilia on the outside, that drives fluid flow through the inside of me, through these filters where

• 1:17:57Speaker 02

  I can capture prey and then eventually digest them, do I get a return on investment for that? You know, every time I add one of these little cells with these little cilia, which are just hairs that move water, is it beneficial to my total metabolism? And so that's a case where, you know, maybe I have a few of those, maybe we're all that cell type, and then I say, "Okay, I make one of us reproductive, and I keep all the other as sort of these gathering cells."

• 1:18:31Speaker 02

  Now, the reproductive cell doesn't have to keep around all these cilia, which it's not using, that's expensive, right? So I've differentiated to this one feature. And now, all of these ciliated cells... Don't need to try and reproduce, right? So I don't need to think about the downstream consequences of what they, what molecules they have to carry around to be able to reproduce. I get efficiencies out of both of that, right? And that's sort of what differentiation is doing. And I think, I think that basic idea that when you take one thing that does everything and you split it up into subtasks that each do part of the thing, but don't have to pay the cost of doing the other thing, but still get the benefit from it. I think that, that's an idea that runs through economics, through biology.

• 1:19:14Speaker 02

  It really is just sort of how economies of scale happen is through, you know, specialization and differentiation. And so I think that, that idea is as true for a city as it is for a little sponge. And it's just about when you specialize, you don't pay, you don't do all the things that you're not specializing in, so you don't pay the cost of trying to, right? And so, you know, I'm not currently paying the cost of trying to become a really good guitar player, which I know is not accessible to me. And so I happily consume really wonderful music from other people and I get the benefit of that without needing to try to do it myself.

• 1:19:56Sean Carroll?

  That absolutely makes sense, but there, there is an extra layer of complexity here because, you know, in a car, the tires and the roof are doing different jobs, but they're also just made of completely different things. And the multicellular organism, all the cells start off kind of from the same basic material. So it's not a top-down plan with different kinds of stuff.

• 1:20:19Speaker 02

  Yes.

• 1:20:20Sean Carroll?

  It's that the different cells in a multicellular organism learn how to respond to their environments and therefore become something different, which is kind of amazing to me.

• 1:20:30Speaker 02

  Yeah, I agree. I think, I think development is, is astonishing, right? That you start off with one cell type and it divides and changes internal composition in terms of what proteins it has and what genes are turned on and, and you go down this whole, you know, developmental cascade. There are ways to replicate where you don't do that, where you say, I'm actually just going to cut off a whole portion of the body that has all the different cell types already differentiated.

• 1:21:01Sean Carroll?

  Yeah.

• 1:21:01Speaker 02

  And then all of those will replicate and rearrange and form a new functional differentiated body. There are a small number of organisms in different categories. I mean, Small number of large multicellular organisms in different categories are able to do that. Plants, to some extent, can, you know, sort of amazing, you can grow the whole plant back from enough of the right tissue excised from an adult plant. And planaria, you know, have all these strange things about how much they can replicate from bits.

• 1:21:34Sean Carroll?

  We had Michael Levin on the podcast talking about that.

• 1:21:37Speaker 02

  Okay, great. Yeah, perfect, yeah. But so there's certainly are cases where you can do that, but it's interesting that it's not the norm that, you know, for certain classes of complex multicellular organisms. I mean, mammals are a relatively narrow taxonomic group, but we don't have any mammals that are just fully cutting themselves in half. And then every cell replicates and builds a second portion of its same tissue and you get a whole new mammal that way.

• 1:22:05Sean Carroll?

  Right. Yeah, okay.

• 1:22:07Speaker 02

  No, plants are a large part of the world and they're planaria everywhere, so it's a little bit of how you count it.

• 1:22:13Sean Carroll?

  But so I do presume that the kinds of logic that we talked about at the very beginning of the podcast, where there are constraints that give you smallest things and largest things, I presume these can be applied to mammals just as well as to bacteria.

• 1:22:28Speaker 02

  Yes, absolutely. And, you know, I think that's actually the classic work that sort of re-kick-started, re-kick-started, that's a double, it's a double rebooting, this sort of whole field and way of thinking. So, you know, this, those optimizations for the fractal geometry of vascular systems in mammals and plants got us thinking again about just how far we could take these physical constraints and the optimizations of those to understand what organisms are doing. And then we moved into the single cells in lots of different ways.

• 1:23:10Speaker 02

  But yeah, mammals have, it's a different set of physics, you know, it's the physics of Fluid flow through vessels, it's the physics of mechanical buckling under gravity. And it's a very different sort of thing, but it still leads to predictions for how their metabolism should change with their overall body mass and what the structure of these vascular systems should look like and how fast they should reproduce and how long they should live. And so there is a pretty well worked out sort of systematic theory there as well. It's just slightly different physics.

• 1:23:45Sean Carroll?

  Good, very good. I think that that inspires me to wind up the podcast with what is probably a completely unfair question.

• 1:23:55Sean Carroll?

  If the harsh conditions, well, let's not say harsh, changing external conditions on snowball Earth prodded little unicellular eukaryotes to come together and start being multicellular. It's arguably, one could say that changing technological conditions on Earth right now are creating very different conditions for life to exist and thrive and so forth. So I would, I would guess that this opens up the possibility for dramatically, well, a new kind of a major transition in individuality.

• 1:24:37Speaker 02

  I absolutely agree. Yes, I have a whole bunch to say there.

• 1:24:41Sean Carroll?

  Please.

• 1:24:42Speaker 02

  So first is, you know, first is, there have been many cases in the past where radical changes to the environment have led to these huge mass extinctions. And then following those mass extinctions, you get what's called a re-radiation or radiation of different organisms that then discover these new innovations. And we're one such thing, right, as mammals that were small and in low abundance in the time of dinosaurs. And certain physiology allowed us to make it through this mass extinction and then to expand and become the organisms we are. So that's one side. I think that's totally a separate question from the ethics and considerations

• 1:25:24Speaker 02

  of mass extinctions from a responsibility perspective for humans. And it's also not guaranteed, right? So I think lots of mass extinctions don't get followed by a recovery. It's not clear that we always would have come out of snowball Earth. You know, it's possible that you find really interesting planets for a long time that then get into this snowball phase. The dynamicists, the planetary dynamicists, will tell you that that alternative steady state, having two steady states, one of which is a snowball, is common for planets that likely can harbor life. And so I think all the time you could get into a snowball

• 1:26:04Speaker 02

  and never recover, right? So major transitions to planets, major shifts in planets, may cause extinctions and be non-recoverable, right? So they're definitely, that's definitely another possibility that that doesn't always get mentioned with the extinctions lead to innovation and these new radiations and lots of cool new stuff. Extinctions sometimes just lead to the end of everything. And that's, that's really important to note. And then I think we're already in the midst of just an amazing time for, and I mean amazing with neither good nor bad, but really in the sense of amazement, time for evolutionary transitions.

• 1:26:44Speaker 02

  So, you know, many of us would say that cities represent a new type of organism, a new type of major evolutionary transition. It's certainly one of the major evolutionary transitions originally outlined in the first book on the subject, and along with with human social groups. You know, we've, we've been able to look at the growth of companies using the same sort of models that we use for organisms. And so we're pretty comfortable talking about companies as entities, as a new sort of entity that's on the planet. And I think You know, different types of AI also represent a major evolutionary transition, if not the internet itself, right?

• 1:27:27Speaker 02

  In all of these cases, we're taking lower level components and combining them into new architectures, right? So cities combine humans in new ways, inside new architectures. The internet combines all sorts of things in new ways and new architectures, as do LLMs, as do human organizations. And so I think we're in the midst of many new types of individuals showing up on the planet, which is really interesting. And then finally, I would say that also just, you know, how humans are changing the selective dynamic of the planet is also apparent. Ron Milo has some really nice work over a few papers showing how much of the planet's

• 1:28:11Speaker 02

  biomass is associated with humans, either our own biomass, or our crops, or the animals that humans tend to eat. And it's an amazing fraction, and it doesn't look at all like any other ecology we've seen in the past over the course of the history of our earth. And so I think that's already a case where the human technology, our ability to organize our environment and plan ahead and construct our own niche, has led to this really radically different ecology, really radically different selective forces. I mean, who looking at the cow and chicken would predict these two organisms are going to grow to completely surprising biomass densities 10,000 years from now, right?

• 1:28:56Speaker 02

  No, no, no normal ecology would predict that. And why cows and not other, you know, mammals at the same size is a totally contingent story that is based on human preference and human technology. So I think we are in this really interesting place where we've created totally new selective pressures for our ecologies, and where we're creating totally new types of entities. And it's, it's where that all goes, I don't think we have theory for. I think it's, we're all figuring out as we go, sort of thing. And there's lots of reasons to be concerned about all sorts of different dimensions of the future. It's a very interesting time on, in the long evolution of this planet.

• 1:29:40Sean Carroll?

  Well, we would, it's completely, that's why I was thinking this is an unfair question, but we would like a theory, we would like to be able to predict, right?

• 1:29:49Speaker 02

  Absolutely.

• 1:29:50Sean Carroll?

  You know, if we do change the conditions in some ways, like, could you, in retrospect, maybe someone could have been able to predict that some small set of livestock animals would become a huge fraction of the biomass, given that human beings were technologically dominant?

• 1:30:10Speaker 02

  Yeah, I think maybe from a efficiency perspective, just to say if you start to really understand one organism well, then you select on it and you pick it. I think there has, in general, and people have written about this, there is a trend towards humans eating less and less diverse things in time.

• 1:30:32Speaker 02

  And so, I mean, if you take, say, an original natural environment, and how many different types of things we ate, you move to agriculture, you move to industrialized agriculture, each of those steps, you're sort of eating less and less objects, right? So if you think about, like, in the United States, the fraction of the diet that is corn, right, is large. So that's really, that's targeting one species, one crop. And why it's corn has historical and interesting reasons. But it's, you know, maybe you could predict that you really do go towards monoculture for any technological species because of these economies of scale

• 1:31:12Speaker 02

  and efficiencies and so forth. At the same time, you know, the other pressure that we see, and we have a whole project trying to understand this, is how and why human systems diversify in cities. So if you, but cities are doing the opposite thing, where as you, as cities get bigger and bigger, you get, you know, a great expansion in the number of diversity of professions, types of restaurants, services provided, you know, that sort of...

• 1:31:43Speaker 02

  Abstracted human landscape is becoming more and more diverse as the system size scales up. Maybe those effects feed back to the types of things we eat. So you can imagine, for example, and there have been movements like this in the US, but you can imagine people's preferences around diverse or heirloom or organic food starts to push things back in a diversity dimension in the same way that cities that have, the cities that are bigger and have more wealth, have a higher diversity of services, right? So you can imagine that feedback starting to push things in the other direction. And there, I think it's complicated to say, well, will we end up with a monocrop? Or will we end up with an unbelievable rich amount of diversity because that's what human preference is? I don't know, I don't have an answer to that.

• 1:32:26Sean Carroll?

  Well, I guess it is one kind of interesting thing that people should keep in mind about constraints and how things evolve with respect to them. Even if there is some tendency to move in some direction and there's a constraint that prevents you from moving too far, it doesn't mean that everything runs right up to the limit. There is very often an equilibrium distribution that allows for some variety in there.

• 1:32:48Speaker 02

  Exactly. Yeah. And I think to your point about what we would predict, the surprise is that in every other ecology, we see one very particular distribution of body sizes. Right? So we see a power law distribution of body sizes in lots of different taxonomic groups, whether that be mammals, or bacteria, or unicellulocariots, or plants. And we have good theory for why that's true. And so the question, so then the big surprise would be, okay, why do I have this one body size that's like a huge peak, right? It almost could be a, almost could be a signal that you have something, some strange organism around selecting on that, right?

• 1:33:31Speaker 02

  You know, I think of leafcutter ants as well that, you know, are growing this one sort of fungus that is likely in much higher abundance than you would expect from any other sort of ecological consideration of that. And those leafcutter ants are also doing farming, right? They're also doing agriculture, happens to be underground. But it's the same sort of thing. They're gathering resources to feed one crop species that they really like, whether you want to call a fungus a crop, or...

• 1:34:01Speaker 02

  Or livestock is probably a debate for a taxonomist. But, but anyway, I think you those sorts of surprises might almost tell you that there's some organism influence environment through technology or intelligence or preference or something like that.

• 1:34:16Sean Carroll?

  And maybe one more reminder that we are not in equilibrium. We're in a state of flux, the modern world right now.

• 1:34:23Speaker 02

  Yes, absolutely.

• 1:34:24Sean Carroll?

  We'll see where we go. Chris Kempes, thanks very much for being on the Mindscape Podcast. This is great.

• 1:34:28Speaker 02

  Thank you, Sean. Great being here.

• 1:34:53Speaker 06

  Cash flow crunch? OnDeck's small business line of credit gives your business immediate access to funds up to $200,000 right when you need it. Cover seasonal dips, manage payroll, restock inventory, or tackle unexpected expenses without missing a beat. With flexible draws, transparent pricing, and control over repayment, get funded quickly and confidently. Apply today at ondeck.com. Funds could be available as soon as tomorrow. Depending on certain loan attributes, your business loan may be issued by OnDeck or Celtic Bank. OnDeck does not lend in North Dakota. All loans and amounts subject to lender approval.