 So for our last talk of this seminar workshop, sorry, a talk by Marc Garida. Ah, me, ah, me, ah, me, ah, me, ah, me, ah, me, ah, me. For a talk entitled, Ontic Colisation in Biophysics. Sorry, again for that. Absolutely fine. Thank you. So I'm presenting some joint work with James Laderman. And I'd just like to say that this is very much work in progress, so suggestions, criticism, very welcome. So here's a brief outline of my presentation. I'm going to discuss ontic causation in the context of several scales within the functioning of a biological system. So my example is going to be the flight of a bird. And we're going to look at it through different scales and see what we conclude from that. So biological systems involve physical, chemical, and biological entities and processes at various scales. I think that's uncontroversial, but maybe I'm wrong. And the causal effects produced by these entities are due to the specific properties and the interactions into which they enter. So we take ontic causation to include physical causation, broadly construed as involving physical, chemical, and or biological entities at various scales. So ontic causation in biology occurs when there is such physical causation within biological entities that contributes to biological function. So we think that human regularity and interventionist accounts of causation have kind of flat structure where the relator of causation are events, but I'm open to being corrected on that. And in contrast, in biology, entities at different scales are relevant to the understanding of causation. And it's not that you can't say more or less exactly the same thing on an interventionist account of causation, but thinking of it in terms of ontic causation makes the importance of scale more perspicuous. So there's ontic causation at different scales, but there is also a mixing of scales and there are no global levels. And we also argue that the separation of the time scales of the dynamics of different kinds of processes within living systems is critical to biological function. So why is it interesting to think about biophysics in this context? So biophysics studies the physical properties of biological systems and their environments and how they interact with biological properties in the context of biological processes and activities. So I disagree that physics doesn't have anything to say about biology. And this is because biological entities are not only composed of physical entities, but they are also themselves physical objects subject to universal laws of physical science at various scales, which is something that has also been highlighted earlier today. And looking at causation from a biophysical perspective can help us identify ontic causation in biological systems that spans multiple scales. So like I said, I'm going to discuss a couple of examples of ontic causation at different scales in the context of the example of the flight of a bird. So starting with cellular respiration. So here's a brief description of what happens in cellular respiration. So in the mitochondria, electrons are stripped from food, and they're passed along the chain of carriers all the way to oxygen, which acts as an electron acceptor. And the energy released in these electron transfer events is used to pump protons across a membrane. So the outcome is a proton gradients over the membrane, and then the membrane acts like a hydroelectric dam. So just as water flowing from a reservoir, drives a turbine to generate electricity in cells in the mitochondria more specifically, the flow of protons through protein turbines, which actually physically rotates, drives the synthesis of ATP, which is the energy currency of the cell. So cellular respiration takes place in the mitochondria, and the inner mitochondrial membrane causes the proton gradients that generates the proton motor faults, which is used to produce ATP. And the proton gradient requires both the physical structure of the membrane, including, in particular, its impermeability to protons, if that is not there, there's no gradients, as well as the proton pumps, which are the proteins that are embedded in the membrane, which actively transport the protons. So it's only the membrane as a whole that can be identified as the entity responsible for causing the proton gradient. The causal processes at the scale depend on the higher-scale entity function as an unchanging environment that determines the causal background. Still within cellular respiration, let's also look at mitochondrial DNA. So in the mitochondria, as everyone knows, descend from independent bacteria and have now become organelles in eukaryotic cells. But they still have their own DNA. So mitochondrial DNA molecules, just like any other kind of DNA, are transcribed into RNA and translated into proteins. But as you also probably know, most mitochondrial genes have actually been transferred to the nucleus over the course of evolution. And there are a number of reasons for that. So for instance, it is thought that transferring genes to the nucleus protects DNA from oxidative damage due to oxygen free radicals and so on. It can also have something to do with maintaining male fitness, because mitochondria are just materially inherited. So there's very good reasons for these genes to have been transferred to the nucleus. But not all the genes have been transferred, and some are still in the mitochondria. So why is that? The genes that have not been transferred to the nucleus are critical genes that are needed to control respiration locally. So mitochondria need to very quickly respond to changes in electron flux, oxygen availability, the ratio of ATP to ADP, and so on. All of these things which are critical for respiration, they need to respond very quickly to these. So the DNA molecules that code for these genes need to be physically located as close as possible to the mitochondrial membrane where respiration is taking place. So it's not just the information content of the genes that matters to cellular function, but also the location of the DNA molecules and the time scale in which they can be used to produce the proteins needed for respiration. So we think that this is a kind of ontic causation in the sense that it is the token molecules themselves located right next to the membrane that cause the adjustment of the levels of certain proteins to maintain cellular respiration working properly. Next, let's look at the macroscopic scale. So in self-powered flights, there are a lot of things happening. At the cellular scale, and this is very summarized, you have efferent neurons firing. They send an action potential down the axon, and they cause muscle fibers to contract. And it's the aggregative effect of the coordinated contraction of large numbers of individual muscle fibers wrapped together in bundles that produces the movement of the wing. So the coordination of the muscle fibers, each of which is contracting on its own, brings about the flapping of the wing, which in birds generates lift and thrust. So self-powered flight, I think, can only be understood as a phenomenon that involves the whole organism. Because the capacity for self-powered flight involves properties of the organism as a whole, such as its size, its mass, its aerodynamic shape, which is complemented by behavioral postural adjustments. Physical structures that are capable of generating lift and thrusts, which in birds, are the same. It's the wings. But in other kinds of flying organisms could be different structures. An example of that is flying squid, which have a kind of jet propulsion, which is not the same thing that generates lift. Sensory systems that provide the central nervous system with data to assess positions, speed, distance, and so on. And a central nervous system that is able to process all that information and adjust muscle movements in response to sudden changes, in pitch, your air currents, and so on. So again, this is a case of ontocrossation. And in this case, it's the organism as a whole entity that causes its own movement through the air in self-powered flight. So what do I think we can learn from this? So causation in a complex system, such as a living organism, involves the effective separation of the spatial, temporal, and energy scales of different processes and entities. So just to compare, at the molecular scale, we have the electric potential of the proton gradient across the mitochondrial membrane is of the order of 150 to 200 millivolts over a distance of 5 nanometers. And ATP production takes place at a rate of 10 million ATP molecules per second within each cell. And then each ATP molecule releases around 8 times 10 to the minus 20 joule of energy when converted to ADP. Which is also happening at an extremely fast rate. And contrast that with a microscopic scale where a small flying bird will typically flap its wings at an average frequency of 10 hertz, which means 10 flaps per second, and has a kinetic energy of about 2 joule. But the different scales are not global. So we're not talking about levels of reality. There is no global separation of physical, chemical, and biological scales. What there is is that the scales are determined by the dynamics of the relevant systems. So there is local separation of scales with different kinds of processes taking place at different scales involving both physical and biological entities. However, the scales are always mixed to some extent. So the local separation of scales is not absolute. So we're denying the existence of these separate ontological levels. And the functioning of the entire organism emerges from the dynamics of these different processes. Just before the questions, would it be OK if I take this opportunity to advertise something? Please do. You have the time. Thank you. You can have them during your talk. So we're going to have a workshop on the philosophy of biophysics in Bristol, 14 to 15 September. And even though the deadline for submissions was actually yesterday, we are still very happy to accept submissions until, let's say, the end of this month. So here are some topics that we would be happy to receive submissions about. And just please email a 500-word abstract to me on that email. Thank you. Let it there for a minute. Plenty of time for questions. Yes. Yes. Thank you very much. This is very exciting work. I wonder when you said that only the membrane is a cause of the proton gradient. And for example, the respiratory enzymes that pump protons are not. I mean, what sense of cause are you presupposing? It seems to me that, of course, the proton pumps, for example, are only partial causes. So they are difference-making causes. So they make a difference with respect to the phenomenon. So turning off the proton pumps will lead to an equilibration of the, for example, when you poison the cytochromoxidase with cyanide, then the proton gradient will equilibrate. So in that sense, it is a cause. It's a difference-maker. You agree? I agree. So I was thinking of the membrane as including the proton pumps. I think I might have said that. So the proton gradient requires both the physical structure of the membrane, specifically the impermeability to protons, as well as the proton pumps. So I'm not saying that they are not a cause. But because they are embedded in the membrane and they're fundamentally part of how the membrane operates, I'm not seeing them as a distinct cause as opposed to the membrane. So it's the membrane which includes not just the bilayer and which is impermeable to protons, but it's also the membrane as including the proton pumps. But I agree that if they're not functioning, then yeah. Careful, yeah, briefly. I can't really say what it is, but something in me resists to viewing the membrane as a cause of the potential. Maybe it's the fact that there's nothing changing, really. The membrane is just a structural constraint, as it were. And nothing is happening with the membrane. Well, nothing that's really relevant to the gradient. In that sense, I have a tendency of saying that's sort of a constraint of the system. I mean, usually by causation in the by now well-known woodwardian interventionist sense, it's change-related. But the membrane, it seems, is static. It's kind of a static structure here with respect to the respiratory mechanism. So I'm not sure somehow I find this strange to call it a cause. OK. So I don't think that it's exactly. So I think you're partly right. But I don't think it's exactly right to say that the membrane is static, and it's not doing anything. So the membrane with its proton pumps is actively keeping the proton gradient. But it is, you're right, in the sense that there is this background and changes in that it's. Exactly. I see it. OK. Because the proton pumps are the part of the membrane that are actively pumping the proton. But that alone would also cause absolutely nothing unless the membrane has an unchanging cause of background of impermeability. So the gradient would collapse immediately. Yeah. Yeah, I have to think about it. Thanks. Caleb? Yeah, thank you so much. This is really interesting. So I'm curious about you do say early on in the talk that you think interventionism has a sort of flat structure and that ontic causation is a superior alternative. Is that sort of where you're pitching it? It's not. You can say yes. I don't think so. If it's what you think. I'm not saying it's superior. I think it's more helpful to think in terms of ontic causation. Because it makes, it highlights the importance of the entities that are causing things, as opposed to just events and things happening. And it makes, and it also highlights the importance of the different scales. That's why I think it's a better way of thinking about it. So I wonder what you would say to a response like this. Well, actually, ontic causation is instead a different scope of explanation, but it's parasitic on something like interventionism. So you've got to eventually say something like the membrane is a difference maker. So there's still an account of causation buried in there. But what you've done is just zoomed out and you've now applied it to a sort of multi-scale biophysical domain. So I wonder if, yeah, what would you say to that? Daniel doesn't like it. Well, entities that cause things are obviously difference makers in the sense that they're doing something and if they weren't there, that other thing would not happen. So in that sense, yes. But I don't really see how the account is parasitic on the interventionist account of causation. Could you say more about that? Well, because ontic causation itself, it doesn't provide an account of causation. It is a sort of scope of explanation that uses an account of causation. And it seems like the account of causation that you're using is interventionism. You could convince otherwise. But that's why I say it's parasitic on it, because embedded in your scope of explanation is an account of causation. It's not David Lewis' account. It's not probabilistic causation. It may be his mechanism, but there's also difference making interventionism in there. So I'm wondering, yeah, please. OK, so if I have to pick one of those, I'd say it's the mechanistic one. I think the interventionist account is a very interesting way of us figuring out what causes what, rather than itself being a good account of causation. But I have to think more about it. And yeah, I think we have a lot to talk about. I kind of want to promote Charles and to say something, because we've talked about this before. But to me, one of the great advantages of talking about organisms and bio-disciplines for me gives one an opportunity that is not granted by talking about organisms in certain biochemical terms, which is that biophysics traditionally has been much more instrumentalist and much more agnostic about units of material. And you can do biophysics without assuming the molecular hypothesis. You can just say, I'm avoiding your weather molecules list, and still go do good biophysics. Because physics has this strongly positivistic history where physicists at some point said, it doesn't matter what the thing is that we're measuring. As long as we measure it, then the measurements are real and you do something like this. Right, Charles, we've had these discussions before. Yes, it's been a long time. You're right, yeah. Right? You've written my only paper in biophysics, which is exactly that. OK. It's a measure I am channeled. OK, now, how does it work? The thing, it turns. It turns. You said it turns like a turbine. Oh my god. I don't know why. That's small. It's a turbine. So biophysics means the techniques often are quite diagnostic about the details of the mechanical things. That biophysics is philosophically interesting to me, at that caveat to me, because of this pervasive agnosticism to what is there. But not that one. No. Yes? Can I respond to that, so then you can go on? OK. So it is true that you can do that, but you don't have to. You don't have to? You don't have to. And biophysics is physics, but it's also biology. And biology is quite committed to the existence of these entities. And I personally am quite committed to a really strong scientific realism. So that, to me, is not the field of biophysics. Although, absolutely, you can do that. Go on. Yeah, just a follow-up to this conversation here. I mean, historically, it's indeed interesting to know that the scientist who proposed this mechanism for the first time, Peter Mitchell, he was very much a biophysicist. And he didn't care much about molecules. And his first publications about this mechanism were full of physical computations of thermodynamic calculations about the feasibility of this mechanism. And he didn't care about molecules at all. I don't think he believed in the existence of proton pumps. This was controversial for a long time. And only once these proton pumps have been characterized was the mechanism with proton gradients, et cetera, described in these terms as you presented them. However, that was completely figured out by biochemists. And I happen to know one of the biochemists who was involved in describing these molecules. He once was my biochemistry professor. And he used to say that, well, we just identify the molecules. And then our job is done. Then we hand it over to the biophysicist. And I think that's pretty accurate historically how. So first was the biophysical hypothesis. Then the biochemists identified the molecules. And then they handed it back. And now the biophysicists are describing the workings of these molecular motors. That's kind of it. I agree with all of that. I think it's nicely we both, Daniel just said. But initially, the biochemists were kind of reluctant to accept the chemo-osmotic hypothesis. Yes, yes, indeed, yeah. Because they thought it's all chemical. There's no chemical. No membrane, no two phases, all in the homogeneous medium. But once they accepted that, then yeah. And that is the model of the molecule, the pump. The ATPase synthase. Daniel, to you. Which one? To Carl Madlin's book, Cross on the Boundaries of Life. Yes, you did, yeah. So there's a chapter in that book on menstrual chemo-osmotic hypothesis. And one of the cool things he mentioned is that well, menstrual had the electron micrograms of mitochondria. And managed to derive a more correct theory of the structure of mitochondria based on the microelectron micrograms, but also in conjunction with the chemo-osmotic hypothesis. So it's an interesting case of this physicalist thinking and instrumental results moving together. So what did I really like here? I like a lot of stuff here. This is really cool. But one thing I really like here is it raises a really interesting question that it's one of those questions that I'm kind of surprised that I never slowed down and thought about, which is sort of when exactly does spatial organization matter? Right? When does spatial organization matter? Because we have sometimes it doesn't, right? Sometimes we write down a Craver diagram, and we don't care where the crap in the Craver diagram. OK, it's got to be able to constantly interact, right? Like, we care that stuff bumps into stuff sometimes, right? But we're not really thinking about the spatial organization of the stuff. And sometimes we write it down, and we really, really, really care about where are the mitochondrial DNA sequences actually getting synthesized and turned into something useful? And that's a really, that's a really cool general question that these kinds of examples, I think, really make you think about. And I haven't spent, it's like, oh, I've never spent enough time thinking about this question. This is a cool question. So I am literally writing a paper right now on spatial structures. So I'm really excited about that question. Most of the time, spatial structure matters a lot more than we think. So there's this guy, Franklin Harold, who thinks that this is not something that we normally think about because of the ways we study cell biochemistry, because most of the ways we study cell biochemistry involve breaking the cell apart and doing just the chemical reactions. But most chemical reactions within cells are directional in space. They're not just, so obviously the cell is not just a bag of molecules. It's a really spatially structured entity. So yeah, I'd say most of the time, spatial organization matters. We're going to make a generical example that I want to at least mention to you, because you're like, we're all right. I have to mention that if the talk of mass study was right, it's not the spatial relation of things. It's a spatial relation of the process. Still, that is not clear in my mind which view is the best. Can I also come back to that? Please do. I think, so I sadly missed my cell's talk, but. I think on YouTube it's OK. Yeah, that's right. Excellent. But I do think it's the spatial structure of things and not just of processes. And here is an example. So a lot of, I don't know if a lot of, but some organisms are able to survive in a state of cryptobiosis, as in frozen solid, for instance, where the only thing that is preserved is the physical structure of the organism, but all processes are stopped. And the fact that it's possible for organisms to survive that, to me, seems to indicate that it is the physical structure, including the spatial structure, that is more important than the processes. And the physical structure is what enables those processes to take place. I would be inclined to follow you if I thought that the organism after you defrosted is the same. Oh, wait, that's what it is. I don't know if it's the same. If it's a process vision, it's not the same individual, biological individual before frozen, and there's a big literature about this. So some organisms use cryptobiosis as part of their life cycle. And it seems to be, OK. But this is what the process guidance says. If the process stops, the organism will die. I'm just going to say that I didn't want to say that. That sounds like bullshit. No, there are objections to that. I think it's the same one. So I'm happy to say it's a plus. But I realize that is a waterfall of reply. Pushing your ideas. Other? Oh, sorry. That's OK. Which one was first I didn't see? Well, I just took a quick finger on this, because I do want to just say, the process ontologists would say something like, well, look, the processes are not just the biological processes that are happening. This process is all the way down. So it's the material continuity. Let's even assume that it's the same organism. There is still some kind of process of preservation of material continuity. And that, at a lower scale or level, whatever you want to say, is I think what the process ontologists would appeal to. Yeah, the membrane is a process. Yeah, that's right. Michael, you're in shock. Sorry, you're in shock. No, I'm not. I will add the rest of Carmen on this book, which I'm going to release out, is not just that structure is important, but that experimentally structure can be done in the test to by proxy, which is a cool feature of biosystems biochemistry, that the actual spatial arrangement of a cell or mitochondria does not have to be studied, but could merely provide a heuristic or experimental work. I don't know how this relates to causation at all, but I just thought that that is one of the cooler arguments of that book, that you can dramatically simplify the actual structure and come up with a theory of the mechanism. Sure, I think there's probably truthful kinds of research that you can always have a model that simplifies a lot of the stuff that a particular range of research is set in, but you can also go down to the nitty gritty details and get each individual atom of models if that's also of interest. So let's thank our speaker.