Into the Impossible With Brian Keating - Could Biological Robots Heal Us from the Inside? | Michael Levin

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Starting point is 00:01:00 You know, we like to think we understand what makes something a lot. DNA, evolution, natural selection, the usual suspects. But what if I told you that cells from your own trachea, sitting in a petri dish right now, could spontaneously organize into swimming robots that heal brain tissue? What if frog skin cells, with no genetic modification whatsoever, could build copies of themselves from spare parts lying around? This isn't science fiction.

Starting point is 00:01:20 This is the work of Michael Levin at Tufts University, and it's completely rewriting the rules of biology. So we took cells from adult human patients, tracheal epithelial cells. Turns out that they too come together and form these little motile creatures. We call them anthrobatts. Those guys have 9,000 differently expressed genes, and they can do cool things like they can heal neural wounds.

Starting point is 00:01:39 This is just the tip of the iceberg. Michael Evans' research challenges our fundamental understanding of what life is and where biological properties emerge from. Michael Levin is a distinguished biologist at Tufts University and director of the Allen Discovery Center, whose groundbreaking research on bioelectricity and regenerative biology is reshaping our understanding of our understanding of how biological systems process information and pursue goals.

Starting point is 00:02:01 His xenobots, living robots built from frog cells, swim around, work together, and reproduce in ways that have never existed on Earth. What does this tell us about consciousness, intelligence, and the nature of life itself? Professor Mike Eleven, welcome to the Into the Impossible podcast. Thank you for having me. It's great to see you. We have so many questions. We'll run out of time before we run out of questions, I'm sure.

Starting point is 00:02:21 But I want to first start with the big picture question. Why is electricity of all the fundamental? forces of nature, nuclear forces, strong and weak, gravitation. Why is it that electricity and not say magnetism plays such an outsized role when we know that electricity and magnetism are unified via Maxwell's equation? So why does electricity play a bigger role than, say, these magnets here that I have on my desk do? It is certainly the case that living tissue is sensitive to magnetic fields, electromagnetism, you know, ultra-weak photons are important. All of these things are important. I have no idea if biology can harness the stronger than, you know, or the weak of force. I just don't know.

Starting point is 00:03:03 You can do it. Yeah, maybe. I don't know. But the special thing about electricity at this point is the following. It is a really convenient modality to serve as what I call cognitive glue. There are, there are other things that do it. There are other things that could do it elsewhere in the universe. I'm sure, you know, it's done by other mechanisms if there's life elsewhere. But But here's the thing that evolution loves about bi-electricity. It's a very convenient way to make electrical networks out of subunits, right? So group subunits into bigger things in a way that allows the whole to have goals, memories, preferences, and basically problem-solving behavior that the individual pieces don't have.

Starting point is 00:03:45 It allows a raising of levels, so to speak, and we can go into great detail how it does it. But basically the exact same thing that electricity is doing in your brain, which makes you more than the sum of, than just a pile of neurons, it has been doing that for bodies, multicellular bodies long before neurons ever came on the scene. It's a way to scale up the cognitive light cone of materials, basically. We'll get to the cognitive light cone because it's impossible for a physicist. That's like, you know, bait for a physicist to evoke Einstein and all sorts of other things.

Starting point is 00:04:17 But before I get there, you know, when I think about electricity, when I think about it as a physicist, I don't normally associate it with things that are squishy unless, you know, somebody threw a toaster in the bathtub. And that would be quite dangerous, obviously. We're not recommending that. But talk about how electricity even arises and what scales does it manifest. I mean, we don't see little anode and cathodes or, you know, positive and negative terminals on cell.

Starting point is 00:04:44 So how does it instantiate itself in a mechanistic way? And you could be very technical. I mean, my audience is, you know, one of the most magnificent and, you know, and. and mindful in the known multiverse. So talk us through, how is a cell like a battery or a magnet with these kind of polarities and dipoles and everything associated with it? Yeah, no cells absolutely have charged particles

Starting point is 00:05:07 that typically ions of potassium, sodium, chloride, and things like this. And what happens is, and the best way to anchor these kinds of discussions is by thinking about what happens in neuroscience. So we understand that our cognition is underwritten by the bioelectricity that it operates in individual neurons and then in groups of neurons and other cells in the brain. So what happens is you have cells and in their plasma membrane, which is basically this lipid kind of membrane, that's usually a pretty good insulator.

Starting point is 00:05:39 What evolution has discovered are special kinds of proteins called ion channels. And these ion channels have some really interesting properties where they let certain charged species like potassium, chloride, sodium, and so on. they either preferentially let them in or out of the cell. And as a result, what you end up with is a voltage gradient. Now, the gradient itself might be on the scale of, let's say, 80 millivolds in neurons, something like that. But because the width across the membrane is actually extremely small, and I don't remember the exact numbers, but it's basically the actual field across that tiny distance is enormous.

Starting point is 00:06:15 And what happens then is that you have these voltage gradients, and two things can happen. One is that the ion channels that regulate the voltage can be themselves voltage sensitive, which means that what you really have is a voltage sensitive current conductance, aka a transistor. And you can imagine that once you have that, you can do all sorts of cool computations. And then the other thing that happens is that there are these electrical synapses

Starting point is 00:06:40 between adjacent cells. And those synapses also can be voltage sensitive. So what you actually have is a network. You have an electrical network through which, voltage states can propagate. So many cells, I mean, in fact, all cells in the body generate these kind of voltage gradients, and most of them have the synapses by which they form into networks, the process information using this, using the differences in electrical potential. And it's exactly what happens in your brain, basically. Yeah, so we'll get to the brain later. I've got

Starting point is 00:07:09 a 3D printed brain that my son made for a conversation with Roger Penrose at one point field here, but I couldn't get it to work. So we'll talk about consciousness later. But I guess if we had to quantify it as a circuit, you know, and let's apply Kirkoff's laws from your native Russia, as I understand, or I guess you were born in the Soviet Union. Is that true? True, true. So Kirchoff had these famous laws that governed how current voltage, resistance, et cetera, related in a circuit. Let's walk through it. What kind of, you know, potentials are we talking about what kind of voltages, currents, resistances, conductances, and even magnetic fields, if you have anything to say about how those might be. play into understanding the chem biochemistry, bioelectricity of life. Sure, yeah. So the typical voltage changes that you're talking about in cells are on the scale of tens of millivolds. So what you will have are, so in the neural case, you have cells that normally sit at

Starting point is 00:08:06 about, I don't know, minus 70, let's say minus 80 with the inside being more negative than the outside. And then in the non-neural bioelectricity, which is the far more ancient version, in typical somatic cells, you will be anywhere from, let's say, 10, you know, negative 10, millivolds up to, again, maybe minus 70, minus 80, something like that. So it's the differences in that voltage between a cell and its neighbor that matter. So what cells actually track and interpret are the spatial patterns. Now, the differences across space. You have a whole bunch of cells in there. If you look, and we developed back in 2000, we developed the first

Starting point is 00:08:43 tools to read and write this electrical information outside the brain. Neuroscience is been doing it for a long time. We developed the first molecular tools to literally take a picture and then a video of these voltage gradients and tissues. And you can so you can see them propagating across distance. And it is those differences that cells read. Now, as you mentioned magnetic fields. So typically, of course, movement of charges absolutely makes magnetic fields, right?

Starting point is 00:09:12 And the magnetic fields in the brain are quite sizable because the voltage spiking is so fast. So, you know, milliseconds, we're talking about milliseconds change. And so that generates a, you know, that DVDT generates a pretty, a pretty good magnetic field, which people, of course, read with, with, you know, various devices. The non-neural bielectricity that we deal with changes very slowly. And it's, uh, the magnetic fields that are induced there are extremely low. I'm not going to say that cells don't respond to those, but there isn't any evidence that I'm aware of right now, that those extremely low level fields. Now, having said that, I know I'm going to get in trouble people are going to yell at me because absolutely like living things do care about magnetic fields.

Starting point is 00:09:51 They sense the earth's geomagnetic field, which is about, you know, half a gauss, something like that. So those things are absolutely important. But the magnetic fields induced by non-neural bioelectricity are unbelievably weak. And I don't know of any evidence that they play a role. The electric change is absolutely play a role. Are there species that don't have as manifest an importance of bioelectricity in their electrophysiology or lack thereof? Well, let's see.

Starting point is 00:10:17 I mean, so for example, something like C.L. against the nematode. I mean, they have neurons, so they definitely have neural bioelectricity. But I am not aware of any evidence yet. Now, there are people working on this, and so this could totally change. But I'm not aware of any stories about the importance of developmental bioelectricity in that model. And my guess is it will change. I think evolution just loves it. It first discovered these things around the time of bacterial biofilms.

Starting point is 00:10:43 So there's a very nice paper by a girl as well from UCSD who shows like brain-like signaling in biofilms. So it's like it's a very ancient phenomenon. Yeah, I've had an Allison Miotry who's worked on brain organoines and launched them into space and a little bit about it. But when I look at the, you know, I'm going to keep nerding out about the physics of circuits because I love to solder and do stuff, although that would be quite dangerous in the human body. But, you know, looking at voltages at the, you know, tens to hundreds of millivolts. And then thinking about, you know, human cells as, you know, not that dissimilar from Ciellegons or something, you know, just scaled up trillions of times. I mean, how is it possible to go from something where, you know, there's essentially no voltage currents, you know, at a measurable level to actual macroscopic voltages that we can measure quite easily here? I can measure my heart rate using my Apple Watch, right?

Starting point is 00:11:32 I mean, I know that to be a fact. So how long before we have electro, you know, encephalograms on our wrist, I have. I have some meditation program that supposedly does that already. So walk us through the kind of reductionist or anti-reductionist. You know, how do we go from basically nothing in, you know, eukaryotic cell, a prokaryotic cells, I think, came first, right? To then these eukaryotic cells and even complex worms and creatures and so forth that have very little electrophysiology to humans, which have huge amounts by comparison of, you know,

Starting point is 00:12:06 millimps and, and millivolts or, you know, intensive volts. Yeah, well, I mean, to be clear, I'm not aware of any creature, including bacteria and various microbes that don't have these phenomena. These go all the way down. When I mentioned Cialigans, I simply meant that I wasn't aware of a morphogenic role in that species for bielectrics. But, I mean, you know, Koshlin did the studies where you say we talked about bacteria as a model neuron. And basically, if you think about the earliest kind of steps towards life, you know, just imagine you've got some kind of membrane that, is the first attempt to separate the inside from outside, yeah, that you've got some kind of barrier that tries to keep the goodies in

Starting point is 00:12:46 and the dangerous external world out. Well, as soon as you've done that, as soon as you've segregated molecules, chances are you're going to have an electrical imbalance because you're keeping something inside, you're concentrating it against the gradient, you're going to have a voltage imbalance. And when you do, then some other very cool things happen as free gifts from physics. So, for example, if you have a system like this and you poke it, let's say it gets injured, It runs into something that injures and pokes a hole through the membrane.

Starting point is 00:13:13 Immediately that you're going to have an injury current that's going to try to go through that location to try to equalize the voltage rating. And so for free now, without having to evolve any kind of additional mechanisms, you now have a vector to the damage. You know exactly where your damage was. And you know that you've been injured because now your voltage is dropping, so you're depolarizing. I would venture to guess that that's the first physical correlate of pain. And you also know immediately where the damage. images because that's where the field lines are going. And so all of that you get you get for free. So this is just just one example of the many amazing kind of free lunches that biology makes use

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Starting point is 00:15:51 So when I look at the kinds of ways that medical technology has been brought over from physics, I mean, one of those is something like a defibrillator, which will provide, you know, on a very short time scales still, you know, huge amounts, you know, 30 amps or something occurring at a thousand volts, but only for milliseconds of time. And as I've understood it, you know, the heart thrives on regularity and the brain sort of thrives on irregularity, although I'm kind of certainly messing up, you know, the terminology here. But can we talk about like how does how do the cells know, you know, I guess it's part of the genotype, but how do they know, you know, for a brain cell, it would be very damaging to have a defibrillator sort of

Starting point is 00:16:34 of device. I mean, that would be maybe like electroshock therapy or something, which is basically outlawed, versus a heart cell, which says, you know, bring it on when I'm not feeling rhythmic. How did these bioelectric properties get instantiated in the cells, you know, rather than just kind of being scattershot through in every cell, basically reacting to voltages, currents, magnetic fields, frequencies, all the same? How does that work? Yeah. Well, what happens is that These cells, there are multiple scales of circuits here. So within a single cell, within any one cell, there is a circuit formed by the different ion channels that exist. So you've got ion channels that pass different kinds of ions, so positive and negative charges,

Starting point is 00:17:19 and they have different sensitivities to the voltage. In other words, you can very easily imagine putting together some kind of a regulator that's going to keep the voltage roughly in, some kind of homeostat that's going to keep the voltage in roughly the right range. So that's the first thing that happens. The second thing that happens is that now you have these and they are arranged in a network because they're not sitting there by themselves. Well, in unicellular organisms, they are amoebas and things like that. But in a multicellular body, all of these things are connected into a network.

Starting point is 00:17:46 And so now you have a circuit of circuits, right? And so now you've got to the tissue level and then the organ level and so on. And so you've got circuits of circuits of circuits. Each level here has its own robustness properties. Each level has its own sensitivities and thresholds such that when something interesting happens, it does kick off, it does do symmetry breaking and kick off various kinds of of, you know, amplification processes. And you've got different kinds of computation. So there are cells that are using these voltages to compute. There are cell groups and tissues

Starting point is 00:18:15 and organs and so on. So all of these things. And we now, the cool thing is that we now have simulators of all of this. So, you know, the first one was my colleague, Alexis Pytak, created this thing called Betsy, the bioelectric tissue simulation. environment and you can you can lay out a bunch of cells and you can say here are the channels that are going to be expressed now go run tell me tell me what's going to happen and then you can do all kinds of cool experiments right so so you can say okay does it do pattern completion the way that we see in flatworms where you cut off a piece of it and you say what happens to the to the rest of the voltage pattern if we just you know we just killed a bunch of cells what happened and and

Starting point is 00:18:52 you can watch these things rescale and you know some of them have really interesting memory properties such that when you change the voltage they remember it and they keep it and so like a like a like an electric memory. So yeah, so we have simulators now for all this stuff, and this is a very active area of development, actually, to be able to predict and infer intervention. So you could say, you know, if I wanted the voltage to be this or that, what would I need to do? And so that's a computational side. Would there be any implantables or would that involve, you know, external stimuli in response or how has that brought into effect? Yeah. Your summer starts now with Memorial Day deals at the Home Depot. It's time to fire up summer cookouts with the next grill

Starting point is 00:19:31 burner gas grill on special buy for only $199 and entertain all season with the Hampton Bay West Grove seven-piece outdoor dining set for only $499. This Memorial Day get low prices guaranteed at the Home Depot. While supplies last, price invalid May 14th or May 27th, U.S. only exclusions apply. See homedipo.com slash price match for details. Yeah, great, great question. The technology for this actually right now is really not about electrodes. Electrodes are really good at two things. really good. So this is the implantables kind of idea that they're they're really good at spiking neurons. So there's some there's some beautiful work on the peripheral nervous system and the and the vagus nerve and all this kind of thing. You know, being able to control the nervous system that way.

Starting point is 00:20:14 So, so they're good at that. And they're also good at establishing a standing electric field that would be used by cells as a guidance cube. Cells love to crawl in electric fields. They can sense electric fields and they have preference. One will go anode the other, another different cell type will go cathode. And if you wanted to make sense. cells migrate, as we often do, for example, for regeneration towards wounds. So somebody like Minzow has done some amazing work on the natural electric fields that are formed when you puncture the skin, you know, when you have various epithelia damage, there's an electric field. And this is like the story I was telling before where the field lines are an immediate guide to the damage. So all

Starting point is 00:20:52 these migratory cells immediately start following the field lines and they hit the side of damage. So those kinds of things, the implantable electrodes are really good at. What they're not good at, at least right now, maybe someday somebody will figure out a way to do it. What they're not good at is at setting up spatial patterns of differential voltage potential, which is what we need here. In order to do the things that we do induce organ formation, limb regeneration, the tumor reprogramming, repairing birth defects, all these different kinds of things. In order to do them, you need to set up complex patterns of,

Starting point is 00:21:28 different voltages across the space. And I don't know of any way, and I haven't seen anybody develop any way to really do that well with with electrodes. So how do we do all this stuff? So what we do is we use ion channel drugs that are chemical compounds that target specific kinds of ion channels. And so we have a computational platform where we can say, this is the pattern we have now. I'd like it to be this instead. Tell me what channels and pumps I would need to open and close in order for them to do that. And the model should give you a suggestion. And then we go to the shelf and something like 20% the last time I looked at 20% of all

Starting point is 00:22:06 drugs are ion channeled drugs. So you have this incredible. Yeah, I mean, it's amazing. You have this incredible of a pharmacopoeia of electrocedables. So basically drugs that can be repurposed, you know, they may be used for neuro neurological symptoms. They may be used for, you know, inner ear or whatever. You can repurpose them for other things if you've got the platform that tells you,

Starting point is 00:22:26 which channels do I want to open and close? If you remember Jurassic Park, that great movie, you know, so Jeff Goldblum, you know, says something like, you know, life finds a way. Life is always right. So I just remember it like that. But the counter example is neutrinos are left-handed, and there's been some conjectures that only left-headed neutrinos, you know, kind of stemming from cosmic ray interactions, could have caused the initial asymmetry.

Starting point is 00:22:51 Still not entirely understood by me, at least. But talk about this breaking of symmetry. And kind of the way that it kind of grows out, again, from objects. We know we can make sugars and we can make a whole mirror version of a human being, according to many people that I've talked to. So that would be quite striking. But how does handiness come into this? And is there potentially, again, a link between the physical world that I inhabit of, say, magnetic fields,

Starting point is 00:23:20 which are also distinguishable at some level using the weak nuclear force alone, as far as we know, is there any way to trace the origin of handiness and embryonic development to handiness, you know, perhaps due to polarized radiation where we have antennas that are circularly polarized left or right? For example, is there anything to this notion that the origin of morphological asymmetry and chirality could come from, you know, some physical mechanism? Yeah, yeah, this is great. This is a favorite topic. And I haven't done work on left right in quite a bit, quite a bit of time. But I used to, this was my PhD was in this,

Starting point is 00:24:00 and I worked roughly until 2016, pretty much on this, on this problem. It's a fascinating problem. Let me just kind of set up what we're talking about here first, and then I'll talk about this, what relationship it might have to symmetry breaking in the universe. So the basic fact is that most animals, and in fact it goes well beyond animals, there are plants that do it.

Starting point is 00:24:23 There are all kinds of weird creatures. that have consistent asymmetries. They have basically a fundamentally a bilateral symmetrical body plan so you can draw kind of a midplane and you can say, okay, you know, to a first approximation, the reflections are the same,

Starting point is 00:24:38 yeah, they're the same left and right. Except that, you find that there are consistent differences. And so in humans, as you pointed out, the heart, the liver, the gallbladder, there's all sorts of the stomach, there's all sorts of organs that are asymmetric. The brain hemispheres are not the same. All kinds of interesting phenomena

Starting point is 00:24:54 such as certain syndromes that affect non-asymmetric structures like shoulders and hips and things like this, sometimes occur more prevalent on one side. There are lots of other creatures that are more obvious crabs and lobsters. Often will have one claw that's quite different from another. Many interesting examples like this, we showed years ago that slime molds, when they're growing out and they want to turn, they preferentially turn in one direction versus another. So even slime molds have a sense of left-right symmetry. and the cool thing about it is that it isn't random.

Starting point is 00:25:27 It's easy enough to come up with a mechanism that will pick one side at random. What's much harder is to have consistent asymmetry where the direction of the symmetry breaking is fixed relative to the other two axes. And I used to back when I talked about this a lot to students, I would say, imagine that you were going to, you discovered some aliens far, far away. All you had was a telephone connection. You couldn't give them objects. All you could do is talk via voice.

Starting point is 00:25:53 And so you're learning each other's language and you've got all the other words down and it's time to decide what left and right needs. So you say, okay, so I'm standing here and let's say that, you know, my sense organs are pointing forward. So that's the first axis. And my feet are pointing towards the center of gravity of the planet. So that gives you the second axis. Now my left hand is the one that what? And now you're stuck, right? Now it's really, now it gets really hard unless, right?

Starting point is 00:26:19 So as you well know, we could do the right hand rule. and we could do something with magnetic fields, and we could do the right-hand rule, or maybe they live in the same kind of universe as us, and they have the same, you know, neutrinos and all of that. But otherwise, at a macroscopic scale, it's really hard. There really isn't, I mean, genetics doesn't distinguish left from right. And so you're going to express, we actually don't,

Starting point is 00:26:47 and that's what I did for my PhDs, discover a pathway of genes that are expressed on the left side differently than they're expressed on the right side. And then I spent my postdoc and some years after that, chasing that back to see what the origin is. And I'll tell you what that is. But it's really fundamentally a very fascinating and difficult problem. And compressing, you know, 20 years of work into a couple sentences, I will tell you that basically what it boils down to is the chirality of a particular little structure. It's part of the cytoskeleton inside of cells. And it literally does the right-hand rule thing. In other words, it has a chirality. The cell has two, the early embryo, the very early

Starting point is 00:27:32 embryo has two other axes. So it anchors this in one direction. It anchors this in the other direction. And then it's got a little feature that points in the actually rightward. And that nucleates a bunch of cytoskeletal tracts along which motor proteins will ride. And they take certain cargo. The cargo they take, among other things, is ion channels. And it sets up literally, when we can see, and we showed this in 2002, there is a voltage gradient between the left and the right sides. And it arises there consistently because this little, little, a nucleating molecule allows the ion channels to be different on one side than the other. And so, you know, your point about the symmetry breaking in physics and so on, I mean, I'm certainly not an expert

Starting point is 00:28:17 on it, but I used to read, read all this stuff. And just this amazing, you know, this, the CPT violation, right? At the, at the basis of it, I always thought it was the most amazing thing. And does, you know, does that actually, so there's two possibilities. And I don't think we know which one is right. One possibility, and people have published papers on this, that because of, because of the parity violation, some in antimers of certain molecules are more stable than others. And the idea is that, not by much, but enough, that evolution. might have picked up on this. And that the reason that we are all a chiral in the same direction is because literally,

Starting point is 00:28:54 you know, because of the way that, you know, I think it was, you know, the electrons get ejected in the weak nuclear force. You are actually more stable. These molecules are more stable in one direction. That's one possibility. The other possibility is that it's a frozen accident. That basically, that basically there is no major difference, but the first successful universal ancestor to life, just happened to have it going one way and it was too hard to change it

Starting point is 00:29:20 after. You know, evolution's full of these things that once you set it up, you can't change it. So I can't tell you which one of those is the case, but I think it's fascinating to think about whether it goes all the way down. I want to stick to physics and I want to also let the audience know that soon we'll get to xenobots, not xenophobia, not xenophobia, not Xena, the warrior princess, but we'll get to Michael's wonderful portmanteau zino bots in just a minute. But Before we get there, I want to ask you a very simple question to you, which is one posed by none other than Erwin Schrodinger himself, Michael. And I think you know what I'm about to say.

Starting point is 00:29:56 Michael, tell us, what is life? Yeah. Yeah, the simple questions, of course. So interestingly enough, we just put out a paper where what I did was I polled about 70 various thinkers that I chose on this question. I gave him up to three sentences. and everybody gave their definitions. And then we had, with the help of some AI tools,

Starting point is 00:30:19 we actually created a conceptual space for all the definitions to kind of look at the structure of how people think about this. Needless to say, there is no real agreement. I'm going to say two things. One, which is weird for a biologist to say, but I'm going to say it anyway, I don't think it's a particularly interesting category. In other words, I think what's a very interesting category

Starting point is 00:30:39 is the spectrum of cognition, which I also think goes all the way down. And I think life is a subset of cognition. I don't think it's important to try to wrestle over difficult corner cases and try to come up with definitions of life that try to make rulings, yes or no. I don't like these binary definitions. I don't think they facilitate research in any way.

Starting point is 00:31:03 However, if we wanted to say what it is that is special about life, I think that we human observers tend to call life those things that are very good at scaling their cognitive lichome. In other words, what you have are, so let me just give a definition. So the cognitive lichon is the size in some particular problem space of the biggest goal that a system can pursue. It's not the reach of its effectors. It's not the reach of its sensors. It is the size of the goal state that you can pursue. So for example, if you're a bacterium, all you really care about managing is the concentration of nutrients and some other things in a very small area. You have a little bit of prediction going forward. You have a little bit of memory going backwards, but that's it, that little

Starting point is 00:31:46 area of space time that you are managing. You could care less what happens anywhere else. You're managing a tiny little area of space time in terms of making efforts to make it be one way versus a different way that entropy would have you go. So if you tell me that all I care about is the sugar concentration within this, you know, the 20 micron region, I'm going to say you're probably a bacteria. If you tell me that, that, you know, you're interested in, you're actively working on goals of what the financial markets are going to look like all over the earth 100 years from now, I'm going to say you're probably a human. And there are many in between cases. So, for example, if you've got a dog, the dog is never going to, to my knowledge, is never going to

Starting point is 00:32:26 be able to care about in the sense of pursuing goals, what's going to happen three weeks from now, you know, three towns over, right? That's just outside of its cognitive light. And it's certainly bigger than the bacterium, but it just isn't going to care. And there's nothing you can do to make it care again, as far as I know, these are all empirical things. You have to do experiments to find out. And so what I think happens is that very tiny things, certainly cells, but I actually think it goes even below the cellular level. There are certain configurations of those things that when they get together, the cognitive lichone goes up. So I'll just give you a very simple example.

Starting point is 00:32:58 Individual cells have little tiny cognitive lichones, and they care about things like their pH level, their hunger level, their voltage state. You know, these kinds of local little tiny things. But groups of cells care about grandiose construction projects. For example, you've got a salamander limb. You amputate the limb. Immediately the cells notice that they've been deviated from the correct state in the anatomical space. They work really hard. They build the limb and then they stop.

Starting point is 00:33:24 That's the most amazing thing is when it's a homeostatic error reduction system, when they've solved their problem and they've reached, they've reduced the error back to acceptable levels, then they stop activity. So the collection of cells are able to, pursue a very large goal. No individual cell knows what a finger is or how many fingers you're supposed to have, but the collective absolutely knows. And you know that by experiment, because if you try to deviate them from their goal,

Starting point is 00:33:47 they will do ingenious things to get back there. That's kind of the definition of it. And so I think what has happened? And this is what we study. We study how electrical networks scale the cognitive light combs. So what happens is that specifically by memory anonymization, stress sharing and some other things, when you make these electrical networks, not only does your cognitive light cone get bigger, but it also projects into other spaces. Individual cells have access to metabolic space,

Starting point is 00:34:14 gene expression space, physiological space, but groups of cells have access to anatomical morphos space. If you happen to have a brain and some muscles, now you have access to three-dimensional space. If you have access to language, then you're into linguistic space and God knows what else. But you get the idea. And so I think when we see things like that, that have a multi-scale architecture where the cognitive lichen of the parts becomes expanded and projected into new problem spaces, we say that that's life. And there are some other things that we could get into about interpreting your own memories and some other things. But fundamentally, that's what I think is, that's what we mean when we say life.

Starting point is 00:34:50 Yeah, well, it's clear, you know, from the moment I click record that we're going to need, you know, probably a bigger boat, a bigger podcast. And we'll hopefully have many opportunities to do this in the future. But the next question on the kind of ease of discussion is sort of a problem I have with my students. And I wonder how you approach it too. That in cosmology, we study the evolution of the universe. The origin is part of it. But the question of what caused the universe to be in existence is not really part of the process of cosmology.

Starting point is 00:35:25 And so likewise, my next question is going to be about what caused life to begin. what is the origin of life as you see it. And if you can throw in the word panspermia, that would be helpful for me because I give away these meteorites that have come from the early solar system. I give them away to everybody who has a dot edu email address that lives in the United States.

Starting point is 00:35:45 So you are going to get one, Michael. I'm going to ship one to you. I love it. Any of your students that you get to sign up for my Magic Monday mailing list at Brian Keene.com. If you have an EDU email address, you'll get one of these beauties shipped via,

Starting point is 00:35:58 not gravity, the way I got it. but via the U.S. Postal Service. But if you don't, you can, I give away some to people that don't have the luxury and the sloth of being like you and me at a university, Michael. So I give those away at briankeating.com slash yT. So please do take us up on that. Michael, tell us, how did life originate?

Starting point is 00:36:16 Okay, I don't have much to say about panspermia. I'm not terribly worried about it because that, yeah, sorry, but that basically just puts it off to somewhere else, right? In that sense, it has to be coming from somewhere else. So I'm not going to worry about that. terribly much. I can I can say a couple of things that I hope are interesting about, you know, how life might have originated. One of the things that, and again, I'm not as worried about life as I am about mind and cognition. And I actually think that that's a superset of living,

Starting point is 00:36:47 of things that we recognize as living anyway. We, there's a, there's a, there's a, there's a, there's a, there's a, there's a, there's a, that, that we found and that we, actually this, this, this, this paper just came out a couple of days ago, actually. Imagine a model of a molecular pathway. So you've got, let's say, 10 different molecules. Each one basically up and down, regulate some others. So you can draw a little network, right, of, you know, positive and negative interactions of chemicals that turn each other on and off or, you know,

Starting point is 00:37:18 potentiate each other's activity or suppress it. Turns out that, and this is something we did a couple years ago, and this was Sarama Bisbuss's work in my group. what we showed was that even those very simple molecular networks, never mind cells or brains or synapses or any of that stuff, just a small group of chemicals

Starting point is 00:37:36 that turn each other on and off, already was able to do six different kinds of learning. They can do habituation, sensitization, and they can do Pavlovian conditioning. They can do associative learning. So that you get long before evolution kicks in. Now evolution, of course, is going to optimize the hell out of it. And we did find that bylaw.

Starting point is 00:37:55 like real biological networks do better at this than random networks, but even random networks do this a little bit. And the other thing we found out just recently, and this is this is the thing that was published the other day, and this is Federico Pagosi's work, that if you compute measures of causal integration, which is to say very sort of very, very, very, very roughly, it's a new, it's a new set of mathematical techniques that allow you to quantify to what extent is something more than the sum of its parts. You know, this was this, this idea that used to be a kind of a philosophical thing is, are there any higher levels of causation or is everything, you know, is a reductionism,

Starting point is 00:38:35 right versus holism? That used to be a philosophical argument through the work of a number of people, including Eric Holtl who works at my center here and Giulio Tononi and Olaf Sporns and some others. There's been a branch of mathematics developed that can actually quantify that in certain systems. You can literally do the calculation and you can say, okay, yeah, the parts are doing all the or the actually there is a higher level that's doing something that the parts aren't doing. So we can apply this math to all sorts of things and we applied it to these pathway models and we found out that every time they learn something,

Starting point is 00:39:07 their causal emergence goes up. In other words, the process of responding to stimuli in a way that trains you, meaning that you will respond to them in the future differently than you responded to them fresh going in, that process makes you more than, it makes you, raises the amount by which,

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Starting point is 00:39:58 This is a job for Indeed, sponsored jobs. On a personal note, you had a wonderful obituary after the death of your colleague, the late great Daniel Dennett. I had the honor of doing his last podcast interview right before he passed. I guess it's obvious. He did it before he passed away. Can you talk a little bit about this, the impact that he had, maybe beyond the laboratory and so forth,

Starting point is 00:40:22 but his modality of thinking, it seemed to really have. affected you. And it's only about a year since he passed away. Yeah, Dan was an amazing person. You know, I grew up reading his books. I have all his books back there that I read when I was, when I was, you know, a teenager and beyond. And I was, I was just, I felt incredibly privileged to take a course with him. When I, when I got to Tufts as an undergrad, he taught the philosophy of mind course. This would have been in, you know, 91 or something like that. I took that course with him and, you know, he was, he was incredible. Now, now, To be clear, I don't, we don't necessarily agree on everything.

Starting point is 00:40:58 There are many things that we did actually agree on in terms of this field. But he was, he was an amazing, first of all, he was a gentleman. He was not interested in any kind of games in one upmanship, any of that stuff. He, he was really interested in getting to a better argument to a better version of, you know, whatever understanding we could all get by interacting with each other. And he was just, just incredible in terms of being clear. making, you know, getting everybody else around him to be clear about what they were trying to say. And then just seeing what, you know, what we could make of it.

Starting point is 00:41:34 And he was, he was always, he was always kind and he was always generous with his time and with his ideas and with his advice. And yeah, I couldn't, I couldn't say more nice, nice things about him. And so, you know, when I came back to Tufts as a faculty member, we collaborated on some things. We wrote a paper together, which I'm very, you know, kind of I'm very proud of talking. talking about cognition all the way down. And yeah, he was, he was, you know, he was an amazing person, an amazing mentor and a very deep think. Yeah.

Starting point is 00:42:03 Yeah, I was very, you know, very distressed when he passed away. I think I got to interview the three of the four horsemen of the apocalypse, at least. I never got to interview Christopher Hitchens, but, but Dan was certainly, you know, at the very top of that very august list. So, okay, I want to finish up for this part one of hopefully many parts together. And that's with your wonderful work, as I promised earlier, about xenobots. So first of all, what are xenobots? And how are they behaving like living organisms, moving, healing, even cooperating, working together without any brain or nervous system?

Starting point is 00:42:40 I mean, to be clear, there are many organisms that don't have a brain or nervous system and they do all kinds of interesting things. That's why I say I call those colleagues of mine at the faculty club, you know. I say jellyfish have existed without brains for 65 million years. So there's hope for you yet. Not you, Michael, but. Yeah, yeah. Well, yes, you said it. I didn't.

Starting point is 00:43:00 But, I mean, look, here's, first of all, I'll tell you what the Zenobots are. So this is joint work between My Lab and Josh Bongard at the University of Vermont. And we are, we've organized this thing called the ICVO, which is the Institute for Computationally Designed Organisms. And the Zenobots are kind of the first, the first, we're the first, um, uh, Bousalho from, from that, that whole effort. And, uh, the computer science part of. this was done by C.M. Kregman in Josh's lab and most of the biology was done by Doug Blackiston and

Starting point is 00:43:29 what we basically found out is that if you isolate some prospective skin cells from the early frog embryo, and this is why they're called Zenobot. Zenopus Lavis is the Latin name for the frog that we're using. And so this frog lays eggs. They become embryos. And at a very early stage, we isolate some cells that are going to become kind of like an outer skin covering. And the deal is that under normal circumstances, these cells get, basically get bullied by the other cells in the embryo to do a very specific thing, to be this boring outer two-dimensional kind of covering for the embryo, keep out the bacteria. And that's that. That's what they do in the natural state because they are hacked by these other cells that are there. If you liberate them, so very specifically not putting in any new

Starting point is 00:44:12 genetic material, no synthetic biology circuits, no genomic editing, no weird nanomaterials or drugs or anything like that. All we have done at this point is liberate them from the influences that they normally get. Then you can ask the question, what are they, what else do they want to do? It's kind of a reboot of their multicellularity. And they could do many things. They could, they could crawl away from each other. They could die. They could form a two-dimensional sheet, a monolid, they could do many things. What they instead do is they get together, they form this, this little ball. And that little ball is covered with cilia. These are little motile, tiny motile hairs that then organize. And they start, the, the, the cilia start waving and they basically align so that the thing can now swim through the water.

Starting point is 00:44:52 Normally, these cilia are used to distribute mucus over the body of the frog, but now, now they can swim. And so they swim around in the water. And I'll just tell you a few things that it turns out they're capable of. Now, you know, they're obviously living organisms. They're made of living cells. The major interesting thing about them beyond the fact that they're a biorebotics platform, so that is we could, once we understand how they work, we could potentially use them for all sorts of cool applications, cleaning up the environment. There's just a million different things. But the other cool thing about them is that unlike the actual frog, if you ask about what sets

Starting point is 00:45:23 the properties of the frog, everybody will say, well, it's a history of selection against specific environments, right? Going all the way back, that's when the computations were done to design what a frog is, it's by testing things against the environment and killing off everything that didn't work. That's why the frog looks like a frog. Well, there's never been any xenobots. There's never been any selection to be a good xenobot. And here are some things they do.

Starting point is 00:45:43 First of all, they express hundreds of genes differently than they would have in the body. So they have a completely different transcriptome. Among those genes, many interesting things. I'll just pick one to talk about. They express a bunch of genes and other creatures are related to hearing. And so we actually tested that and we put a speaker underneath the dish and we played certain frequencies. And we found out that, yeah, in fact, they changed their behavior depending on the sound vibration that you're giving them. They do this other crazy thing we call kinematic self-replication, which is if you sprinkle

Starting point is 00:46:13 a bunch of loose epithelial cells into the dish. They do what the kind of von Neumann's dream of a robot that goes around and makes copies of itself from parts, from materials it finds in the environment. They will literally, both singly and as a collective, they will go around, they will collect the cells into little balls. And because the cells themselves are in a gentle material, just like the ones we started with, the little balls mature and become the next generation of Zenobots. And guess what they do?

Starting point is 00:46:38 They do exactly the same thing. They run around. They make the next generation. So now, you know, there's the. To our knowledge, no other creature on Earth reproduces this way. I don't think there's ever been a kinematic self-replication on Earth. So they raise these kind of biobots and other kinds of constructs, raise these very interesting questions of where do the properties of novel beings come from

Starting point is 00:46:58 if they don't have an evolutionary history? This is something that we are now confronting as a society with AIs and with cyborgs and hybrots and all these weird things that we're all making. Where do their properties actually come from? And here, if we had, you know, maybe next time we'll talk about it because I think it is this platonic space of forms where the truths of mathematics come from, actually. But so that's Zenobots. And we have another thing that was developed by a Gazem Komushka in my group was a PhD student.

Starting point is 00:47:25 We call them Anthrobots because some people said, well, Zenobots, you know, the amphibians are kind of plastic and it's embryonic. So maybe it's a one-off kind of special thing. So fine, what's the furthest you can get away from embryonic frog? Well, adult human. Let's try that. So we took cells from adult human patients. cratial epithelial cells, turns out that they too come together and form these little

Starting point is 00:47:45 motile creatures, we call them anthrobots. Those guys have 9,000 differently expressed genes, half the genome then, right? And they can do cool things like they can heal neural wounds. So if you put them on a bed of human neurons, you take a scalpel, put a big scratch through it, they can settle into that wound and form what we call a superbot cluster. And when you lift them up four days later, what you see is that they took the two sides of the gap and they healed them together. And again, there's never been any anthropos. There's never been selection to be a good answer robot. You know, we have to understand where do these things come from?

Starting point is 00:48:16 And who would have thought that your tracheal epithelial cells, which sit there quietly dealing with pollen and, you know, who knows what else, are able to make a self-motile little creature that can go around and heal things like neural wounds. Right. And this is just the tip of the iceberg for these things. Well, instead of a frog makes, humbly suggest the elephant next time as the mascot of Tufts. I'm from near Somers, New York, which, if you know, is right where Bar, Norman Bailey got their start and we're tough Scott, part of its start. So Michael Levin, this has been phenomenal. I knew it would be. It's two years in the making. I'm glad you took so much of your time. You're so generous. Thank you so much. And I hope that we'll do it again. As I said, we have parts. I have questions enough for I'm counting up here, parts up to part four. So maybe in person even that would be great. Thank you so much, Michael. I have a wonderful. Very good to meet you. Okay. Great. Thank you.

Starting point is 00:49:04 The implication of Michael Levin's work extends far beyond biology touches upon the very foundations of physics, consciousness and our place in the biological cosmos. If cognition really does go all the way down, what does that mean for human understanding of intelligence? And what does that mean for other artificial and alien intelligences throughout the universe? I know if you enjoyed this conversation about the electric basis of life and consciousness, I know you'll enjoy my episode with Sir Roger Penrose and Stuart Hammeroff, where we explore quantum mechanics in the brain and whether consciousness might emerge from quantum processes in microtubules. Two brilliant minds, two revolutionary your ideas about the nature of consciousness and life itself.

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Into the Impossible With Brian Keating - Could Biological Robots Heal Us from the Inside? | Michael Levin

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