Scientist Regrows Frog Legs With 24-Hour Treatment, Then Does Nothing for 18 Months

Michael Levin [00:00:00] So there are these other spaces. We live in them. We don't know how to visualize them, for sure. And we're very bad at recognizing intelligence in those spaces. We don't know what it looks like. This is why people feel very uncomfortable when I say, your body organs have a kind of intelligence and they think, oh my god, this, you know, this is just crazy. This is Joseph

Vance Crowe [00:00:22] Ring. I'm a cattle feed lot operator in Northern Illinois, and you're

Michael Levin [00:00:26] Listening to

Vance Crowe [00:00:27] The Vance Crow podcast. Welcome back to the podcast. I'm glad you're here today. Michael Levin returns. If you'll recall during the first interview, we sat down with Dr. Michael Levin and learned all about bioelectricity and his work on getting animals to regenerate specific limbs or maybe even an eye. And at the time we were just talking about salamanders and some kind of ideas about where all this could go. Well, Dr. Levin has published some new reports. He's done some stuff on frogs. He's in a whole new paradigm, and really it's just us keeping pace with the very, very rapid speed with which he's conducting, really cutting edge science. And I can tell you that this conversation spans some of the most interesting work we've ever done on the podcast. Not only does Dr. Levin talk about the regeneration of limbs in a much deeper and more complex way, we also talk about things like electroceuticals, which is a totally different form of medicine that I had never heard of, but that we, as we discussed, you find out this is likely a large part of the future of medicine. We also get into conversations about what is life and can you even determine that at all? And it is really just a wide ranging and fantastic fun conversation with a brilliant mind. We're gonna get to that, but right now you probably have noticed, we've been talking about Legacy Interviews. Things are getting big and busy because we are building out our own studio, and we are going to be doing a lot more of these interviews, particularly in person.

Vance Crowe [00:02:04] We are finding that there are people that want to have their parents or grandparents brought into a studio. We sit down for about 90 minutes and we talk about what, what are your family stories? What was your childhood like? What was your career? How did you think about marriage and parenting? And really what legacy do you hope lives on? Because we're building out this studio, and so much of them are gonna be done in person. Ben Anderson, my executive producer and I are trying to fill up the time between now and then with Zoom interviews, which is something we'll probably do a little bit less of in the future. And so if you have a loved one, maybe it's a parent, a grandparent, or even a child, and you would like me to do a Zoom interview with them, then sign up. Because starting May 1st, these are gonna become a lot less available. And you can do that by going to store Articulate Ventures, and you can book a Zoom interview with me. And if, if you use the promo code Vance V-A-N-C-E, we'll give you a 20% discount. This is only for the time between now and May 1st, because we wanna use that time productively. And then once the studio goes, it'll be a different situation. So anyway, now we are going to go to the interview with one of my favorite guests, Dr. Michael Levin. Dr. Michael Levin. Welcome back to the podcast.

Michael Levin [00:03:25] Thank you so much. It's great to be here.

Vance Crowe [00:03:27] Thank you. So last night I was doing a little research. I knew we were having you on for a while, and I was like, oh, I'll just go check out a paper or two that Dr. Levin is put forward. And I realize actually you are cranking out papers like a factory all the time. So maybe the best question to say is what's the latest PA paper you've published and what's it on?

Michael Levin [00:03:47] I suppose the very latest one would've been the one that came out

Vance Crowe [00:03:49] Last

Michael Levin [00:03:50] Week, which was the Frog Leg Regeneration Study. So this is, this is work that was spearheaded by Rocha Mor, who's currently a junior faculty member in Canada. And I was done with my partner David Kaplan. And this was the result of, of, of a really long experiment to try to get adult frogs to regenerate their legs. It's a stepping stone in our overall, you know, research program to get, to get to limb regeneration. And these are uniquely, these are adult large animals. These are not froglets that, you know, have been used in, in prior studies. And yeah, it was, it was, it was rather remarkable that a 24 hour exposure of the amputation wound to a cocktail of drugs in the bioreactor that David Kaplan's group made. And that 24 hour exposure kickstarted a year and a half of leg growth, we did not intervene in the slightest during that year and a half. We did nothing beyond the first 24 hours and the frogs regenerated legs that were, they had structure, they had size, they had feelings. So if you tickle the very tips of the, of the toes, they could feel it. They would stand on these legs, they would use them to move and, you know, to move around. Yeah, it was kind of v validation of this concept that we have, which is that we should be looking for triggers, not ways to micromanage the really complex process. I mean, we have no idea how to, how to construct a leg from scratch.

Michael Levin [00:05:21] Right. But the animal does. And so if we can find the triggers, then a very brief intervention at the very beginning when the cells are just making a decision about what they're gonna do, we'll kickstart this whole program.

Vance Crowe [00:05:33] Now, when you were putting forward the plans for this, did you know it would go this far? Or like, were you confident that it would look like this when, like, what was your imagination of how this would turn out?

Michael Levin [00:05:44] Yeah. Well here, I'll, I'll tell you the things we got wrong and the things that we got right on. On the one hand, I, I'm, I'm very confident in the approach in general. So we did this involving, you know, numerous of people or lots of other people involved in my group and in, and David's, we put all the resources into it because in my gut, I know that this kind of approach is the way to go and it's going to work specifically with this. We, you know, of course, you never know how a specific experiment is going to turn out. And it's important to note that this particular, so we report a particular cocktail, it's got five ingredients with us, you know, very specific dosages. This was not the result of us fiddling with that cocktail, trying out lots of different combinations. And then here we're showing you the best one that worked. This was our first guess, our first stab at this, at this cocktail. That's what it did. And so to me that I'm very excited by that because that's, you know, the odds that we picked the best cocktail our first time out are very low. That means that this is not the best cocktail. This is just, you know, the first one that we picked and that imagine, imagine what the optimized version is gonna do, right? So, so I'm very excited about that. So of course we didn't, you know, this was a huge risk because again, you're trying one, one set of dosages, who knows if that's right or wrong. Watching those animals progress, knowing that we did nothing except for that first 24 hours was incredible. It was, we would sit, we would, we would, you know, weekly we would look at these and we would ask ourselves, you know, we'd love to know what's going on, check the, check the gene expression, check the anatomy, do sections, and so on.

Michael Levin [00:07:15] But of course, once you do that, that, that's, that's a, that's it. The, the, the cells won't grow after that. So you're constantly doing this trade off between do we intersect, you know, do we, do we stop it and check what's happened now? Or do we let it, or do we keep it going? And of course, you want to keep it going because you wanna see what it'll do. So about a year and a half into it, we just said, okay, we gotta, we gotta stop somewhere. So this is it, the thing. So, so, so I think, you know, I I I was very hopeful that it would work. The details were amazing to me when I saw it happen. The thing that we got wrong about it was that initially the goal of using frogs was going to be as a rapid screening method. So we thought that what we would do is very rapidly screen early responses in these frogs, and then eventually go to mice and, and, and do these more complicated studies. What we saw was once it starts growing, you don't want to stop, and then you want to see what it does. And that took a year and a half. So this was, it was fantastic, but it was by no means a rapid, it was in no way a rapid screening process.

Vance Crowe [00:08:12] And when you're talking about this regrowth, it's, it's presumably not just the skin around it, it's the bones, it's all of the correct veins and everything. So it, it took, did it take a year and a half for it to get all the way to being a full-sized leg,

Michael Levin [00:08:27] Basically? Yeah. And, and in fact, and in fact we may, we could have kept on going it, you know, it was, but many of the animals were not perfect at the end. And so, you know, the webbing and just some of the, some of the very distal features were not, were not quite there at the end. We could have probably kept it going for another six months or more,

Vance Crowe [00:08:45] You know, and what happens next? So you have a big success. Do you go back and do frogs again and try and perfect that to make it go faster? Or you just try and spread out to other, you know, parts of the animal kingdom?

Michael Levin [00:08:57] I think we, so, so we are, and this is, you know, in kind of a disclaimer that I have to do here because, or a disclosure, they say, because David Kaplan and I have a spinoff company, so, so we're called Morph Pharmaceuticals Inc. And this, this company is formed around the idea of taking this closer to some sort of clinical application. So we are, right now, we are in experiments with mice. So the idea is to try to do the same thing in a mammal and eventually, hopefully in into biomedically relevant context.

Vance Crowe [00:09:27] And can I ask how far you are in the, in the mice process?

Michael Levin [00:09:32] I can't really say much that's not peer reviewed, right? So if I, I can't give a lot of details, but, but let's, let's just say this. I'm, I'm very excited about what's happening. We're very optimistic. We've got a lot of experiments going. We're in an expansion phase. Yeah, this is, it's, it's great. I'm, I'm super, super excited about it.

Vance Crowe [00:09:50] What do you think the experience is like for the frog as they are regrowing the leg?

Michael Levin [00:09:58] That is an interesting question. I think more generally the question of what is the experience of anything for any other creature, even you and I, right? Is philosophically a very, very difficult one. I don't think it's possible for us to say what anybody's experience really is of anything except ourselves. And even that is, has issues. So yeah, I couldn't possibly that, that's, that's the classic problem of other minds. I couldn't possibly tell you what it's like to be a frog.

Vance Crowe [00:10:29] So I was reading some of your papers last night, and there was one that came up, I believe, about breast cancer tissue and about how the difference between the left and the right breast is actually something you can detect. Can you talk about that?

Michael Levin [00:10:43] Yes. Yep. Absolutely. This, this was a, this was a collaboration. I, I'm not the primary, you know, the primary mover on that. And the, the paper pulls together three, three areas that, that are very, very important to me. And these are, these are areas that I've worked in for a long time. So my, my PhD was in left right asymmetry and trying to understand how individual cells, while they're making an embryo, figure out which direction is left and right. How do they, how do the different organs know what side they're on? How do, how, how is it reliably that your, your various organs end up on the left or the right side correctly, right in, in every embryo. And then of course, cancer is something that we look at in my group as a kind of a failure of cooperation of cells towards anatomical goals. And yeah, and, and of course, ion channels and bioelectricity is something that we're very interested in, in terms of the informational medium that binds individual cells into larger Yeah, a lot larger, larger kinds of selves. So this, this, this, this paper was, was, was very interesting because it tied, tied all of that. It tied all of that together. And so the, you know, the, the PI here was my collaborator, Mar Maria Rooke, and Sophia Mazuli was the, the first author who, who did a lot of this work. And yeah, it turns out that, that there are left right differences in the electrical properties of, of, of breast cancer. And there's actually, there's been older data to suggest that tissues from the left and right are not identical.

Michael Levin [00:12:17] And seeing that, and of course, early embryos, they're absolutely not identical because their bioelectrical properties are different. That's part of how embryos know left and right is because of the voltage gradient that's distinct across the left and right sides. So to know that this is true in adults and in particular in this important disease state is, you know, it's amazing to me,

Vance Crowe [00:12:36] You know, you're talking about everything from amphibians to human breast tissue and then into electrical pulses. As you're, as you're looking at the world and you're trying to answer questions, what part of your education are you like, man, I really wish I would've paid better attention in, in this subject, or I wish I would've spent more time doing this.

Michael Levin [00:12:57] Yeah, many, many areas in general. I, well, it's, it's, it's hard to know, you know, what would've been the most helpful? Because of course, if one doesn't have it, then you don't know what you would've done with it. I always wish I was better in math. I was never particularly good in math. I wish I was better in math. I wish I had done more physics. Yeah, I guess, I guess those, those are, those are the things I, I think about sometimes. Yeah.

Vance Crowe [00:13:26] Discoveries that you made, does this, where where does this lead when you think about it in terms of how this would impact cancer research?

Michael Levin [00:13:36] Well, I think The, there's a long kind of path and a short path. The, the, the big picture is that I think this helps us to understand what, what cancer really is, which is a disorganization of cell cooperation and cell cell binding into, into higher level cells. And this is, this is yet another inroad to be able to understand how these cells perceive their environment, you know, in, in order to be different on the left and right sides, they have to know what side of the body they're on. So this, this gets us into this question of what do cells actually know about their environment? Why do they act differently in different kinds of environments? You know, these are very fundamental questions in, in the short term. I think this is consistent with something that I've said all along, which is that ion channel drugs are an amazing toolkit of electroceuticals. And that someday soon when we are better at understanding the bioelectric code, we will be able to use these Zion channel drugs not just as markers, not just to be able to say that this is different from that, but to actually control the decision making of those cells. And we've, of course, we've shown a lot of that in, in the frog model, but I think, I think this is all this is going to be, this is going to come into use in, in mammals

Vance Crowe [00:14:50] Electroceuticals talk. Talk more about that.

Michael Levin [00:14:53] Well, it's, it's simply the idea

Vance Crowe [00:14:55] That

Michael Levin [00:14:57] If, if we understand that cellular networks make decisions, they make decisions about anatomy, they make decisions about physio physiology, they make decisions about what they're going to do, then the obvious question is, well, how do we manipulate those decisions? Right? And so, so as, as with any, as with any system, you want to modify its behavior, you want to impact it by the kinds of signals it knows and perceives. So if it's, if it's, if you're trying to train an animal, you use rewards and punishments and signals and cues that you, you know, that, you know, the, the, the, the animal can, can comprehend. And so the bioelectric state of cells is really important. And all cells pro, they sort of expose a really interesting interface to the rest of the world. They've got these ion channels on their surface. And you can think about that as, you know, to computer scientists, it's an API to, you know, it's like a keyboard where you get to, they're, they're, these cells are telling you the kinds of signals they're going to process, and you can open and close those channels at will to give them various signals. And so how do you do that? How do you open and close channels? I mean, there are genetic ways and so on, but that's tough in human patients. It's tough to do trans transgenes and gene therapy, but, but drugs are, are, are great in terms of using the existing panel of ion channel modulators. So these are small molecule compounds that open and close channels. Many of them are already human approved. We're gonna be, of course, people will discover lots of new ones in the years to come.

Michael Levin [00:16:29] And I, I think these are fundamentally electroceuticals. They're not just for cardiac issues and migraine and, you know, epilepsy and things like that, that people take them for. They are a profound set of reagents, an alphabet that you can use to, to communicate with cells and tissues and try to push them into health state.

Vance Crowe [00:16:49] It strikes me as you're describing this as I remember when the panic began about losing antibiotics, right? And it was like, once we lose antibiotics, there's nothing left. And then if you go out and kind of explore science, you find out, well, there's phage research maybe that will come up. But this is a, a different paradigm of medicine for me. This is not something I've ever even considered before. Where else do you think this applies? How do you think people should understand the future growth of, of electroceuticals?

Michael Levin [00:17:19] Yeah. I, I think you're right. I think, I think it is a new, a new, a new domain and a new way of, of addressing this for, for two reasons. First, let's just talk about areas of application. So realize that in medicine, almost everything except for infectious disease. So other than infectious disease, almost every other problem would be solved if we knew how collections of cells make decisions about what they're going to build. So birth defects, traumatic injury, reprogramming tumors, degenerative disease, aging, all of these things would be solved if we knew how to take a group of cells and say, you're going to be a normal heart or you're going to be a liver, or you're short a finger, you're gonna need an extra finger. If we knew how to communicate those anatomical goals to cells, which which means basic research to understand how that's decided in the first place during embryonic development, if we knew how to do that, massive areas of medicine would be solved. And I see future regenerative medicine as really providing a, a, a fundamental solution to all of these things. You know, whatever, whether cells are con are, are whether tissues are damaged from, from a injury or they're never there in the first place because of a birth defect or they're old, whatever it is. If we knew how to communicate to those cells, here's, here's what you need to be building. This would be a transformation in medicines. That's, that's the first thing. And, and how we're going to do that, I think is in large part going to be bioelectrical because the decisions that those cells are, are making together are mediated by a kind of bioelectrical communication that's like the glue that binds them together.

Michael Levin [00:18:52] It, it sounds, you know, it sounds we weird and everything, but, but realize that that's basically what, what neuroscience has been saying all along, right? How do we arise, you know, you and I have this like centralized perspective. We feel like a, like a separate individual, but we're a collection of neurons, really. And so how is it that this collection of cells, this collection of neural cells can have memories, goals, preferences that don't belong to any of the cell individually. It belongs to the collective. So all cells do this, not just neurons in your brain, all cells do this. It's just that the rest of the cells in your body are thinking about shape and physiology, not behavior. That's, that's the only difference. So I think much as we communicate with each other with signals that ultimately turn into electrical signals, right? Things you see, things you smell, you hear, you taste, all of those things come into the brain as electrical me media, then the exact same thing happens to the rest of the tissue. We can communicate with them electrically and hopefully if we know what we're saying, if we understand the, the, the, the code, we can get them to do various things. The other, the other thing that's going to be fundamentally different, I hope, is that right now almost with, with the exception of antibiotics and surgery, most of the medical interventions that we have don't actually solve anything. They don't fix anything. They address, they address symptoms. And as long as you keep taking them, hopefully the symptoms are reduced and hopefully the side effects aren't too bad. Which, although that's major problem of course, and if you were to stop taking them, you go right back to where you were because these things don't actually repair anything, right? And so I think that what's, what's really important is, is going to be to take advantage of the learning, the intelligence of cellular collectives, to really push them into a health state.

Michael Levin [00:20:33] Not to try to micromanage it, not to not to try to be there with your drug 24 7 to sort of force at the, at the very end, you know, sort of force the, the outcome that you want. But to, to move the whole system into, into a place where the whole dynamic is different and you're not there all the time having to, having to push it. I think that's going to be for reasons we can ex explore if you want. That's, that's going to really help with the whole side effects issue. And it's going to be much more powerful. And, and this, this will all be, bio electrics is a, a key way to do that. There may well be others, I don't know. There may well be other ways.

Vance Crowe [00:21:06] Now when you imagine, and I'd like to explore the, the more deeply, but when you imagine detecting what's going on with some of these bioelectric signals, are you imagining, hey, we cut you open and then we put these connectors on there to, to check the wattage? Or are you imagining, I I mean I can't even, I can't even wrap my mind around how do you even check the, the, these things that you're thinking about repairing, using electroceuticals?

Michael Levin [00:21:30] Yeah, so, so the way we do it now in our model systems is with something that are, that's called a voltage sensitive fluorescent dye. So these are, these are chemicals that you can bathe. So let's say you have a frog embryo, and you would like to know when the frog embryo makes a decision as to how big the brain is going to be, right? What are the electrical states that tell you where the edges of the brain need to be, in fact that that's a thing. That's, that's how the brain decides how big it's supposed to be. So, so what you can do is you can soak it in the solution of this dye. And this dye has this amazing property that it fluoresces, which you can see on a camera with different wavelengths and different brightness depending on what the local voltage potential is. So at every cell, so what it does is it, it it temporarily goes into the cell membrane that covers every cell, and depending on the voltage around that membrane, and this is what we're trying to track at these patterns of voltages, it will release light and we capture that light with a camera. So we literally have, and you can see this in our, in the supplements to our papers, or you can see this in the, in the TED talk, we have videos. You can take movies of this stuff. You can, you can literally see all the electrical conversations that cells are having with each other. And you can see that changing over time. Now, how is that gonna work in, in humans? So, so the big limitation of this technology right now is that it's purely optical, meaning that if you can see it, that's great, but beyond the first three or four

Vance Crowe [00:22:47] Level layers

Michael Levin [00:22:48] Of cells, you can't see down there. It's opaque. So, so with a human, you're not gonna be able to see too far down. Now certain things, for example, diagnostics for skin cancer, let's say on the surface of your skin and the oral mucosa, things like that, that that's, that's already solvable now. And we have some, some thoughts around that. Things like tracking bioelectric states when you're doing surgery to remove a tumor so you can see where the edges, what, you know, the tumor margins, how much do you need to take out, right? That that's right there and open to the, to the, to the surgeon. So you should be able to, you should be able to do that. As far as the rest of it, I think the rest of the body, I think we're going to have to wait for the development of better reagents that report not in the visual, you know, dimension, but maybe, maybe some sort of ultrasound reagent that, that gives you different ultrasound signals based on the voltage or maybe, you know, some sort of tomography or something like that. These are, these are coming, they're already, there's chemists already working on this stuff. But there's another really interesting thing that I should mention, which is this idea of surrogate site diagnostics. So one thing we, we noticed, and this was actually the work of a, of an undergrad in the, in the lab Sierra Busi. And she, she noticed that when you have a, we have a frog litt, and if that frog lit loses one of the hind legs, the opposite leg, and you're tracking voltage during this whole process, the opposite leg lights up in exactly the same location where the other leg got injured. So you can tell what's going on in the opposite leg by tracking the voltage in the intact leg.

Michael Levin [00:24:22] Okay? And this is, this is not the first time we've seen this because there are, we, we've, we have a number of papers showing that, you know, whether you get a tumor on one side, one part of the body or or whether the organs are shaped correctly, is in part a function of voltage all the way across the other side of the body. Meaning, again, not terribly surprising. Electrical networks share information. That's what electrical networks are for. So, so part of the, the, what this network is doing is letting all many, and maybe all, I don't know, cells within the body know what's going on at distant locations. Okay? It's an integrated system. So that means that maybe someday, if you want to know what's going on in one area of the body, you can look somewhere else, somewhere that's easier to, to check. So maybe if you've got a region on your body that's really easy to get voltage imaging from, maybe maybe, you know, inside the mouth, maybe the tongue, maybe in the eye, who knows, maybe you can extract from that electrical map information that will tell you what's going on elsewhere. That may be really hard to, really hard to get to. So that, that kind of surrogate, you know, that kind of surrogate diagnostic. So, so obviously everything we've done is in the frog. I, you know, I'm not saying by any means that this already works in humans or that we're ready to do it in humans we're not. But fundamentally, I think that information about health and disease is present throughout the body, and I'm sure we can, there, there can be clever ways of, of getting that

Vance Crowe [00:25:41] Without cutting anybody open. You know, with this being something that is so new or at least new to people like me, I, I always think about when people are describing medicine from back and say the middle ages, right? Where they're like, oh, there are the four humors and we kind of mock them for being so silly and so simple minded. But you have to wonder if all of the television shows that have ever been made about medicine will look rather silly when they weren't considering the, the, like the electric charge going on inside of organs or inside of the whole body. How, how quickly do you think this becomes a field that is down the graph as I call it, like where, where more and more people know about it and kind of just accept it as, as a part of the science medicine lexicon?

Michael Levin [00:26:26] Yeah, I think, Let me just address that first part for a minute. 'cause I think it's super interesting. I, I think you're right. I think, I think things are going to look in medicine, going to look very silly in coming decades. And, and the reason it's gonna look very silly is not necessarily just because we didn't know about, about, about bioelectricity and things like that. It's going to be about the level of interaction. It's going to be about the fact that we were trying to fix things at the hardware level when we were dealing with this incredibly complex machine that has all kinds of interesting software that you could have taken advantage of. Like I say, you know, I say to my students sometimes to the why is it that when you want to go from, from Photoshop to Microsoft Word on your laptop, you don't get out your soldering iron and start rewiring. Why don't you do that? Right? You don't do that. And it's laughable because, because we know that this, the machine is amazing. It's reprogrammable at the software level, you'd be crazy to try to program it at the heart. I mean, some people do for specific applications, but, but most of the time you don't program, you don't rewire the hardware, you don't program in machine code. You have these really high level ways of communicating with that machine. You give it experiences with keyboard presses and things like that, right? So at some point people are gonna look at this stuff and say, can you believe they were trying to fix these, these fundamental disease states at the level of the hardware they were in there, rewiring pathways, they were trying to change the genome for, for, for god's sake. This will be, I I think this is gonna be very amusing to, to to to the future.

Michael Levin [00:27:57] It's like, it's like if I give you a, I bring in a computer to you and I say, you know, this thing, this thing, this thing isn't, you know, isn't isn't booting quite right? There's something funky about the way the screen is formatted and you say, well, we're gonna have to readjust that silicon boy, you know, the silicon aluminum is all, is all wonky, you know, you can do some things that way, but, but not very much. I I think that's the part that's gonna seem the most amusing in, in in the future. You know, if you're asking me how long that's gonna take, I, I never give dates for anything because I don't know, you know, it depends on how the science goes. It depends on how the funding goes. I will say that what I think the field is, what I think is gonna be the watershed moment is the killer app. There's going to be pe people are already very ready to, to have this take off. Okay? People are are paying attention. The the, you know, this is, this is something that everybody's very interested in. What everybody's waiting for is very much like in, in, in computer science. You know, the first spreadsheet was a key, a watershed moment because for the first time, normal people realized what is this thing good for that, right? That the, that the techies were so excited about. Regular people could see, okay, now I understand why this is, this is important to me, so this is what it's waiting for. I think this field is looking for some sort of application. Maybe it's it's finger regeneration, maybe it's brain repair, maybe it's a cancer reprogramming. It's, it'll be one of these things that will be, that will become the flagship application where everybody will say, okay, now we see how this works. No doubt there are other ways to do things like it.

Michael Levin [00:29:30] And then from there on it should be, you know, it should be just an, an explosion of work. But

Vance Crowe [00:29:35] Yeah. It seems like you're kind of describing the hello world, right? Like the idea of, of the first time you send a message across, is there anybody that's not excited about this? Do you find anybody that's like, this is smoke and mirrors or anybody that is resistant to this idea as a scientific concept or, or medicine concept?

Michael Levin [00:29:53] Sure. There's, there's a few ways to be resistant to it. One way is, you know, kind of just the fact that there's only 24 hours in a day. So people who are not in this specific field, they are in, you know, they've, they are in let's say, you know, mainstream biomedicine or mainstream molecular biology. The attitude often is, I, I'll, I'll, I haven't read it, I don't know anything about it. I'll, I'll deal with it once it becomes, you know, mainstream, right? Whatever, whatever that means. And okay, fine, everybody has to make decisions about what they're gonna spend their time studying, you know, that's fine. That's a, that's a, that's a personal, that's a personal choice. So I think, I think that it's gonna be, it's, it's harder and harder to ignore this stuff. I mean, it's in very mainstream papers. It's in the textbook now, it's in the developmental biology textbook. We had a, we had a, a review and sell about it the last year. So it, it's out there, but, but again, some people just have never heard of it. I, I, I give talks and some people say that, you know, I, that that's, that's, that's amazing. But I've never heard of any of this stuff. How was, you know, how's that possible? There's another, there's another way to, to be skeptical about it. And that is this kind of mainstream assumption that the right level of explanation and interaction with living things has to be at the molecular level. So some people really love chemistry, and the idea is that everything of value should be done at the level of chemistry. And I've had this, I've had this happen where I give a talk.

Michael Levin [00:31:25] And so the first half of my talk is about bioelectricity, and this is, this is, it does, you know, we can do this and this and this. And then in the second half of the talk, I show the mechanism, I show how it works. So when the bioelectric pattern changes the cells, the decision has been made. Now that percolates down to the control of gene expression, to the movement of morphogen, to cell shape, to epigenetics, all this other stuff. And that's how it, and then, you know, people, people have said to me, I, I, I was really interested in the first half of the talk because it sounded amazing, but now that I see the mechanism underneath now, I don't care anymore. Now I just think, well, I can just go, I, I should just be targeting whatever stuff, whatever the underneath mechanisms are, right? And I, I I, I, I think that's, that's fundamentally mistaken in a couple of different ways. One, one way, one thing about it is that if you're disappointed to see the mechanism, something's really wrong. What did you think was gonna be under there? It wasn't gonna be magic. It was going to be chemistry or there's no, and physics, there's no getting around that. No, nobody said this was gonna be magic. So, so that's, that's the first thing to me. To me, knowing the mechanism is, is better. It doesn't remove the mist mystery. It makes the whole thing, it makes the whole thing more interesting. The second thing is that it neglects this, this, this neglects, this approach neglects the, the fact that, again, interacting with things at the lowest level is extremely difficult. So if you want to make an eye or a limb or something else, and you think you're going to control the tens of thousands of gene, the individual genes and, and, and, and millions of cells and everything else, maybe that's possible in some world at some point, that's gonna be something you can do.

Michael Levin [00:32:59] But why, why would you want to control it that way? It's like, it's like try, you know, it's like trying to program your computer by, by adjusting the electromagnetic fields. I mean, you could do that, I suppose, but, but, but you're missing the whole point of the device evolution has given you this amazing control system that is how the system actually makes information. Why wouldn't you interact with that? Right? And it sounds like reductionism, except it's not. People say, well, you should be more reductionist, you should go down. It's not really reductionism because they always stop at chemistry, you know, if you push them and you say, oh, so you want to do this in terms of quantum foam, I guess. And they say, no, no, no, that's stupid. No, chemistry is, is the way to go. So that's not really reductionism, that's just picking a level, you know, you have your favorite level and you're sort of stuck there. So lots of people now, you know, Dennis Noble has some beautiful work on there being no privileged level of causation and biology. And, and, and the most interesting work is actually the e Eric Hole. I don't know if you've talked to him or had him on your show, right? But he, he, he, he works. Wait,

Vance Crowe [00:34:01] The writer, the, the guy that wrote the revelations Eric Hall, correct? Oh, yeah, yeah, yeah. The podcast knows him well, he's great. Yeah,

Michael Levin [00:34:07] Yeah, yeah. He, yeah, he's amazing. And, and, and, and he, so, so he works at my center and we, we hired him specifically because he has this incredible work on causal emergence showing that, that you can now the question, the question of which level of description? Is it the atoms? Is it the molecules? Is it the, you know, tissues, whatever that used to be a philosophical question that people just had opinions about. No longer he, he actually produces a mathematical formalism where you can quantify with math, in other words, not, not not opinions, but, but you can actually calculate which layer does the most work. And it's not always the lowest layer that that problem has been solved. That was kind of, I, I, I'm amazed that, that, that more people are on fire about this. And I mean, some people are, but, but this should be more known. I think it's, it's incredibly profound.

Vance Crowe [00:34:53] And to restate that in a different way, to make sure I understand, it's to say, Hey, it's not that everything starts on the lowest base layer and is all controlled by that very simple kind of Stephen Wolfram new kind of science, like the, the on off. But that actually could be a middle out thing. It could be somewhere along the chain, somewhere between organs and the molecular level of the cell. It could be some other thing kicks off the, the cascade of reactions that have to happen. Is that right? That,

Michael Levin [00:35:23] That that's exactly right. That, that,

Vance Crowe [00:35:24] Basically

Michael Levin [00:35:24] What it says is that, is that when you are looking for a good answer to the question of what causes things, right? So, so something happened and, and you say, well, what caused that? And somebody will say, well, it, it, what, what caused it is this, this event right here. And then somebody will say, no, no, what really caused it is zoom, zoom down lower. It's when this electron zagged this way rather than this way. That's what really caused it. The other stuff is, is, is epiphenomenon. It's, it doesn't really exist, right? And so it's like, it's, it's very much like in, in the, in the wolf firm case, you know, when you have your, you have your cellular at Automata world, and you see these gliders, you know, in the game of life, they get these gliders. You could, you could be a skeptic about that. And you could say there are no gliders. All there are are individual cells in this world, right? They turn on, they, they light up or they don't light up, they don't even move. And there's no, there's no such thing as a glider. You're just, you're imagining that with your, with your wacky visual system. But the problem with that is, well, in that, in that world, that's a real problem. Because if you think that way, you won't be motivated to do things like, Hey, we can build a touring machine in that world out of gliders as as puffs, you know, puffs of information. You would never do that if you don't believe in gliders, right? So already we know that, that there's some benefits to be had about not being too much of a skeptic about these higher levels. But yeah,

Vance Crowe [00:36:40] Lemme interrupt you for a second. So for people that aren't familiar with Stephen Wolfram's work, he wrote a book called A New Kind of Science. And I would say one of the most awe inspiring experiences I've ever had of reading the first 100 pages of a book, is him describing that you can either, you can have this binary system, something is either on or off, and very simple rules. If there's on on, then the next one equals off, or the one below it does something else. And from this Wolfram proves that you can make fantastically in intricate and complex things from just this on off situation. And what you're describing is, yes, you can get down to the base layer and just say, Hey, are they on or off? And, and kind of what's that rule set all the way down at the base, but that Eric Hillel's work shows it. That's not necessarily just because you can observe those things happening all the way on that, on off the, the actual mechanism, why it's happening, what's occurring, what, how it's spreading out to other people, may not have started at the bottom, may have started in the middle, may have started higher up. What, whatever that means.

Michael Levin [00:37:49] That's, that's, that's correct. The, the best, the best answer to why is it happening is may not be, sometimes it is, but sometimes it's not. And, and Eric provides a way to calculate that. Sometimes that answer is at other levels. Now, you know, some people in the past, some people have, this was always treated, the people have been arguing about this for millennia. And so at one point it was treated as a philosophical thing. Somebody would just define it and it would say, look, all causes are causes at the bottom of physics. Everything else is fluff. Everything else is just epi, epi phenomenal. It's like a shadow. It's, it doesn't, it doesn't do anything, right? So, and that was an opinion, and that was a way to define you, you know, you could define causes this way, but what what's now clear is that if, if by cause you want something that is the most powerful control knob, right? You wanna know what is the, what is the leverage point for the system? What is the place where I can give the smallest amount of influence to get the most bang for my buck in terms of making things happen that may not be at the lowest level. And intuitively it was kind of obvious for a lot of things, but it was never mathematically tractable until, until Eric did it. So I,

Vance Crowe [00:38:57] And you can understand why a collection of thinkers over time, people doing the scientific method would want to say, let us just have an assumption. Whatever the lowest level you can measure it at, that's where the causation happens because it allows you to, to share some understanding. And when you come to the conclusion like, hey, it might be the base layer, but it might be somewhere in the middle or somewhere far higher. Now all of a sudden, rules can't be, can't be created. And it, it, i I imagine it makes people feel very uncomfortable. In fact, even for me, like you think about all the things that you think of that you, you base yourself on, causation starts from the base layer and goes out. If you don't have that, then what causes what becomes more complicated?

Michael Levin [00:39:43] I'm not sure I, you know, I don't know that I agree with that. I think I, it's, it's not, it never. Now keep in mind the thing isn't that you can't have rules. It's not, this is in no way saying that there aren't rules or that anything goes, or that the rules are somehow mysterious or not objective. It's not anything like that. It's just that what it, what it says is that the rule, the best rules might be at some sort of middle level. And frankly, if you think about it, everything we know about Daily life and, and and, and any kind of standard experience that we may have is all, all the questions of why did something happen? The answer is never because, because he, well, I'm gonna give you a long list of electrons. I've numbered them. See, and there's, you know, there's trillions of them. And because this one's zagged here and z one's that, that's why I, you know, I scratched myself or I ra you know, I walked over here why this thing fell down. It's never that. And, and I, I honestly, I don't know, I i, it, it never seemed that plausible to me at all intuitively, that that would have to be where all the best explanations were found. Now of course, there's some very smart people that that, that, you know, that do believe that. And, and so this has been something that, that everybody's argued about for a long time. But I don't, i I don't think it should make people more upset. I think it should make everybody happier that there's actually some, which doesn't always happen in science, where there is actually a, a, a, a a, a provable underlying, rigorous framework for the things that we always assume. You know, we kind of assume that there are reasons why we do things, not just because electron zig then Z, but because there are, there are actual reasons there, right?

Michael Levin [00:41:19] It's, it's, it's, I think, I think people should feel better that there's actually some, some support for that.

Vance Crowe [00:41:24] Well, it seems to fit, and correct me if I'm wrong on with the Richard Watson concepts about evolution, right? So he was saying, look, everybody knows survival of the fittest, you know, whichever one allows you to propagate your jeans the fastest, that's what survives. And it's always at the individual level. And he really kind of said, well, there may be induction going on here, there may be forces here that, that you have to reconcile in order to fully understand why nature played out the way that it did.

Michael Levin [00:41:51] Yeah. Yeah. Richard, Richard, I think has some very profound work. He's, he is his, his work is some of my favorite stuff hands down. There have been, there have been lots of people who have argued against lowest level selection being the only game in town. There, there have been lots of people, you know, who, who have given all various alternative accounts to that. But one thing that that's emerging from, from Richard, and, and you know, again, I I give the, the, the, the disclaimer that, you know, he and I worked together on some stuff. So, you know, I'm not exactly un unbiased, but, but I think that, I think that part of what's very powerful about it is that he connects in a very rigorous way, concepts from, from machine learning, which basically is just the logic of how learning happens. The, the, the thing, the thing about machine learning unlike, unlike learning in, in bi you know, studying learning in biology, is that you're not tied to a specific material or a specific implementation. It's not about synapsis necessarily. And it's not about synaptic proteins and various, you know, other mechanisms that are thought to be at play during learning. It's about generic, almost a cybernetic approach. It's like, okay, what's the, nevermind the material, what's really at the bottom of learning? What does it mean for, for, for something to learn regardless of what it's made of? Right? It's so, you know, it's, it's not about, it's not about what the material is. It's about what is essential about learning. And so, so, so he takes those kind of concepts for machine learning and analyzes the evolutionary process to say, when evolution, the course of evolution produces complex systems with specific properties, they're made of parts, the parts are working together, they seem to be goal directed.

Michael Levin [00:43:25] They're doing all these interesting things. What has that process learned, if anything, and how does it learn? And he has some really interesting models, and I mean, he, he's, you know, he is much better to tell you all the details, but, but basically this idea of how different dynamics of not, not just selection, I mean, selecting among variants is great, but first you gotta get those variants, right? If your variants don't include any of the, of the interesting things you want, selection's not going to do the, that job for you. So you need both parts. You need the, you need, you need a very rich source of potential complexity. And then, and then you have section has something to act on. So, so Richard has some, some great ideas about natural induction and the way that, that, that evolutionary process learns regularities, it learns patterns in the environment, you know, every, every creature is, is in effect a hypothesis. Every creature is a hypothesis about the environment and about good ways to, so you can think about this, this is, this is interesting. We are, we're, we're very good at noticing agency in medium-sized things, moving around in the world at medium speeds, right? So, so that's, that's all of our experiences for children. We have some, some, some sense organs. We sort of look around and you understand, okay, that's a bowling ball and there's only certain things that's gonna do, that's a cat that's gonna do a lot of different stuff in different ways that you, you can't use the same rules to understand what it's going to do that you can for the bowling ball, okay? We are really not very good at looking for that kind of agency in really diverse novel embodiments.

Michael Levin [00:44:59] So one thing you might imagine is look at a whole lineage, let's say, you know, 50 million years of some reptile or something. That whole lineage, you can imagine that as a single agent making decisions and testing hypotheses about the environment, every individual of that giant lineage is one hypothesis. And when I say hypothesis, I mean in, in like, like the Fri Carl Friston sort of active inference way, right? You, you hypothesis about what the, what's gonna be successful in the environment, what's gonna work. And those hypotheses are rejected or, or supported by their interactions with the environment. And if you're a terrible reptile, that hypothesis is going away. And if you're a great one, that gets, gets propagated into the next one. It's a, it's a, it's a, you can think of that whole system as a, as a primitive hypothesis generating and testing machine, as our brains do all day long to make sense or, or you know, of the world around us.

Vance Crowe [00:45:55] That is nothing short of mind blowing. I mean, to think of them as just one continuous string is very hard to, to initially come to that idea because your individual experiences, I came from parents, I'm gonna leave children, this is my finite experience. But to imagine yourself as a part of a longer chain,

Michael Levin [00:46:14] You have to, we have to try because, because our, our, the experience that you're talking about now, where we are, this self-contained creature is, is just one perspective. It happens to be the perspective largely of our left hemisphere and, you know, and verbalized in the way that the left hemispheres can verbalize things. But that's not the only perspective. And we need to be, at least in the scientific realm, we need to be, we need to get better at recognizing other useful perspectives. You can, you can imagine this very easily, for example, shrinking down, imagine shrinking down to the size of a single cell inside a fish embryo, for example. And you're looking around and you're seeing all the noise. There are cells being born, cells dying, cells moving. Everything is noisy. You know, there's interference coming from all sorts of things. The, the chemical gradients are, you know, not very sharp and so on. If you didn't already know what embryonic development was, never in a million years would you be able to say that, oh, I, I know what's gonna happen every single time. This whole mess that I'm looking at, this is gonna turn into a fish. You would never be able to say that from that perspective. You just wouldn't, you wouldn't be able to see it. And, and we as tiny agents with very short lifespans, very, very small sensory, you know, radius, we, we find it very difficult to think about what is it like to be an evolutionary lineage lasting millions of years. We, it's, it's like if you were shrunk down, it's, it's, we're missing the same amount of reality as you would if you were to shrink down inside an embryo, you, you wouldn't see any of it.

Michael Levin [00:47:44] So our specific scale, size and composition gives us blinders where we're good at noticing certain things, we're terrible at noticing other things. So that's, that's one, one thing I like, you know, in this, in this field is to try to basically, it's, it's a search for symmetry. It's, you know, twist all the knobs and see what happens when you leave certain things the same, but then you radically change other things. Can you still Right what looks the same, right? What looks the same under that transformation? And I think thinking of evolution that way as a learning agent, even though it's, it's, it's a weird learning agent because it's super large and it's super like long lasting and the pieces aren't stuck together the way that our neurons are, you know, it's something that required Soleil would call a liquid brains, you know, he has a phrase for this. Liquid brains, meaning the pieces of it are moving around relative to each other. Our brains are solid, right? But, but an and colony is a kinda liquid brain, right? Everything's moving. So thinking, thinking about things in that way, I think is, is, is is very helpful.

Vance Crowe [00:48:40] Yeah. I mean it also kinda gives you the perspective of, we think of the universe right around us. It's maybe it's so large that it's that it's not dissimilar from trying to shrink yourself down to being in the embryonic cell. It's just so much bigger that you can't gain context in order to be able to understand it. Yeah.

Michael Levin [00:48:57] Not only, not only is it, it's, it's absolutely there's a size, but there's some, there's something else too, which is different problem spaces. So, so again, let's go back to the fact that since, since we're born, all of our sensor organs point outwards basically at the three-dimensional world. So we're good at understanding movement in three-dimensional world. When, you know, when, when, when a, when a when an ape is using a tool to open a lock or he goes and bury some stuff and then picks it up later, we say, ah, that's intelligence. I see it, you know, you're solving a problem we're very good at that in the three dimensional world. Imagine if we were born with a, like a, like a biofeedback sense that was, that allowed you at every moment to consciously sense what your pancreas was doing, for example, or your liver. So if you knew exactly what that organ was doing at every, at any moment in time, and you could feel, oh man, you know, the potassium level just spiked, but no worries. My, you know, my, my, my, my, my liver took care of that. You would have no problem recognizing intelligent behavior in physiological space. It's not an issue of size. It's a completely different space. It's not the space of three dimensions. It's the space of different physiological states. What are your, you know, however many, I mean, there's probably hundreds, but, or thousands, but, but, you know, potassium, sodium, all the different things that that, that your organs are, are, are managing form an action space. And the other way to think about this, and this is gonna sound really weird, but, but I think it's a useful way to think about it. You can, the way we have robots that move in three dimensional space to do simple tasks and make decisions, you can have robots that move in other spaces, for example, physiological spaces.

Michael Levin [00:50:30] What's a robot that moves in physiological space? Well, imagine an insulin pump. An insulin pump or a, or a pacemaker or something that's there. Now, those are very simple robots. They generally just do, for now they just mostly do the same thing all the time. But, you know, 20 years from now, we are going to have implants that are measuring all kinds of, you know, all kinds of parameters, making decisions about what to do, and then readjusting their position in state space. So if now, if currently my potassium is too low and I'm down here and I take an action to rise it, I've now moved up along the axis, along the potassium axis in my physiological space, right? So there are these other spaces. We live in them, we don't know how to visualize them, for sure. And we're very bad at recognizing intelligence in those spaces. We don't know what it looks like. This is why people feel very uncomfortable when I say, your body organs have a kind of intelligence and they think, oh my God, this, you know, this is just crazy. We're making stuff up. And it's not about any kind of magic and mystery. It's about recognizing that they solve problems in spaces other than three dimensional space. And we, we have devices that do it now. It's, you know, it's not, it's not, it's not magic. It's, but we have to, we have to get better at, at being able to think about these things.

Vance Crowe [00:51:45] Yeah. And there's something in there that kind of helps you rethink the, the will of, of beings, right? I you imagine the, the grass that has bioreactor, right? The, the turf, that somehow it's measuring that there's something not correct with the soil. So it's gonna move from one direction to another. But that, if you can understand that there are other things that beings could react to on different timescales at different, you know, size scales, then your ability to recognize something, what we were talking about in the first interview we did together. Like, what has a will? What is, what is alive? What, you know, and and what responsibility does that impute on you if you recognize that other beings can be driven by things that you don't even have access to, to understanding that you could be driven by those things.

Michael Levin [00:52:32] Very, very much so. And, and the, the way I like to think about this is o oftentimes you can have, you can have a very simple thing, whether it be a paramecium or a bacterium or a, or a thermostat or something, and you see that it has gold directed activity, meaning it expands energy to achieve a certain state of affairs. Even when you sort of push it and deviate it off, it still tries to, and that, that would be in, in three dimensional space, in physiological space and so on. And, and I, and, and, you know, and I'll say something like, okay, so that's a, that's a tiny bit of, of, of will. There, that thing has a pre, it has an actual preference, it has goals and so on. And people say, that's crazy. You're mis you're misusing the, the terminology. You can't, you can't use those terms for these simple things. Start backwards. Start, start with an, with an uncontroversial example of those things. Let's say a human right. Now, there's some people that, that, that claim that humans don't have them either. Let's put that aside. I don't, I don't really know what, what to do with that. So let's, let's, let's assume that, that, that you and I sitting here have whatever, whatever pres preferences, goals, what, whatever those things are, we have them, okay? In some sense. And now, now that, now that you've sort of fixed the right end of that spectrum, and you know that's real, just work backwards. Just go backwards in two ways. Go backwards in evolutionary time and say that, well, here's some primitive humans and here's some non-human, the hominids. And then here are some, you know, here, here are some mammals before that. And here, just work it all the way back until you get to bacteria. And the one thing you won't find anywhere is that magical, bright, as, as, as Dan Dena calls it, a bright red line.

Michael Levin [00:54:06] You're not gonna find this crisp moment where, ah, that's where it kicked in. Right? There is no such thing. Biology offers no support for a, any idea that there's somewhere, there's this, there's this clean line after which, so you had some parents that didn't have any of that stuff. They were sort of just physics as people like to say, and then they had an offspring. And bam, that offspring now has true cognition. True, you know, true memory that that never happened. And so, so every every every individual had parents that were pretty much like itself. So the whole process is very smooth. So there is no place where you can say that, that this kind of thing just sort of came into the world. And if that's true, then you have no way of saying that, that, that these very minimal systems, 'cause you go, you're going all the way back to bacteria if you want go back for before that. And you know now that from, from that simple thought experiment, you know, that there will have to be minimal systems that look like physics. They look like they're just physics, but they already have some degree of preferences. They'd rather this happened than that happened. They have, they can make decisions, they can have memories. It has to be true because there's no break in this continuum, right? It, you know, pres scientifically, if you thought that, if you thought that, you know, God sort of created the stuff the way it is, you could be, you could think that way. That, that we are radically different. That's, that's gone. That that worldview is gone. And we have to now understand that we are a chain of, of, of connected evolutionary steps all the way back to the most primitive, the most basal systems.

Michael Levin [00:55:37] And if we have it, then so did they, in a much smaller degree. It's just a matter of in, you know, in, in inflating these things. The other thing to think about is on a much smaller timescale is where we came from. So here you are, you and I are sitting here and we have, you know, true, true preferences and motivations and memories and, and everything else. Well, some number of years ago, we were one cell, we were a fertilized egg. And that fertilized egg, that somebody could look at it and say, well, that's, well, that's just a bunch of chemistry. I mean, the molecular biology tells us everything you need to know about that, that, that, that there's a system doing all the basic physics and, and we can calculate all, all, you know, everything that's going on in there. There's no, there's no preferences in there. There's no memory, you know, there, there's no cognition. It's just, it's just physics. Okay? But nine months later, and you know, sometime thereafter, now there is there, there's no, you know, biology offers no spot where that suddenly clicks on. So we all took the journey, all of us took that, it's that journey across this Cartesian cut that goes from just physics to cognition and, and, and consciousness and whatever else you have. It's a smooth journey. It takes a long time. It's a, it's a step-by-step thing. There are no breaks in this process, so, so all the way down. So, so that to me suggests that you have to, to the

Vance Crowe [00:56:50] Extent that these things

Michael Levin [00:56:51] Exist at all, they go all the way down.

Vance Crowe [00:56:53] It's interesting when you start thinking about that level and going all the way back. At some point in time you had single celled organisms, you know, and then somehow they combined to then make, you know, the, just the mitochondria, right? Once, once that has existed, and now it can have DNA and it can pass down and it becomes multicellular and then organs and all of these things. At some point there was a jump from chemistry to biology. And in your world, that jump is some kind of electricity being added or some, some sort of energy being added that stimulates that. First of all, is that a, a correct characterization?

Michael Levin [00:57:31] Well, two things. I, I, I would say two things. One is, I, I don't believe in chemistry and biology and almost anything else as sharp categories that really exist. These are labels. We paint onto things we can, you know, if you wanted to, if you had a human brain and you wanted to treat it as with physics, you certainly can. It's a great paperweight. And you can know exactly how much, like, like what kind of a wind it would, you know, you can use it to prevent papers from flying away and what forced winds. Yeah, that's fine. That's all true. It's not, not true. It's, it's, it's a lens through which you can view this object. You can look at it through chemistry, right? And you can find out, you know, you can dissolve it and find out what the components are. And you could treat it with biology, you could treat it with a psychology. You could say all of those things may be true. But what I'm really interested in is why is it so anxious all the time? Or why is it, you know, how is it that, that it knows how to get, you know, how to calculate prime numbers or, you know, why does it care about the, the, the, you know, the, the, the, the poor or the, you know, whatever there are levels. All of these are different lenses that we used to look at these objects. So, so I think we have to be careful to imagine that it something really objectively crosses from physics to biology. Like that's a tough, you know, that, that, that's you. We gotta be careful about that.

Vance Crowe [00:58:49] Well let, okay, so let me, let's probe on this before we go further. So, at some point, this earth that we have was, you know, a massive rock and water. And I think we could probably agree there was some point in time where there was what we consider to be life, you know, was, was not here, right? It was, it was inanimate in some way. And at some point there was a jump from this inanimate self-organizing thing with will that, that like kickstarted. And then once the kickstart begins, then you can have something where the, the, the energy laden object, the thing that has, has its own kind of circle that once the, the circuit is cut, then it, it's no longer exists. So it starts taking some of those chemicals that were toxic to us and converting them into, let's say oxygen. And we get enough oxygen around and more things can be built off of that. When you think about that energy jump, do you have a name for that? Is there a, like, is there a, i it's hard for me to even formulate this question.

Michael Levin [00:59:52] I, I think it is a hard, it's a hard question. People have dealt with it before. I don't have a name for it.

Vance Crowe [01:00:01] The people you know better

Michael Levin [01:00:03] Than me have, have addressed this, this issue. I will say that, I'm not sure. I'm not sure it's a jump. I have a feeling it's a crawl. I think that there are in between, you know, people talk about Phase transitions and these ideas that there are really sharp jumps that, that may be, and there certainly are is such a thing as phase transitions. I think the, the burden is on them at that point to show that it's a sharp transition. I, I, I think sharp transitions, transitions are very rare. So I think it's probably, you know, some kind of a crawl that, that produces a, a new plateau. I don't think it's bioelectricity per se, because there isn't, there isn't anything fundamentally magical about bioelectricity. Bioelectricity is a really convenient piece of physics that you can use to do things like compute store memory, organize information across distance. Like an evolution picked up on this immediately around the time of bacterial biofilms. Evolution noticed that that was, that was true. I don't think that's because electricity is in some way, you know, unique. I'm sure there are other ways of doing this, and there may be, you know, planets out there where things could go on in other, in other ways. It just happens to be, I think, the best example we have, right? And it's the one that, that makes it most clear to see how, how stuff like that has happened. But I, I don't have a ton of thoughts on what was going on before cells were cells. You know, other, other people have done a lot more study on that. Most of the things that I can talk about really begin, begin after you've got bacteria and, and you know, sort of you've already got individual cells.

Michael Levin [01:01:41] I don't know. Yeah, I don't, I don't have anything super, to

Vance Crowe [01:01:44] Me, this is a profound, I don't know pattern in you, right? There's one of the best pieces of advice I ever got from a scientist. I was working in agriculture and he said, Hey, the most important thing you can do is not fall in love with your work, right? As soon as you fall in love with it, then all of a sudden you start building a relationship with concepts that don't, don't help you. And it's, it's interesting because your bioelectricity the, you know, the fact that you are pretty high up on the mountain peak of the bioelectricity world, it would be very easy for you to fall in love with this thing and say, ah, this is the key insight or the key stroke that other people haven't found. So to me, it, it enunciates some form of humility that I think is good for you and good for the field, but is also very rare.

Michael Levin [01:02:34] Well, I, I, I would be lying if I said I wasn't in love with bioelectricity. Okay? I, I probably, I probably am. I think, I think it's fantastic. I, I love, I think about it all day long every day, but basically, but, but I, but I, but I think you're right in that we always have to be very careful of asking about what is the essence of things? What is in any particular scenario, what is fundamental and what is contingent or just, you know, sort of, it just happens to be, and I, I I, when I was, when I was young, I did a lot of studies of various, and in fact, and I, I met a lot of people who were, they were, they were pioneers in various areas and Right e either, you know, either rightly or wrongly. But, but they had a particular view and the one particular thing they were digging, and, and one thing that, that I noticed was exactly what you just said, which is that they would use that lens for everything, right? Everything, you know, once you, once you like, you know, a certain thing, oh man, you start, you start to see it everywhere, right? It's, it's a, you know, you just interpret it that way and, and this idea that, you know, if, if, if once you have a hammer, then everything looks like a nail. I mean, part partly that's, that's good because that, that enables you to use the tools you have. And I'm, and I'm the first person to take concepts from one area and ask, okay, well where else does this apply? Right? So I'm, I'm all for that. But I do think that it's very important to ask what is fundamental and what's not. And so when I look at bioelectricity, yeah, I ask myself, what, what is fundamental about this?

Michael Levin [01:04:04] And there are certain features of it that are really cool and really convenient and, and, and really instructive for us. But they're not, they're not the answer to everything. And, and it's important to kind of, you know, keep, keep, keep that in mind.

Vance Crowe [01:04:19] So it's actually kind of funny, I I, I, as I'm hearing you describe these things and you push back on some of my like, categorization things, I find myself getting frustrated, which I think probably is something that you have to deal with in your life. Where we talked about this during the first interview, it's much easier to have conversations with people where the categories are simple. We can just decide that this is where things fit. Because I'm thinking back on my interview with Lee Cronin and the realization that he was saying, Hey, I'm trying to create life from chemistry, so I'm trying to jump some Gulf. And it seems to me that when we look at the world from Lee Cronin's perspective, this is an entirely accurate and, and valuable paradigm to look through.

Michael Levin [01:05:02] Absolutely.

Vance Crowe [01:05:02] And then, and then we come from yours and we say, no, no, that, that doesn't work. That doesn't help us. Talk to me a little bit about, about this like, difficulty here.

Michael Levin [01:05:11] Yeah. Well, I, the, the, I certainly am not claiming that, that that view is not helping us. It's certainly helping Lee do good science, so that that's fine. More generally, I think that a lot of the things that we talk about are specific lenses that we use to view the world. We all cut up the world differently. Many of them are useful. There's not, I'm, I never claim that there's only one useful way to look at things. What I do insist on is that in, in choosing between them, we should be humble and let go of our armchair preconceptions about what the best lenses ought to be. That, that, you know, lots of people here and they say, that can't be right. And I, and I say, well, what experiments have you done to decide that that's not right? He, it just doesn't sound right and say, okay, well now, now we've left the realm of, of the realm of science. So, so, you know, I I most of the time use a different lens on this than Lee does. But that's perfectly fine because it helps him do the experiments that he needs to do, which he wouldn't have done with my lens, and I wouldn't have done the experiments that I have done with his lens. And I, I think there are many lenses that are all compatible with this. Some, some need to go. I've seen some that have been used for years, and I think, I really think they're holding us back more than they're helping us at this point. But, but nothing I say is supposed to mean that there's just one right way to look at this. And, and, and, and, you know, and here's, and here it is, and I've got it and, and everybody else is wrong. That's, I just think that's, that's not the right way to look at it.

Vance Crowe [01:06:44] So if you try and think of, imagine a world in which bioelectricity is not critical to what you're saying, you know, that, that there's an alien civilization that somehow is transcending just basic chemistry to be able to propagate itself.

Michael Levin [01:06:58] What else

Vance Crowe [01:06:59] Could there be?

Michael Levin [01:07:00] Wow. Well, now, now you're asking me to compete with the science fiction of, of many of many decades, which, which I certainly wouldn't, wouldn't try to do, but okay, let's, let's, we can, we can, we can try it. Let's, let's just ask ourselves what do we think the bioelectricity is, is really letting us do here in biology, one of the things that I think it's letting us do is scale up tiny homeostatic. So, so I think the primitive atom of all of this stuff is the most basic homeostatic loop. And what I mean by homeostatic loop is something that your thermostat does, which is take a measurement of something, compare it to a very simple memory that it has of whether it's right or wrong, and then take action to try and get closer if, if, if the measurement is not right to get close, right? So your thermostat will heat or cool depending on where you are relative to the set point. Okay? Now, this is part of why I don't spend too much time talking about the origin of life, because you have to have gotten to the point where you even have homeostatic loops, and I don't have a lot of great ideas about how you got there. That's, you know, I'm gonna leave that, leave that for, for, for other people to, to, to work on that. But, but these homeostatic loops are already there in simple chemical systems for sure. They're there by the time you get to bacteria. So, so we're, we're pretty well back. Okay? So what the bioelectricity allows you to do is to take these homeostatic loops and connect them together so that, whereas individual loops are now, to me, once you have a homeostatic loop, you are a goal seeking system. So your thermostat, and I know some people are gonna gonna hate this kind of talk, but, but, but I'm gonna say it because I think, I think there's no way around it.

Michael Levin [01:08:36] Your, your thermostat has a little tiny nano preference about what the temperature should be. Okay? It has a true preference, same as you do, just really tiny and really simple. And that preference is that the temperature has to be in this, in, in such and such a range. That is a very simple number. It's, it's only measured right around, right at where wherever the thermometer, you know, thermocouple ha happens to be. So the goal that this thing is pursuing is tiny. It's very, it's physically very small. Bacteria are the same way. They are. If you, if you got a ER that is trying to climb up a sugar concentration, it's measuring the concentration of sugar and it wants more. That's it. And, and it, that, that's all it can do though. These are really humble little, little, little tiny goals. What bioelectricity allows you to do is to take a bunch of cells that can do that and connect them into a network where the, the things that it measures, the set points and the actions that take all that, that it takes to, to implement that set point. All of these things become larger and larger. So once you have a bunch of cells connected with an electrical network, when they take a measure, when every cell takes a measurement, it's not just a measurement of going on what's going on at that particular cell. It includes information from all the other electrically connected cells, which could be a huge tissue. So now what you're now measuring is something like the length of a finger or the, the, you know, the distance from the brain or the, these, these massive quantities that don't exist for single cells, right? So it's a, it's a huge IQ boost by connecting electrically to other cells, you're becoming this much more complex creature that can measure giant things, that can store memories of things like, here's what the face is supposed to look like.

Michael Levin [01:10:10] No individual cell can, can remember that, but the, but a huge network of a tissue, a huge eum tissue can. And so that connectivity, that electrical connectivity, allows you to scale your memory, to scale your iq, to scale your goals, and to scale your stresses, the things that you could possibly be stressed by. Right? That's a, that's a real good mark of the intell of the agency or intellectual level of a system is what are the things that stress you out? You know, is it just the local level of sugar and you're probably a bacterium? Is it, you know, is it the what the, what the economical system is gonna be like on earth a hundred years from now? You're probably a human is, you know, and, and everywhere and everywhere in between, right? What is the, what is the scale of things that, so to get back to your question, right? So, so bioelectricity is not the only thing that can do that. So I suppose if I wanted to be, you know, in sci-fi, and I'm sure people have have done this, I could come up with some kind of a thing where these little homeostatic loops are some sort of, you know, crazy exotic chemistry happening in a space cloud somewhere. And where the connections between them are magnetic fluxes and not electricity at all, or radiation, or I don't know what the hell they could be. It could be anything as long as it allows you to, to scale the set points of your homeostatic system. So,

Vance Crowe [01:11:28] So

Michael Levin [01:11:28] In

Vance Crowe [01:11:28] This set point, really, it sounds to me like you're describing in order to be alive, you have to have memory in some way. You have to have something that allows you to say memory. And maybe that's not the right way to describe it, but is, is life memory.

Michael Levin [01:11:45] I, I'm, I'm gonna agree with the second portion. I think, I think memory is absolutely essential. I think if you don't have memory, you don't have any of the things that we're interested in when we talk about this stuff. I, I, I will say with the respect to the word life, it's one of the things I almost never really talk about because I'm not sure I, I don't have a good definition for it. I'll, I'll leave that one to Lee and Sarah Walker and, and people who like actually talk about what life is. I have no clue. I, I don't know if it's a, you know, how you, to to, to most of the stuff that I work on, it's, no, it doesn't do a, it doesn't carry a lot of water. It, it just doesn't do anything for us. We never ask whether things are alive or how, I'm not sure. I'm, I'm, I'm sure there are other reasons to have that concept. I'm much more interested in the concept of cognition. And if you ask me what the Venn diagram would look like between cognitive and living systems, I would say I, I'm not sure what life is, but, but I'm interested in cognitive systems. And a lot of them you might not say are alive because I'm sure a lot of them will not look living. They'll be either look like weird physics or, or computer software or something else that doesn't look alive to you. I just don't know what to do with the whole li life label. I don't know what it does for us. But cognition, I, I do know what to do with, and that memory is absolutely bedrock for that. That is, that is, that is fundamental to, to cognition.

Vance Crowe [01:13:05] I, and this is just the amateur observation, but I would imagine by the end of your career, you will likely have to grapple with life at, at some, at some definitional level. If, if only, because that seems the universe is punishing in that way, right? Things are circle.

Michael Levin [01:13:20] It could be. It could be. And if we need to, we will. But it could also be that we find out

Vance Crowe [01:13:27] That

Michael Levin [01:13:28] It isn't a great term that helps us out too much. You know,

Vance Crowe [01:13:35] So when I, Yosha Bach came on a couple weeks ago, we had a really good discussion about science fiction books. So he rapped about Dune and the three Body problem and what was the last one? Something by asthma foundation. And this has really got me thinking about the science fiction books that kind of kick open the door for individuals, particularly people that are in the sciences, but people that are doing, you know, just bigger thinking.

Michael Levin [01:14:00] Yeah.

Vance Crowe [01:14:00] Do you recall science fiction books of your past, of your childhood that really kicked open a door for you?

Michael Levin [01:14:06] Yeah, yeah. I'm gonna, I'm gonna pick one. And, and I, I'm, I'm terrible about remembering specific instances of this stuff. I, I read a lot of sci-fi as a kid. I mean, I probably, you know, read almost everything that, that, that, that is well known.

Vance Crowe [01:14:19] I believe that yeah.

Michael Levin [01:14:20] Including, including, you know, including a lot of the old Russian stuff that may or may not be widely, you know, widely disseminated. I don't know. But the thing, the thing that, that really

Vance Crowe [01:14:30] Goes

Michael Levin [01:14:31] With, and it's probably time to reread all that stuff, but it's the, the Siberia by Stanislau le So he is a Polish, he is a Polish writer. It is, it is amazing stuff. It's, it's very much like, it's, it's very humorous. It's a little bit like the most, the most modern thing, it might be similar to is like Futurama kind of, it's like, it's full of just crazy creatures that break. He, he breaks every category that, that you could think of is broken in terms of what the ca who the characters are and what they're up to and what their worlds look like. But at the same time, it has, you know, there's a lot of the same kind of drives and there's, you know, people are, you know, fighting and arguing about things and whatever. But, but it, that to me was incredibly mind opening because it just, it just like, like I was saying before, it twisted all the knobs in terms of here's a schema, here's, you know, two creatures in this kind of particular relationship. Now I'm gonna take one of them and I'm gonna, I'm, I'm just gonna say, okay. And, and, and this one is, is is, you know, ma made, made of a mailbox that sends mail for its, you know, instead of its, you know, signaling the dynamics and it's just super slow. I mean, I'm making that up. I don't think that was an actual story of his, but you get that. You, you just sort of twist all the knobs and you say, well, now what happens? And to me that was, I, I, yeah, I'll never forget, I'll never forget that. I think that that's, that's some of my favorite stuff. He has lots of, lots of short stories as well as some, some novels.

Vance Crowe [01:15:57] I'll, I'll put a link to that in the show notes. 'cause I, yeah, you know, I'm, I run this Lindy book

Michael Levin [01:16:01] Club

Vance Crowe [01:16:01] And we try and read books that are 30 years or older and, and really when we call it Lindy, really what we're just saying is like, we want books that have stood some test of time. Yeah. That they'll be around in the future. And the science fiction genre seems to be, there's a sorting mechanism there, right? There are some people that can handle the fantasy aspect of it, and there's some people that absolutely can't. But, but it's been a, I think the science fiction are my favorite kind to do in book club. When you read a book, because you are a prolific reader, it appears so if you look at your Twitter feed, if you look in your, you know, your background right now is filled with books. What is your experience of reading books? Are you, describe what's going on in your brain as you pick open a book and you're reading it?

Michael Levin [01:16:50] I, I, I generally, the way, the way my brain works is I try to squeeze gen i I try to squeeze deep upshots out of everything to the point where, so, so I'm reading something, I'm like, okay, that's what the actual example is. What, what, what is that really telling me? What's the, what's the deep message behind this? Right? What, what, you know, what does this apply to more, more broadly than to whatever it is that it's about to the point where I could read, I could read a whole novel and not be able to tell you what the name of the main character is at the end. Because, because I don't, I don't internalize details like that. Now, now, now, that's not to say that's not important, right? The, the author might've spent, you know, months wrangling over what the name should be, and I probably missed it. And, you know, that's, that's, that's, that's just me. But, but I'm not very good at retaining details that don't seem like they're fundamental. This, this was, this was a killer to me in school when, you know, a lot of the smart kids were like sponges. They would read something, they would just, you know, they would just remember everything there is about it. I would remember nothing, none, none of the details at all. I, I do, you know, do really badly on, on, on tests in high school and things like that because I, I just couldn't remember any of the details because when I read, I, I, I, I sift and I try to, and I say, is this something worth, you know, sort of storing up there? And if it's not, it's gone. And at the end, I, I could tell you what I think, what, what it did for me and what I think the main message was, but I won't be able to remember any of the details. That's just, you know.

Vance Crowe [01:18:21] Yeah. I, I, as I've thought about this question, you know, my reading is probably, it takes me about, I don't know, maybe 30 seconds to a minute and a half to stop seeing the words. And then I'm just kind of in an imagination place. And I, I recognize that this is like a great gift that the, that the, the universe gave me. But I, like you, I can't see the faces on the character. I can't any of the extraneous details, they're just

Michael Levin [01:18:45] Right. They're just gone.

Vance Crowe [01:18:46] I do

Michael Levin [01:18:47] That. Yeah.

Vance Crowe [01:18:47] So you might have spent a long time describing, you know, the, the flowing gowns, but unless it has something to do with the motivation of that character, and I, I can find, like I can tell you about the deep, deep motivations, even stuff that I'm imputing that, that the author didn't. But you're, I find it very similar to you. There's a whole bunch of stuff. I just don't care about it. I wanna know about, you know, did the time that elapsed matter to the way they feel about something? Not how much time elapsed. Yeah,

Michael Levin [01:19:15] I, yeah. Yeah. And, and there's other, and I think, you know, I think people Do this in different ways. Everybody's got slightly different cognitive systems. My wife will often say to me during about a show or a book or something, you know, well, who do you imagine yourself? Which, which of the characters do you see yourself as? I'm like, I don't even begin to answer that question. I have no idea what you're talking about, because I don't, I I never see myself in this. I'm not in a story. I'm, I'm out here trying to, you know, squeeze this thing for all it's worth in terms of what I'm supposed to take away from it. I don't see myself in any of these things watching, you know, watching shows or, or, you know, reading.

Vance Crowe [01:19:49] Yeah, you and I are remarkably similar there. The, the, the other thing, if I'm watching a movie, I care so much more about like, how it was framed and why did they do it from that corner or that side, or that whatever. It's, it's, my wife finds watching movies to meet with me to be the most like grading experience, because I'll be like, I wonder why they're making the camera shake that much. Do you really think that adds to the, to the, but to me it's all about the, i I think over time I'm coming to the realization that perspective and motivations are really what matter to me. It's why Eric Well's books, which are really all theory of mind, right? It's about dropping into the minds of other people. And his explanations around that were so profound to me because that he's like writing the kind of book that allows me to just sail through a book as opposed to like, fighting with all of these other characteristics.

Michael Levin [01:20:37] Yeah. Yep.

Vance Crowe [01:20:39] Well, Michael Levin, this has been a wonderful conversation. I'm so glad you decided to come back on. As always. I, I want people, if they wanna learn more about your work, the, particularly in Electroceuticals and some of your mouse projects, if they wanted to look into that more, where would they go?

Michael Levin [01:20:56] Everything's on our website. So the lab, the academic lab website is dr mike eleven.org. You can also find me on Twitter at, at dr mic 11. Our companies have various sites as well, but that's, that, that's all linked to the main j Just go to the main website and you can find everything.

Vance Crowe [01:21:14] Yeah. And I guess just to finish, I would give a huge shout out for your Twitter feed. It is nothing but positive energy coming out that it's, it's excerpts from books you found little, like the inside title covers. And I mean, I really, really like your Twitter and whatever you're doing there, man, just keep doing it.

Michael Levin [01:21:30] Cool. Thank you. Thanks so much. Yeah, I, I started Twitter a, a while back, not having any idea what it is. I was very skeptical about it. I don't use social media generally. I don't do Facebook, I don't do any of that stuff. And I thought, okay, here's another one of these, you know, kind of useless things. And I started, but then I, I noticed

Vance Crowe [01:21:46] Actually that

Michael Levin [01:21:47] It's an amazing, I, I, I find, I find an, the, the community that, that follows me is an amazing source of information. I find papers there that I have never seen before. I post questions all the time. Scientific questions that people come back to, you know, with, to me, with, with specific ideas. It's amazing. I find it super useful. And yeah, at this point, you know, I, I, I am just, I'm going down the shelves left to right, and I tweet a book a day among, among the other, oh,

Vance Crowe [01:22:12] Is that how that's going? I, that's

Michael Levin [01:22:14] All that is.

Vance Crowe [01:22:15] I was like, my God, how does he read this much? Like how Read No, no, no, no, not like

Michael Levin [01:22:19] That. Yeah, I, no, no, no. I, at this point, I, at this point, I read, I have to read mostly papers. This is all, this is all past reading. I'm, I'm not reading any of this stuff now. So this is all, you know, we're talking early eighties onwards, right? These are things that I've had since childhood, basically. And so I'm just going left to right along the shelves, one, one per day, and I do the inside cover and the table of contents. That's all. It's,

Vance Crowe [01:22:40] Well keep doing it. It's, it's a breath of, of warm leather bound air or something. I really like it.

Michael Levin [01:22:47] I love it. I love it. That's very poetic. Thank you. That's great. Thank you for the conversation. It was really good to see you. Thank

Vance Crowe [01:22:51] You, Michael.