COMPLEXITY: Physics of Life

Chris Kempes on The Physical Constraints on Life & Evolution

Episode Notes

Why is the internal structure of Bacteria so different from the architecture of a nucleated cell? Why do some kinds of organisms stay small, whereas others grow to enormous size? What evolutionary challenges drove life’s major transitions into more and more complex varieties…and what does studying these areas reveal about the changing landscape of our global economy?

New research into the science of scale — how physics operates on systems of different sizes — reveals universal speed limits imposed on biology by the energy required to make or repair component parts. It explains the varying evolutionary pressures on organisms to reallocate resources and change their body plans as they grow. It helps to resolve fierce old debates about just how much contingent history limits a creature’s future evolutionary options. And it illuminates how tradeoffs in resiliency and efficiency constrain the strategies of animals and human institutions alike, favoring self-reliance in some contexts and cooperation in others. Scale helps us prune the tree of possibilities and understand what are and are not likely futures for this planet.

We have a lot to learn from germs and insects…

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Episode Transcription

Michael: Well, Chris Kempes, it's a pleasure to have you actually back on Complexity Podcast.

Chris: Yeah, thanks. Good to be here.

Michael: Yeah, you were on episode two, which we recorded at #IPFest on Origins of Life, but it's nice to give your own episode and to go and do your research with a lot more granularity. Before we dig into your papers, I think the place to start is to talk a little bit about how you got into your work, how you became a scientist or ... And whatever way you understand that. And then how you ended up at SFI?

Chris: Yeah, that's a great question. I mean many people point to childhood as a place where they develop certain types of interests and that's definitely true for me. As a kid I was fascinated by both astronomy and paleontology. I had this dual interest in the stars and in fossils and both are pretty strong. I don't know, there's always this sense in society that people are picking something to do or they have like one very specific thing that they want to do someday. When people would ask me, what's the thing you wanted to do? I had this conflict of like, "Well, how do I take these two things I really love?" Then eventually I'd say, "I want to be an astronomer and a paleontologist." Most people really laughed at that. Amazingly enough, that's what I've done over my scientific career is to combine biology and thinking about the history of life with questions of physics and astrobiology.

If you take paleontology plus astronomy, I think you get life in space and the history of life and how physics guides all of that. I think those early interests very much have stayed with me over the years.

Michael: And so now you're here and you're working with an excellent team on scaling laws and so on. Yeah. What drew you to SFI, or like, how did SFI select you?

Chris: Yeah, that's another interesting question. In undergrad as I was still wrestling with this physics or biology question, I had done a lot of research in ecology while also majoring in physics. I was looking for places where those two combined and an early mentor pointed me towards a bunch of papers in scaling theory and how physics was influencing biology. I was hooked. I actually came to Santa Fe Institute as an undergrad researcher a couple of times during my undergrad career. I spent a summer here. I did a month long independent study as part of my curriculum at a different time. Then that really started to inform the types of research I did thereafter. My PhD was in physical biology which is a program that we created at MIT focusing on how you could start to bring physics into different biological processes beyond simple things like protein folding but really trying to get it at the macroscopic laws of biology.

Things like scaling laws combining that with evolutionary theory and then the rest is history after that. Yeah.

Michael: Excellent. Well, okay so it seems like the place to start today is with a 2012 PNAS paper that you lead authored on “Growth, Metabolic Partitioning, and the Size of Microorganisms.” You did this with Stephanie Dutkiewicz. Am I saying that right? And Michael Follows and this is a piece comparing the way that various energetic processes in a cell are allocated to growth and maintenance and how that differs between prokaryotic organisms and you eukaryotic organisms. I'd like to have you start with a little bit about the background in the thinking that motivated this research, why you decided to go here and then why this is a particular area of surprising and counterintuitive results. Then we can kind of dive into the details of this particular study.

Chris: Yeah, that sounds great. Some of the classic work done in scaling theory is really trying to understand how architecture relates to various types of functions. Primarily how it relates to metabolic functions and then how you can drive a bunch of other features from those metabolic functions. There's this strong architectural connection there. Then if you think about it, you could say, "Well, as you go down the scale of size in life you start to cross all these different architectural boundaries." So as you go to unicellular eukaryotes, obviously you're transitioning from a multicellular organism that may or may not have a vascular system to unicellular organism. Which definitely isn't part of a larger network of cells and the avascular system is living as a free living cell and an environment, but still has some internal structure to it, the mitochondria, the nucleus, various other internal membranes.

Then as you go smaller you crossover into bacteria which lose a lot of the internal structure that you see in the unicellular eukaryotes. Now I've told that story is the size-based way backwards but that's actually the opposite of the evolutionary direction, which went from these simple bacterial cells to increasing complexity and architecture. Anyways, so we see these shifts in architecture. We know that architecture is fundamentally related to metabolic processes and deriving scaling laws. Then we should expect to start seeing shifts in these relationships as you make these major transitions over architecture. There is some empirical work. Just before we did this paper showing that to be the case and putting forward a few hypotheses about what's shifting in the architecture.

Then we said, "Well, what happens if we take that and start to build detailed energetic theories of single cell organisms in the same way that's been done for multicellular organisms, to start trying to understand physiology and growth in connection to these shifts in scaling relationships driven by shifts in architecture?”

Michael: Starting with the per-unit cost thing about biosynthesis and maintenance being conserved in linear across all these different groups, right? What is the one thing go into a little bit of detail about this piece but the one thing that all of these different organisms have in common and then how you were able to use that to start to investigate the differences and the basis for those differences? That seems like a great place to start.

Chris: Yeah, I mean I think one of the really amazing things that we saw was how much energy it takes to maintain or repair an existing unit of material in an organism. It appears to be roughly constant across all of life. I mean there's a huge amount of variation in that but there aren't systematic trends with size, for example. This says that to keep a unit of bacterial mass alive in terms of repairing it and maintaining its existence is roughly the same as keeping a unit of mass in a mammal alive. We thought that was really interesting that there isn't an architectural shift there. Then a lot of the biosynthetic terms, so how much energy it takes to manufacture a new unit of mass also appear to be roughly constant across all these different classes of organisms.

Again, that's a slight simplification of some significant variation that's there. We take these two things together then once you have these differences in how metabolic rate changes with size. Those constants and this changing metabolic rate with size lead to these really different behaviors in the growth rates. Because that overall metabolism has to be broken down or partitioned into the energy you need to repair and keep existing biomass alive and the energy you can use then to synthesize new biomass. And so as you get bigger you get more metabolic power per unit mass. Then you can grow faster and faster as you get larger, and that's what you see in bacteria. If as you get bigger you have less metabolism per unit mass like in mammals then eventually your growth rate has to slow down and you stop growing in size.

Contrasting bacteria to mammals, bacteria have this ever-increasing accelerating growth rate over their lifespan. Mammals have this decelerating growth rate that eventually leads to a fixed adult size like most humans have for example.

Michael: This is butting up against the episode that we did with Melanie Moses on scaling. In the question of why is it that you see this upper bound on the size of bacteria? Like there's a point at which the metabolic rate required to grow that thing just becomes unsustainable, right? That's the transitions that like Lynn Margulis and other people are talking about in endosymbiotic transition. How does the architecture of a nucleated complex cell enable this and why does that lead to an inversion of this power law in the way that like metabolism and maintenance are allocated in a cell?

Chris: Yeah, great question. We had exactly that same puzzle after finishing this first paper that we were just talking about. As bacteria get bigger, they have more and more metabolic power per unit mass. They have faster and faster growth rates. All of that's what you want. If you can grow faster than other organisms you can out-compete them. These all seem like good things to have. Our question was, well, why don't the bacteria continue to get bigger forever, right? Their architecture seems to favor this ever accelerating growth rate that in certain environments is really advantageous. You can out-compete slower growing things if there's enough resources around. We hypothesized in this paper that it must be something about some piece of the physiology not being able to keep up with those increasing metabolic rates.

So it's actually not a metabolic problem that the largest bacteria run into it. It's likely some physiological problem where some basic biochemical rate or process simply can't keep up with the energy-harvesting capacity of these organisms. And so in a follow-up paper, looking at the composition of bacteria in terms of the main physiological features they have … So,  how much protein do they have? How many ribosomes do they have, or these machines that basically translate the stored information about what a cell is in the genome to the actual functional proteins of the cell, how many of those do they have? And we were able to write down some simple theories that show that as this growth rate increases eventually you get to a point where to keep up with that rate, you would need to put more stuff in the cell then the cell has space for.

Basically the largest bacteria run out of physical space to pack in all the things they would need to keep up with this ever-increasing rate. I mean it's like if you had this huge power source, how many components would you need to use that power efficiently? Eventually that exceeds the space at which those can be packed into. That's what we think happens to bacteria is that they grow too quickly. They run out of the fundamental space for all the components they need to keep up with that fast growth rate and then there's something about the eukaryotic architecture that helps fix that. That's an unsolved problem in my opinion that has not been fully worked out, so how it is that eukaryotes then start having a slower metabolic rate with increasing size and why that then drives them to grow more slowly?

I think there's a fundamental question about why that's true and it may all be tuned to the speed limit. We think that there might be a universal speed limit in the growth rate and forced by these internal space constraints that are reached by the bacteria and then saturate for the unicellular eukaryotes and then start to do really weird things in the multicellulars which is a whole other story that that gets even harder.

Michael: Right, right. I'm realizing now that I totally jumped ahead into the next paper with that question, but before we go there and dig into that a little bit more. There are a couple of interesting points in this paper that I felt were worth unpacking a bit. One of them is about the reproductive strategies in eukaryotes and specifically you look at the budding yeast C. albicans, which rather than just standard fission is doing this budding thing and its growth rates are then reallocated at different points between the growth of the mother cell and the budding cells. You make an interesting point in here that the growth of the buds can be predicted by assuming that the bud is using all of the growth energy of the entire complex and the buds grow more rapidly because of the assistance of the entire complex rather than if these are growing in isolation.

This is again a spot where you're starting to get into questions of the incentives for multicellularity. It just reminded me of as a personal link to this "It takes a village to raise a child" saying. And like we were talking about around the kitchen this morning about this issue of the economics of parenting — and this is a huge leap, but I'm curious how you feel this fits into the biophysics about as our nuclear family becomes a more dominant form and individual family groups are more self-reliant and more spread out. It seems as though that may be somewhat to do with the decline in child birth rates like industrial western countries like the United States over the last few decades. The increased self-reliance assumed or required by the family and how that seems to be inversely related to the productivity of a given family.

Chris: I think there's an interesting analogy to draw there. Economists, several times different economists have told me that in developed nations understand decreased birth rates and how much longer people are waiting to have children in terms of integrating when you think you have enough resources to provide a child with the same level of lifestyle that you have. As the world gets more complicated that number may be harder to achieve. Now I haven't looked at any of those papers. I haven't seen what those calculations are but that at least seems to be the word on the street from certain economists that that may be what's going on.

What's interesting here is that thinking about the whole process of giving birth to young from mammals all the way up to then communities raising children, I think what's happening with these yeasts that's really interesting is it's almost a primitive gestation. What's cool about that is that when you have this big complex then devoting most of its metabolic energy to grow in a small thing. It can make that thing look like it is growing like it's a much bigger thing growing in terms of its growth rate because there's all of this energy being distributed from many cells into one small cell. If you fit just that small cell without considering the whole complex, you'd say, "This thing has unbelievable energetic efficiency or it's somehow managing to get a huge amount of metabolic rate per that little mass." Really what it is, is an optimization of the complex, choosing not to grow the larger cells but been said meet that metabolic energy to growing small cells at a really high rate.

And so this gestational strategy can help you produce lots of little offspring quickly. I mean, so it's an interesting community way to do that. Now where that starts to maybe potentially relate to groups of things collectively raising offspring, I think would be mostly about where are the efficiencies of energy harvesting amongst a group. Then deployed to a set of collective children or how much risk are you incurring when it's a larger group sharing resources composed to a very small group, those would have very different risk dynamics. You can imagine in certain, say,  hunter gatherer societies that these risks would be very different. Whether it's a small group, one nuclear family or a larger group collectively sharing things and that certainly would relate to offspring and how many individuals are in effect responsible for a particular offspring.

Michael: There are plenty of other questions that come out of this particular piece, but I think that they relate just as well to the next article that you already touched on which is “Evolutionary tradeoffs and cellular composition across diverse bacteria.” This is just looking within bacteria. This is a 2016 paper you did with Wang, Amend, Doyle and Hoehler. This piece like you said this is about the way that different pieces of bacterial architecture scale as the whole thing gets bigger. I think it's worth actually starting at the end with this puzzle that you're left with, which is that even though like you said a moment ago, the growth rate scales superlinearly with the size of the bacterium, all of these components are scaling sublinearly. All of these components are scaling slower. And so something funny is going on here that leads to this emergent thing happening here.

I'm curious, this is maybe like leading the horse with the cart, but what is this, why is this happening? It's not really a question you answer in this paper, but I mean, you've had plenty of time to think about it.

Chris: Well and the answer is we still don't know. There's some follow-up work that we're doing now. We're trying to do certain types of global optimizations of the physiology to understand how all of these different components are related to each other.

One thing we can say really nicely from this paper is if you take ... So, the ribosome which again is this little machine that basically takes these little tapes, little transcripts from the DNA and turns those into functional proteins. Its job is to read these tapes and produce proteins. Some of those proteins make itself up, so it’s also self-replicating itself. If you say, "We know how fast a cell is growing and we know how many proteins it has to replicate in order to divide,” then we have a really nice theory for how many ribosomes the cell needs. We take our theory for growth rate and we combine it with observations of how the number of proteins changes across cell size and then we can predict how many of these little ribosomal machines you actually need in a cell.

That then does a very good job of predicting observed data. It says that for most cell sizes, most of the range of cell size is you have this sublinear scaling and the number of ribosomes. As the cell’s getting bigger, the ribosomes are diluting out — until you start to get towards really large cell sizes where the growth rates continue to go up. And then you get this rapid curvature and eventually this asymptotic behavior where the number of ribosomes that you would need to put in the cell goes off to or towards infinity. What you start to run up against there is the cell division time starts to look like the time it takes for a ribosome to replicate itself. You have these little machines that are doing replication inside the cell. The cell doesn't notice that replication timescale until it's trying to divide or replicate in the same time that one of these little machines are, and then it starts to run into all of these problems.

That is this speed limit, is this ribosome replication rate, when the cell rate start to approach that, that's one of several ultimate speed limits on life. We understand that why that eventually becomes all of cell volume just these ribosomes. How all the other parts of the physiology are changing? Lots of interesting scaling relationships, they're all with really different exponents, all with hard to interpret exponent at first glance. We are building a more detailed theory to try and get at those but fundamentally we don't know yet.

Michael: You just explained in detail what you call in the paper, the ribosome catastrophe. This is larger class of the error catastrophe. I learned about in college and actually is what got me into complexity thinking in the first place was this paper co-authored by Martin Nowak and now-SFI President David Krakauer on the evolution of syntax and language. There's a really interesting generalization that I think can be made from this math that gets into ... I want to see if you feel like I'm making the analogy correctly: that the DNA of a given bacterium is like the memory of an individual person and then the ribosomal volume is like the amount of words required to communicate that are like evolutionarily relevant in a given language.

I mean, again, that's a little messy because it's not exactly intercellular signaling but there is the sense, which as Nowak and Krakauer mentioned in their work, that you reach a point where the burden on memory to remember every word you need to in order to get along in the world is just  unfeasible. You start getting copying errors and you fail to communicate. That seems to be the point at which you start getting syntax and language the way that you're getting the complexity of the eukaryotic cell that there's a new syntactic architecture emerges to cope with the informational requirements of this. I mean that's again, that's a little rough, but…

Chris: No, I think there's some really interesting interconnections there. On this end of the ribosome using this language analogy, I think what you would say is that there's a storage system of the words that you could speak and then spoken words have utility and then there's this process in between that allows you to go from the words that you could speak to actually be actually vocalizing those words. Right. There's some computational effort there that's required. You have to in this case transcribe and translate the copied word to the spoken word, and there's a little device, this ribosome, that does that. If you think about the organism's pressure is all at speaking words, right. Having the spoken words out in the world where they actually have utility. Then yeah, one of the constraints for cells is how fast this internal machine can actually speak, right?

How fast it can transcribe and then translate as a system. And eventually the rate at which you would need utility from words exceeds that speaking capacity. I think that is another limit. Yeah, I mean I think in this space there are lots of really interesting biological limits. The error catastrophe certainly is one, this ribosomal catastrophe is one. And I think as part of a larger research program it's really useful to go through lots of different ways of looking at life and think about where these ultimate limits are, and then think about how to start to abstract them so that we can get beyond the particular evolutionary history that we've seen on this planet and think about biological function in general from either an alternate origins of life perspective or an astrobiological perspective.

That's actually something that David Krakauer and I've been thinking about and writing about a lot recently. I think, yeah there's really interesting intersections between these different types of limits and between these different types of abstracted processes in biology.

Michael: Yeah, to verge on the astrobiological question, one of the things that you mentioned earlier is that there is this cup shape and the fraction of the drive volume of the cell that's taken up by ribosomal material. You end up with, what is in the middle zone, what is taking up the volume of the cell, if not drive volume? You talk like in a lot of cases its water, right? So as a right-brained artist type, I was like, "Oh that's funny because the graph looks as though it's like holding, like a vessel for this thing."

Chris: If only we thought to say that in the paper!

Michael: You start to speculate here on the evolutionary benefits of less of the cell being taken up by stuff and more of it being available for fluids. I'm curious to hear about this and then how this links to why you're going to find cells of different sizes occupying different niches and in different environments — and then how that might yield some predictions about where you're going to find very small cells, where you're going to find very large cells, and so on.

Chris: Yeah. I think that's fascinating. One of the things we've been thinking very hard about is, is this water a requirement, right? Part of what having increasing amount of water to all these different molecules does for you is change the effective diffusivity these. How fast something can diffuse in the cell depends a lot on what the concentration of things in water are because that will adjust how likely you are to bump into another molecule or have a short-timescale weak bonding event with another molecule. We think actually we might be able to predict how much water you need thinking about these diffusive constraints.

That's part of this upcoming work that we've been going through is getting at that. Now to your question about different niches and where these different organisms might live. We in this paper were slightly wrong about a pretty strong prediction we made, which was saying, "Okay, what will all the smallest cells look like?" Another way, thinking about that as, "What does a cell have to do to get very small," right? Well, it needs to have less proteins expressed inside the cell. It needs to have a smaller genome, all of these sorts of things. How do you start to reduce a genome? How do you start to get rid of genes and the need for certain expressed proteins? Well a lot of genes are kept around for dealing with lots of different types of environments, having lots of different metabolic options available to you and so forth.

And so we looked at a lot of the smallest cells at the time, and saw that most of these are mammalian parasites. What does being a parasite inside of mammal do for you? Well, you have incredibly constant temperature. You have incredibly constant pH relative to other environments. You have this soup of amino acids around that you can use. These organisms in some cases don't even need to synthesize their own amino acids, right? They can just suck them up from the environment. You get these incredibly small slow-growing mammalian parasites that have tiny genomes and almost no stuff inside because they can rely on this incredibly rich and stable environment from a host. Cool, so I at the time would have said, "I expect all of the smallest cells in the future to be parasitic organisms that you see."

A few years later, Jill Banfield's group discovered the new world record holding smallest bacteria, or set of bacteria. They're all groundwater microbes. They discovered them in this groundwater system. Not in another organism, not parasitic, not stable. What's interesting is that a lot of the work ... While those bacteria agree with us in terms of how big they are, they didn't agree in terms of the types of environments where we expected to find them. What's interesting is that a lot of her recent work out of the Banfield group is showing that it may be the case that many of those smallest bacteria are living in close association with larger bacteria. They may either be syntrophic meaning that there's some mutualistic co-metabolism where the small ones and the big ones are helping each other in some way, or they could be parasitic. We don't know.

That's an interesting thing to follow up is what have they done to get such small genomes. At an abstract level it's consistent with this idea of a parasite in terms of, if you want to get a small genome you have to start living in a more complicated community. That community could be you as a completely negative parasite on some host or it could be you as either a beneficial or negative symbiotic living with some other community of bacteria so a lot more really interesting things to follow up there.

Michael: To abstract that even further. I think a lot about the modern human brain case is smaller than that Neanderthal brain case or I've heard also like even the Cro Magnon brain case. That seems to be related to the issue of outboard memory again and the way that we are externally storing the necessary information required for human groups selection and collective computation. That there was like a transitional point where the emphases like left the individual and moved to groups of people.

Now we're at this point where I remember David Krakauer gave an ACtioN Network talk in New York a while back, at UBS talking about technology and the vestigial human brain and comparing our evolutionary future to, like, tunicates, which at some point like loose, they decephalize. It's no longer required because they're just filter feeding which ties into this related thing that I've been thinking about which is how group life in some cases, yields a clam, where you're just positioning yourself in a flow of nutrients. And in other cases yields schools of fish, yields a smarter collective. To bring this back into economics a little more, this gets into questions about the emergence of the city and the emergence of the nation state, and how these kinds of concerns that you're addressing in this paper start to get into, like with the ribosomes, there are functional limits to the length of a sustainable supply chain, and like a minimum size for a nation and a maximum size for a nation. So here we are in 2020 and it's starting to look like a certain first-level analysis of global economic activity is woefully inadequate, and that certain economic processes are better at a global scale and others are worse.

I'm curious, if you're willing to go out on a limb here, do you think … I know in his novel Bluebeard, Kurt Vonnegut said, "Any country larger than Denmark as a damned fools mistake." So I wonder if you think any kind of meaningful analogies can be drawn here that suggest that point us in a direction that yields fruitful shifts in economic policy. Or maybe, to take on a humbler goal, gives us concrete realistic predictions for what it's going to mean to be a human being in the years to come. I don't know, there’s absurd breadth there, but yeah.

Chris: Yeah, I mean I would say yeah there's that interconnects with a lot of classic ideas and evolution and ecology. I'd say one of the simplest evolutionary ideas that we might think about from say bacterial ecology would be ... Okay so if I maintain a huge genome with lots of different metabolic possibilities and all different genes for responding to particular environments and so forth, that's great right? I as a single species have this capacity to be resilient and respond to a huge range of stresses from the environment. But I also have the cost of maintaining all of those genes, right? Every gene comes with some amount of overhead. If I want to replicate that gene into the next generation, I spend energy on replicating it. If I want to make sure that that gene isn't getting damaged, I spend energy repairing it.

If it accidentally gets turned into a protein that I don't want, I have to respond to that and get rid of that protein, right? There's all of these different challenges to having larger genomes. There's some really nice recent work on thinking about the cost of maintaining genes amongst a small community of people. We've talked about it a little bit. Michael Lynch at ASU has talked about it. Nick Lane and Bill Martin have talked about it some. I think there is this really nice growing field of ways of thinking about those costs and how they relate to evolutionary dynamics. That's one end of the spectrum. But I have to be able to maintain the cost of this huge genome and any time that that cost is greater than the benefit I get out of it, there's an evolutionary pressure for me to get rid of these genes.

Great. Other end of the spectrum is I have a tiny genome and I rely on ecology to help me do all the things I need to do or survive. Right. That's great because now each individual organism has this amazing efficiency because they have small genomes. They're just doing what they need to do. They rely on other organisms for different types of exchanges. Great. That may be more efficient, but it's also a fairly susceptible to perturbations, right. For that to work, I need to be able to rely on seeing those same partners of organisms in the future, right? One easy way to do that is to create such close associations that every time we divide in our transporter, we go somewhere else together as like a clonal organism and we've worked some on that, but you need to guarantee that you're going to see the same partners in the future.

You sacrifice resiliency for efficiency and then the problem becomes likelihood of interaction and exchange in the future. Now how those ideas get scaled up to the global economy, and certain questions about size and efficiency, what happens in groups of people in cities? I think there's a huge richness in that biological thinking that can be translated into those spaces. It's not something I already know a huge amount about.

Michael: It seems like one concrete example would be the way that you have entire cities in China devoted to manufacturing a particular good then how dependent those cities are on a thriving global economy. It's related to that issue of, when I was in a school for paleontology, the takeaway about how to survive a mass extinction was you don't specialize. That if you want to survive that you become a generalist. That's where you get into the survivalist thinking of people that move out of food deserts and start growing their own food and learning these strategies, and so on. Again, like you just said that that doesn't seem as like the amount of time it takes to learn those life skills is just absurd if you're going to participate in the modern economy.

And so this work all points to a generalized balance between at what scale are you going to operate … Like obviously a Mennonite community is more resilient to global economic shutdown, but less capable of producing something that is of value to that economy, and then less capable of individually specializing, in the sense of like Maslow self-actualization. I mean I’ve got to be careful here but it does seem like that we are empowered to pursue hyper-specialization by the same biophysical constraints that make this planet more and more susceptible to perturbations. Like we talked about that with Matt Jackson in terms of hyper-connected bank networks and like cascading failures and so on.

Chris: Yeah. I think a lot of this touches on these really classic economic ideas of specialization and efficiency. I think it's interesting that even in just the evolution of particular genomes and bacteria, you see the same thing.

Michael: This seems like a great point – we're already here basically – in the last paper I want to touch on with you, which is the paper you wrote with M.A.R. Koehl and Geoffrey West on ... This is in Frontiers in Ecology and Evolution on “The scales that limit: the physical boundaries of evolution.” This is really cool because this is where we zoom out from microbial life and unicellular stuff to trying to articulate a more general theory of evolution, and to bring the biophysical constraints into the picture. Like I asked you the first one, I think it's important to understand how the approach that you authors are working towards in this paper differs from the legacy thinking about evolutionary dynamics that we've inherited up to this point. Why is it important to bring these new considerations into the picture here?

Chris: Yeah. I think a lot of classic thinking in evolutionary history especially thinking about comparative life history and so forth has very much seen the amazing complexity of individual species as the product of very detailed evolutionary histories, with a lot of contingency and path dependency and happenstance. All of which is true. That leads to a very specialized species living in a particular niche that can only really be understood in terms of this complicated history. And that’s all valid. A lot of that has been documented, how much of that is just random processes, how much you get locked into things, how much contingency is there? What we wanted to try and say is well all of that is happening in a physical world. That physical world has known constraints and those constraints could either be really close to a physical law, something like diffusion or they could be physical laws that have downstream effects in terms of forming some particular environment.

What we wanted to say is really how much of evolution can be explained by thinking about those physical constraints first. When do those physical constraints matter more than all these other processes? And how do we just start to think about all of that? So we wrote down a framework really for interpreting when evolution should see a physical constraint, when these other processes are more important and how you're looking at the right physical constraint for understanding a particular organism. Scaling laws are a great example. Why do you see a scaling law across all organisms have vastly different size?

A lot of the work coming out of the scaling world is really saying, and what we really try and argue in this paper is, that you see those scaling laws when there's a dominant physical constraint that applies to organisms of vastly different size. And that constraint matters enough compared to other processes that it shows up in evolution. Or that constraint is independent enough of all the other processes that it shows up in evolution. Some of the simplest early thinking about predicting scaling laws is saying, "Well if you imagine a spherical cell and if that spherical cell is just passively living in a bit of fluid, then it's going to have some resource supply rate that is just diffusing to it." From the laws of diffusion you can derive the limitations of resource supply to that cell and get a maximum metabolic rate. That gives rise to a really nice scaling law.

Now that's all fine unless some of those features have many constraints they interact with, or if there's some internal contingent limitation based on other parts of the physiology. So for example, you might want to optimize some part of a mammal to dealing with say mechanical stress given its size and the gravitation of a planet. But you can't quite achieve the optimal because there's some historical part of the physiology that you would need to change to do that and it's just too hard to change that, or every small step, it was taken that change space comes with such a big cost that you can't escape this thing and so you can't actually optimize some part of the physiology. Then that's just a really then easy way to ask whether you think something's going to be completely driven by physical constraints or whether the optimization that evolution is doing through this random search process is best understood from the existing set of things you have and how they interact.

We argue it's mostly comes down to how big an effect does the physical constraint have. So if you change a trait a little bit under some physical law, how much does that change your growth rate? If that's big enough, evolution will see it and you'll be able to start optimizing that physical constraint. And how independent is that optimization from all of the other traits of an organism. We argue since you see lots of scaling laws that can be interpreted in terms of a few physical constraints. It seems like lots of evolution has parts of physiology, parts of the organism's traits that are independent enough, or that the physical constraint is dominant enough, that it shows up in evolution. We think that's really exciting.

Michael: It seems like for those who want to anchor this in the existing argument, it seems like this is a way of resolving the classic Stephen Jay Gould, Simon Conway Morris argument. Like you were saying, it's contingency versus convergence, and path dependency matters given the degree to which the constraints are actually in operation on an organism. You end up with a way to rigorously and quantitatively answer questions like, why is it that the golden age of mammals around 50 million years ago looks so very much like the golden age of dinosaurs, with all of these similar niches occupied and comparable temperature and oxygen levels in the atmosphere and so on? The substantial differences are due again to that contingent evolutionary history that each of these groups has to proceed from, right?

You give some really cool examples in this paper. One of them is on the biomechanical constraints of an insect leg and the size of insects, and why we're not going to get THEM – like, giant ant stuff. We discussed this with Melanie Moses around the issue of vascularization and nutrient delivery in insects. But you take a different approach and you look at structural strengths and like the architecture of insect exoskeletons and of their musculature. I'd love to hear you unpack that a little bit because this is a really cool consideration when you're looking at like something like the size of a Hercules beetle and you're like, "Damn, that's a big thing." It's not going to get any bigger. And why?

Chris: Yeah. Mimi Koehl did a lot of this work, almost all of this work for this paper in terms of thinking about these biophysical constraints in insects. From a very top level, what I would say is ... and we had a lot of conversations about this as a group internally, is that part of this is where the contingency does come into play, right? Once you're committed to a particular body plan or a particular set of structures or physiological traits, biomechanical traits, then the optimizations occur. The evolutionary optimizations again, random process over time, that's how the optimization is happening. Those occur contingents on having a particular structure or body plan. And so the constraints that are going to be optimized for an exoskeleton and the types of things you have to put into your evolutionary optimization problem there is very different than an endoskeleton, right?

If you have an internal skeleton like mammals, you're going to face different optimization challenges then if you have an exoskeleton. I think that's a lot of what we wanted to think through. That's actually where some of the contingency comes through is that you have to condition on knowing a particular structure of an organism.

Michael: The one example that I really appreciated was that molting seems to limit the size of arthropods because everything has to reattach. There's a vulnerable phase there.

Chris: Yeah. I thought that was one of the most interesting examples, right? That's because of this need to molt to get larger, you enter a phase of extreme predation risk relative to pre-molt. That then starts to interface with a bunch of niche considerations, behavioral strategies, right? Do you hide just after you've molted, how do you deal with some of those challenges? I think on one end of the spectrum, this is where we have this purely biophysical perspective. On the other hand, you have to think about the richness of interacting features. That's really what we're trying to get after in this paper is how do you do both, right? How do you start to separate out the purely biophysical optimizations you do for an organism and then all of these other rich considerations about behavior and niche and evolutionary history and so forth? I think the molting is a nice example of that.

Michael: Just to get into like speculative biology here, some of these constraints lead to the transition point at which you start to see sociality in insects. Then similarly, different constraints seem to lead to sociality in endoskeletal vertebrate organisms and you get a breakdown where it goes from a “solid brain” as a computational entity to a “liquid brain.” I'm curious what constraints would have to be lifted mechanically in order to offer a much, much larger individual organism than anything that we see on the planet today? And then in terms of design, bioengineering, new forms of life, for other worlds. I mean obviously gravity is a constraint, available free energy as a constraint, but what within the organism itself do you see as something that can be changed on Earth's surface to yield a Godzilla type creature? Something that's vastly larger than anything we see in the fossil record or alive today.

Chris: Yeah, so many answers to that. I mean changing gravity's the cop-out. It's true but that's easy one. Choosing to put everything in a liquid medium is another thing you could do to make really large organisms and we do see, yes that would be one possibility. But I think from this more general question of, okay if you wanted something with a particular function of endlessly-increasing size or as big as covering a planet or something like that, what are the challenges? If you wanted some sort of brain spanning an entire planet, what are the challenges there? I mean, I think a lot of the principles that start to come out and thinking about that are questions of transport, right? Just exchange. If you have lots of individual components doing simple computations, how do you wire all those together?

Melanie Moses has done a lot of work on that and thinking about chip architecture and certain scaling laws there. That certainly becomes a challenge in terms of how do you wire all these things together? How do you get information from A to B and at what timescales? Then there's a rate question for the overall system and then there's an energy flux question. So I think there are calculable questions about what would be the maximum number of bits you could … What’s the maximum computation rate of a planetary surface given solar flux, right? I think that's a calculable thing if you make some assumptions about different types of architecture and then start to work through the exchange problems and so forth.

Now maybe not, in terms of how complicated the algorithms would need to be or there might be a whole algorithms-combined-with-architecture optimization there that I don't know if there's an answer to. But I think yeah, in terms of the things that you want to relax, you also want to relax competition because a lot of the things that you would do optimally, you can't if there are other species competing against you. Having a small mobile brain inside a skull that can easily run is a nice way to protect that brain from predators. But if you don't have any predators then you can start to do all things with your morphology wouldn't have to otherwise. We talked about that a little bit with the insect case, right? That certain things that you decide to do are all about predator evasion, right? They're not most efficient for slow speed locomotion. They're all set so that I don't get eaten when a predator comes, right? I'll sacrifice a little bit of day-to-day efficiency as long as I can evade a predator. Those are part of the constraints are actually the ecological contingencies.

Michael: This seems to tie into ... I hate to say this but it seems to lend some credence to predictions made by people like Nick Bostrom that the future of the biosphere is a singleton. It's just like one giant creature that is in competition with nothing. I mean that's been a prognostication of various troubled legacies of evolutionary thinkers like Teilhard de Chardin for decades. But it  sounds like you think that may hold some water.

Chris: I don't know. I mean a few counterpoints to that one would be I think it's a possible evolutionary end point. I would say the challenge of exterminating all bacteria is daunting, right? I mean the number of environments you find bacteria living in, how deep in the subsurface active bacteria are found, how long that seems to have been going from lots of recent cores people have done of finding all different fossils, microbial fossils. I would say that they're likely to always be around the task of getting rid of all bacteria to me almost seems impossible. Whether that's bacteria and a singleton that to me seems like a more likely endpoint than just a singleton.

Also getting to a singleton, I just don't know how stable certain trajectories towards that actually are, right? I don't know how stable a species like ours is right, in terms of all the hurdles that would need to be overcome to go that direction. All of the various ethical and aesthetic considerations we might make in the future about what kind of ecology we want. That may not necessarily be the end point. And also, yeah you have to always think about anytime you have a singleton, what's the likelihood of something invading? If a singleton goes for a long time without competitors, it may start to optimize itself for efficiency in ways that make it very susceptible to invaders. Then the question is just, is there an invader, is there another species around that can start to invade in that niche and that is likely to be true especially if there's a huge seed population of bacteria around. So yeah, I don't know how either likely or stable a singleton is. I see lots of problems for it.

Michael: To wrap that back around to the earlier pieces of this conversation, it seems as though really like a s  ingleton would presuppose or evoke the same kind of challenges that you get into with these limits to cell size and that it may be that what we're talking about is not some hypothetical future, but actually again the viability of a global economy — and why it seems like we're under such pressure now, simultaneously, to try and integrate all of these different local economies at the same time that we are casting our glance to other worlds, to invoke again the InterPlanetary Festival thing. Maybe the answer is multicellularity and it's not that really this kind of thing isn't feasible. That like you said, it's too complicated. It's too vulnerable without the competition. Yeah. Anyway.

Chris: Yeah, I think the other thing to point out there too that's really interesting is that many of the evolutionary transitions that we've seen haven't eliminated the life that they evolved from. Bacteria and Archaea become, unicellular eukaryotes, they aren’t then outcompeted by unicellular eukaryotes. Right, in the same size ranges because they do have some overlap in size. They can live in the same environments. There's coexistence of these, these very diverse things. Multicellulars don't out-compete the unicellulars. You get coexistence. And so I think that's a really interesting thing that even with these radical shifts in architecture and huge transitions in evolution, they don't then exclude everything that came before. In some cases.

Michael: So we are the microbiome of civilization, roughly speaking? Well, okay. Thanks for indulging all that. What's next for you? Like where is this research taking you now and what are you working on?

Chris: Yeah I mean, I'd say it's a few main directions. One is as we start to understand these different physical constraints and what they mean for organisms and scaling laws, how much can we start to then generalize or abstract that to think about life that's not  like the one we already have? Can we generalize some of those ideas so that we get away from exactly the physiology of all known organisms that we have and start to think about life in general — which I'm interested in both for astrobiological questions and also origins of life questions.

I think that's one program. Another program is really thinking about continuing to connect biophysics and evolution together. There's lots of people now starting to work on this in lots of interesting ways. There's a really interesting classic literature on all of this.

I think that's another really interesting direction to go is to say, “We have this huge body of evolutionary theory. We're now starting to see where the physical constraints come in. How do we start to put all that together to get a more predictive power, more universal theories of biology?”

Michael: Wonderful. Chris. It's a pleasure. Actually it's always a pleasure to talk to you.

Chris: Yeah, thanks.

Michael: Where would you tell people to follow up if they're interested in this kind of stuff?

Chris: I don't have a great answer for that.

Michael: I mean, obviously they can go to the SFI website.

Chris: Yeah. We'll look into the SFI website, follow the SFI Twitter. That's all I have. David Krakauer and I have a paper that hopefully will be coming out soon and so there's lots of interesting, more on this generalizing life question. Yeah, lots of things coming soon.

Michael: Wonderful. Thanks.