Ep 3: Animal Size and Godzilla's Breakfast (with Jon Harrison and Jim Brown)
Jim Brown
Jon Harrison
Is there a limit to animal size? Could Godzilla actually exist?
Tune into this episode to hear Art and Marty talk to Jon Harrison and Jim Brown.
Jon Harrison (Arizona State University) studies the physical limits to insect body size and furthered our understanding of the giant insects that once roamed our planet. Luckily for us, his research indicates that Mothra may never exist.
Jim Brown (University of New Mexico) famously put forth the universal quarter-power scaling law, which predicts how many ecological and evolutionary variables (including metabolism, life span, reproduction) of plants and animals change with body size. For example, his theory was able to explain the fact that all mammals average the same number of heartbeats (~ 1 billion) over their lifetime, regardless of how large they are (mice to elephants) or how long they live (3 years or 70 years)! Elephants’ hearts just beat really slow.
Cover photo: Godzilla Extended Look by BagoGames / CC by 2.0
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MM = Marty Martin
AW = Art Woods
JH = Jon Harrison
JB = Jim Brown
MM: I’m Marty Martin.
AW: And I’m Art Woods.
MM: Welcome to the Big Biology podcast. Today, we're talking with Jim Brown and John Harrison. Jim is an Emeritus Professor of Biology at the University of New Mexico, and a member of the National Academy of Sciences. John is a Professor of Biology at Arizona State University, and a fellow of the American Association for the Advancement of Science.
AW: Jim and John come from different scientific backgrounds. Jim from ecology, and John from physiology, but they share a passion for our topic today, which is called Scaling. Scaling describes how the traits that organisms have change with body size in non-intuitive ways.
MM: Scaling is a big deal because it's such a fundamental part of biology. It also matters for a bunch of practical issues like: how we could serve wild populations, and even how we prescribe drugs. Over the past 100 hundreds, biologists have been struggling to understand how and why traits scale.
AW: How traits scale has been the easier problem. we now know a lot about this. Why traits scale has been much harder to answer, and there's been a lot of controversy and competing ideas. Both Jim and John have been major players in scaling research. And today, we discuss with them the how and the why of scaling.
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(Intro music plays)
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AW: So Jim and John, welcome to the show.
JB: Happy to be here!
JH: Thanks Art and Marty.
AW: So I want to start by taking apart these two traits: size and metabolic rate. And let's focus first on organismal size. So if we just set aside the effect of body size on metabolic rate, can you guys explain why is body size so important in biology?
JB: The size range of living things is absolutely enormous. It's about 20 powers of 10, so that's 10 with twenty zeroes after it. And to give you a feeling for that: if you look at your skin, there are literally millions of little microbes—mostly bacteria—living on your skin that are so small that you can't even see them. And at the other extreme of the size spectrum we have giant sequoia trees and great whales that are larger than tractors trains or trucks. And weigh literally tons. So organisms have managed to diversify and fill up the world with an incredible variety of sizes and other aspects of form and function that go along with that.
AW: John, you have anything to add to that?
03:14
JH: Yeah, I would add, yeah so this creates a tremendous amount of the biological diversity, and I guess the other point to lead into what's to come is that how big you are affects so many things about the world that you experience. So for a tiny bacteria or a small, very small, microscopic animal they're living in this viscous world that is very different from what it's like for a very large organism [word?]. So there's tremendous differences in the way they experience the world: competition among the different animals and organisms of different sizes, and so it really structures and creates a huge amount of the diversity that we see.
AW: Is there a lower limit to how large organisms can be?
JH: There's some very very small invertebrates that are, umm, yeah I suppose there is a lower limit set by the size of molecules [word?].
AW: And what about the other end of the spectrum? I mean is there an upper limit in some respect to how large the largest organisms can be? And if so, what sets those limits?
JB: Well the largest extant organisms way above 200 tons—animals—and those would be the largest of the great whales, and the more recent data we're getting on dinosaurs suggests that the biggest dinosaurs were of comparable size. And a number of people have suggested reasons why it's difficult to be much bigger: It's simply that quantity of food—which will play into I think what we'll talk about with metabolic rates in a bit—the quantity of food required by such organisms is enormous, and a correlate of their size and their metabolic rate is that they live very slowly. So it takes them a long time to mature; they grow very slowly, and they live a long time. Some whales live on the order of centuries, and the largest plants live thousands of years. But it's difficult to imagine pushing those limits very much farther.
MM: So Jim, you're saying that Godzilla's out of the question?
JB: (Laughs) Probably, yes. You know, you'd have to figure out how much he would eat, and we actually did some calculations—I can't remember the numbers now—but we actually calculated if you scale the reproduction of primates up to the size of Queen Kong, estimated how many children she could have, how far apart they would be spaced and so forth, that's the kind of thing you can do with these ideas about scaling.
(Marty laughs)
JH: I guess I think a really good thing to emphasize though is we really don't know the question of what sets the upper limit, so certainly food availability is a possibility, and we certainly see fewer large animals, I think, undoubtedly for this reason that it becomes...you can only have so many to some extent supported large animals (who) have to be supported on the production of plants and things they're eating, but certainly there's been many arguments for other things, such as biomechanics of the skeleton. People have argued about that, and this is something that's gone back and forth.
06:14
AW: Is that why the largest mammals occur in the ocean and not on land? Does it have something to do with [words?]
JH: That's been one of the arguments, and one of the reasons people have argued about dinosaurs, and whether or not the really big dinosaurs had to walk in, you know, walk in rivers. I mean I think most people are arguing now that that's probably not the case, but it's still and active area of research.
MM: So shall we shift gears and talk about the other piece of what will eventually be scaled? Let's switch over to metabolic rate, and if we can hear from both of you about what is metabolism? Why do so many biologists care about it? I think maybe some folks who have made the argument that metabolic rate is an integrator of sorts, so if that word is useful. I guess at the end of the day, medical biologists to ecologists—they all get excited about metabolic rate to some capacity, so if you wanna speak to what makes it so interesting.
JB: Well I would start by defining metabolism, and say what we mean by metabolism, and defining metabolism very broadly as the biological processing of energy and material. So organisms make their living by taking up resources from their environment, and those resources include oxygen from animals that John was just talking about, or carbon dioxide for plants. They include a source of energy, either sunlight for plants or food for animals, and then all the other things that the bodies of the organisms are made of; all the other chemicals the bodies are made of. And then, inside the body, these resources are transformed, and they're really transformed, from my point of view, into two avenues of the majority of the energy that's taken in—and a lot of metabolism focuses on energy, and energy runs the world, and energy runs organisms—but the majority of energy that's acquired either as food by animals or from sunlight by photosynthesis for plants, the majority of that is spent for what we call respiration: to power the energetic cost of living. It's basically burned, chemicals are oxidized, and the energy is transferred into an amazing biological molecule that we call ATP (Adenosine triphosphate) that is then itself shunted around the body and used to do all the things that the body does: it's used to contract muscles, and send nerves, move things across membranes, and so forth and so on. And then a smaller fraction of that energy that is taken in is retained as biological biomass energy, and shunted on through in the process that we call production.
09:31
JB: So that's used to produce new biomass, either by growth or reproduction. And then, the waste products from these transformations that are going on within the body are excreted back into the environment. And I view whole thing and all of the chemistry and physiology that's involved as metabolism. But as I say that much of the emphasis has been on energy, because without energy, the biological machine runs down. Organisms die, ecosystems disappear, et cetera. I guess that's how I started at defining that process.
AW: John, do you have anything to add to that?
JH: Yeah, I think that was great, and also I like to think that the definition of life, what life does is transform inorganic material into organized form. It kinda defeats entropy, so it's about taking energy and using it to build organized bodies, and then to do work on the world. If you think about it, those are really essentially what organisms do. Metabolic rate, I agree with Jim that metabolism is a network of chemical reactions that connect all the different things that organisms do. Metabolic rate is something we can measure; it has a direct definition, and it can be measured in a number of ways by heat production. So this would be kind of the waste of heat left over as an index of all the transformations—the chemical transformations—happening in the body. For an organism that is like us, that produces the vast majority of its ATP from using oxygen, you can measure oxygen consumption rate as a measure of metabolic rate. So when we talk about metabolic rate, that's usually what we people are talking about: that would be the energy turnover that Jim was talking about, and I would agree with Jim that it sits that's a measure of all the other things that the animal is doing to move itself toward more organization and less entropy—or to do work on the world.
JB: The thing that John mentioned is this ability of this metabolic process to produce these highly organized systems that we call living things, that we call organisms, which are able to persist far from thermodynamic equilibrium. And we have examples of physical systems that can highly organize themselves as well—thunderstorms, for example. And there are a number of other good examples of purely physical systems. But what none of those systems do is the other thing that life does, which is to faithfully reproduce itself generation after generation after generation. And you know, that requires this almost magical kind of setting-the-clock-of-aging, which is related to metabolism: Setting the clock of aging back to zero every time that new fertilized egg is produced.
13:13
AW: Okay, good. I wanna sort of redirect back towards scaling now, so let's put these ideas about body size and about metabolic rate together. And I'd say in different ways you guys both study what biologists call scaling. And what does that mean? John, you wanna take the first shot?
JH: Sure. So, really, scaling is about how body size affects function. And you know, certainly engineers use this when they design dams and planes, and there's a long history of biologists doing this, going back to Galileo and probably earlier—Aristotle—people talking about the effect of size, and people noted a long time ago, for example, that larger mammals have thicker bones, and that this would be necessary in order for them not to break their bones while walking. So there's this classic surface-to-volume ratio as organisms get larger. So as animals get bigger, in general their weight increases faster than the diameter—if they were just scaled up perfectly, their weight would scale much faster than their diameters or their bones or their surface areas or their skin, and this causes changes in the way organisms have to function. I talked before about the way that animals experience the world in terms of how viscous the surface, the fluids, are around them; it's things like that. So it's basically discussing the general topic of how size affects the way organisms or bridges function.
AW: And what about metabolic scaling per se?
JH: So from the 1800s, we've known that in some animals, the general pattern is that larger animals use more energy in total, but less energy per gram. And this has been a very broadly demonstrated pattern across mammals, to fish and insects and all different kinds of animals. It may not occur in plants or bacteria—there's been some controversy in the literature but, I don't know, Jim may know about some newer stuff. My general impression that it looks like it's turning out to be primarily animals where we see this pattern of lower energy use per gram, in larger animals.
AW: And let me just state this in a different way to see if you guys agree. So, the sort of naive expectation that I think most people would have, is if you double the body size of an organism, you would also double the metabolic rate. But that's not what happens. In fact, if you double the body size, you get about a 75% increase in metabolic rate. Not a 100% percent or a doubling of the metabolic rate. Is that a better way to say it?
16:36
JH: Yes.
JB: Yeah.
AW: So Jim, do you wanna add anything to the, sort of what overall is scaling, and what's the way to think about metabolic scaling?
JB: You know, I think the way that I used to introduce scaling to students when I would talk about it, is that life as it's evolved has faced this enormous challenge that it's all based on essentially the same stuff at the molecular level. Organisms are made out of this thing, molecules, and they use basically the same chemical reactions to do their work. Then somehow, as life increases from bacteria to whales, systems have to be put together in such a way that they keep working as they get bigger and bigger. And I think, for me the essence of scaling is that it involves two elements. So on the one hand, there are things that are absolutely invariant—that don't change, and these are the molecules and reactions. And then there are other aspects of the system that have to be scaled as the system gets bigger and bigger. Let me make the analogy to a building. We have buildings that range from small houses to gigantic skyscrapers, and if you look at those, the fundamental building blocks of those systems are the same: the tiles on the floor and in the ceilings, the structure of the concrete, the outlets for the electrical appliances, the faucets in the bathroom—all of those things are invariant. They don't change with the size of the building, they're constant. But then as we make a building bigger and bigger, there are other things that we absolutely have to change, or the building won't work. We have to change the size of the beams and the support structure, and this is similar to the biomechanics that John talked about. We also have to change the system for supply and resources. So the size of the water mains and electrical mains that come in, and how those branch to get to the endpoints that are invariant. And we have to change the size of the heating and cooling system, so that the system can maintain a relatively constant internal climate. All of those things have to be scaled, and there are very rigid constraints what I call rules, almost laws as to how those aspects of the system have to change as organisms have evolved over these many many orders of magnitudes and body size. Or even over the life cycle of an individual organism. You know, a tuna fish starts life as an egg that is almost microscopic, and it grows to a mature size that can be a metric ton in mass. And as that organism grows, it has to continually make these changes so the building blocks are put together in ways that are supported and work and support the structure and function of the whole system.
20:09
MM: In the last 20 years or so, there's been a large debate—one of the larger ones of which I'm aware in biology about why metabolism scales. So do you wanna take a crack at what the debate is, and especially why the argument has been so intense? I mean it'd be great to hear each of your perspectives here.
JH: I'd be happy to start. So maybe I'll start with a little history. Really the first explanation for this goes back to the surface-area-to-volume ratio. So we had several French and German scientists who argued for basically the scaling rate of mammals being related to the balance in heat loss and heat production. So as we said a larger mammal has a relatively lower surface area, so that would mean if they were really just trying to keep their body at a constant temperature, they would have a lower rate of heat loss, and therefore they would need to have a lower rate of metabolism. And this was sort of the basic starting idea, I think, of why metabolic rate was lower in larger mammals was because they had a lower rate of heat loss. And as it became clear that this also applied to animals that don't regulate their body temperature, people looked for broader explanations—and there have been many many put forward—and I think there's a number of things that have made this controversial and difficult. And one of them is that actually fundamentally it turns out to be difficult, I think, to test these big evolutionary patterns. So we're used to doing studies with organisms where we can do direct experiments, and manipulate things about what that organism is experiencing. We can really see cause and effect there. And I think with patterns that go across whales to tiny parasitic wasps, it's much more challenging. And I think that's one of the fundamental reasons, is how we think about how to test these, and how to put the models together. But yeah, we could talk more about some of the specific. I'll let Jim talk about his, you know, he's put forward some really important models for understanding the process. But I guess the general point I'd like to say is that there have been many proposed reasons: some have been ecological, like there's not enough food for large animals; some have been biomechanic, related to the cost of movement and how that changes with size, and that might then drive other changes in metabolic rate; some are related to oxygen delivery; some have been talked about all different kinds of things—the forces, the very needed force, circulation of blood, for example. So there've been many different explanations, and people have had I think a hard time just coming to grips with all the diversity, and how to address this kind of broad evolutionary question.
23:31
JB: You know I think the challenge for almost the last century now, in all this, was put forward by a biologist by the name of Max Cliver [spelling], who was in the School of Veterinary Medicine at the University of California, Davis. And he measured the metabolic rates of a large number of mostly domestic animals, from mice and canaries to cows and horses. And he found that instead of the scaling going as a surface-to-volume relationship, a relationship based on thirds, it seemed to go on a relationship based on fourths. And so here's the thing, that if we have a deer that weighs ten thousand times as much as a mouse—which is approximately correct—the deer only uses a thousand times as much energy as the mouse. We call this sub-linear scaling or whatever. That seems surprising, because you'd think the easiest way to scale up an organism would be to just, you know, scale it up. If you've got ten thousand times as much protoplasm there, you'd need to feed it ten thousand times as much food to keep it alive. But that's not the way organisms work, and it's relatively easy to show why. For example, one of the things we've done is work out models for the supply system, particularly the arteries that supply oxygen and nutrients to the body. And so you have the supply running from the heart of a mammal out to the capillaries where those resources are taken up by the cells, and you can actually work out that if you had as many capillaries out in the tissues of an elephant or a whale as you do in a mouse—the supply, the metabolic rate of a mouse—the mammal would be impossible. It would require more blood than the volume of the mammal, because you'd not only have to have all this blood in the capillaries, but you'd have to have those capillaries hooked up to the heart with a whole network of vessels, and you'd calculate up. And what the volume of the blood and those vessels would be—it would be impossible to supply that. And so I think one of the things that is clear is that organisms have evolved to our size only because they're able to scale back. I think it's gonna turn out that this is true even of plants in that parts of plants may continue to operate at the same metabolic levels as the plants change size. In particular the leaves may, but as plants get bigger and bigger, a larger and larger fraction of the plant is made up of stems and trunk, and that is supporting and conducting tissue that has very low metabolic rates. And so the actual metabolic rates of large trees is lower on a per gram basis than it would be for a little herb just the same way that it's lower in an elephant on a per gram basis than it is in a mouse.
27:08
AW: I wanna just sort of give you my perspective on how I see this debate having developed over the past couple of decades, and I wanna just pose this and see if you guys agree. To me it seems like the argument has been in large part about supply and demand for energy. And by that I mean an organism, to use your building analogy, an organism is like a building in the sense that it has resources and energy coming in. And then it's using up those resources and energy to carry out the activities that are going on inside of it. And I would say, you know, Jim, you and your colleagues have focused on the networks that supply resources and energy inside organisms, and have made the argument that those networks constrain metabolic rates in large organisms to be lower than they otherwise would. I think that's a restatement of what you just said about blood supplying capillaries. John, you and other physiologists in the field have argued more about the demand side of it, and have constructed arguments that invoke changes in the demand for energy rather than changes in the supply of energy as being the driving force in what's shaping these patterns of scaling. So to put this in terms of the building analogy, I would say, if you had buildings of different size that use different amounts of energy, is the argument about whether or not the water mains or the electrical grid constrain the way those buildings use energy versus is it something about the actual activities going on inside those buildings that shape or constrain the total amount of energy that they use?
JH: Yeah, I think it's interesting to think about with the buildings. So I think, yeah, you're right to identify the question of is it a supply-limited phenomenon—so Jim laid out the argument that it's really impossible for a large animal to deliver adequate oxygen to the tissues, and that's been what many of their models have argued for—and yeah, that would sort of be the idea of those pipes up through the building; it would be impossible to make the pipes big enough to have the same number of sinks per room, say if we were talking about just water use. It would be impossible or too expensive to have big enough mains, so therefore as we built the buildings bigger, we would have to have fewer sinks per floor. You know, that would sort of the analogy. And the demand side might be something like, well you know, the taller the building, the views get really good, and richer people live there, and want bigger spaces. I guess they'd have fewer sinks, because they have big living rooms and bedrooms. So that would be the demand thing. The bigger building would have fewer sinks, and that's why there would be a reduced water use per square foot of the building, or cubic foot of the building. So yeah, that would be a good way to think about the supply versus demand way in the building context. I think that's the essence: so is there really a limitation on supply, or do big animals—have they been selected to use energy at a lower rate? And therefore they have reduced supply.
AW: So Jim, do you agree that that's a fair characterization of the debate from a 20,000 foot view?
JB: I think it's, you know, a fair characterization of a lot of the debate that's gone on over the last couple of decades now. But I think ultimately it's misplaced, maybe? I think that to talk about supply and demand may be actually a false dichotomy. Much of the work that we did, I think, shows how it was possible; how some of these systems have been designed, and what the physical and geometric principles of design are that allow larger animals to be supplied. But that's really not the whole story. Some of the more recent thoughts that I've had have tended to focus more on an aspect of this whole metabolism business that has played big in the biomedical sphere, which is the aspect of time, and how long these systems last.
32:16
JB: And because one of the things that we know is that these little bacteria, which have very high metabolic rates per gram also turn over at very high rates. So they live on the order of, you know, minutes! Whereas whales and sequoia trees are living on time scales of centuries. And we know that there are many phenomena related to aging that appear to be due to the long-term deleterious effects of metabolic processes; to the accumulation of oxidizing compounds that are created by metabolism. You know, that's why these advertisements for herbal medicines emphasize antioxidants and all that sort of stuff, right? But metabolism inevitably produces compounds—oxidizing compounds—that escape from the mitochondria and get out there into the cell and into the tissues, and cause damage, all kinds of damage: some [word?] mutations, metabolic damage, you know, reduced elasticity of tissues, and so forth and so on, and cumulatively those things add up to aging and ultimately to death.
AW: So Jim, let me just jump in here. So are you suggesting that large organisms have relatively metabolic rates to avoid that oxidative damage?
JB: No. I think, again, I mean one of the whole problems with scaling is that it's really difficult to separate cause and effect out from correlation. I think it's difficult to say "because", but if you're gonna build a very large organism, it's inevitably gonna take longer. And if that organism is then gonna be able to reproduce and replace itself, it's gotta live longer! You know, it takes longer to build a giant skyscraper than a 1000 square foot condominium. One of the really intellectually exciting things about scaling, one of the things that's still very much up in the air, is how we tease our way through this sort of web of interconnected phenomena, which shows up in correlations to understand what the really important first principles are. The principles of physics and chemistry and biology that dictate that these systems essentially have to be constructed within some fairly narrow set of design rules.
MM: So that's the second part, when it comes to the kind of mechanisms to allow organisms to live long enough to reach their maximal size. That seems to diverge the kind of first principles—physical constraints on size influencing metabolic rates—[word] does that not take a left turn? How do you get to that place from the supply side arguments?
JB: Well, I think—and John intonated this very early on—that ultimately, life has a lot to teach us about some of the most fundamental aspects of science, including thermodynamics. And this whole thing that, you know, life creates these far-from-equilibrium complex systems, and it does this by processing energy and using it to build and maintain and reproduce these systems. You know, that's very—thermodynamically—very unlikely. One of the things we need is a better understanding of the time dimension of life, and how that factors into the structure and function of the maintaining and growing the system aspect of life.
36:28
MM: John, do you wanna add anything?
JH: Well I think that, you know this has been really interesting because I think, I agree with Jim about what's interesting to think about aging, and this sort of fits in with trying to think in an organized fashion about all these diverse ecological and physiological things that change with size, and you know, there's a lot of different ways you could think about it. But the way that it was crystallized in my mind from the demand side was thinking about small animals in general being selected for high performance, and large animals being selected for safety. And by safety, that would include things like being able to live a long time, and have a low metabolic rate to avoid reactive oxygen production, reactive oxygen damage, less exposure to risk by being less active, and on the small side, being selected for higher growth rates. So you can have your generally small animals tend to be in more restricted, maybe time-restricted habitats, or space-restricted habitats where they're growing fast. And the other thing that happens, I think especially with animals, is that animals with different sizes compete for resources. They're out foraging, sometimes they're preying on each other, and small animals are, I think, because they're competing in an absolute, not in a relative world, they need to try to see as well, react as fast, move as fast as the bigger animals. And they can't do it quite as well, but I think there's lots of evidence that smaller animals have been selected for high neuro-locomotory performance: tending to have bigger brains, tending to have faster muscles, all these sort of things.
AW: So you're saying that the small animals have high metabolic rates so that they can avoid getting trampled on or eaten by the big guys, is that it?
(JH laughs)
JH: Yeah, and get their share of the food, right? And so there's gonna be a general gradient with size. There's a classic old paradigm that I sort of stole for this idea, the fast-slow life. People have talked about that. Some species that are the same size operate, grow quickly, and have short life spans, and others—sloth kind of animals—move very slowly and eat slowly and have long life spans. So this is the idea of thinking about that sort of gradient, but across body size. One of my favorite examples of this the posture of animals. So if you look at mammals, if you look at a mouse or a rabbit, gerbil—they tend to be in this crouched position that gives them lots of acceleration and mobility. And if you look at a big mammal like a horse or an elephant, they've got straight legs that reduce their mobility and agility, but have reduced forces on the joints that potentially would cause them to have broken legs. And so this is again, I think, an example of the selection for performance versus safety. Again, I think this has been in the literature for a long time. People have been talking about things like this. This sort of variation and demand with size could potentially be explaining the pattern.
40:01
MM: John, in light of what you were talking about with respect to small animals being selected to get away from predators—which I guess they're not always that successful at, but that's selection nonetheless—it strikes me, I have to ask you why are bats and rodents the things that carry around all the diseases that make us sick? Are they really that bad? Parasites aren't the same as predators. It tends to be smaller taxa that are at least the bad guys when it comes to our own health. So have you thought about defense? How defense is scaled? Is that one of the reasons to get the scaling arguments, the mechanics of scaling, right?
JH: I think the scaling of defense is a really—as an immune system function—is a really fascinating question. I haven't really seen a good study of it. I think there's some evidence for some aspects. Certainly vertebrates have some major leaps in immune function relative to invertebrates that's partly correlated with size. I don't know. Jim, do you know? I haven't really seen good studies of scaling of immune function. Have you, Jim?
JB: No, I haven't kept up. And there's been a lot of interesting stuff done on that whole area of disease ecology and so forth. But Marty, your question just triggered me into comprehending something that I just thought of, which is, think about it for a minute, I think you're right. These diseases that get over into humans and become really serious epidemic/pandemic threats, usually come from small organisms which live comparatively fast lifestyles. If you think about it from the standpoint of the disease, the disease has evolved in those organisms to operate quickly. Because it has to replicate itself before the host dies, right? So the diseases have been selected in the sense to have high growth rates and high infection rates. Then they get over into humans which are slow. You know, they ravage through the body very quickly, and they're passed on very quickly. Much more quickly than a disease that might have come to equilibrium in a large-bodied organism like a human, because there's also evidence that many of the disease organisms co-evolve with their host not to be too [word?] Because if they kill off all the hosts, the disease eventually dies out similarly with parasites for example. This association, where diseases of small mammal reservoirs may be because the diseases that have evolved through those small organisms represent adaptations to the host having short life cycles.
43:02
MM: That's really interesting, but I wanna get back to the broader question of resolving what causes metabolic rate to scale as it does? What's the value? Why continue to have this debate, or continue to do the research?
JB: Once you start thinking in this way, there are whole questions that open up that have barely been touched in modern research. One of the things we've been doing is applying this scaling to the performance of organisms and ecosystems, [word?] not to the interaction among individual species that John was talking about—the competition and predation and disease—but the role of organisms in fluxing energy and materials through ecosystems, because again everything, every calorie of that energy came from a green plant. And one the things that goes on in ecosystems then is that it's passed up through the food chain, through the metabolic machinery of a series of organisms, from the plant to an herbivore, all the way up to the top carnivore which can be several steps up through the food chain. And there are powerful constraints that those relationships place on the organization of natural ecosystems, and there are implications of that. For example, for the impacts of humans on things like the sustainability of fisheries. If we're beginning to realize for example, that humans can potentially have large impacts on fisheries for large fish, and on eventually conservation on whales by heavy fishing on small fish—anchovies and krill that form the base of their food chains—and you can actually apply the metabolic theory to make some quantitative estimates of what the value or what levels of exploitation some of these populations—human exploitation—these populations can withstand and so on. There are biomedical implications. When we started doing our work, we were amazed to get telephone calls from physicians, who said that the way drugs are prescribed to kids versus humans (adults), they don't take differences in metabolic rates into account! They just scale up linearly, they just multiply. So, you know, if a dose for an adult is 10X, and you have a kid that weighs a tenth of that, you give the kid a tenth of the medication. But the kid actually has a higher metabolic rate per gram. It's processing things faster. The biomedical community wasn't taking that into account believe it or not!
45:50
JB: You know I'd also like to say that some people argue that scaling might explain 70-80% of the phenotypic variation in animals. It's a big, one of the really big patterns in earth, and if we don't understand the basic why that's happening, that's really comparable to people that are living on an island, and there just happen to be cars there, and they're driving them but they have no idea about how an internal combustion engine works. It's just a very fundamental aspect of the way the world works. And it's hard to predict what will come out of understanding that, but I guess I would argue that getting an appreciation of how the organisms are built to accomplish tasks at different scales can have really wide-ranging applications that are hard to predict. I mean, how metabolism is controlled is really important for long-term advancing of better surgical techniques and anesthesia; how to send, in all the Sci-Fi movies, people can go into deep sleep into space—that's all about being able to understand how we control metabolism. We're working with engineers who are interested in understanding how to build really tiny pumps modeled on insect hearts so they can more efficiently deliver drugs. You know, a battery-less pump was inside a human. There are all kinds of really fundamental advances that are even hard for us to conceive because we don't understand the fundamentals of how it's working. And because body size is ubiquitous and important, I think there is a tremendous amount to do.
MM: The last question we had was about resolution. Art said just a minute ago that the 20,000 foot view might be supply versus demand. I wanna fly up higher to 30,000 feet, and ask you whether it might be more about the approaches different scientists with various sort of training baggage take when we ask questions. And try to use that if a path forward to resolution will come via that route. And what I mean by that, I mean Jim you work with Geoffrey West, a theoretical physicist? I just heard a podcast with him, I think it was Sam Harris recently, and he was blown away by how little mathematical theory there was. He was frustrated, so I'm wondering if, this is A) some part of the debate doesn't come from the side of the tracks that you approach the question; and B) whether resolution might come from the integration of, you know, these different approaches.
48:42
JB: I mean we're just beginning to understand the phenomena that are involved there. And I think it's going to take scientists of many perspectives—theorists and empiricists and physicists and chemists, as well as biologists—to really work out the full implications of this. And I think it's still early days. Even given an enormous rate of progress, it's going to be decades probably before a lot of the really interesting debates are resolved, and the questions are answered.
JH: These are big problems, absolutely gonna be important to bring more and more mathematical approaches, and linking together different scales of energy turnover, and within an evolutionary context down to the biophysics of transport through tubes—if that ends up being a constraining factor, you need to link those things together in a way that's still very challenging. And I think there's the question of models: if a model fits, is it right? You know, and there's been a lot of work trying to—the statistics of testing models, cause and effect in models, that's a really important area. But I also think that, it's probably just my heritage is to think that the experimental approaches and comparative approaches with animals are gonna continue to be very important to answer these questions, because what I've found, animals seem to always surprise us. I feel like like every time I make a hypothesis for an experiment, it turns out wrong.
(They all laugh)
JH: And you know, I think we have a lot of simplifications that we make that, and people outside of our field—the mathematicians and computer scientists, network people that we might pull in to pull these together—they'll have even more simplifications, and I think that fundamentally it's gonna take a lot of teamwork between people that work on organisms, people with strong evolutionary backgrounds, mathematicians, physicists. Yeah, it's a big, really important question with a lot of implications. I think engineers have a lot to add too because they come in with a sort of mindset of using mathematical and physical-chemical approaches to addressing functional problems.
JB: I would just add to that, to the young people who are listening to this, who may wanna go into areas that are related to some of that: I would like to stress the importance of math, and the importance of not fearing the math. Because of my dyslexia, I'm probably the most mathematically challenged theoretical biologist in the world, but it is really important ultimately to understand some of the basic mathematics that underlines these. And we haven't talked about Log-Log relationships, and so forth. But if you're gonna get into this, you've gotta understand what a logarithm is, and what an exponential relationship is. I don't think there's any getting around that to do 21st-century whole organism and ecological and evolutionary biology, as well as 21st-century cellular molecular biology.
AW: Okay well I think we should stop there. Thanks so much guys, and we'll be in touch!
JH: Bye!
JB: Sure. [word?]
MM: Take care, bye. Thanks to Matt Blois for production and editing help. Thanks also to Haley Hansen, Steve Lane, Roman Wasso, and Gerard Sapes.