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Nick Lane on Origins of Life, Consciousness, Alien Life, Krebs Cycle, and Evolution
September 19, 2022
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The Economist covers math, physics, philosophy, and AI in a manner that shows how different countries perceive developments and how they impact markets. They recently published a piece on China's new neutrino detector. They cover extending life via mitochondrial transplants, creating an entirely new field of medicine. But it's also not just science they analyze.
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Nick Lane is a biochemist, a writer, and a professor at University College London, whose book, Transformer, exposits on the origins of life, not being so heavily contingent on RNA as many think, but instead in something called the Krebs cycle. Poetically, you can think of this as the difference between an information theory of life, which is the current dominant view, to one of the thermodynamic energy flow of life.
Which is Nick Lane's view. As usual, click on the timestamp in the description to skip this intro. My name is Kurt Jaimungal, I'm a Torontonian filmmaker with a background in mathematical physics, and this channel is dedicated to the explication of the variegated terrain of theories of everything.
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Why don't we go over your primary thesis about how the Krebs cycle predates life? And perhaps you can contrast that with a reverse predominant view, which is that genes cause metabolism or genes create metabolism or the conditions for metabolism. Yeah. I mean, this is a, this is an argument that goes back decades in work on the origin of life. And you mentioned the Krebs cycle already.
Those ideas also go back decades, this is nothing particularly new for me, but what's changed is that there is now some experimental evidence and that's been lacking. So I guess the whole field of biology has been obsessed with genes and information since the 1960s, since the code was cracked.
And the idea that RNA, which is the kind of the template taken from DNA, it can catalyze things. It can also supposedly copy itself. It can act as a template for itself and so on. So it's a beautiful idea. It's called the RNA world. It's been around for quite a long time now. And it kind of takes you further and further away from biology as we know it. And I end up in a place where, as a biochemist, I'm
I just don't recognize the landscape. So these ideas of metabolism first, I suppose the problem there is that it asks a lot of the environment. Effectively, it's asking one specific place, one specific setting to start out with something like carbon dioxide and hydrogen and not much else, and to make everything from it. In the absence of genes, in the absence of enzymes, it's a big ask.
And people who've argued this, Harold Morowitz, one of the great biophysicists who worked a lot on the origin of life, he linked it in with metabolism first and the Krebs cycle very early. And he was largely dismissed because there wasn't any serious evidence that it could actually work.
And now what's happened over the last five or six years is it's beginning to look as if it really does work and it's not just the Krebs cycle, not as a complete cycle but as a kind of a linear pathway with parts of it, it's not the whole thing. But also other core biochemical pathways seem to just spontaneously happen and they make so much more sense of the whole structure of biochemistry and then also how it is that information comes into biology because it comes in
Do you see the metabolism question or solving metabolism as being a biochemistry question or physics question or biology question? Yes. Are those distinctions important?
They are important from the point of view of people's backgrounds, they're not important from the point of view of the question because the question is a question in science, the question is it needs physics, it needs chemistry, it needs biology and geology and so on and this is part of the problem that it's been a kind of collision of disciplines each of which have you know 100 years or more of its own intellectual history and ways of seeing the question. So I think
The dominant way of seeing the question over the last, really since the Miller-Urey experiment in 1953 has been through the lens of chemistry. And what the chemists have tried to do is what synthetic chemists try to do, which is to say,
You tell me I need to make a nucleotide. So I'm going to make you a nucleotide. I'm going to make you nothing but nucleotide. It's going to have a high yield. It's going to be pure. I can make you 70%. And I need to start with cyanide. Therefore, this is how life starts. And from a biologist's point of view, well, you'd see it the other way around. You'd say, well, natural selection optimizes things that were worse at the beginning. And now they're better because selection optimized them.
And therefore, what we're looking for is a process that kind of works a bit, but is really very bad. That means I want a low yield. It means I want low purity. It would bring any self-respecting synthetic chemist out in hives to try and do it that badly. But that's really what a biologist wants to see. What a geologist might want to see is what kind of an environment is conducive to
any of these chemistries? Are there settings on the ancient earth that are conducive to cyanide for example or to co2 or whatever it may be? So there's this collision really between disciplines and ways of thinking about it and we can't all be right and people have spent decades of their lives seeing a question from a particular point of view
And it's very difficult for any human being to kind of step back and stand on a soapbox and say, well, I got it all wrong. I've just wasted the last three decades of my life. Often the answer is somewhere between different theories, different hypotheses. It's a bit of this and a bit of that, but you can't test that. You've got to be purist about what you test. And most of us are going to be wrong about most of it. And that can mean that you end up with
Quite unpleasant personal animosities between the researchers in the field. OK, so the chemists or the synthetic chemists see that there are certain building blocks to life and they want to create those in the lab artificially or starting from simpler ingredients. And then the biologists say, no, well, look, if we have these ingredients, the way that evolutionary biology works, that we start from something that's less pure and then we work up where
Yeah, the real difference here, I suppose, is that what the chemists have done is as if you say, right, we need nucleotides, the building blocks of RNA and DNA, we need amino acids, we need to have fatty acids, the building blocks of membranes and so on. So go make them for me. And the chemists go away and they make all of these things.
And they've started with CO2, but it doesn't work very well. The yields are low and so on. So they put that aside as an unworkable chemistry and they start with cyanide or something which is very energetic. But I mean, large amounts of cyanide. You're practically asking for an atmosphere which is just saturated with cyanide.
And the chemistry works. It produces the building blocks of life, but with a starting point that no life ever uses via pathways that life never uses. And so it kind of leaves you with the same question, which is to say, okay, so if that's how it started, then you end up with an environment that's got all these building blocks floating around. You've got the perfect primordial soup, but then what happens? And there isn't really an answer to that. I mean, you may as well say then a miracle happens. Everything has to self-organize.
Whereas why does it invent biochemistry as we know it if that's the worst possible way of doing it? So what I have been looking for as a biochemist and a bunch of other people is do these pathways at the core of biochemistry happen spontaneously in the right environment? Not very well, just a little bit, but
whole you know pathways with 10, 15, 20 steps in them that you might say well that's asking a lot of the environment can it happen though and the answer is often yes. At levels that were undetectable 20 or 30 years ago but you know we're in a lab we're doing we're looking at a very small subset of possible conditions we don't really know what the right conditions are so to make it happen at all is a big step forward.
The issues with the synthetic chemists is that they can produce the building blocks of life, but then they don't show a way of how those building blocks interact in order to create life or that the conditions necessary to produce those building blocks are so unrealistic. To my mind and the chemists, of course, would disagree. And, you know, we don't know so much about what the early Earth was really like. So they probably have a point.
But to my mind, it's not consistent with what we do know about the early Earth. It was mostly a water world, mostly an ocean. There was probably one to ten bars of CO2 in the atmosphere. It's highly doubtful that there was very much cyanide, if any. Perhaps there were some.
And the pathways that they've come up with look nothing like biochemistry as I know it is a biochemist. And so even when you've answered the problem, you've still got to say, OK, so how did life start then? You've got all the building blocks, but then what happens next? Whereas if what you're looking at is an environment which is kind of dynamic and continuously, you've got a continuous flow in, say, a hydrothermal vent, you've got a continuous reaction going on. And remember that we are
We are a continuous chemical reaction. If you put a plastic bag over your head and stop breathing, then your continuous chemical reaction stops and life stops. So we breathe, we have lungs, we have a cardiovascular system. We've got all of this sophisticated way of making sure this reaction is happening in each and every one of our cells. So take all of that away and say, well, how can you have a continuous chemical reaction that's happening, which is converting the environment into more of me, you might say,
When you use the word pathways or biologists use the word pathways, is that referencing the recipe that creates some end product?
What is the word Pathways? Yes, sorry. A lot of people have seen a metabolic map, which is like the map of the London Underground or something, except a whole lot worse. Really detailed.
Lots of names of particular chemicals with arrows going from one to the next one and names of enzymes connecting up the arrow. So a pathway would be you start with this compound, you end up with that compound and there's 10 steps along that way and you link them all up and that's the pathway. That's a biochemical pathway which starts with this substrate and ends up with this product.
And it links them up in a way which all life does pretty much in this, in the heart of biochemistry is universally conserved, not always the genes or the enzymes, but the chemistry itself that underpins it is almost always the same across all of life. Ah, so you're not just looking for the products. You're also looking for a similar pathway or pathway that's similar enough that conceivably with variation, it could have moved onto what exactly. Yes. Yes.
And this this altogether is is we're talking about scores of reactions, maybe a couple of hundred types of reaction all linked up in very specific ways, which we see in life, which is now encoded by genes, but the
Okay, and part of the reason why it's
strange to think of genes first producing the metabolism is because the way that we think of genes is operating is sequentially and incrementally and these pathways are so well it would it's difficult to think of half of a Krebs cycle or half of one of these steps as working? Yes and if you take it that way I mean there are various ways of thinking about this but how does a pathway let's say you've got 10 steps in this in this biochemical pathway
And let's say it's invented by genes. What do those genes do? So there's two main ideas. One of them is, well, you've got plenty of the product in the environment. But let's say there are organisms out there and they're beginning to eat that product in some way. And so now there's less of it. So if you can come up with a gene which takes the precursor to that product and converts it into the product, then you've got an advantage.
So you kind of start at the end of the pathway and work your way back one step at a time. Or you can do it the other way around. You can start with the precursor and work your way up one step at the time. But both of those ideas basically assume that all of the intermediates along that pathway exist at high concentrations in the environment and that you can get at them and that they are useful in some way. And all of these are very hand-waving ideas and there's basically no truth to any of them.
Whereas if what you're assuming is that actually going from one to another along this pathway at a low level, it just happens. You know, these things just interconvert into each other. And so at that point, a gene which speeds up any step will tend to increase the whole pathway.
So it's much it's much easier as a question in evolutionary biology, but how do you then kind of ramp up because all you're doing is increasing the flux through a system that exists anyway. And where does energy enter into this the way that I understand your the difference between you and how biology ordinarily thinks is with regard to information based is the biological way of thinking and then yours is energy based. So I haven't heard energy come into this. Yes. Yeah. Yeah. Yeah. So
So the way that life works generally, if you look at the tree of life, and this is another way in which biology has kind of intruded into the question of the origin of life over the last couple of decades, what does the tree of life say about the very base, the kind of bacteria that are the most ancient, the very first ones? They're not the very first ones. These are things with genes, with enzymes, they're pretty sophisticated cells. This is a common ancestor of all of life as we know it.
And you could say, well, it's not got much to do with the origin of life. Or you could say, well, perhaps it points in that direction. We can keep an open mind about that. So what does it do? What do these deepest branches in the tree of life do? Well, they're bacterial-like things, archaea and bacteria. And they're pretty much autotrophic, which means that they are converting gases in the environment into organic molecules, like photosynthesis, except probably not photosynthesis.
And they're almost universally starting with CO2 and hydrogen and that's the very core of biochemistry. You react CO2 and hydrogen and you get Krebs cycle intermediates. That's the first things that you get and from there you get amino acids and from there you get nucleotides and so on.
The problem is that hydrogen and CO2 don't react very easily. This is the problem that the chemists had for a long time. You can heat them up, you can add a catalyst. It does work, but it's difficult. It's only been in the last few years that people have succeeded in doing it. Now, what life does is it uses effectively an electrical charge on the membrane around the cell to drive that reaction.
The problem is it's thermodynamically favored, which is to say, if you've got a mixture of hydrogen and CO2 and you mix them up at, say, 50 degrees centigrade, thermodynamically, you should get cells. It's actually more stable to have cells than it is to have a disequilibrium of hydrogen and CO2. They want to react so long as there's no oxygen around. But kinetically, there's a barrier and they don't react. And that kinetic barrier is broken down by this electrical charge on the membrane.
Sorry, just to clarify, when you say you get cells, you don't mean cells as we know it as life, you mean that there's a membrane and it's oily and then there's a separation or? I mean that if you look at the thermo, this is theoretical thermodynamics that goes back to Jan Amund and Tom McCollum, and they have considered under the kind of conditions that I'm thinking about, this is 20 years ago now, under the kind of conditions that I'm talking about in alkaline hydrothermal vents, at 50 degrees centigrade in alkaline conditions,
Energy is released to make amino acids and fatty acids and overall total cell biomass releases energy from hydrogen and CO2. So, yes, it's favored. It's actually energetically more favored to have literally cells than it is to have a mixture of gases. That's what's driving life.
The problem is that there's a barrier to it happening, and that barrier is broken down by this electrical charge on membrane. So my kind of driving question is, where did that come from? How did it get going? Why do you think it is that there's so much disagreement about the definition of life? So in mathematics, you just simply state the definition. There's no squabbling over that. But have you come up with a definition of life in mathematics? I mean, the answer is no. It's basically, it's not
It's not easy to put it into an equation. I personally think it's the wrong question because life is a process over time. It's not a thing. The origin of life is not a moment. There isn't one moment where something becomes alive. It's a continuum from prebiotic chemistry right the way up to quite sophisticated cells with genes and macromolecular machines, motors and what have you.
And every step along that way, there isn't one moment where you would say it's now alive. There's suddenly something goes like that. And, you know, you can you could argue about is a virus alive or not? I would say it is, but it doesn't have a metabolism of its own and it wouldn't fall within most definitions of life. What about jumping genes, retro elements, these kind of things? Are they alive? What about something which is dormant to spore in deep space? Is it alive? No, it's not living now, but it could come back to life. So there's all these ambiguities about
I think what is living is a much better question. It's very easy to wave your arms and say, well, it needs metabolism, it needs information, it needs compartmentalization. Those things are probably true. But more than that, any definition that you come up with of life can usually be attacked. The classic one is known as the working definition of life from NASA.
And I probably can't get this quite right, but it's roughly a self-sustaining system capable of making copies of itself or capable of evolving or something along those lines. And I have a real problem with the word self-sustaining because it's basically sustained by the environment, by disequilibria in the environment. But people have poked fun at it by saying, well, by that definition, a rabbit is not alive. Only a pair of rabbits would be alive because only a pair of rabbits could make a copy. Right, right, right.
Okay, so there's some arbitrariness to it because it's akin to saying when does a grain of sand become a heap by adding more and more grains. Okay, so then it would be better to characterize it as a real number rather than zero or one.
It's certainly not binary, yes. I mean, you might even say death looks binary, doesn't it? But even death is not, because when we die, some of ourselves will stay alive for a while longer. It feels binary, and therefore the origin of life perhaps feels binary for exactly the opposite reasons. You wonder about when does life begin in humans? There's terrible arguments about that kind of question, and there isn't really a correct answer to it either.
So a better question may be when is living or what is living?
Living is an active process over time and it's a continuous reaction that is converting the environment into, in one way or another, more of itself. Whether that more of itself is just replace the broken bits, or if it's a case of make a copy of the whole cell.
Or fuse with another cell and go through some complicated process of sex and so on. But in the end, life is effectively parasitizing the environment to make copies of itself. And it does that through metabolism.
Okay, so two thoughts occurred to me. So one is, is there a way to put a number, like I mentioned a real number, but perhaps it's not as simple as that? Is there a way to place a number to how much something is characterized by living in the same way that you may say, well, consciousness is either you either have it or don't. But then there's some theories like Tononi's integrated information theory, where you have phi, which is like, okay, if you have a large number,
Okay so that's the first thought and then I'll say the second one then I'll come back to them just so that I don't forget them. Then the second thought was how far can we generalize this is so-and-so living because in the self-development world when you read you walk by the sections in the library they'll say yeah you're alive but you're not living you're not living your purpose. Well that's that's kind of that's playing with semantics
Okay, so that's taking it too far. Okay, okay. So let's focus on the first one. Is there a way I mean, I'm using living in the in the in the in the broadest possible sense, in the sense of alive as well. So so about, you know, consciousness, you know, if you look at the medical literature, there's all kinds of gradations of conscious states, whether you're fully anesthetized, or fully unconscious, or in some lower level of consciousness, and so on. And it's
You know, it's worth looking at that medical literature every now and then to realize that it's not an on or off switch there either. Yeah, I'm super interested in speaking with you about consciousness. So we'll get to that toward the end. Just so you know, I've been just absorbing your work for the past maybe two weeks or so every single day. And I have my own Nick cycle. So people have Krebs cycle have a Nick cycle in my brain. That sounds good.
Sounds hard. So just so you know, my background is in math and physics. Yeah, yeah, yeah. And I don't like biology because there's so many terms. Too many terms. There's pyruvic acid, which I assume... So I can only apologize about my book. I mean, you know, it's basically a problem with biology and physicists always have this problem with biology. Yeah. And, you know, it's understandable.
And there are, I think the most interesting questions in biology now really have questions in physics. But because we've had this almost kind of phase separation between physicists and biologists, there's not enough people who are biophysicists who are grappling with the biophysics of life. And so biology has gone off in the direction of information, but without really a very serious grounding in information theory, as a physicist might understand it, is really about, you know, just
Let's sequence the hell out of everything and see if we can find a pattern. And that's kind of intellectually very shallow. There are patterns there and we've learned almost everything about the world from doing that. But it doesn't really tell us your question, what is life and what is living and those things. The answer is not to be found in sequencing all the organisms. You have to take a step back and think about what is metabolism and what are genes and which came first and how do they relate to each other.
What processes on the planet are driving this whole process? And these are often questions in physics. But biology is so intrinsically complex that physicists very often get pissed off and back away and, you know, can't deal with too much pyruvate.
Yeah, there's a flurry of unmitigated polysyllabic terminology that is difficult to become acquainted with. The way that I imagine is that you become used to it over time. And so if you first encounter it, then it's overwhelming, at least for me. But you and Michael Levin are responsible for turn in tow in this channel toward more to interviewing more biologists. Michael Levin is doing amazing work. And, you know, all this electrical fields controlling development,
is most biologists at the moment, if you say that to them, would probably freak out. Probably back, I don't know what he said to you about this, but you know, he's obviously right. He's obviously found something which is really important. You know, is Nobel Prize winning stuff that he's doing, in my opinion. And it's profound. And this is the direction of 21st century biology.
It's trying to understand what actually is this language of feels in cells. It's early days in terms of that. But most biologists still now would back away from it and treat it in some way as pseudoscience or as just not real.
And yet there's corners of zoology which deal with electric eels and electric fields in fish or magnetic fields in navigation systems in birds and insects and whatever else. Biologists have known about this stuff for a while, not necessarily the development pathways, but it's a marginalized small corner of a field of information in terms of gene sequences is completely dominant.
Like I mentioned, I have a NIC cycle in my head.
But I mean that in many ways because I started bicycling more just to get your audio book in my head. So cycling is a great word. Certain words that you say strike me because your book is in my working memory currently. And you said 20th century biology is going to be the biology. Sorry, 21st century biology, the biology of fields. OK, why don't we expand on that? So so that was right at the end of the book. We're talking about consciousness, really.
but also development and how cells know when to stop, know where to go. There's all kinds of questions that Michael Levin talks about. From my own point of view, I've been thinking for a long time about bioenergetics. That's my own kind of specialty.
What cells are doing in the mitochondria is effectively pumping protons across the membrane and generating a charge on the membrane and that charge on the membrane is driving everything else. But I hadn't thought very much about fields as such because to generate coherent fields you would need to have quite specific morphology.
And it's not something I really worried about very much. But if you look at mitochondria under a microscope, what you'll often see is these membranes which are parallel to each other, which are offset by the same degree. And there's a very detailed structure there. And the more we know about these structures, the more we realize that they play a really important role in how mitochondria and energy works. It's not a trivial thing. Those membranes are arranged that way for a reason.
And we realize now as well that the motors, the ATP synthase, they're dimers at the end of these Christie, and all the rest of the complexes are in the middle. And so you've got a circuit going on. You've basically got an oscillating charge, which is going to produce a field. And we've got multiple parallel Christie all lined up next to each other. And if they're oscillating in phase, then these fields should be strengthened.
Now I'm talking in a language where you're much more comfortable than I am. Things that have happened in neurology relatively recently, if you cut an axon, for example, and separate it by up to about 40 micrometers, an action potential can still hop the gap. We've known about the EEG for more than a century.
the electroencephalogram. So we know that the brain is basically electrical but amazingly people don't really know where are those charges coming from. There's an assumption which is that oh it's just depolarizing neurons, there's some action potential going down this neuron, there's a network of all these neurons all doing their thing, hundreds of cells, maybe thousands of cells all firing simultaneously or in a circuit or whatever, that's what we're picking up on. But do we actually know that?
I don't think we do. The fields are quite weak on the membrane itself, but inside the cells, we've got all these mitochondria with stacked Christi generating what ought to be quite powerful fields, which should interact with the fields on the membranes as well directly and interfere with whether or not they're sending a signal or not.
And this is a whole area of biology that, you know, the moment is hand waving. We don't know if any of this is true. And it makes a very specific prediction about the orientation of membranes. If they're all offset to each other, then the fields would interfere with each other and it would never work. So, you know, there's quite specific requirements for this to work. But it does seem to be oriented that way. It does seem to work that way. And then you end up with really interesting questions to me, which is, well, why
The mitochondria, why these fiddly things inside cells? Why not the level of neural networks? And the reason for me there goes back
Actually, I wrote a book 10 years ago, 12 years ago called Life Ascending, and there's a chapter in there on consciousness where I failed to answer the question at all to my own satisfaction, at least. Well, everyone does. You're in a comfortable company. Well, I was left with two uncomfortable conclusions. One of them was that, and I was really only reporting on what other people said. One of them is that it's a property of physics, it's a property of matter, it's an unknown
unknown property of matter and when we know a bit more physics then we'll understand what consciousness is and so the Sun is conscious in some way or another it's panpsychism and it's got a you know people like Roger Penrose and and and and Hammeroff and so on have been arguing along these lines for for a long time. I find it uncomfortable
I don't really believe that the sun or the moon is conscious in a meaningful way. I tend to think of it as a, well, basically a property of a nervous system. But if you think of it just as a property of a nervous system, then it comes down from my point of view as a biochemist, you've got a depolarizing neuron, you've got sodium ions rushing in, potassium ions, ions are changing around.
that gives rise to a feeling and what's the feeling in physical terms if it's not a property of matter what actually is it and what you know is it simply in that sense an illusion that's concocted by a central nervous system and I find that very unsatisfying as an answer as well and it also kind of says that
It's a property of central nervous system. So what did selection act on? And this is where Michael Levin's ideas are really important because he's saying that, no, it's much wider than that. All cells have these fields. All cells are communicating electrically. It goes right back to not just the earliest animals, but probably back to single cells critters as well. And then when you start thinking about
Well, the charges in mitochondria are inside cells. Well, mitochondria were bacteria once. They were free living ones. And so the charges that they have on their membranes is separating the inside of the bacterial cell from the outside world. And so it has much more meaning. You can understand why selection would act on that. It's effectively telling you, how am I doing in the world right now? Am I about to die? Is something gone wrong? It's a real selective value that this is kind of giving you an
And integrated real time feedback on your state in the world as an electrical field that integrates the whole cell. And when you start thinking in those terms and you start realizing that well driving this reaction between co2 and hydrogen at the origin of life requires an electric and an electrical charge on a membrane.
And so electrically charged membranes go right back to the beginning. And it's the only way really of integrating the cell as an entity in relation to its environment. Then there's a beautiful idea there. I'm not really saying that bacteria are conscious in a meaningful way. It's just that there are kind of integrated states of their state of being in the world. Either they're doing well or they're stressed, you know, that kind of level of feedback.
and it's calibrated by a field and those fields are used during development to say okay now you've grown enough now stop now you're in a high or whatever it may be and this is a whole language of how fields are communicating in biology which is we've barely touched the tip of the iceberg okay let me see if i got the stream so earlier we you mentioned that there is an axon you can cut it and then you can separate it such that
Chemicals shouldn't be able to be interchanged between here, like neurotransmitters. It's too slow for that. Yes. So it'll just hop over as if there was no gap. However, there's still a signal and that signal is called an action potential. Yeah. Okay. And one of the reasons you think or people think mitochondria are important are because you use this word Christie, which I believe refers to the these are the membranes inside inside. Yes, exactly. Yeah. Okay. And the reason why these
Folds are important is because they have plenty of surface area, even though they're small. Yes, they have a lot of surface area, but they also have a structure and an orientation. They're lined up in parallel very often. And they have a very high charge. And ironically, it's very difficult to measure that charge. Why? Because if you're measuring the charge in a neuron,
You can insert a microelectrode into a neuron, and originally it was all done with giant neurons in squids and things like that. But still, you can insert an electrode into a neuron. But remember, a mitochondrion is a small part of a cell, so it's much smaller than a neuron. And people have done this. People have inserted microelectroses into mitochondria.
And the irony is they've never really measured much of a potential difference. And the reason for that is almost certainly that they've just inserted it into what's called the matrix, which is the main kind of bulk space inside the mitochondrion. And so they're measuring a difference between that and the rest of the cell. And it's not much. But then you've got these structures, the cristae, which are very tight membranes, which is basically impossible to poke a needle into. And that's where all the charge is. So to try and measure that charge is a really difficult thing to do.
And people are getting closer to it now. There's some really clever, ingenious ways of trying to measure what exactly is the charge in this closed space, really narrow closed space. But it's a very difficult technical problem. You can basically calculate it. You can show it with dyes, but you never really know what the dyes are interacting with otherwise. So it's intrinsically difficult.
Okay, do you imagine that this is a technological problem that will be solved in the near future, or there's some in principle reason why it can't be done? No, I think, I mean, it's just difficult, but I think we can do it. I mean, I intend to give it my own best shot, but there's a few other people thinking along these lines as well.
Now the fact that mitochondria may be important for consciousness, does that imply that the bacteria which don't have mitochondria are not conscious or at a much lower level of consciousness and protozoa? So protozoa do have mitochondria.
and you know you can see videos of the way that they behave and they're astonishing I mean watch videos of protozoa the way that they move around and they go fishing they do all kinds of that the control of their behavior is exquisite it's the kind of thing that would you know should make people believe in God it's just so beautiful so it's not a matter of genes being expressed there's something controlling this system which is
which is happening in nanoseconds. It's happening extremely quickly. And it's the whole cell which is doing this. It's not just one bit of the cell. Imagine you're a molecule. Finish the book this way. Imagine that you're a molecule. Shrink yourself down to the size of a molecule. And the cell is like a city. And where I am now, I'm in London and 15, 20 miles away through to Canary Wharf or Greenwich or somewhere like that.
there would be other molecule you know the people over there would be like me as a molecule as a pyruvate molecule inside a cell or something so what is it that unites me with this person 20 miles away in a cell and the answer is well you know in the city not much some kind of shared sense of identity as a londoner or something but you know you know you you know that you're living in a city where that's conscious awareness but in a cell where we're dealing with molecules
How does something happening over here happen over there simultaneously, essentially simultaneously, effectively 20 miles away, so that we're integrated in real time and doing the same thing? Now fields can do that for sure, so how would you have a field that operates on the whole cell? Well if it's on the membrane that surrounds the cell
And if what that membrane is reporting on is how are you doing in relation to the environment? Because if you're taking up food from the environment and burning it and using the energy to generate an electrical charge on the membrane and there's plenty of food, you've got a nice charge, everything's good. So it's telling you that the whole cell has got a nice electrical charge on the membrane. There's a nice field crossing the cell, oscillations of water molecules within the cell are kind of locking things in some kind of phase.
And that is telling you about your state. If you move into an area where there's toxins or where there's no food or whatever it may be, then they're going to interfere.
with how this charge works is going to change the field and you're going to shift, you're going to change what you do, you're going to move over there, you're going to set your phagellum worrying or something, you'll change your behavior but you do it at the level of a whole cell and what's integrating at the level of the cell in my view now is the charge on the membrane generating a field which is integrating all the component molecules in the cell to act as a
There's one question. If we have one cell and it's, we imagine that it may have some proto form of consciousness because it's interacting with the outside. Okay. And then if we have two and they're interacting with one another, then we have a consciousness that is of the two as a whole. Not necessarily. If they're in, if they're locked in phase in some way, as they may be with two neurons locked in phase in a multicellular organism,
then yes they could be but if they're not in phase then they would interfere with each other in some way. There's actually lots of evidence that for example pollinating insects when they arrive on a flower can sense electrically whether or not it's already whether the nectar has already been taken so they don't bother to go there. There's interference that I don't know very much about but
You know, there's quite a lot of evidence that the animals have fields that are capable of interacting with each other. We just don't know a huge amount about it. And the idea that cells would do the same thing. I mean, you can see it under the microscope. We don't know exactly what's going on. I don't think we've ever measured it. But I'm fairly persuaded that fields would be one of the most powerful ways of trying to explain the interactions you see between single cells. Yes.
Now this locked in phase quality I imagine is also a spectrum and not zero to not binary or is it? I know well you tell me you're the physicist I mean I would imagine that there's something of a spectrum but but there's some element in which once you get interference then you don't have you would not have any locked in phase. What I'm thinking is that
I'm imagining the brain akin to there's vertices, or there's points, there's vertices, and then there's edges between them, and then there's a slew of them, and then they're interacting with one another. And that any subset of these, not any subset, but there will be manifold subsets, so plenty, not manifold in the math sense, but many, many subsets that will be in phase with one another at any given point in time. And so any individual comprises perhaps more conscious
subsets then there are atoms in the universe if you do some analysis of how many subsets and so on that is to say that nick is not just one consciousness it would be trillions or 10 to the trillions but i don't know because i don't know what counts as consciousness here yeah i mean i'm not i'm not a neurologist and i'm not working on consciousness as we know it in human brains what bothered me
It's a question in philosophy as well. It touches on AI and whatever else. If you've got an extremely sophisticated processing system, and the brain is an extremely sophisticated processing system, does it need to be conscious? Is there some kind of emergence? And if so, what governs that emergence? And it may be that that is the case.
I find emergence one of those words which is overused it has a real meaning but it's very easy to say oh it's an emergent property and you know it basically says I haven't a clue what I'm talking about it's just a nice word. So I had this problem I can imagine
the classical philosopher zombie, which is capable of behaving in a perfectly normal human way without experiencing any emotions or any feelings or anything else. And I can imagine robots and AI being like that as well, capable of being enormously intelligent and having conversations that would persuade us that they are human, but without feeling anything.
And so I'm background to this question of, well, what is a feeling? Is it real? Is it a concoction of a central nervous system, an emergent property? What actually is it? And to my mind, natural selection always works on something else. There are simpler systems. So I'm perfectly happy to believe that a dog, for example, is not necessarily
that intelligent? I don't know, but I would think it's consciously aware and capable of feelings capable of emotions. And the idea that a dog will pine after its masters died or whatever is very familiar to most people. And it seems obvious to me that that would be the case. And from a biologist point of view, why would it not be the case selection has to act on something? Why would one central nervous system be utterly different to another one?
There's a matter of, it's a continuum again. We have a really high powered processing system, but our feelings, our emotions, you know, I think we've probably shared them with a lot of other creatures and it's very easy to imagine that, you know, a chimpanzee can be in love or can feel pain or any of these feelings. They feel animalistic to me and we can nuance them with all kinds of
intelligence and thoughts and language and whatever else, but the feeling of malignant sadness underneath everything else, it's not something that you have much control over, or a feeling of just being overwhelmingly in love with someone. We have no control over these feelings. They're very separate almost from a parallel processing system. They can be overwhelming.
So what are they? And this is where I think this language of feels and so on comes in. And I'm not saying that a bacterium is conscious in a way that any of us would recognize. I'm just saying it's the germ of a kind of a something which tells you about your state and which is not just more than the sum of all of these parts. It's something which gives you an integrated feedback on, am I effectively sad or happy, you might say? Am I
Okay, so to be clear, you're not claiming that this solves the hard problem of consciousness, but rather if consciousness was to have some physical explanation, perhaps we should look at what's occurring at the cell membrane electrically.
Well, the membranes inside in the mitochondria and so on. Yes, I think that's the language. I think that provides a selective basis for how it began. I think it's, you know, this question about what purpose is consciousness in natural selection.
If you think about it at the level of single cells, if you think that it's giving you this real time integrated feedback on your state in the world and whether or not you make a decision as a cell to go over there or to stay here or to depolarize your membrane and kill yourself immediately if you've been infected by a virus or all of these kind of decisions that you take as an entity, this is providing you with a kind of language for the entity.
You immediately see what selection is acting on and the hard problem in consciousness is to a large extent about what are feelings, what are emotions in physical terms. People have been talking about electrical fields for quite a long time in that sense as well. This is again nothing particularly new but why that language
why why would electrical fields give you some kind of feeling of being conscious when you take it out of the environment of a nervous system and put it into the environment of single cells and this real time feedback
on their environment, their state in their environment, then you see it's the only language which is going to integrate you as a unit, which is going to tell the other half of the cell 20 miles away over there that your action is for the whole cell.
And so when you put two cells together and you build multicellular organisms, you're using these fields to control the development of the organisms, as Michael Levin says. And then as you end up with a central nervous system, it's channeling more of that energy into circuits. And, you know, whatever the explanation is, it has to correspond to what we already know about neurology, about the way that neural networks actually work. And the problem I have, for example, with
With Penrose and Hameroff and the idea that it's all to do with microtubules, for example, is that it's not very obvious how they correspond to, at least it's not to me, how they correspond to what we already know about neurology, about neural networks and so on. Whereas mitochondria are completely integrated into that. They're part of the neurons, they're part of
the depolarization of neurons they can interfere with this electrically and so on. So they're linked in with the structure I think of the neurons in a different way. The reason though that I came back to this and started taking it seriously
And you know, lots of people seem to think that I'm barking at the wrong tree altogether and should never talk about neurology again or consciousness again. But the reason is an interaction with a biophysicist called Luca Turin. And he came to see me a few years ago and was talking about anaesthetics, general anaesthetics. We don't really know how they work. And
And he was interested in xenon in particular, which is an inert gas. And it doesn't really have a shape. It's a sphere of electron density. So it's not obviously going to interact with any type of receptor. And all the different general anesthetics, they have different shapes and different chemical properties. And it's not obvious that there's any kind of type of receptor that would deal with them all.
And it doesn't really have any chemistry, but it can transfer electrons. And so it can interfere with electron transfer. And what Luca Turin had shown, which really made me excited, is that they do interfere with the transfer of electrons to oxygen in respiration. Now, that doesn't prove it's causal. That just shows that anesthetics interfere in some way with respiration.
And maybe if they simply suppress what the rest of the cell is doing, that would have a knock-on effect on respiration. You could say that that would be the case. But he didn't find anything else that a general anesthetic was having an effect on. And so if you put it together with what I was saying about the requirement for cells and the electrical charge on the membranes to integrate their state in the environment, then suddenly it's a rather thrilling idea.
Doug Wallace is another person who's been working on these fields in mitochondria for some time now and again he's out there on a limb as far as biology is concerned. He's one of the few people who's willing to talk about parallel Christi generating strong electromagnetic fields that are reinforcing each other and communicating across distances. This is not
This is not the language that biology is used to and Doug Wallace is very distinguished and so people will kind of tolerate him towards the end of his career talking about these things. Luca Turin is, I won't say he's an outcast, but he's on the edge of scientific respectability and it's not because he's not a good, he's a brilliant scientist, it's just that he's saying things that people in biology don't want to hear.
Interesting. Turin has found that xenon interrupts or interferes with respiration. And when you say respiration, you mean cellular respiration? With the transfer of electrons, yes, which is to say this is what's going on in mitochondria. So you basically have a current of electrons going from food to oxygen.
and gases like xenon interfere with that current of electrons. And that means that it makes respiration less likely to occur. And by the way, what is cellular respiration? I assume it's taken oxygen, but I don't know if that analogy between my respiration. Yeah, I mean, basically, yes. No, it's exactly right. I mean, we're stripping electrons from food by the Krebs cycle. That's what the Krebs cycle is doing. It's taking electrons from food. It's feeding them into the membrane.
Then we have a current of electrons in the membrane going to oxygen. Oxygen picks up two electrons and two protons and it ends up as water. Basically, we're reacting hydrogen, the electrons and the protons, we're taking hydrogen from food, we're reacting it with oxygen, but we're not doing it in one step. That's rocket fuel. That's what's powering a rocket.
We've basically got a current from one to the other and that current is powering the extrusion of protons across the membrane and that's what's putting the electrical charge on the membrane. So now we have an electrical charge on the membrane and the orientation of these Christi structures means that this is a current of protons. It's an oscillating current of protons and that's what's generating the field. Is there a radio wave associated with this? Turin found that somehow... Yes.
There is, yes. I have to say I don't quite understand that.
Well, there's a funny story that he tells about that, because the guy who, I forget his name now, the guy who discovered the EEG in the first place, the electroencephalogram. Michael Cohen or no? No, that's different. No, no, this goes back much before. I just have different snippets of the book in my head. I remember Michael Cohen said something like, no one understands. No, we're going back 100 years or more.
to the discovery that the brain is generating electrical signals that can be detected with the electrodes on the scalp. He was actually looking for radio waves. He was looking for long distance communications between people. I think he'd had some premonition that a terrible accident had befallen his sister or something. Lots of people have these premonitions that something terrible has happened to a friend.
I have them as well and every time I have them it never turns out to be true but you know for some people it's true. Is it true? Is it true because it's real or is it true because it statistically is going to be true sometime? I don't know. I've never looked exactly but that's what he was interested in. That's what he was looking for. Communication by radio waves between people at a distance of maybe hundreds of miles and he discovered the EEG instead and it's ironic because
The key, we're on your ground again here more than my ground, but there's an Israeli scientist who's shown that electron spin, if it's passing through a chiral medium, ends up in the same spin state. So it's been polarized. And a chiral medium includes proteins because proteins are made of amino acids and amino acids are always in the left-handed form.
And so all the current of electrons that flows from hydrogen to oxygen goes through proteins in this membrane and those proteins are chiral and that means that the electrons that are transferred are actually locked in the same spin state and when you lose that spin state that emits a radio signal and that's what leukoturine has detected.
You mentioned something interesting, which is that there's apparently a psychic phenomenon unverified, or maybe it has been, but we don't know. As far as I know, it's unverified. Will people believe they can communicate to one another? One of the reasons why on theories of everything, I don't mind talking to some people who believe they've done studies and they're excluded from academia for whatever reason, I want to find out the validity of those, because I think that there may be something to a certain
Aspects of what people consider to be paranormal that their explanation for why it works may be incorrect There may be some physical basis like it's that we work obviously communicating right now We don't think that there's any psychic abilities involved because we're just going through the computer But perhaps something similar where radio waves are being transmitted and if it's of a strong enough distress Then perhaps the person feels it. I think that science is intrinsically very conservative And there was a lovely phrase from Peter Meadow who said science is the art of the soluble
which is to say problems that we can actually solve. So problems that we can't solve because we don't know how to go about it. We tend to put to one side and reject is not science. And that goes for all kinds of things, including ESP and so on. Now, to my mind, there's two questions. Number one is, is it real? And then number two is, well, can we then explain it? And
I don't think very many scientists get involved in the question of is it real? It's just not part of what science asks because we don't have a way of answering it really, so we don't ask it. So it may be real or may not be real, I don't know. I think there's another factor though which is that
Occam's razor, which underpins all of science really, which says don't multiply causes, try and find the simplest explanation that explains everything we need to know. It may or may not actually be true, but it is what governs science, which is to say you first of all take the simplest possibility and test that. And if it doesn't work, then try the next simplest one and work your way up until you end up with something mad.
But the problem with anything like ESP is it's almost certainly not the simplest explanation for things. Now, if someone were to show that it's real and that it really is happening, and statistically in some kind of trial, it would have to be with the power of a clinical trial, and then it's going to cost a lot of money, and there's going to be so many comebacks from people who are determined to demonstrate that it's not true, that it would be a very, very difficult thing to do.
and
Then it boils down to personal experience. I've never really, you know, I don't really believe in ghosts because I've never seen one or I don't see any reason why they would exist. And I've never had any experience with them, but perhaps if I did, then I would change my mind. I don't really believe in ESP because I have these feelings that other people have that says something terrible has happened, but I phoned them up and nothing had happened. It was just a figment of my imagination. Well, you know, there's a simpler explanation, which is just that my brain is active.
You're thinking about someone. Probably for most people, most of the time, that's the real answer. I'm skeptical of these things, but there's a whole lot more out there than we know now. I've been talking about fields and consciousness and so on. That is already pushing the barrel out for most biologists in terms of what are we willing to accept now. I think there's very strong grounds there for accepting those kinds of things.
We can begin to push it into looking at other languages and genes. But if I then start spouting on about ESP or something, then I'll be cold-shouldered by the entire community and I have no desire to go down that path because I have no strong reason to think that exists anyway.
Okay, I don't have a question, but I have a some thoughts. So then I can just take them and then hear what your responses to them. So number one, when it comes to Occam's razor, I always find that a bit tricky, unless someone's speaking about something in physical law, something mathematical, Occam's razor, it's unclear to me what constitutes as an assumption. So for example, in physics, the way that you say that
a certain model is simpler is that you use less parameters to specify it so it's actually quantifiable how simple the model is and that's one of the reasons why people say string theory is the most beautiful because it can supposedly reduce it all down to one parameter it's still one parameter like there's no yeah there's still some freedom there but it's one as opposed to 26 or so yeah and then so let's say the principle of induction in science is that one assumption or is that two assumptions or three assumptions because it presumes there exists a future and a past and then
I'm sure you've heard of the problem of induction. The point is, if it's not mathematically stated, then to me, because my brain is so analytical, it's difficult to see, well, what's being assumed and what's not? Like, is God the simplest assumption? Well, then God has the trouble of explaining. Like, you can't predict from that. But God certainly is the most simple assumption. Well, yes. I mean, it depends what... But then it's not simply simplicity. Is God five assumptions? Well, I mean, as soon as you start wondering,
where God came from. Hear that sound?
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If you use that code you'll get two years worth of blades for free. Just make sure to add them to the cart. Plus 100 free blades when you head to h-e-n-s-o-n-s-h-a-v-i-n-g dot com slash everything and use the code everything. You know what what gave rise to cards in the first place there's a lot of assumptions behind that so something is
As profound and all encompassing as God requires in some way an awful lot of assumptions behind it. But then we know a lot about the world as well. We don't understand it all. But it's definitely four and a half billion years old. There's definitely signs of bacteria from four billion years ago. There was definitely stasis for about two billion years. There was definitely oxygen appearing
around two billion years ago. There were definitely more complex cells appearing after that. Animals certainly appeared around the time of the Cambrian explosion, 540-50 million years ago. And so, you know, any assumption that God did it would require either a deist God that set it in motion at the beginning and then it follows its own path, or a God that's kind of involved all the way along with every little bit here and there. And there's no
There's no need for that, as Voltaire said, there's no requirement for God to kind of get involved in this species of bacteria differentiating from that species, you know, that's the level of detail he would have to be involved in. So there's no need for that hypothesis. Deism,
I think will be very difficult to reject for most scientists who had an open mind. But deism I don't think is something that most people who are religious would be terribly happy about because I think for most people God is
communicating with them personally in one way or another. So the idea that there's an aloof God somewhere at the other end of the universe that sets the laws of physics in motion and then steps back and is never seen again is not much of a comforting figure for most people. But frankly, what we know about the world, if it's consistent with any form of God, is more consistent with a deist form of God, I would say, than anything else.
So then there are assumptions and science works on these assumptions and they may or may not be the simplest ones but they underpin everything and one of them is that it's naturalistic, that it's not miracles, that's not science, that's an assumption. We assume that life started and that we can understand the principles that govern the origin of life and the evolution of life and so on
It may be that...
There were miracles. It may be that it was delivered from outer space. There's all kinds of things that could have happened, but we make a simplifying assumption that it happened here on Earth and it happened for naturalistic reasons and therefore we don't call on a miracle and that we can understand those naturalistic reasons. These are three huge assumptions that may not be true. There's nothing scientific about them, but all of science is built on those ideas. And the reason that I believe it to be true and most scientists would is that
Well, everything we know about the world is consistent with that idea. So everything I was saying earlier on about you start with carbon dioxide and hydrogen and you get Krebs cycle intermediates and you have electrical charges on barriers in these hydrothermal, all of this is, is consistent with the naturalistic origin of life. It's a long, long way from proving that that's what happened, but everything I know about it is consistent with it sufficiently that I have some faith
I'm using the word deliberately, faith that the gaps between the bits that I know a little bit about and this long spectrum of things that I don't know much about can be filled in in due course if we keep on thinking constructively in that way. So I think, you know, science is always based on assumptions and it's always based on some form of faith which most scientists are very reluctant to use the word faith because in a religious sense faith very often means belief in something which
which is irrational in some way, that it goes against the evidence. Whereas in science, faith is perhaps more about, I have faith that there'll be more of this kind of evidence that will explain the way that the world is. It's a form of faith. It may or may not be true. It may be delusional. Hear that sound?
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It's very powerful because it's led to all these scientific advances that we see in the world and that leads people and most people to to begin to believe that science really can explain the world and there really isn't a need for a god to explain the world unless it be a deus god that put these principles in place in the first place and that you know
That's the way I would see it, but I have a lot of sympathy with people who prefer a religious view of the world. And I certainly couldn't argue against the deists' position.
I wouldn't say that it's a minority, the deist position. Well, when I say minority, I mean, it's a sizable minority if it exists. Because when I was looking at the Pew research data on belief, I believe something like 10 to 20 to 30, let's say 10 to 30% of people believe in a deist God of those who say that they believe in God, that's sizable, because I thought it would be 0.02.
Yes, I would expect it to be smaller as well. Yeah, it's an extreme amount. And then secondly, that there's a sizable portion of people who believe that the definition of God is reality. So by science, one is studying God. And it's not so I used to be the same. I love that as an idea. I have to say, I don't personally believe in God. But the idea
that people who have tried to understand the world in the past as the world that God put there, I have a huge fellow feeling with them that they were trying to understand the world, they were trying in some way to understand the mind of God. What is nobler in this world than trying to understand these things? And whether or not you put the word God at the end of it, it seems to me almost a trivial distinction
I remember my grandma saying to me years and years ago that to her God was the voice in her head that told her what was right and what was wrong. It was basically her conscience and I remember saying to her, well I have a voice in my head that tells me what's right and what's wrong and I don't think that it's God and she was shocked and horrified that effectively I was saying I don't believe in God and it hurt her deeply and I've never quite forgiven myself and you know I'm very careful
To try not to offend people because to me it's not very far away. It's just ways of phrasing things, ways of seeing things and there's no need to be deliberately offensive to people when actually we may both see the glory of the world and want to understand it. Okay, let me get philosophical here for a moment.
I think that was about as philosophical as I can get. I'm agnostic when it comes to this. I'm not coming at this from a religious perspective, just so you know, so you can feel safe to surmise in any direction. What basis so your mother, sorry, your grandmother had a basis to believe in the in the to follow her conscience. If you don't believe that comes from some higher place, what does higher mean? Who knows? For the sake of this, let's just put that aside and assume that we can intuit that. Then why should you follow your conscience?
Because our conscience has evolved in the context of society, of human societies, of groups, of human groups. To my mind at least, you know, there's all these interesting questions about human evolution. When and why did we develop in the way that we did? When did the human mind take on the ability to be creative, to do art, to believe in gods and what have you?
the things that we think of as human. And it's not obviously to do with tool use, for example, they often, you know, the use of flints and things and spearheads goes back hundreds of thousands of years, if not more than that, and didn't change very much over a long time.
And things like fire, it's a little difficult to know exactly when was fire invented. And language is another thing that we tend to, as soon as we've got language, then we develop our minds in some way. The one thing that it seems to correlate with most interestingly is population density. This is work that I know of from Mark Thomas, who's a colleague at UCL.
And that corresponds to human migrations, it corresponds to climate change, all kinds of things that we're very familiar with now. But if you have multiple groups of people that are interacting with each other regularly, whether it be through warfare or whether it be, you know, much more congenial interactions,
Those interactions are forcing creativity and ingenuity and, you know, sense of loyalty or tribalism or whatever it may be. And right and wrong can hardly help, but it has to emerge in that kind of an environment. And it has to be very conflicted. You know, surely anybody knows that the people in the tribe over there that you've been brought up to hate are human beings too and have, you know, have everything that you have.
Why do you hate them? Because your tribe brought you up in some way. You know, we are horribly conflicted and our sense of right and wrong comes from this kind of conflicted feeling of fellow humans and loyalty to groups and whatever else. And no wonder we can't agree about it. It's grounded very deeply in our emotions as individuals in the social context.
Let me stay on this philosophical course for just a few moments longer. So firstly, this assumption, which I believe is a great assumption, but I do believe it to be an assumption that we're all human. The reason why I say that is that, well, human biologically, yes, but human also has a connotation of you being worth a certain amount and having dignity afforded to you and your rights to be the same as mine. That's fairly, fairly new. Genghis Khan, for example, well, many, if you just go back 1000 years or 2000 or 3000 years,
Human is my tribe. You're not human. You're inhuman. You're subhuman. Yeah, yeah. I mean, I don't know enough history to comment on that. I mean, I find it hard to believe that that we could ever really have felt that way. It seems, I mean, you know, culture and society will tell us that there are differences between people and racism and everything else. You know,
has stained human history but it's kind of obvious and we know now, you know, genetically and scientifically that there are essentially, we're amazingly similar to each other as humans.
evolutionarily very closely related to each other. We diverged very recently and we have all of these systems for, you know, categorizing people. And I'm part of it in the sense that I work in a university and I, you know, mark exams and things like that. And I'm very conflicted over exams because they, they, they, they mark a certain type of intelligence and they give credit to, and, and, you know, there's so many different types of intelligence that we're not adept to categorizing.
And very often to my mind the people who are the best researchers, they're not necessarily the people who do best in exams, they're the people who think about things in their own way and who are obsessive about the question and who keep on pondering it and don't give up very often. And there are some effortlessly brilliant people but there are also, Darwin himself was probably
not necessarily the sharpest cookie in the basket, but he asked and kept on asking these questions and ended up coming up with answers that were more important than anybody else's. It is different forms of intelligence. And, you know, Western civilization, Western culture has tried over centuries to categorize and to have a hierarchy and to put the white man at the top of the hierarchy. And it's so patently not true.
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Okay, so then here's some more thoughts.
Again, a few questions, but just thoughts. And then we'll get back to some, well, these are biological questions. So we're saying that, hey, humans are so related to one another. And so it's difficult for you to imagine that other people would think of other people as not being human. But then to me, I was like, okay, well, we have another spectrum issue there, because it's arbitrary, where we define the line as being sufficiently different enough to not call human. And then secondly, it's unclear as to what makes you you is it purely your DNA, but or is it also the culture and the ideas that you
Of course it's the culture and the ideas. And then if so, well then what we can say is this tribe has a right to say that you're sufficiently different than me unless you convert to me. I mean this is the nature of human history isn't it? It is tribalism and it is generating a sense of difference. I mean you could almost say that culture has gone out of its way to erect differences where they don't exist.
I think individuals will always, if two people from any culture anywhere in the world are left as the only two people left on the world and are forced to talk to each other, they will realize they have everything in common with each other. It was true for practically anybody on earth now and always has been. But this idea of human or non-human, biology is so full of continuum, was a neanderthal of human being.
The last point is that if we agree that tribalism is natural and is almost universal, then what if one's conscience
led them in the direction of saying hey in order for my genes to survive it's better that my group compete with your group and my conscience is telling me so so this gets back to the question because i was asking yes well why follow your conscience and you were saying well because it developed evolutionarily well what i'm saying is yes yes in other words you're saying is wrong it grew up in the context of tribalism
and antagonism between different groups of people. Therefore, and I said, you know, the sense of right and wrong is deeply conflicted and probably not a good guide to things. One of the, I think one of the great things about, I suppose, the history of
From the Renaissance onwards, it's an attempt to break down some of these barriers, to think in broad terms about what human rights are and what are humans. You know, it's been a very, you know, it admitted women for a long time, it admitted different groups for a long time, but it was an attempt to begin to give people rights and see people as
as equal. And this idea that we're equal is obviously, again, we're not equal. We're not equal genetically. We're all different genetically. We're all unequal almost by definition. That doesn't mean to say someone's better than someone else. It's different. And we come from societal cultural contexts which are different and which condition you to think differently about things. And those are breaking down. And thank God for that. We lose things when they break down.
We lose our culture, our tradition. Groups lose languages. There's a loss to seeing humanity as a single unit, a global family, if you like. There's all the cultural histories that groups have which are wonderful and often different but similar.
they can be engulfed and they can be lost and it's in a way is tragic but at the same time if what we do is cling to the differences and the cultural things that set you apart from everybody else and then look down on other groups I don't think there's anything in biology that says that that's the case. So you know what we need is somewhere
In the middle where we're proud of our cultures, we're proud of traditions, but we somehow understand other groups as equally human with equally valid and important traditions that we live side by side together. One of the lovely things about living in a place like London is it's often called a melting pot, but different cultures live side by side, I won't say happily, but reasonably happily.
People from countries that are at war elsewhere in the world will rub shoulders together in a place like London and get along together okay and maintain something of their culture and their own sense of identity and self-worth without hating everybody else.
Okay, let's get back to the book. This is a great transition, because you mentioned it would be great if we thought of ourselves as a part of a larger whole. In the beginning of the book, I recall there was an analogy made between a city and a cell and saying, okay, let's zoom out at a helicopter view and look at a city and it looks akin to a cell. Perhaps the cell is well, I think a cell is well, I don't know if that's true, but
And then there was a line that said, the cell is living, potentially, the cell is living, but
It's but obviously the city is not something like the obviously yes thinking is it is it obviously that the city is not like what makes something living is it just something that this is obvious that the city is not its own conscious being if if one of our neurons has some proto consciousness but then the collection of them also have a larger consciousness are we a part of a larger consciousness or is it slow transmission speed yeah what you're back to there really is is consciousness an emergent property of a sufficiently complex system
And what I was arguing earlier on is that it's not. That it is a property of an extremely complex central nervous system. But it wasn't an emergent property from it. It was something which was an integral part of that complex system from the very beginning. I was talking about the language of electrical fields and cells and so on. And this is what has been ramped up. And so the very
complex feelings and so on that we have now are effectively, they've been through a process of natural selection. They have real meaning for us because they've really been selected. It really does matter if you're starving or if you're dying of thirst or if you are in love or whatever it may be. These feelings are real because they've been through
Essentially, uncountable generations where they bore some resemblance to what happened to you, to people, to animals, to organisms in their lives. That if you have this overwhelming fear of something and you run away, you will do better. If this overwhelming sense of something
has a selective value and at the level of single cells it has a selective value just in terms of integrating the cell as a unit as something which can physically go over there rather than have this flagellum firing that way and this one going another way you know what what integrates this system.
So you have a system which is capable of a purpose, if you like, to read too big a word into it. And that has been honed by selection and ends up in a central nervous system. It's not an emergent property, it's something which was built in from the very beginning and has just been kind of raised as part of the edifice. Now, from that point of view, a city
It hasn't been through generations. It hasn't given rise directly to an offspring city. It hasn't competed. It hasn't died. It doesn't have any of these biological mechanisms of selection. So I think any biologist, and maybe we're very limited here, but any biologist would immediately say a city is not alive as I did. Any physicist would probably say, well, hang on a minute. Are you really so confident that you know what life is that you can say that a city is definitely not alive?
That boils down, you know, I had a subtitle of an earlier book was why is life the way it is? And the question to me is actually a really serious question, which is, does it have to be this way? Or could it have been a different way? Could we have Fred Hoyle's Black Cloud? Could a city be alive? Can AI become alive? You know, they're very interesting, difficult questions.
And unless we understand, I think there's two ways of going about it. One would be to say, oh, you've got a closed mind and you're a biologist and you're thinking about carbon and you're thinking about cells and open your mind and be open to other possibilities.
Yeah. And the other way of seeing it is to say, well, I don't know. Does life have to be these things? We know the only example of life we know is life here on Earth. And we know that it's carbon-based. We know that it's cellular. We know it thrives in water. So did it have to be that way? Or could it have taken a different turn? Or could we? If we understand why life is carbon-based, then we can begin to say, well, life has to be carbon-based. Or no, it doesn't have to be carbon-based. Or some spectrum in between.
And this is where physicists will very often by temperament and by training split off from biologists because physicists will want to see the universe as almost infinite possibilities with a very small number of laws governing it. And a biologist will want to see
study the example that we have in front of us realized there are no laws but there are some principles that guide us that you know there are no laws in biology and so it's fuzzy and it's it's uh it's immediately irritating for any self-respecting physicists but that doesn't mean to say that there isn't something to understand from life on earth as we know it and and there's you know this the origin of life field has in a strange way almost tried to ignore what life actually is
we know about and to my mind if we were to find life on a thousand different planets throughout the Milky Way or something then just because carbon is so good at the chemistry that it does because it's so abundant it's one of the most abundant
elements in the universe. It's really good at producing molecules that are quite large. Water is also extremely abundant and it does very interesting things with organic molecules. You can have membranes that are not soluble and you can have proteins that are soluble. There's a wealth of possibilities there.
So you take into consideration the abundance and how good it is at doing this chemistry. And then you think, well, is there an important distinction between an outside and an inside? Do you need a compartment? And if you're going to keep your inside different to your outside, stuff has to come and go. Does that give a size? Are there constraints on how large something can be and how active it can be? Obviously, there are. You don't need to really understand exactly what governs those constraints.
So let's talk about life on other planets.
Potential life an interesting phrase that people say when they speak about life is life as we know it I always found it to be interesting life as we know it because again like coming from math You just have the definitions you just say here are the necessary and sufficient conditions and then that's it to say some so-and-so as we know it is
implies that there could be something else why by what basis will we have to call that life as if we have an intuitive feeling as to what life is and we point to certain examples and say this is living this is not living we haven't quite captured it with our explicit language but it's there implicitly that's the only way that i can make sense of life as we know it but i mean i think i think there's an emotional charge to that phrase life as we know it says
out there there is life as we don't know it or there may be life as we don't know it and our little limited experience is really just a tiny kind of bit of the universal possibilities. I think we all as human beings thrill to the idea that there could be something majestic out there, life as we don't know it, something much bigger than the human mind to consider and you know God would probably fall into that category but that's kind of make-believe in some sense
Because it doesn't ask the question, so what would it be like then? What are the principles that govern life as we know it and are they binding principles or are they loose and could it be many other different kinds of ways?
I think one of the most powerful ideas in biology is natural selection. And again, a lot of physicists have a problem with natural selection because it's just so damn simple and easy. And it's hard to believe that something as trivial as that can be as profound as that. But it becomes amazingly complex. It becomes the stuff that can be explained by
by how selection works is genuinely astonishing. It's so rich as an idea. I mean, you're talking about ideas in physics that the fewer parameters you can boil it down to. I mean, natural selection gets it down to very few parameters with enormous possibilities and reach.
And biology as a discipline has spent, you know, 100 years or more thinking about, well, how does selection actually work? What are the units of selection is acting on genes, on cells, on organisms, on groups and so on. And I would say we have a fairly decent understanding of a lot of it. And it's it's, you know, it's it's capable of
It's capable of amazing feats, but the actual processes underlying it are quite simple and rely in the end on forms of copying. And Richard Dawkins has talked about memes and so on. And yes, they can copy and cultural evolution can happen, but it requires the units of living people underneath it with a central nervous system, which is capable of propagating a meme and so on, or a computer, which is capable of, in the end, making copies of itself. So, you know, AI can come alive. I have no real
I don't think that a planet can bootstrap itself up from nothing to give AI without the intermediary of humans along the way, or at least complex animals, because I don't think that silicon
as a tool is ever going to get beyond sand on a planetary scale. Carbon is so much better at what it does. It may be limited compared to silicon in the end in terms of processing power, but in terms of how do you start? What you have with carbon is a Lego brick. You have CO2. It sits there in the atmosphere. You pluck it out of the atmosphere and you build your other amazing Lego kits, which is life.
When I was younger and I was watching the Discovery Channel,
There was, I remember hearing this phrase that, hey, if life exists on other planets, maybe it's silicon based because silicon serves the same purpose as carbon. I don't know. I was too young to understand what that meant. I haven't followed up on that since you just reminded me of it right now. So is that indeed true or not? That silicon is just as versatile? No, it's not nearly as versatile. And that's the problem. I mean, carbon forms much stronger bonds.
than silicon does. It's capable of forming much more interesting molecules than silicon ever can and silicon for the most part forms silicon oxides which are sand and they're basically giant macromolecules that a single grain of sand is an enormous number of atoms in it and it's just a repeating pattern of those atoms. It's a giant crystal. It's not a building block. A single CO2 is a building block. It's like a brick. It's your Lego brick. Whereas
You know, I suppose trying to build from silicon would be like trying to build from enormous piles of Lego and try to put two piles together and fashion it into some kind of unit. I recall you saying that fact that bacteria are limited in size on Earth, at least has some implication for life in the universe. I don't remember the line of reasoning. So please, if you know what I'm referring to, can you expound on that? Yes. I mean, it's really an observation.
on earth that bacteria are, they're not always tiny but they're mostly, to a first approximation, they're small. They're a couple of micrometers long and that's it. And when you look at them under a conventional microscope you don't see very much going on. Now in terms of their biochemistry, in terms of the molecular machines and all of these things, they're enormously sophisticated. In terms of their
Genomes, they've got a different structure to their genome. So a single E. coli cell might have about 4,000 genes and we have about 20,000 genes. But an E. coli has what's called a metagenome, which is to say other E. coli have different genomes and they swap genes among themselves. So an E. coli might have a kind of access to a genome with 30,000 genes, which gives it a lot more scope for changing, for evolving, for switching about.
But it means that no two E. coli are exactly identical to each other and they all have a small genome and that tends to mean that if you try and build a multicellular organism from cells that are genetically different to each other then what you end up with is a fight basically that would put fights between different human groups where we're basically genetically close to identical to each other in the shade. What we're dealing with cells that are
It's huge differences. You put them together and you're never going to make anything as complex as a flea out of bacterial cells because they don't have a large enough genome. What we do is we have a large genome and we switch these genes on in the brain and we switch those genes on in the kidneys and these genes in the heart and so on. We're all genetically identical but we switch off different genes in different
Now to get a genome that's that big requires I think the kind of radical restructuring of genomes and the reason for that is that any giant bacteria that we see and there are a few around they always have thousands of copies of their complete genome dotted right next to the membrane and it seems that they're there because they they need to control this electrical charge on the membrane which is
Which is the charge, which is I'm saying is responsible for consciousness, but it's responsible for driving CO2 fixation and for making energy the currency, the ATP currency of life and so on. It's used for pretty much everything and it's a charge which is enormously strong. So if you shrink yourself down to a size of a molecule again and the electrical field strength that you would experience if you're sitting next to that membrane is 30 million volts per meter, which is equivalent to a bolt of lightning.
So we're dealing with a membrane which is five millionths of a meter thick, five nanometers thick, five millionths of a millimeter, sorry, thick, so 10 to the minus nine of a meter. So it's enormously thin and the charge across it is about 100 millivolts or 150 millivolts or something like that, but there's a field strength that's very high.
You need genes to control that. They need to be next to it. And the problem with bacteria is if they try and just expand up, you end up with this enormous cost of having all of these genomes sitting next to that. Now what we have with mitochondria, we have the same what's called extreme polyploidy. We've got thousands of copies of the mitochondrial genome, but they've been whittled down to almost nothing. There's only, I mean, there's, I think,
38 genes in the mitochondria left in humans and they only are encoding the machinery and the proteins that are doing respiration, that's it. So they're basically, you could think of them as the same power as a bacterium to generate energy but without all the overhead costs that a normal bacterium would have. So we've got multi-bacterial power, like multi-horsepower or something.
And what that allows us is to have a swollen nuclear genome with 20,000 genes and lots of regulatory capacity and lots of energy for expressing those genes so that we can make tens of thousands of copies of the protein rather than just a thousand copies or something. So we can scale up in a way that is basically impossible for bacteria.
And that came about as a result of an endosymbiosis, which is to say one cell gets inside another cell, which is pretty rare in itself, and it has to survive there and, you know, they have to get along. So the whole history of complex life on Earth is a history of antagonism and cooperation and eventually overcoming the obstacles and the hurdles and becoming integrated as a functional unit.
I didn't realize that there were only 38 genes in the mitochondria. That's not so tiny. It's very few. And for that reason, they're mostly ignored. So the people who work on the human genome, 20,000 genes, sequence the genome, look to see which genes are responsible for diseases. People do what are called GWAS studies, which is a genome wide association studies. So you look for
this this single letter change here or that one there is associated with epilepsy or Alzheimer's disease or whatever it may be and maybe there's maybe there's a few hundred of these or maybe there's thousands or millions of them but a few hundred may may kind of crop up and you say ah people who've got that letter change there are slightly higher risk of Alzheimer's disease and if they've got this one as well it's a little bit more and people ignore the mitochondria but the mitochondria are what makes us alive it's the difference between just information
And a living system where it's growing, where it's capable of powering all the work that cells need to do. You get anything wrong with those genes or they don't work properly with a nuclear background and you've compromised the entire living system. So there's not many of them, but they are the most important genes for making us who we are, you may say.
making us alive for being for being here at all. And mitochondria, they have DNA or RNA. They have DNA. Yeah, they have RNA as well. But the genome is made of DNA. The blob of DNA in the nucleus is that called nuclear DNA? Yes. Okay, so there's mitochondrial DNA, there's nuclear DNA. Yes. All right. All right. And they better work together.
Right, right, right. I read that there was some, in your book, that there was some compatibility condition between the mitochondrial DNA and the nuclear DNA. And I think Doug Wallace was investigating this and he took my DNA and put it into Hamster. Yeah, that was quite a long time. Lots of people have done similar work since then. But even within, so some of my own work is on Drosophila, different groups of Drosophila.
We're all within the same species, but if you kind of mismatch their mitochondrial DNA to the nuclear background, then it increases the risk of all kinds. I mean, basically the rate at which some flies age compared to others or how fertile they are. There's various kind of phenotypes and exactly the same principles should apply to humans as well. And somehow this is a driving force or at least is proposed to be a driving force behind speciation. And I don't recall how that line of
reasoning went? Do you know what I'm referring to? Yes. So the idea, and this is, I won't say it's a speculative idea, but there's not very much evidence that it's really true, but it's a very interesting idea. So in effect, because mitochondrial genes evolve much faster than genes in the nucleus, about 10 times faster on average, maybe more, maybe 50 times faster, we don't actually really know.
But they're changing very quickly. Now there's this selection happening in the female germline. So whenever new oocytes, egg cells are being made, there's a process of effectively winnowing out the bad mitochondria and bringing the better mitochondria together. And an egg cell has as many as half a million mitochondria and copies of mitochondrial DNA in that egg cell.
And they're all as close to a clone as it's possible to make them without killing yourself in the process. And these genes are evolving very quickly and can effectively fail to interact properly with the genes in the nucleus. So if you imagine two populations that are diverging,
standard idea of speciation. There's two populations on different sides of a mountain and they don't mix for thousands of generations or something.
And then they come back together again and they mix. And so which genes are going to be involved? Sometimes they'll intermix perfectly well and other times there will be some kind of, it's called hybrid breakdown. Basically the offspring, the standard biological definition of a species is if you can't produce viable offspring, if the offspring are sterile or don't develop properly.
then you've got two different species. Very often different species can interbreed perfectly well. This is a very bad definition of a species. It's another example in biology where there isn't a firm definition. They're just separate. Now the genes that are evolving the fastest and changing the fastest, the mitochondrial genes, are the ones that are most likely to cause trouble.
those circumstances. They're the ones most likely to not work well with the nuclear background of the other population from the other side of the mountain. This is the idea. And so incipient speciation may be driven by the rate of change of the mitochondria, which may, you know, if these guys live in a hot climate and these guys live in a cold climate, then maybe the mitochondria specialize to different tasks and that can drive these differences. What we found with flies, interestingly enough, is
You can end up with 50 or 60 different letter changes in mitochondrial DNA, which is quite a lot. Whether or not you have
observable problems, for example, not developing properly or aging very quickly or not, doesn't depend on the number of the differences. You might expect there to be a correlation. If you've got 50 letters different, then it's more likely to go wrong than if you've only got five letters different. And that's not the case. What we actually find is it's an absolute flat line that if you've got five letters or one letter difference, it can cause some catastrophic problems if they're bad letters.
And if you've got 50 letters difference, then it can be catastrophically bad, or it can be fine. There is not necessarily any worse. And these are the levels of differences that we see across humans as well. There is a possibility that different human races could interbreed and then produce offspring that were not functional. No one's ever seen it, but it's a theoretical possibility that this work seems to say, no way, that's not going to happen.
Because we can see individuals who have a problem because there's an unfortunate mismatch and incompatibility that we've always known about these things to people just don't work together for whatever reason. But it's nothing to do with races or with speciation.
Once you've got really deep divergence, say between a mouse and a rat or something between a chimpanzee and a human being, then you would see then you would see. So now we're dealing with thousands of thousands of letters, changes, difference. And then you begin to see that there really is some kind of breakdown. But within within populations that are basically homogeneous, as the human populations are, we don't see those changes. Think Verizon, the best 5G network is expensive. Think again. Bring in your AT&T or T-Mobile bill to a Verizon store today.
How many letters make up the mitochondrial DNA? Do you know approximately?
It's about 18,000. Oh, wow. Great, great, great, great memory. Okay. And then DNA is drastically more sorry, nuclear DNA is far more. We're dealing with about 3 billion then. Okay. Why is it so strange that certain mutations so certain letter changes in the mitochondrial DNA produce
Well, that troubled me a lot and I didn't understand it. It's not what I expected. And I actually find it quite welcome in a strange way, but it took me a long time to understand why, what's going on there. And I think the reason is that there has to be quite a lot of tolerance for different types of mitochondrial function.
So women and men are different in dietary needs, in outputs of one sort or another, in metabolic rate. On average, men have about 20% higher metabolic rate than women do. So there are all these differences. And the mitochondria, we inherit them from our mothers only. And that means in principle that they adapt to being in the female line,
And, you know, your mitochondria, my mitochondria, they're going nowhere. If you have kids, then they're not going to get your mitochondria, your mitochondria going in the bin. And that means that they can never really be fashioned to work, to be adapted to being in men. Now, the nuclear background can kind of fashion them to work in men.
the Y chromosome for example can control genes that upregulates those that make female mitochondria effectively work better in men. So there are biological ways around this but the bottom line is there are different requirements on the system in men and women but there are different requirements as well depending on is it in the brain where
The genes that are expressed in the nucleus is a completely different set of genes compared to those in the kidney where the mitochondria have a different task and the same genes in the mitochondria have to work with a different set of nuclear genes with different requirements. So basically they've got to be generalists. They've got to have a lot of slack that they can operate well enough in completely different tissues, completely different diets. You know, different human groups have very different diets and different
You know, fat intake or calorie intake or whatever it may be that puts pressures on mitochondrial functions, which can be very different, different temperatures that you're operating at. And especially that was even even worse with things like flies that are cold blooded. And if you change the temperature, then the whole body temperature changes.
So basically they have to be generalists, and that means that they can tolerate a fair amount of change, and most of the changes that happen are tolerated, but some of them are not. And if you're unlucky enough to have a change that is not tolerated, then it affects all of the organs, it affects both the sexes, it affects absolutely everything. And so then you've got a problem.
Because it's so fundamental just to the process of living. I believe there's a concept called mother's curse, which is about okay. So firstly, if you don't mind saying what that is, and then also, why can't we follow the same logic of mother's curse and say that men should have drastically shorter lifespans or be far worse off? I mean, it may be this what may be a why question. Well, men do have men do have shorter lifespans by about five or six years, I think, on average, something of that order.
So mother's curse, I've actually kind of already described this in a way, it's basically because the mitochondria pass down the female line, so they're inherited from mother to daughter to daughter to daughter and so on, they become, any mutation which is bad for the daughter would be selected against
Whereas any mutation that is fine for the daughter, but bad for the son is not necessarily going to be selected against because the son's mitochondria are not going anywhere. They're a dead end. So there's no direct selection. There can be indirect selection. They can be, you know, if all your sons die, then they can be, you know, indirect forms of selection, but there's no direct selection on them. And so mutations that are effectively, if there are differences between females and males in metabolic requirements, and there are,
and the mitochondria pass down the female line only, which they do, and some mutations may be harmless or even beneficial to women, but detrimental to men, then selection will select for the ones which are harmless or detrimental in women, and the harmful ones to men will tend to accumulate. There's no mechanism of selecting against them, no direct mechanism of selecting against them. So that's mother's curse. And
A lot of mitochondrial diseases, for example, are two or three times more common in men than in women. A lot of diseases that have a mitochondrial aspect to them, like Parkinson's disease, are twice as common in men than in women. And men age more quickly and die earlier than women. And all of these things have a mitochondrial component.
and may be linked in some way to mother's curse. So it's real, but I use the word direct selection on several occasions. The genes in the nucleus can compensate. And so for the most part, most men don't have mitochondrial diseases and men live almost as long as women and so on. So mostly,
The fact that we inherit mitochondria that could be riddled with mutations that are not good for men are compensated for by genes in the nucleus that are specifically male, which effectively offset those disadvantages. And this is where the problem, if you then go and breed with a completely different population that doesn't have those compensating genes in the nucleus, that's where this speciation effect can potentially come in.
These compensating genes in the nucleus, they don't detrimentally affect women? Are they relegated to the Y chromosome, for example? Yes. There are differences in what's called gene expression between men and women, which is to say the Y chromosome controls it, but there's only a handful of genes on the Y chromosome, but those genes
Say you, you, you, you, you, you, you, you make your proteins, you, you make proteins, you shut down. Um, and so, you know, it's, it's biology is not about which genes you have so much as which genes are active now and a specific stage of development and so on. Um, and so there are, you know, in men, the, the, the genes which are expressed at a certain time, uh, can be very different.
Yeah, geez, it's staggering, staggering, staggering. The complexity does your head in. There's no question. Yeah. So okay, now let's talk about what's not complex. Well, maybe it's complex, but you made an analogy between a cell and the planet, because one is charged on the inside. Okay, can you talk about that? That's interesting. And then I wondered, how far does that analogy go? Does it go to the galaxy? I mean, yes, I mean, no, I don't think we'd go to the galaxy level, but it and it is an analogy. It's, it's not
I mean I think you will be unwise to take it too far but it's a kind of a beautiful analogy and there's definitely some truth in it. I mean a cell is in effect, this electrical charge on the membrane that I keep talking about, on the inside it's basically saturated in electrons. We've got organic molecules have taken CO2 and they've added hydrogen on and hydrogen is an electron and a proton basically.
And so in making organic molecules, we've taken electrons from the outside and put them inside. And so it's reduced. It's more reduced inside than it is outside. That's the technical term. And reduced is one of those terms that, you know, anybody who's not a chemist backs away from immediately tries to escape from the room. So oxidized and reduced. But in effect, there's more electrons inside than outside. And there's more protons.
It's more negative inside, yes. And so it's relatively positive outside. And there are protons outside that's partly what makes it more positive outside. And we've got this charge on the membrane, which is basically relatively positive outside, relatively negative inside, and the membrane itself is extremely thin. And so we have a charge on it. Now, the planet is basically the same.
Iron, raw iron is electron dense, you might say. When iron rusts, it's effectively losing electrons to oxygen. Oxygen is stripping those electrons from it and you end up with three positive charges on the iron. The iron atom itself ends up with three positive charges and the oxygen gets the electrons and that has a negative charge and you have iron hydroxides and oxides and so on and that's what rust is.
Now, the core of the planet is not rusty at all. There's no oxygen down there. It's got all these electrons sitting on the iron. And so it's relatively negative inside. And the outside, the atmosphere and the oceans and so on, because the gases that are coming from volcanoes and so on are such a high temperature, they tend to have lost their electrons and think you get gases like carbon dioxide.
Coming coming out and the sun will also tend to oxidize the surface the planet will would tend to for example, you can the sun would split water. Water is H2O and it can be split in effect into hydrogen and oxygen and the hydrogen is light enough to escape into space.
And the oxygen will react with rocks like iron and you get rusty rocks. And this is more or less what happened on Mars. That's why it's the red planet. The oxygen that was formed from spitting water reacted with iron in the rocks, turning the rusty red color. And the hydrogen escaped to space. A lot of the oceans were lost that way on Mars. And so you end up with a relatively positive charge in the atmosphere and this relatively negative charge inside, which is basically the same structure as a cell.
And just as a cell membrane has proteins that sit in it where you have movement between the inside and the outside, hydrothermal vents are the equivalent conductance between the negative charge of the interior and the positive charge of the exterior. You have movement going through vents, connecting it up.
And within these vents, the pores inside the vents have got the same structure as well. They're effectively inside, they're filled with the material that came from inside the Earth and the outside, they're surrounded by the material that came from the oceans. And so again, we have a negative charge inside, positive charge outside, relative to each other. It's not that there's an actual charge, it's just that the electrons want to move from here to there.
Now, do you believe this to be a coincidence or that life is somehow mimicking cellular life is somehow? No, I don't think it's a coincidence at all. I think this is exactly how cells work. And what this is doing is effectively there's an electrical charge on the Earth between the inside and the outside. There's an electrical charge in the pores in these hydrothermal vents between the inside and the outside. There's electrical charge on cells between the inside and the outside. They're all equivalent topology because they've all been formed
from the same processes you might say because the hydrothermal vents is where there is the mixing zone between the inside and the outside so it naturally forms pores where we have this the same charges forming and those charges are more or less necessary to drive the reaction between hydrogen and carbon dioxide to make the organic molecules that make up life at all. So I find it a beautiful conception it doesn't mean it's true but I find it beautiful that the the planet has the same
basic topological structure as a cell. Cells emerged from the mixing zone between the inside and the outside, effectively part of the circuit, and are driving copies of themselves by making more miniature Earths, if you like, by reacting the hydrogen from the inside with the CO2 from the outside to make organic molecules. It's a planetary scale and it's a beautiful conception. Something I love about you,
is firstly, you write beautifully. And secondly, you are not afraid to ask why. And you mentioned that you're the most biologists don't like to ask the why question, perhaps because it teeters too much on the religious side, and they would like to stay away. Or for whatever reason, physicists don't like to as well. There's a famous or an infamous video of Feynman, who is castigating a fairly, at least in my opinion, well intentioned interviewer for asking why question you recall that
I don't remember that one, no. I mean, I love listening to Feynman, but yes, he could castigate people. I thought it was a perfectly reasonable question. And Feynman said, yeah, but you shouldn't ask why, because so-and-so. So why is it that you don't mind asking why? And simultaneously, why do others not like asking why? To be honest, I don't really know. I mean, it's partly I'm just confused, and I can't tell the difference between how and why.
And I think most biochemists are happy asking how, how does this system work? And I can't quite distinguish that from why, why is it working this way rather than a different way? That's kind of almost another way of saying how. And I think why is one of the most human questions. And it's a childlike question. Children always want to know why.
And I think it's the motivation for many people to go into science. And one of the things about science is it tries to stop you from being too naive and tries to impose a method on you to be objective and to not ask questions that are unanswerable in some way, to stick to the, as I mentioned, the art of the soluble before. We'll never know why, but we can't help asking why. And as I say, I can't tell the difference between why and how anyway. So it's very exciting asking why.
And perhaps it's more forgiven in books than it is in papers and you know the more scientific literature. Books I think are a good place to ask why and maybe that's why I write books in part because it gives me this outlet to wonder about things, to wonder about the world and in the end that is what science is. It's about how do we explain
the world, which is to say, why is the world this way, when it could have been so many other ways? I think why is it is in fact, you know, it's a question in physics, why are the cosmological constants that way, rather than some other way, that's the theory of everything supposed to explain that. It's a why question to me, you could say, how did it come to be that way? I see the strengths of science as being what you mentioned, the focusing on what's soluble, and then the weakness is also that to
The reason why I say that, but I don't know how to solve this. So I'm just going to pose this as a question. If one was to go into a PhD program, but produce no papers in four years or produced papers with all negative results, then you would likely not be hired. And so, yes, when you're a young person, when you're at your most creative, you're disincentivized for pursuing wild ideas that because most likely they won't work, but they may also lead to breakthroughs.
No, there's a bit of a tragedy about that. It means that we prioritize certain incremental progress versus these substantial. I completely agree. My lab mostly works on the origin of life and I have PhD students and postdocs and so on and I face this problem every day that most of the results we get are negative. What are we going to do? How do I
I don't want my students to all fail to publish any papers, fail to get any positive results and finish their careers. That's the last thing I want for them. So you've got to juggle. You've got to aim for the lowest hanging fruit. You've got to keep the big picture at the back of your mind and try to think of experiments that will work in one way or another.
And you've got to not forget about the bigger questions behind this and keep on trying them. So I think you have to move people around so that if something starts working and one student's had two years of getting nothing, then you've got to give them something where they're going to get something now. It's difficult and it's difficult not because of the scientific questions so much because of the human aspect of people's careers that they need to be able to come out of it with
with, you know, a career ahead of them, something to look forward to. Why do you think it is that negative results aren't seen as worthy as or as worthy as positive results? Because to me, just as an outsider, I see this as data, even if you were to say so and so it doesn't work. Great. Now we know so and so it doesn't work. There's the replication crisis in psychology, particularly because people are incentivized to find affirming or new results rather than disconfirming.
I think it's, I mean, we've got a paper coming up. It's probably going to be under embargo, but it's actually out there as a preprint anyway. So I'll tell you about it anyway. This is about how ATP is formed. Now we've found this is Silvana Pinner, who did her PhD with me and she finished a while ago. And this is her big paper from this.
What she found was actually what she did was was effectively repeat some earlier work from a Japanese group from 20 years ago and they had found by chance that a corroding iron electrode when they got ADP in solution around that electrode actually formed some ATP and they looked into it and it turned out that ferric iron which is a iron with three positive charges on it
will catalyze the formation, this had to be in the presence of something called acetyl phosphate, which is just a two carbon compound, that would catalyze the phosphorylation of ADP to ATP, which is what our mitochondria are doing all the time. But instead of having all this molecular machinery like the ATP synthase, it's just happening in water with ferric iron as the only catalyst. So that's pretty amazing.
So she repeated this, it took a while to figure out exactly how they'd done it and this is very often the case and for a period I remember we were concerned that it would not be possible to replicate it and then she succeeded in replicating it and I find that increasingly pleasing just simply to replicate other people's work because of this problem that sometimes it's made up, sometimes
Sometimes it's not as cynical as that, but it's for whatever reason, there was some aspect of chance that allowed it to be able to replicate science, I think is the perhaps the single most important thing in science. And so it's very pleasing when you succeed in doing it.
Now, she is probably the single most careful scientist that I've ever met. She really is amazingly precise. You could never see her error bars, because the repeats were so similar to each other that there really wasn't one. But all the rest of her data was negative, which was very interesting. So it worked with ferric iron, but she tried with about 10 other different metal ions. And none of the other metal ions worked.
And she tried with about seven or eight different phosphorylating agents instead of acetyl phosphate. And none of those worked. And she tried with the other bases. So instead of ADP, she tried with GDP and CDP. So the other letters in RNA and UDP and so on. None of those worked either. So this is a paper made up entirely of negative data apart from one result, which had actually been done by someone else 20 years earlier and replicated by Sylvana. Now, this is where negative data really comes into its own.
Because it basically says there is something favored about ADP compared to the other bases and about acetal phosphate compared to the other phosphorylating agents and about this metal ion compared to those other metal ions. This is favored chemistry. Why is it favored? We could come up with a mechanism for it and so on. But there the negative data is effectively saying there's a limited number of ways that this will happen.
And here's one way where it does. Maybe there are other ways that does as well, and we just look at those, some other metal ion that was not in our panel. You know, you can have huge combinatorial panels, but we looked at all the metal ions that seem to have any relevance to life or any relevance to geochemistry, and this ferric ion was the only one that worked. Now, the problem there
is that imagine that ferric iron didn't work either. Then you would have a paper where everything was negative. Let's just say that she didn't know about that paper and that she never tried ferric iron and that she tried all the others. What she would have had would have been a completely negative set of data which would be unpublishable because nothing worked. Now maybe if she tried some other irons then it would have worked like ferric iron did.
But if you don't happen to choose that one, then you'll never know. And so you can never rule something out. If all your data is negative, it doesn't mean it can't work. It just means that everything we tried under the conditions that we tried it, it never did work. And at that point, we decided to pull the project because this poor PhD student is never going to get a paper out of it. So we explored it as well as we could. But the reality is we've got to move on. And so you've never disproved it, but you've kind of just given up trying to prove it now.
Whereas the fact that someone had done it before meant that that was the one that she tried first which meant that when the paper comes now we have something which is really exciting which is to say the reason that ATP is the universal energy currency is precisely that it works as prebiotic chemistry in water all by itself just with one metal ion as a catalyst and that works and nothing else does work and that's why it's this way. So suddenly you've got a very sexy message which in the end is based on the fact that someone else had found
out something 20 years ago that was really a serendipitous discovery that they were not applying to the origin of life or anything else it's just you know and science is built this way science is built on it's kind of network of the efforts of different people doing different things for different reasons and you try and put it together and you've got to you know juggle what works what doesn't work when do you give up and and very rarely can you ever disprove anything formally in a way that a physicist would understand disprove
That's why the positive results are important because they give you something to say, whereas the negative results don't give you anything to say. They just say, everything we tried didn't work. It's possible that something else would have worked, but we don't know because we didn't do that. So that's not going to sell any papers.
I'm not entirely sure about that. Well, you would know in your domain, but in physics, there's something called no-go theorems. So for example, there's the no-go theorem, which says that you can't have a graviton in 4D quantum field theory. And then you're like, well, what's the hope for gravity? And then that's one of the reasons why people think that there's ADS-CFT correspondence of the holographic principle. Because, okay, there was a hidden assumption that wasn't stated by Witten, actually, and he's a careful person, which is that
You can't have a graviton in your same three plus one quantum field theory, but you can in a different quantum field theory. So you can have, that's why you have this universe within another border. Okay. But anyway, so a negative result can still lead to breakthroughs. Like it leads to whole there's ADS, CFT is like almost a whole field in and of itself. The way that when I hear this, what I'm wondering is, hmm, why is it not the case that studies in different fields,
I think a lot of clinical trials pre-register in that sense. So a clinical trial that is negative and there is often funded by a pharmaceutical company or something you have some interest in not publishing negative data, but the regulators or it's in the public interest that it should be published. And so this idea of pre-registering is a good one, but there's a kind of a big difference.
The big clinical trials are very expensive to set up. They're very constrained in the way in which they're set up. They're being set up so statistically they can demonstrate a difference between a different treatment or no treatment or whatever it may be.
They come up with an outcome and the chances are it's going to be about as reliable a statement as you can make. But it's very unwieldy. It might take five years to do it. It might cost 20 million pounds or something. Whereas a lot of smaller scale science is much more maneuverable. No PhD student would ever
No, and I mean, there's also this competitive side in science as well. Whereas if you told everybody what you were doing, then they would do it quicker than you could. So there's, you know, there's some element in which people don't want to say what they're doing necessarily. I'm not sure that that's a good thing, but it is the reality. Basically, what I was saying, what I was thinking is that, hey, the negative results themselves, maybe there were 30 other people across the history of biology that have tried to formulate ATP
using those metals that didn't work. But Sylvana, your assistant couldn't sorry, your PhD student, correct? Yes. Yes, your PhD student couldn't
didn't see the literature because everyone else said no and so then she wasted her time too and those 29 other people wasted their time and i was thinking well then if you publish negative results does that just bloat all the journals or like is there another reason to not well i mean the journal the journals are already bloated i i actually think that reading too much of the journals is not good for you which is to say
When I have new students starting, very often they're encouraged to do a literature review and they'll often get bogged down because literature is overwhelming. There's so much of it out there and it's written in such a way as to imply that the results that they did were decisive in some way. And you'll come out with the feeling that everything's been done and there's really nothing left to do here and well, you might as well despair at that point.
So it's actually much more productive not to know about any of that, to be deliberately ignorant and to just blunder around for a while until you begin to see something and then at that point is the time to access the literature. So have other people done this before? And the answer is often yes they have but we did this bit different and we did that bit different and they did this but we did that and so on and so on and so
You often end up getting different results to what they got. And you realize that, well, if we'd just taken for granted what they said and didn't do anything, we would never have found that. And if you find exactly the same as them, then that's kind of nice to know as well. And you'll probably try and drop it into a paper somewhere just to make it clear that you have successfully replicated someone else's work. It's worth saying that you've done that. But very often,
You know, a paper may close down an area by saying this is not possible. And in fact, they were wrong because they did the wrong experiment. And there's so many possible experiments you can do that is so long as you don't close yourself down by believing them, then you'll go on and find something new. So I would sing the praises of blundering around in ignorance and the scientific undergrowth, because it's the way to make progress.
Let's wrap. I just got to use the washroom once more. And I would be remiss if I didn't ask you Carl Friston's questions. He sent me some to ask you. Oh, I see. Right. Yeah. Is that all right? Of course it is. Yes. With TD Early Pay, you get your paycheck up to two business days early, which means you can grab last second movie tickets in 5D Premium Ultra with popcorn, extra large popcorn,
Now this question comes from Carl Friston, number one. Is the increase in diversity and complexity of phenotypic forms a universal feature of evolution? And if so, is there any principled explanation for this?
I mean, the simple answer is yes. And I suppose the reason is simply mutations, which leads to diversity. So mutations are almost impossible. I mean, all of evolution is based on mutations. And they have an enormous power. The standard way of seeing
natural selection from a population genetics point of view. So I'm not a population geneticist, but I'm in a department of genetics and I work with some population geneticists who, you know, worked with some of the founding fathers of the field, people like JBS Haldane and John Maynard Smith and so on. And that field kind of only lets itself see
detrimental mutations which is to say mutations that are bad for you in one way or another. Now we know that there are neutral mutations, most mutations are neutral, don't make really much of a difference, and there are a few beneficial mutations but the ones that are effectively bad, detrimental, are the ones that the field of population genetics has historically really focused on because they are the ones that are most likely to be selected against
So neutral ones will be ignored by selection or almost ignored. Beneficial ones are very rare in comparison and detrimental mutations are very common. And I find this quite difficult to get used to because I want to think positively about beneficial mutations. But I've become used to thinking in this framework and I'm shocked at how much power it has. So we have a paper out just recently with another PhD student of mine who's a physicist by training, Marco Colnaghi.
And this is asking about bacteria. I mentioned earlier on, bacteria have this metagenome where an E. coli might have 4,000 genes but access to 30,000 genes from out there somewhere. And they do what's called lateral or horizontal gene transfer, which is they pick up bits of DNA from the environment and they bind it into themselves. And various people have shown that this
It's a little bit equivalent to sex, which is to say it's doing recombination. It's changing the gene set that you've got. And even if on average you pick up genes that are worse than the ones you've got, on average you'll benefit from it because you're generating variation that selection can act on. And if selection sees differences between individuals, then it will select against the ones with the detrimental mutations and the ones that don't have them will flourish and so on.
So basically selection is all about the differences between individuals and mutations generate differences between individuals, but moving genes around bilateral gene transfer amplifies those differences. And sex is an extraordinary machine for generating differences between individuals. And it uses the same machinery that bacteria use, but it organizes it completely different. And so there's this question, why? And the answer, I think we've found part of the answer at least,
I mentioned mitochondria before that mitochondria allow you to have a much larger genome and having a very large genome gives you a problem with preventing it from being degraded by mutations and the way that bacteria prevent the genomes being degraded by mutations is picking up bits of DNA from around the place and patching it in and it works for a bacterial sized genome but if you have a much larger genome and let's say five times larger
And you pick up a random bit of DNA from the environment. In effect, the chances of you getting the right bit is much lower.
And really the only way around it is to pick up large chunks of DNA from the environment. And then there's a problem that if you've got any sequences that match somewhere else in your genome, and this is more like the larger your genome, the more likely to have repeat sequences you are, the more likely to delete information you are when you bring this bit in and throw away your bit. So you end up with a system which is only set up to
eliminate detrimental mutations can account for the transition from bacterial lateral gene transfer to what's called meiosis and sex where you bring two cells together, they fuse together, they line up the chromosomes and so on.
So the whole thing is based on generating differences between individuals so that selection can act. So to come back around in a long circle to Karl Friston's question about divergence between things is driven by mutations and it's basically inevitable and it will be a property of any biological system that's got information at the base of it.
All right, he has a second question. It's right. Carl Friston says, What is the role of sequestration and isolation and evolution at the molecular or cellular scale? sequestration? Yeah, sequestration. So I'm not quite sure what he specifically had in mind there. I just want to message once more over chat. Yeah. So
Yes, I mean, what I immediately think of when I read sequestration is sequestration within cells, which is to say you have compartments, you sequester the machinery for respiration within the compartment of mitochondria, for example. Now, I don't know if that's actually what he had in mind, but there's a lovely point about bacteria, which is that they are essentially indivisible. They don't have any sequestrated bits.
So there isn't a compartment which is responsible for respiration. There isn't a compartment which is responsible for, you know, putting the genes in for protecting genes and so on. It's a single open system with a mem- no, it's well, it's not a super, they have to go quite a lot of structure.
There's a lot of interest these days in phase separations between effectively liquid-liquid phase separations and the genes in a bacterial cell are phase separated from the cytosol.
And there's no membrane between the two of them. So the compartment is not a complete compartment in the same way. Whereas the mitochondria have got a membrane around them and it sequestrates the inside of the mitochondria from the rest of the cell. And that allows you to have enormously more power. It allows you to charge up those membranes from the inside. Let me just give one example to do with with with with sequestration and mitochondria.
When anybody thinks of mitochondria, they'll tend to think of a kind of sausage-shaped thing with membranes inside the cell, and there are all these sausage-shaped things in there, and that's not really how they are at all. They will actually fuse together. They're very dynamic, they're moving around, they fuse together, they're fishing apart, they separate out, but a lot of the time they're fused together into a giant network
which fills up the volume of the cell as a branching network in there. You can think of it as power cables. This is a much more efficient way of generating energy because the charge is distributed across the entire surface of this network and is much better for distributing oxygen around because it dissolves better in the fatty membranes than it does in aqueous solution.
And so it's probably the more efficient way of structuring a network to generate power. You can think of it as a power grid. But if you prevent it from splintering up again, then the cell would generate and die.
It seems that it's important for mitochondria to go back to being little independent sausage shaped things. If you stop them from doing that, then the system doesn't work. So why? Well, because with this independent sausage shaped thing, you can sequester a copy of the mitochondrial DNA. So now what we have is a little sausage with a genome of its own.
And that genome is responsible for making sure respiration works in that mitochondrial. So it generates an electrical charge on the membrane in its own little sausage thing. So now we have a relationship between a genotype and a phenotype. The genotype is that mitochondrial genome, the phenotype is the membrane potential, the electrical charge on this membrane.
And if this mitochondrial DNA is damaged, it's mutated and it can't generate membrane potential, then the cell machinery can see that and kill it at that point. So it's a quality control mechanism.
And if what you have is an open network with, let's say, 500 copies of mitochondrial DNA in there, and one of them has got mutations, selection can never see it because its effect is hidden by the 499 other ones that are all contributing to the shared common phenotype of the electrical charge across this entire network. So you'll never notice it. So you can't get rid of it. So more mutations can happen.
So the very fact that we all have mitochondria which are still functional after two billion years of evolution is because of selection on the mitochondrial DNA which is because of sequestration of the mitochondria within the eukaryotic cell and that is the difference between lots of E. coli between a planet full of bacteria that basically can never get beyond bacteria and the planet full of eukaryotic life, plants and animals and everything else. That's the result of sequestration
bacteria inside other cells with their own DNA. Now I don't know if that's what he had in mind but that's what comes to my mind when you ask me about that.
Sure, and now a near final question comes from a user rh0d3z, which says, this is much more of a technical question. What are profilanes views on mitochondrial risperosomes slash super complexes in disease? This may be particularly important, seeing that they can omit complex two and bypass Krebs cycle pathways.
Yes, very interesting question. There are actually some recently there's one super complex has been discovered with complex two in it, but mostly whoever asked the question is quite right, complex two is not normally part of it. So for people who don't know,
The super complexes, normally what you have or normally how we're taught and what we imagine is that we have four or five complexes from complex one, complex two, complex three, complex four and the electrons pass from one to the next one to the next one and so on. Complex two is always a little bit on the side in that sense. They go from complex one to complex three and then to complex four then to oxygen. Now
The respirosome or the super complexes are where these complexes are brought together very often with a specific stoichiometry so you might have two complex ones and one complex three and one complex four or various other stoichiometries of these things where you have fixed numbers of these things they fit together in snug ways and until about 10 years ago
It was, their existence was kind of denied almost. It was quite difficult to demonstrate that they really do exist, that they're really real. Now it's generally established that they are, and there's a lot of cryo-electron microscopy shows that these things are real, but there's a lot that's still not known about them. Do they really speed up respiration, for example? Seems that they do, but there's, you know, it's early days in this field. Now the specific bit about complex two,
part of the Krebs cycle. It's the only enzyme in the Krebs cycle which is anchored into the membrane itself and which is effectively passing electrons directly but is excluded from these super complexes. How that works I don't know. I think it's
I mean, there's some very strange factors here. So complex one is the only one that oxidizes NADH. I don't want to get too technical here, but it's the only one which is really capable of spinning the whole Krebs cycle. So if complex one is deficient or broken, then the Krebs cycle can't work properly.
If it's part of a respirosome, it's likely to be operating at a faster rate, and it's likely to spin the Krebs cycle faster than it would otherwise be able to spin. But it also depends on the structure of the Christi and all kinds of other factors. So there's a kind of macromolecular scale of organization of mitochondria that we don't know a lot about yet. And it's definitely important. I mentioned fission and fusion of mitochondrial networks, and all of this is linked. It's a very dynamic system.
The interesting thing about complex two is it pumps fewer protons than complex one. If you put electrons into complex two and then they go into three and then four, you can pump a total of six protons. Whereas if you put them into complex one, they can pump a total of 10 protons. So you may think then that there's more power, if you like, but it's actually it's not power so much as gearing.
So it's like being, if you're using complex one, it's like being in a high gear on a bike. You can be in 10th gear or something and you can coast very easily along a flat road, but if you get onto a hill and you want to go down to a lower gear. And a lower gear in the mitochondria, if you're putting electrons into complex two, effectively you've got almost the same amount of power, which is to say the
Energy that's released when the electrons that go into complex two get through to oxygen is not quite as much as when it's coming from an adh but it's nearly the same but that total energy amount is only pumping six protons rather than 10 protons so you've got nearly the same energy pumping fewer protons and that means you can pump them against a higher potential. You can go uphill now, you can effectively
switch down to, you know, second or third gear or something and keep on going. Now how all of this works itself out in terms of super complexes and Christie structure and everything else, I don't really know. It will have a feedback effect on the Krebs cycle because the Krebs cycle needs to go through this step if it's not going to increase succinate levels which leak out and that's an epigenetic switch which switches genes on and off. This is, it's hardly been
explored. I mean this is a fantastic thing about science, in some ways we seem to know so much and in other ways there's this kind of jungle of dynamic mitochondria that are changing shape, that are forming Christies, that have got an organization, they're probably generating electromagnetic fields, that are forming super complexes, that have, you know, if you've got a closed Christy structure and you're pumping protons into it, there's a, you know, the limit that
Hear that sound?
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The differences in membrane potential is only hardly been touched on between one Christie and another Christie. If you've got a super complex or you don't have super complex as if complex two is part of it or not part of it. You know, there's a world out there that we've barely discovered and it's a world frankly of physics. This is
This is about charge, and it's about pushing against charge, and it's the power, and it's the energetics of the whole thing. So it's not conventional biology, but this is, to my mind, where biology needs to go. Thank you, Professor, and we didn't get to talk. Maybe next time we can talk about, if I'm so blessed as to be with you, again, thank you, to talk about the reverse Krebs cycle and aging.
It will be a pleasure to come back. That was a lot of fun. Thank you. Yeah. Do you mind ending by reading the poem from the last chapter or the last bit of your book? I believe it's a short poem. If you have it near you. I'm happy to do that. Do I have a copy of the book anywhere near? I have to go and get one. Just give me a moment. I don't know that this will make sense to anybody who hasn't read the book, but it's a beautiful poem anyway. I don't know how much sense it would make
Even without the context of the book, yes. So this is Like Most Revelations by Richard Howard. It is the movement that incites the form, discovered as a downward rapture. Yes, it is the movement that delights the form, sustained by its own velocity. And yet, it is the movement that delays the form, while darkness slows and encumbers. In fact, it is the movement that betrays the form,
Well, thank you.
Thank you, Professor, for being with me, with the Toe audience for so long. Thank you for having me on. It's been a pleasure. Okay, all right. Thank you. Thank you for sticking around for two and a half hours, maybe longer. I appreciate that. I hope that it was enjoyable to you. Again, there's the website theoriesofeverything.org. That's a place that you can go to support Toe if you're interested in that. Like I mentioned in the intro, there are several benefits. You get an ad-free audio version. You get that
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quite a few benefits you can text me if you like there's a number at least we're testing that for about one week or one month or so again that's theoriesofeverything.org thank you all for watching it's great to see you in the live chat i appreciate all of the love thank you thank you so much
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▶ View Full JSON Data (Word-Level Timestamps)
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"text": " The Economist covers math, physics, philosophy, and AI in a manner that shows how different countries perceive developments and how they impact markets. They recently published a piece on China's new neutrino detector. They cover extending life via mitochondrial transplants, creating an entirely new field of medicine. But it's also not just science they analyze."
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"text": " Nick Lane is a biochemist, a writer, and a professor at University College London, whose book, Transformer, exposits on the origins of life, not being so heavily contingent on RNA as many think, but instead in something called the Krebs cycle. Poetically, you can think of this as the difference between an information theory of life, which is the current dominant view, to one of the thermodynamic energy flow of life."
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"text": " Which is Nick Lane's view. As usual, click on the timestamp in the description to skip this intro. My name is Kurt Jaimungal, I'm a Torontonian filmmaker with a background in mathematical physics, and this channel is dedicated to the explication of the variegated terrain of theories of everything."
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"text": " That is, primarily from a theoretical physics perspective, so for example, grand unification and quantum gravity, but as well as understanding the role consciousness has to play to the fundamental laws, provided these laws exist at all in a form knowable to us. Two quick announcements. Firstly, there's a physics and consciousness contest on this channel, the link to which will be in the description as well as a thumbnail is over here. Essentially, it's the physics version of the three blue one brown math contest, except ours is for physics and consciousness as well."
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"text": " Patreon may decide to shut you down for whatever reason they like. There are also a variety of benefits that come with being a member on the Toe website. For instance, you get an ad free version of the shows that are coming out, an audio ad free version. That is to say you get a private link to the RSS feed to download the audio versions and they come out about 12 to 48 hours, sometimes even one week prior to you seeing them here on YouTube. Just so you know, the way that it works is that I finish editing and then I have to do another run through and go through timestamps and catalog references and so on."
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"text": " Another benefit is that there's a number to text me. Again, if that's what you're into, we're testing this out for about a month. And yes, this is something where I am texting you back to your phone. Throughout much of this, you can see that the artwork here is exquisite on the website. And that's because it's been done by Boris Martinez Castello. A link to his Instagram is in the description as well. Thank you, Boris. Thank you so much."
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"text": " As for today's sponsor, it's Brilliant, Brilliant.org. Now Brilliant has been with Toe since near the beginning. I recommend you check out Brilliant.org slash Toe if you're interested in learning math and physics and science. So Brilliant is a place that you go to learn about STEM subjects in an interactive manner. They have these bite-sized courses. It's extremely easy. You may think that special relativity is beyond you. No, it's not. It's something that someone can understand in elementary school. The way that Brilliant breaks down these"
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"text": " extremely advanced concepts is elementary. At some point, I'll be doing an introduction to information theory. In particular, there's David Deutsch and Chiara Marletto's constructor theory. And because I'd like to learn that I decided let me brush up on the fundamentals of information theory."
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"text": " Why don't we go over your primary thesis about how the Krebs cycle predates life? And perhaps you can contrast that with a reverse predominant view, which is that genes cause metabolism or genes create metabolism or the conditions for metabolism. Yeah. I mean, this is a, this is an argument that goes back decades in work on the origin of life. And you mentioned the Krebs cycle already."
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"text": " Those ideas also go back decades, this is nothing particularly new for me, but what's changed is that there is now some experimental evidence and that's been lacking. So I guess the whole field of biology has been obsessed with genes and information since the 1960s, since the code was cracked."
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"text": " And the idea that RNA, which is the kind of the template taken from DNA, it can catalyze things. It can also supposedly copy itself. It can act as a template for itself and so on. So it's a beautiful idea. It's called the RNA world. It's been around for quite a long time now. And it kind of takes you further and further away from biology as we know it. And I end up in a place where, as a biochemist, I'm"
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"text": " I just don't recognize the landscape. So these ideas of metabolism first, I suppose the problem there is that it asks a lot of the environment. Effectively, it's asking one specific place, one specific setting to start out with something like carbon dioxide and hydrogen and not much else, and to make everything from it. In the absence of genes, in the absence of enzymes, it's a big ask."
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"text": " And people who've argued this, Harold Morowitz, one of the great biophysicists who worked a lot on the origin of life, he linked it in with metabolism first and the Krebs cycle very early. And he was largely dismissed because there wasn't any serious evidence that it could actually work."
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"text": " And now what's happened over the last five or six years is it's beginning to look as if it really does work and it's not just the Krebs cycle, not as a complete cycle but as a kind of a linear pathway with parts of it, it's not the whole thing. But also other core biochemical pathways seem to just spontaneously happen and they make so much more sense of the whole structure of biochemistry and then also how it is that information comes into biology because it comes in"
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"text": " Do you see the metabolism question or solving metabolism as being a biochemistry question or physics question or biology question? Yes. Are those distinctions important?"
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"text": " They are important from the point of view of people's backgrounds, they're not important from the point of view of the question because the question is a question in science, the question is it needs physics, it needs chemistry, it needs biology and geology and so on and this is part of the problem that it's been a kind of collision of disciplines each of which have you know 100 years or more of its own intellectual history and ways of seeing the question. So I think"
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"text": " The dominant way of seeing the question over the last, really since the Miller-Urey experiment in 1953 has been through the lens of chemistry. And what the chemists have tried to do is what synthetic chemists try to do, which is to say,"
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"text": " You tell me I need to make a nucleotide. So I'm going to make you a nucleotide. I'm going to make you nothing but nucleotide. It's going to have a high yield. It's going to be pure. I can make you 70%. And I need to start with cyanide. Therefore, this is how life starts. And from a biologist's point of view, well, you'd see it the other way around. You'd say, well, natural selection optimizes things that were worse at the beginning. And now they're better because selection optimized them."
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"text": " And therefore, what we're looking for is a process that kind of works a bit, but is really very bad. That means I want a low yield. It means I want low purity. It would bring any self-respecting synthetic chemist out in hives to try and do it that badly. But that's really what a biologist wants to see. What a geologist might want to see is what kind of an environment is conducive to"
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"text": " any of these chemistries? Are there settings on the ancient earth that are conducive to cyanide for example or to co2 or whatever it may be? So there's this collision really between disciplines and ways of thinking about it and we can't all be right and people have spent decades of their lives seeing a question from a particular point of view"
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"text": " And it's very difficult for any human being to kind of step back and stand on a soapbox and say, well, I got it all wrong. I've just wasted the last three decades of my life. Often the answer is somewhere between different theories, different hypotheses. It's a bit of this and a bit of that, but you can't test that. You've got to be purist about what you test. And most of us are going to be wrong about most of it. And that can mean that you end up with"
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"text": " Quite unpleasant personal animosities between the researchers in the field. OK, so the chemists or the synthetic chemists see that there are certain building blocks to life and they want to create those in the lab artificially or starting from simpler ingredients. And then the biologists say, no, well, look, if we have these ingredients, the way that evolutionary biology works, that we start from something that's less pure and then we work up where"
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"text": " Yeah, the real difference here, I suppose, is that what the chemists have done is as if you say, right, we need nucleotides, the building blocks of RNA and DNA, we need amino acids, we need to have fatty acids, the building blocks of membranes and so on. So go make them for me. And the chemists go away and they make all of these things."
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"text": " And they've started with CO2, but it doesn't work very well. The yields are low and so on. So they put that aside as an unworkable chemistry and they start with cyanide or something which is very energetic. But I mean, large amounts of cyanide. You're practically asking for an atmosphere which is just saturated with cyanide."
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"text": " And the chemistry works. It produces the building blocks of life, but with a starting point that no life ever uses via pathways that life never uses. And so it kind of leaves you with the same question, which is to say, okay, so if that's how it started, then you end up with an environment that's got all these building blocks floating around. You've got the perfect primordial soup, but then what happens? And there isn't really an answer to that. I mean, you may as well say then a miracle happens. Everything has to self-organize."
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"text": " Whereas why does it invent biochemistry as we know it if that's the worst possible way of doing it? So what I have been looking for as a biochemist and a bunch of other people is do these pathways at the core of biochemistry happen spontaneously in the right environment? Not very well, just a little bit, but"
},
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"text": " whole you know pathways with 10, 15, 20 steps in them that you might say well that's asking a lot of the environment can it happen though and the answer is often yes. At levels that were undetectable 20 or 30 years ago but you know we're in a lab we're doing we're looking at a very small subset of possible conditions we don't really know what the right conditions are so to make it happen at all is a big step forward."
},
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"text": " The issues with the synthetic chemists is that they can produce the building blocks of life, but then they don't show a way of how those building blocks interact in order to create life or that the conditions necessary to produce those building blocks are so unrealistic. To my mind and the chemists, of course, would disagree. And, you know, we don't know so much about what the early Earth was really like. So they probably have a point."
},
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"text": " But to my mind, it's not consistent with what we do know about the early Earth. It was mostly a water world, mostly an ocean. There was probably one to ten bars of CO2 in the atmosphere. It's highly doubtful that there was very much cyanide, if any. Perhaps there were some."
},
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"end_time": 901.886,
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"text": " And the pathways that they've come up with look nothing like biochemistry as I know it is a biochemist. And so even when you've answered the problem, you've still got to say, OK, so how did life start then? You've got all the building blocks, but then what happens next? Whereas if what you're looking at is an environment which is kind of dynamic and continuously, you've got a continuous flow in, say, a hydrothermal vent, you've got a continuous reaction going on. And remember that we are"
},
{
"end_time": 929.667,
"index": 38,
"start_time": 902.329,
"text": " We are a continuous chemical reaction. If you put a plastic bag over your head and stop breathing, then your continuous chemical reaction stops and life stops. So we breathe, we have lungs, we have a cardiovascular system. We've got all of this sophisticated way of making sure this reaction is happening in each and every one of our cells. So take all of that away and say, well, how can you have a continuous chemical reaction that's happening, which is converting the environment into more of me, you might say,"
},
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"end_time": 953.114,
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"text": " When you use the word pathways or biologists use the word pathways, is that referencing the recipe that creates some end product?"
},
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"end_time": 969.292,
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"start_time": 954.036,
"text": " What is the word Pathways? Yes, sorry. A lot of people have seen a metabolic map, which is like the map of the London Underground or something, except a whole lot worse. Really detailed."
},
{
"end_time": 991.374,
"index": 41,
"start_time": 969.292,
"text": " Lots of names of particular chemicals with arrows going from one to the next one and names of enzymes connecting up the arrow. So a pathway would be you start with this compound, you end up with that compound and there's 10 steps along that way and you link them all up and that's the pathway. That's a biochemical pathway which starts with this substrate and ends up with this product."
},
{
"end_time": 1017.568,
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"start_time": 991.664,
"text": " And it links them up in a way which all life does pretty much in this, in the heart of biochemistry is universally conserved, not always the genes or the enzymes, but the chemistry itself that underpins it is almost always the same across all of life. Ah, so you're not just looking for the products. You're also looking for a similar pathway or pathway that's similar enough that conceivably with variation, it could have moved onto what exactly. Yes. Yes."
},
{
"end_time": 1032.517,
"index": 43,
"start_time": 1018.012,
"text": " And this this altogether is is we're talking about scores of reactions, maybe a couple of hundred types of reaction all linked up in very specific ways, which we see in life, which is now encoded by genes, but the"
},
{
"end_time": 1055.845,
"index": 44,
"start_time": 1033.131,
"text": " Okay, and part of the reason why it's"
},
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"text": " strange to think of genes first producing the metabolism is because the way that we think of genes is operating is sequentially and incrementally and these pathways are so well it would it's difficult to think of half of a Krebs cycle or half of one of these steps as working? Yes and if you take it that way I mean there are various ways of thinking about this but how does a pathway let's say you've got 10 steps in this in this biochemical pathway"
},
{
"end_time": 1114.258,
"index": 46,
"start_time": 1086.459,
"text": " And let's say it's invented by genes. What do those genes do? So there's two main ideas. One of them is, well, you've got plenty of the product in the environment. But let's say there are organisms out there and they're beginning to eat that product in some way. And so now there's less of it. So if you can come up with a gene which takes the precursor to that product and converts it into the product, then you've got an advantage."
},
{
"end_time": 1142.432,
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"start_time": 1114.77,
"text": " So you kind of start at the end of the pathway and work your way back one step at a time. Or you can do it the other way around. You can start with the precursor and work your way up one step at the time. But both of those ideas basically assume that all of the intermediates along that pathway exist at high concentrations in the environment and that you can get at them and that they are useful in some way. And all of these are very hand-waving ideas and there's basically no truth to any of them."
},
{
"end_time": 1163.029,
"index": 48,
"start_time": 1142.892,
"text": " Whereas if what you're assuming is that actually going from one to another along this pathway at a low level, it just happens. You know, these things just interconvert into each other. And so at that point, a gene which speeds up any step will tend to increase the whole pathway."
},
{
"end_time": 1193.404,
"index": 49,
"start_time": 1163.951,
"text": " So it's much it's much easier as a question in evolutionary biology, but how do you then kind of ramp up because all you're doing is increasing the flux through a system that exists anyway. And where does energy enter into this the way that I understand your the difference between you and how biology ordinarily thinks is with regard to information based is the biological way of thinking and then yours is energy based. So I haven't heard energy come into this. Yes. Yeah. Yeah. Yeah. So"
},
{
"end_time": 1223.012,
"index": 50,
"start_time": 1194.258,
"text": " So the way that life works generally, if you look at the tree of life, and this is another way in which biology has kind of intruded into the question of the origin of life over the last couple of decades, what does the tree of life say about the very base, the kind of bacteria that are the most ancient, the very first ones? They're not the very first ones. These are things with genes, with enzymes, they're pretty sophisticated cells. This is a common ancestor of all of life as we know it."
},
{
"end_time": 1252.056,
"index": 51,
"start_time": 1224.019,
"text": " And you could say, well, it's not got much to do with the origin of life. Or you could say, well, perhaps it points in that direction. We can keep an open mind about that. So what does it do? What do these deepest branches in the tree of life do? Well, they're bacterial-like things, archaea and bacteria. And they're pretty much autotrophic, which means that they are converting gases in the environment into organic molecules, like photosynthesis, except probably not photosynthesis."
},
{
"end_time": 1270.213,
"index": 52,
"start_time": 1252.244,
"text": " And they're almost universally starting with CO2 and hydrogen and that's the very core of biochemistry. You react CO2 and hydrogen and you get Krebs cycle intermediates. That's the first things that you get and from there you get amino acids and from there you get nucleotides and so on."
},
{
"end_time": 1293.558,
"index": 53,
"start_time": 1270.896,
"text": " The problem is that hydrogen and CO2 don't react very easily. This is the problem that the chemists had for a long time. You can heat them up, you can add a catalyst. It does work, but it's difficult. It's only been in the last few years that people have succeeded in doing it. Now, what life does is it uses effectively an electrical charge on the membrane around the cell to drive that reaction."
},
{
"end_time": 1324.036,
"index": 54,
"start_time": 1294.377,
"text": " The problem is it's thermodynamically favored, which is to say, if you've got a mixture of hydrogen and CO2 and you mix them up at, say, 50 degrees centigrade, thermodynamically, you should get cells. It's actually more stable to have cells than it is to have a disequilibrium of hydrogen and CO2. They want to react so long as there's no oxygen around. But kinetically, there's a barrier and they don't react. And that kinetic barrier is broken down by this electrical charge on the membrane."
},
{
"end_time": 1354.07,
"index": 55,
"start_time": 1324.718,
"text": " Sorry, just to clarify, when you say you get cells, you don't mean cells as we know it as life, you mean that there's a membrane and it's oily and then there's a separation or? I mean that if you look at the thermo, this is theoretical thermodynamics that goes back to Jan Amund and Tom McCollum, and they have considered under the kind of conditions that I'm thinking about, this is 20 years ago now, under the kind of conditions that I'm talking about in alkaline hydrothermal vents, at 50 degrees centigrade in alkaline conditions,"
},
{
"end_time": 1380.606,
"index": 56,
"start_time": 1354.633,
"text": " Energy is released to make amino acids and fatty acids and overall total cell biomass releases energy from hydrogen and CO2. So, yes, it's favored. It's actually energetically more favored to have literally cells than it is to have a mixture of gases. That's what's driving life."
},
{
"end_time": 1409.48,
"index": 57,
"start_time": 1380.913,
"text": " The problem is that there's a barrier to it happening, and that barrier is broken down by this electrical charge on membrane. So my kind of driving question is, where did that come from? How did it get going? Why do you think it is that there's so much disagreement about the definition of life? So in mathematics, you just simply state the definition. There's no squabbling over that. But have you come up with a definition of life in mathematics? I mean, the answer is no. It's basically, it's not"
},
{
"end_time": 1438.677,
"index": 58,
"start_time": 1410.589,
"text": " It's not easy to put it into an equation. I personally think it's the wrong question because life is a process over time. It's not a thing. The origin of life is not a moment. There isn't one moment where something becomes alive. It's a continuum from prebiotic chemistry right the way up to quite sophisticated cells with genes and macromolecular machines, motors and what have you."
},
{
"end_time": 1468.763,
"index": 59,
"start_time": 1438.899,
"text": " And every step along that way, there isn't one moment where you would say it's now alive. There's suddenly something goes like that. And, you know, you can you could argue about is a virus alive or not? I would say it is, but it doesn't have a metabolism of its own and it wouldn't fall within most definitions of life. What about jumping genes, retro elements, these kind of things? Are they alive? What about something which is dormant to spore in deep space? Is it alive? No, it's not living now, but it could come back to life. So there's all these ambiguities about"
},
{
"end_time": 1496.169,
"index": 60,
"start_time": 1469.718,
"text": " I think what is living is a much better question. It's very easy to wave your arms and say, well, it needs metabolism, it needs information, it needs compartmentalization. Those things are probably true. But more than that, any definition that you come up with of life can usually be attacked. The classic one is known as the working definition of life from NASA."
},
{
"end_time": 1526.544,
"index": 61,
"start_time": 1496.8,
"text": " And I probably can't get this quite right, but it's roughly a self-sustaining system capable of making copies of itself or capable of evolving or something along those lines. And I have a real problem with the word self-sustaining because it's basically sustained by the environment, by disequilibria in the environment. But people have poked fun at it by saying, well, by that definition, a rabbit is not alive. Only a pair of rabbits would be alive because only a pair of rabbits could make a copy. Right, right, right."
},
{
"end_time": 1538.968,
"index": 62,
"start_time": 1527.142,
"text": " Okay, so there's some arbitrariness to it because it's akin to saying when does a grain of sand become a heap by adding more and more grains. Okay, so then it would be better to characterize it as a real number rather than zero or one."
},
{
"end_time": 1570.845,
"index": 63,
"start_time": 1541.015,
"text": " It's certainly not binary, yes. I mean, you might even say death looks binary, doesn't it? But even death is not, because when we die, some of ourselves will stay alive for a while longer. It feels binary, and therefore the origin of life perhaps feels binary for exactly the opposite reasons. You wonder about when does life begin in humans? There's terrible arguments about that kind of question, and there isn't really a correct answer to it either."
},
{
"end_time": 1594.326,
"index": 64,
"start_time": 1571.408,
"text": " So a better question may be when is living or what is living?"
},
{
"end_time": 1619.565,
"index": 65,
"start_time": 1595.879,
"text": " Living is an active process over time and it's a continuous reaction that is converting the environment into, in one way or another, more of itself. Whether that more of itself is just replace the broken bits, or if it's a case of make a copy of the whole cell."
},
{
"end_time": 1635.094,
"index": 66,
"start_time": 1619.957,
"text": " Or fuse with another cell and go through some complicated process of sex and so on. But in the end, life is effectively parasitizing the environment to make copies of itself. And it does that through metabolism."
},
{
"end_time": 1660.094,
"index": 67,
"start_time": 1636.186,
"text": " Okay, so two thoughts occurred to me. So one is, is there a way to put a number, like I mentioned a real number, but perhaps it's not as simple as that? Is there a way to place a number to how much something is characterized by living in the same way that you may say, well, consciousness is either you either have it or don't. But then there's some theories like Tononi's integrated information theory, where you have phi, which is like, okay, if you have a large number,"
},
{
"end_time": 1683.387,
"index": 68,
"start_time": 1660.094,
"text": " Okay so that's the first thought and then I'll say the second one then I'll come back to them just so that I don't forget them. Then the second thought was how far can we generalize this is so-and-so living because in the self-development world when you read you walk by the sections in the library they'll say yeah you're alive but you're not living you're not living your purpose. Well that's that's kind of that's playing with semantics"
},
{
"end_time": 1706.817,
"index": 69,
"start_time": 1683.507,
"text": " Okay, so that's taking it too far. Okay, okay. So let's focus on the first one. Is there a way I mean, I'm using living in the in the in the in the broadest possible sense, in the sense of alive as well. So so about, you know, consciousness, you know, if you look at the medical literature, there's all kinds of gradations of conscious states, whether you're fully anesthetized, or fully unconscious, or in some lower level of consciousness, and so on. And it's"
},
{
"end_time": 1734.36,
"index": 70,
"start_time": 1707.346,
"text": " You know, it's worth looking at that medical literature every now and then to realize that it's not an on or off switch there either. Yeah, I'm super interested in speaking with you about consciousness. So we'll get to that toward the end. Just so you know, I've been just absorbing your work for the past maybe two weeks or so every single day. And I have my own Nick cycle. So people have Krebs cycle have a Nick cycle in my brain. That sounds good."
},
{
"end_time": 1762.398,
"index": 71,
"start_time": 1735.162,
"text": " Sounds hard. So just so you know, my background is in math and physics. Yeah, yeah, yeah. And I don't like biology because there's so many terms. Too many terms. There's pyruvic acid, which I assume... So I can only apologize about my book. I mean, you know, it's basically a problem with biology and physicists always have this problem with biology. Yeah. And, you know, it's understandable."
},
{
"end_time": 1793.029,
"index": 72,
"start_time": 1763.029,
"text": " And there are, I think the most interesting questions in biology now really have questions in physics. But because we've had this almost kind of phase separation between physicists and biologists, there's not enough people who are biophysicists who are grappling with the biophysics of life. And so biology has gone off in the direction of information, but without really a very serious grounding in information theory, as a physicist might understand it, is really about, you know, just"
},
{
"end_time": 1822.585,
"index": 73,
"start_time": 1793.524,
"text": " Let's sequence the hell out of everything and see if we can find a pattern. And that's kind of intellectually very shallow. There are patterns there and we've learned almost everything about the world from doing that. But it doesn't really tell us your question, what is life and what is living and those things. The answer is not to be found in sequencing all the organisms. You have to take a step back and think about what is metabolism and what are genes and which came first and how do they relate to each other."
},
{
"end_time": 1840.538,
"index": 74,
"start_time": 1823.148,
"text": " What processes on the planet are driving this whole process? And these are often questions in physics. But biology is so intrinsically complex that physicists very often get pissed off and back away and, you know, can't deal with too much pyruvate."
},
{
"end_time": 1870.384,
"index": 75,
"start_time": 1841.203,
"text": " Yeah, there's a flurry of unmitigated polysyllabic terminology that is difficult to become acquainted with. The way that I imagine is that you become used to it over time. And so if you first encounter it, then it's overwhelming, at least for me. But you and Michael Levin are responsible for turn in tow in this channel toward more to interviewing more biologists. Michael Levin is doing amazing work. And, you know, all this electrical fields controlling development,"
},
{
"end_time": 1896.681,
"index": 76,
"start_time": 1870.879,
"text": " is most biologists at the moment, if you say that to them, would probably freak out. Probably back, I don't know what he said to you about this, but you know, he's obviously right. He's obviously found something which is really important. You know, is Nobel Prize winning stuff that he's doing, in my opinion. And it's profound. And this is the direction of 21st century biology."
},
{
"end_time": 1918.831,
"index": 77,
"start_time": 1897.09,
"text": " It's trying to understand what actually is this language of feels in cells. It's early days in terms of that. But most biologists still now would back away from it and treat it in some way as pseudoscience or as just not real."
},
{
"end_time": 1947.022,
"index": 78,
"start_time": 1919.155,
"text": " And yet there's corners of zoology which deal with electric eels and electric fields in fish or magnetic fields in navigation systems in birds and insects and whatever else. Biologists have known about this stuff for a while, not necessarily the development pathways, but it's a marginalized small corner of a field of information in terms of gene sequences is completely dominant."
},
{
"end_time": 1966.254,
"index": 79,
"start_time": 1947.312,
"text": " Like I mentioned, I have a NIC cycle in my head."
},
{
"end_time": 1994.497,
"index": 80,
"start_time": 1966.766,
"text": " But I mean that in many ways because I started bicycling more just to get your audio book in my head. So cycling is a great word. Certain words that you say strike me because your book is in my working memory currently. And you said 20th century biology is going to be the biology. Sorry, 21st century biology, the biology of fields. OK, why don't we expand on that? So so that was right at the end of the book. We're talking about consciousness, really."
},
{
"end_time": 2018.285,
"index": 81,
"start_time": 1994.923,
"text": " but also development and how cells know when to stop, know where to go. There's all kinds of questions that Michael Levin talks about. From my own point of view, I've been thinking for a long time about bioenergetics. That's my own kind of specialty."
},
{
"end_time": 2045.282,
"index": 82,
"start_time": 2018.797,
"text": " What cells are doing in the mitochondria is effectively pumping protons across the membrane and generating a charge on the membrane and that charge on the membrane is driving everything else. But I hadn't thought very much about fields as such because to generate coherent fields you would need to have quite specific morphology."
},
{
"end_time": 2073.524,
"index": 83,
"start_time": 2045.725,
"text": " And it's not something I really worried about very much. But if you look at mitochondria under a microscope, what you'll often see is these membranes which are parallel to each other, which are offset by the same degree. And there's a very detailed structure there. And the more we know about these structures, the more we realize that they play a really important role in how mitochondria and energy works. It's not a trivial thing. Those membranes are arranged that way for a reason."
},
{
"end_time": 2101.971,
"index": 84,
"start_time": 2073.916,
"text": " And we realize now as well that the motors, the ATP synthase, they're dimers at the end of these Christie, and all the rest of the complexes are in the middle. And so you've got a circuit going on. You've basically got an oscillating charge, which is going to produce a field. And we've got multiple parallel Christie all lined up next to each other. And if they're oscillating in phase, then these fields should be strengthened."
},
{
"end_time": 2127.585,
"index": 85,
"start_time": 2102.756,
"text": " Now I'm talking in a language where you're much more comfortable than I am. Things that have happened in neurology relatively recently, if you cut an axon, for example, and separate it by up to about 40 micrometers, an action potential can still hop the gap. We've known about the EEG for more than a century."
},
{
"end_time": 2154.189,
"index": 86,
"start_time": 2127.91,
"text": " the electroencephalogram. So we know that the brain is basically electrical but amazingly people don't really know where are those charges coming from. There's an assumption which is that oh it's just depolarizing neurons, there's some action potential going down this neuron, there's a network of all these neurons all doing their thing, hundreds of cells, maybe thousands of cells all firing simultaneously or in a circuit or whatever, that's what we're picking up on. But do we actually know that?"
},
{
"end_time": 2175.964,
"index": 87,
"start_time": 2154.684,
"text": " I don't think we do. The fields are quite weak on the membrane itself, but inside the cells, we've got all these mitochondria with stacked Christi generating what ought to be quite powerful fields, which should interact with the fields on the membranes as well directly and interfere with whether or not they're sending a signal or not."
},
{
"end_time": 2205.964,
"index": 88,
"start_time": 2176.254,
"text": " And this is a whole area of biology that, you know, the moment is hand waving. We don't know if any of this is true. And it makes a very specific prediction about the orientation of membranes. If they're all offset to each other, then the fields would interfere with each other and it would never work. So, you know, there's quite specific requirements for this to work. But it does seem to be oriented that way. It does seem to work that way. And then you end up with really interesting questions to me, which is, well, why"
},
{
"end_time": 2215.964,
"index": 89,
"start_time": 2206.442,
"text": " The mitochondria, why these fiddly things inside cells? Why not the level of neural networks? And the reason for me there goes back"
},
{
"end_time": 2241.152,
"index": 90,
"start_time": 2216.783,
"text": " Actually, I wrote a book 10 years ago, 12 years ago called Life Ascending, and there's a chapter in there on consciousness where I failed to answer the question at all to my own satisfaction, at least. Well, everyone does. You're in a comfortable company. Well, I was left with two uncomfortable conclusions. One of them was that, and I was really only reporting on what other people said. One of them is that it's a property of physics, it's a property of matter, it's an unknown"
},
{
"end_time": 2264.616,
"index": 91,
"start_time": 2241.63,
"text": " unknown property of matter and when we know a bit more physics then we'll understand what consciousness is and so the Sun is conscious in some way or another it's panpsychism and it's got a you know people like Roger Penrose and and and and Hammeroff and so on have been arguing along these lines for for a long time. I find it uncomfortable"
},
{
"end_time": 2294.599,
"index": 92,
"start_time": 2265.111,
"text": " I don't really believe that the sun or the moon is conscious in a meaningful way. I tend to think of it as a, well, basically a property of a nervous system. But if you think of it just as a property of a nervous system, then it comes down from my point of view as a biochemist, you've got a depolarizing neuron, you've got sodium ions rushing in, potassium ions, ions are changing around."
},
{
"end_time": 2315.282,
"index": 93,
"start_time": 2294.889,
"text": " that gives rise to a feeling and what's the feeling in physical terms if it's not a property of matter what actually is it and what you know is it simply in that sense an illusion that's concocted by a central nervous system and I find that very unsatisfying as an answer as well and it also kind of says that"
},
{
"end_time": 2340.35,
"index": 94,
"start_time": 2316.135,
"text": " It's a property of central nervous system. So what did selection act on? And this is where Michael Levin's ideas are really important because he's saying that, no, it's much wider than that. All cells have these fields. All cells are communicating electrically. It goes right back to not just the earliest animals, but probably back to single cells critters as well. And then when you start thinking about"
},
{
"end_time": 2370.009,
"index": 95,
"start_time": 2340.862,
"text": " Well, the charges in mitochondria are inside cells. Well, mitochondria were bacteria once. They were free living ones. And so the charges that they have on their membranes is separating the inside of the bacterial cell from the outside world. And so it has much more meaning. You can understand why selection would act on that. It's effectively telling you, how am I doing in the world right now? Am I about to die? Is something gone wrong? It's a real selective value that this is kind of giving you an"
},
{
"end_time": 2390.572,
"index": 96,
"start_time": 2370.435,
"text": " And integrated real time feedback on your state in the world as an electrical field that integrates the whole cell. And when you start thinking in those terms and you start realizing that well driving this reaction between co2 and hydrogen at the origin of life requires an electric and an electrical charge on a membrane."
},
{
"end_time": 2418.302,
"index": 97,
"start_time": 2391.067,
"text": " And so electrically charged membranes go right back to the beginning. And it's the only way really of integrating the cell as an entity in relation to its environment. Then there's a beautiful idea there. I'm not really saying that bacteria are conscious in a meaningful way. It's just that there are kind of integrated states of their state of being in the world. Either they're doing well or they're stressed, you know, that kind of level of feedback."
},
{
"end_time": 2443.268,
"index": 98,
"start_time": 2418.677,
"text": " and it's calibrated by a field and those fields are used during development to say okay now you've grown enough now stop now you're in a high or whatever it may be and this is a whole language of how fields are communicating in biology which is we've barely touched the tip of the iceberg okay let me see if i got the stream so earlier we you mentioned that there is an axon you can cut it and then you can separate it such that"
},
{
"end_time": 2470.896,
"index": 99,
"start_time": 2443.985,
"text": " Chemicals shouldn't be able to be interchanged between here, like neurotransmitters. It's too slow for that. Yes. So it'll just hop over as if there was no gap. However, there's still a signal and that signal is called an action potential. Yeah. Okay. And one of the reasons you think or people think mitochondria are important are because you use this word Christie, which I believe refers to the these are the membranes inside inside. Yes, exactly. Yeah. Okay. And the reason why these"
},
{
"end_time": 2496.749,
"index": 100,
"start_time": 2471.186,
"text": " Folds are important is because they have plenty of surface area, even though they're small. Yes, they have a lot of surface area, but they also have a structure and an orientation. They're lined up in parallel very often. And they have a very high charge. And ironically, it's very difficult to measure that charge. Why? Because if you're measuring the charge in a neuron,"
},
{
"end_time": 2521.152,
"index": 101,
"start_time": 2497.261,
"text": " You can insert a microelectrode into a neuron, and originally it was all done with giant neurons in squids and things like that. But still, you can insert an electrode into a neuron. But remember, a mitochondrion is a small part of a cell, so it's much smaller than a neuron. And people have done this. People have inserted microelectroses into mitochondria."
},
{
"end_time": 2550.469,
"index": 102,
"start_time": 2521.749,
"text": " And the irony is they've never really measured much of a potential difference. And the reason for that is almost certainly that they've just inserted it into what's called the matrix, which is the main kind of bulk space inside the mitochondrion. And so they're measuring a difference between that and the rest of the cell. And it's not much. But then you've got these structures, the cristae, which are very tight membranes, which is basically impossible to poke a needle into. And that's where all the charge is. So to try and measure that charge is a really difficult thing to do."
},
{
"end_time": 2574.121,
"index": 103,
"start_time": 2550.862,
"text": " And people are getting closer to it now. There's some really clever, ingenious ways of trying to measure what exactly is the charge in this closed space, really narrow closed space. But it's a very difficult technical problem. You can basically calculate it. You can show it with dyes, but you never really know what the dyes are interacting with otherwise. So it's intrinsically difficult."
},
{
"end_time": 2592.039,
"index": 104,
"start_time": 2574.48,
"text": " Okay, do you imagine that this is a technological problem that will be solved in the near future, or there's some in principle reason why it can't be done? No, I think, I mean, it's just difficult, but I think we can do it. I mean, I intend to give it my own best shot, but there's a few other people thinking along these lines as well."
},
{
"end_time": 2607.927,
"index": 105,
"start_time": 2593.336,
"text": " Now the fact that mitochondria may be important for consciousness, does that imply that the bacteria which don't have mitochondria are not conscious or at a much lower level of consciousness and protozoa? So protozoa do have mitochondria."
},
{
"end_time": 2637.09,
"index": 106,
"start_time": 2608.507,
"text": " and you know you can see videos of the way that they behave and they're astonishing I mean watch videos of protozoa the way that they move around and they go fishing they do all kinds of that the control of their behavior is exquisite it's the kind of thing that would you know should make people believe in God it's just so beautiful so it's not a matter of genes being expressed there's something controlling this system which is"
},
{
"end_time": 2665.23,
"index": 107,
"start_time": 2637.432,
"text": " which is happening in nanoseconds. It's happening extremely quickly. And it's the whole cell which is doing this. It's not just one bit of the cell. Imagine you're a molecule. Finish the book this way. Imagine that you're a molecule. Shrink yourself down to the size of a molecule. And the cell is like a city. And where I am now, I'm in London and 15, 20 miles away through to Canary Wharf or Greenwich or somewhere like that."
},
{
"end_time": 2694.002,
"index": 108,
"start_time": 2665.811,
"text": " there would be other molecule you know the people over there would be like me as a molecule as a pyruvate molecule inside a cell or something so what is it that unites me with this person 20 miles away in a cell and the answer is well you know in the city not much some kind of shared sense of identity as a londoner or something but you know you know you you know that you're living in a city where that's conscious awareness but in a cell where we're dealing with molecules"
},
{
"end_time": 2716.442,
"index": 109,
"start_time": 2694.411,
"text": " How does something happening over here happen over there simultaneously, essentially simultaneously, effectively 20 miles away, so that we're integrated in real time and doing the same thing? Now fields can do that for sure, so how would you have a field that operates on the whole cell? Well if it's on the membrane that surrounds the cell"
},
{
"end_time": 2745.981,
"index": 110,
"start_time": 2716.954,
"text": " And if what that membrane is reporting on is how are you doing in relation to the environment? Because if you're taking up food from the environment and burning it and using the energy to generate an electrical charge on the membrane and there's plenty of food, you've got a nice charge, everything's good. So it's telling you that the whole cell has got a nice electrical charge on the membrane. There's a nice field crossing the cell, oscillations of water molecules within the cell are kind of locking things in some kind of phase."
},
{
"end_time": 2760.623,
"index": 111,
"start_time": 2746.561,
"text": " And that is telling you about your state. If you move into an area where there's toxins or where there's no food or whatever it may be, then they're going to interfere."
},
{
"end_time": 2790.828,
"index": 112,
"start_time": 2760.913,
"text": " with how this charge works is going to change the field and you're going to shift, you're going to change what you do, you're going to move over there, you're going to set your phagellum worrying or something, you'll change your behavior but you do it at the level of a whole cell and what's integrating at the level of the cell in my view now is the charge on the membrane generating a field which is integrating all the component molecules in the cell to act as a"
},
{
"end_time": 2820.094,
"index": 113,
"start_time": 2791.22,
"text": " There's one question. If we have one cell and it's, we imagine that it may have some proto form of consciousness because it's interacting with the outside. Okay. And then if we have two and they're interacting with one another, then we have a consciousness that is of the two as a whole. Not necessarily. If they're in, if they're locked in phase in some way, as they may be with two neurons locked in phase in a multicellular organism,"
},
{
"end_time": 2845.401,
"index": 114,
"start_time": 2820.589,
"text": " then yes they could be but if they're not in phase then they would interfere with each other in some way. There's actually lots of evidence that for example pollinating insects when they arrive on a flower can sense electrically whether or not it's already whether the nectar has already been taken so they don't bother to go there. There's interference that I don't know very much about but"
},
{
"end_time": 2871.084,
"index": 115,
"start_time": 2846.152,
"text": " You know, there's quite a lot of evidence that the animals have fields that are capable of interacting with each other. We just don't know a huge amount about it. And the idea that cells would do the same thing. I mean, you can see it under the microscope. We don't know exactly what's going on. I don't think we've ever measured it. But I'm fairly persuaded that fields would be one of the most powerful ways of trying to explain the interactions you see between single cells. Yes."
},
{
"end_time": 2892.244,
"index": 116,
"start_time": 2871.613,
"text": " Now this locked in phase quality I imagine is also a spectrum and not zero to not binary or is it? I know well you tell me you're the physicist I mean I would imagine that there's something of a spectrum but but there's some element in which once you get interference then you don't have you would not have any locked in phase. What I'm thinking is that"
},
{
"end_time": 2920.572,
"index": 117,
"start_time": 2892.671,
"text": " I'm imagining the brain akin to there's vertices, or there's points, there's vertices, and then there's edges between them, and then there's a slew of them, and then they're interacting with one another. And that any subset of these, not any subset, but there will be manifold subsets, so plenty, not manifold in the math sense, but many, many subsets that will be in phase with one another at any given point in time. And so any individual comprises perhaps more conscious"
},
{
"end_time": 2946.288,
"index": 118,
"start_time": 2921.135,
"text": " subsets then there are atoms in the universe if you do some analysis of how many subsets and so on that is to say that nick is not just one consciousness it would be trillions or 10 to the trillions but i don't know because i don't know what counts as consciousness here yeah i mean i'm not i'm not a neurologist and i'm not working on consciousness as we know it in human brains what bothered me"
},
{
"end_time": 2977.022,
"index": 119,
"start_time": 2947.244,
"text": " It's a question in philosophy as well. It touches on AI and whatever else. If you've got an extremely sophisticated processing system, and the brain is an extremely sophisticated processing system, does it need to be conscious? Is there some kind of emergence? And if so, what governs that emergence? And it may be that that is the case."
},
{
"end_time": 2994.838,
"index": 120,
"start_time": 2977.312,
"text": " I find emergence one of those words which is overused it has a real meaning but it's very easy to say oh it's an emergent property and you know it basically says I haven't a clue what I'm talking about it's just a nice word. So I had this problem I can imagine"
},
{
"end_time": 3022.227,
"index": 121,
"start_time": 2995.247,
"text": " the classical philosopher zombie, which is capable of behaving in a perfectly normal human way without experiencing any emotions or any feelings or anything else. And I can imagine robots and AI being like that as well, capable of being enormously intelligent and having conversations that would persuade us that they are human, but without feeling anything."
},
{
"end_time": 3048.097,
"index": 122,
"start_time": 3022.5,
"text": " And so I'm background to this question of, well, what is a feeling? Is it real? Is it a concoction of a central nervous system, an emergent property? What actually is it? And to my mind, natural selection always works on something else. There are simpler systems. So I'm perfectly happy to believe that a dog, for example, is not necessarily"
},
{
"end_time": 3074.735,
"index": 123,
"start_time": 3048.882,
"text": " that intelligent? I don't know, but I would think it's consciously aware and capable of feelings capable of emotions. And the idea that a dog will pine after its masters died or whatever is very familiar to most people. And it seems obvious to me that that would be the case. And from a biologist point of view, why would it not be the case selection has to act on something? Why would one central nervous system be utterly different to another one?"
},
{
"end_time": 3104.599,
"index": 124,
"start_time": 3075.213,
"text": " There's a matter of, it's a continuum again. We have a really high powered processing system, but our feelings, our emotions, you know, I think we've probably shared them with a lot of other creatures and it's very easy to imagine that, you know, a chimpanzee can be in love or can feel pain or any of these feelings. They feel animalistic to me and we can nuance them with all kinds of"
},
{
"end_time": 3134.189,
"index": 125,
"start_time": 3105.009,
"text": " intelligence and thoughts and language and whatever else, but the feeling of malignant sadness underneath everything else, it's not something that you have much control over, or a feeling of just being overwhelmingly in love with someone. We have no control over these feelings. They're very separate almost from a parallel processing system. They can be overwhelming."
},
{
"end_time": 3159.855,
"index": 126,
"start_time": 3134.599,
"text": " So what are they? And this is where I think this language of feels and so on comes in. And I'm not saying that a bacterium is conscious in a way that any of us would recognize. I'm just saying it's the germ of a kind of a something which tells you about your state and which is not just more than the sum of all of these parts. It's something which gives you an integrated feedback on, am I effectively sad or happy, you might say? Am I"
},
{
"end_time": 3183.763,
"index": 127,
"start_time": 3160.213,
"text": " Okay, so to be clear, you're not claiming that this solves the hard problem of consciousness, but rather if consciousness was to have some physical explanation, perhaps we should look at what's occurring at the cell membrane electrically."
},
{
"end_time": 3199.94,
"index": 128,
"start_time": 3184.599,
"text": " Well, the membranes inside in the mitochondria and so on. Yes, I think that's the language. I think that provides a selective basis for how it began. I think it's, you know, this question about what purpose is consciousness in natural selection."
},
{
"end_time": 3226.476,
"index": 129,
"start_time": 3200.435,
"text": " If you think about it at the level of single cells, if you think that it's giving you this real time integrated feedback on your state in the world and whether or not you make a decision as a cell to go over there or to stay here or to depolarize your membrane and kill yourself immediately if you've been infected by a virus or all of these kind of decisions that you take as an entity, this is providing you with a kind of language for the entity."
},
{
"end_time": 3250.145,
"index": 130,
"start_time": 3226.852,
"text": " You immediately see what selection is acting on and the hard problem in consciousness is to a large extent about what are feelings, what are emotions in physical terms. People have been talking about electrical fields for quite a long time in that sense as well. This is again nothing particularly new but why that language"
},
{
"end_time": 3263.746,
"index": 131,
"start_time": 3250.486,
"text": " why why would electrical fields give you some kind of feeling of being conscious when you take it out of the environment of a nervous system and put it into the environment of single cells and this real time feedback"
},
{
"end_time": 3281.715,
"index": 132,
"start_time": 3264.309,
"text": " on their environment, their state in their environment, then you see it's the only language which is going to integrate you as a unit, which is going to tell the other half of the cell 20 miles away over there that your action is for the whole cell."
},
{
"end_time": 3309.497,
"index": 133,
"start_time": 3282.449,
"text": " And so when you put two cells together and you build multicellular organisms, you're using these fields to control the development of the organisms, as Michael Levin says. And then as you end up with a central nervous system, it's channeling more of that energy into circuits. And, you know, whatever the explanation is, it has to correspond to what we already know about neurology, about the way that neural networks actually work. And the problem I have, for example, with"
},
{
"end_time": 3335.572,
"index": 134,
"start_time": 3309.77,
"text": " With Penrose and Hameroff and the idea that it's all to do with microtubules, for example, is that it's not very obvious how they correspond to, at least it's not to me, how they correspond to what we already know about neurology, about neural networks and so on. Whereas mitochondria are completely integrated into that. They're part of the neurons, they're part of"
},
{
"end_time": 3357.346,
"index": 135,
"start_time": 3335.981,
"text": " the depolarization of neurons they can interfere with this electrically and so on. So they're linked in with the structure I think of the neurons in a different way. The reason though that I came back to this and started taking it seriously"
},
{
"end_time": 3381.63,
"index": 136,
"start_time": 3357.91,
"text": " And you know, lots of people seem to think that I'm barking at the wrong tree altogether and should never talk about neurology again or consciousness again. But the reason is an interaction with a biophysicist called Luca Turin. And he came to see me a few years ago and was talking about anaesthetics, general anaesthetics. We don't really know how they work. And"
},
{
"end_time": 3405.435,
"index": 137,
"start_time": 3382.346,
"text": " And he was interested in xenon in particular, which is an inert gas. And it doesn't really have a shape. It's a sphere of electron density. So it's not obviously going to interact with any type of receptor. And all the different general anesthetics, they have different shapes and different chemical properties. And it's not obvious that there's any kind of type of receptor that would deal with them all."
},
{
"end_time": 3433.899,
"index": 138,
"start_time": 3406.203,
"text": " And it doesn't really have any chemistry, but it can transfer electrons. And so it can interfere with electron transfer. And what Luca Turin had shown, which really made me excited, is that they do interfere with the transfer of electrons to oxygen in respiration. Now, that doesn't prove it's causal. That just shows that anesthetics interfere in some way with respiration."
},
{
"end_time": 3461.51,
"index": 139,
"start_time": 3434.258,
"text": " And maybe if they simply suppress what the rest of the cell is doing, that would have a knock-on effect on respiration. You could say that that would be the case. But he didn't find anything else that a general anesthetic was having an effect on. And so if you put it together with what I was saying about the requirement for cells and the electrical charge on the membranes to integrate their state in the environment, then suddenly it's a rather thrilling idea."
},
{
"end_time": 3487.056,
"index": 140,
"start_time": 3461.869,
"text": " Doug Wallace is another person who's been working on these fields in mitochondria for some time now and again he's out there on a limb as far as biology is concerned. He's one of the few people who's willing to talk about parallel Christi generating strong electromagnetic fields that are reinforcing each other and communicating across distances. This is not"
},
{
"end_time": 3517.142,
"index": 141,
"start_time": 3487.807,
"text": " This is not the language that biology is used to and Doug Wallace is very distinguished and so people will kind of tolerate him towards the end of his career talking about these things. Luca Turin is, I won't say he's an outcast, but he's on the edge of scientific respectability and it's not because he's not a good, he's a brilliant scientist, it's just that he's saying things that people in biology don't want to hear."
},
{
"end_time": 3537.312,
"index": 142,
"start_time": 3518.08,
"text": " Interesting. Turin has found that xenon interrupts or interferes with respiration. And when you say respiration, you mean cellular respiration? With the transfer of electrons, yes, which is to say this is what's going on in mitochondria. So you basically have a current of electrons going from food to oxygen."
},
{
"end_time": 3567.5,
"index": 143,
"start_time": 3537.79,
"text": " and gases like xenon interfere with that current of electrons. And that means that it makes respiration less likely to occur. And by the way, what is cellular respiration? I assume it's taken oxygen, but I don't know if that analogy between my respiration. Yeah, I mean, basically, yes. No, it's exactly right. I mean, we're stripping electrons from food by the Krebs cycle. That's what the Krebs cycle is doing. It's taking electrons from food. It's feeding them into the membrane."
},
{
"end_time": 3596.049,
"index": 144,
"start_time": 3567.978,
"text": " Then we have a current of electrons in the membrane going to oxygen. Oxygen picks up two electrons and two protons and it ends up as water. Basically, we're reacting hydrogen, the electrons and the protons, we're taking hydrogen from food, we're reacting it with oxygen, but we're not doing it in one step. That's rocket fuel. That's what's powering a rocket."
},
{
"end_time": 3624.445,
"index": 145,
"start_time": 3596.783,
"text": " We've basically got a current from one to the other and that current is powering the extrusion of protons across the membrane and that's what's putting the electrical charge on the membrane. So now we have an electrical charge on the membrane and the orientation of these Christi structures means that this is a current of protons. It's an oscillating current of protons and that's what's generating the field. Is there a radio wave associated with this? Turin found that somehow... Yes."
},
{
"end_time": 3633.695,
"index": 146,
"start_time": 3625.179,
"text": " There is, yes. I have to say I don't quite understand that."
},
{
"end_time": 3657.773,
"index": 147,
"start_time": 3634.497,
"text": " Well, there's a funny story that he tells about that, because the guy who, I forget his name now, the guy who discovered the EEG in the first place, the electroencephalogram. Michael Cohen or no? No, that's different. No, no, this goes back much before. I just have different snippets of the book in my head. I remember Michael Cohen said something like, no one understands. No, we're going back 100 years or more."
},
{
"end_time": 3684.616,
"index": 148,
"start_time": 3658.2,
"text": " to the discovery that the brain is generating electrical signals that can be detected with the electrodes on the scalp. He was actually looking for radio waves. He was looking for long distance communications between people. I think he'd had some premonition that a terrible accident had befallen his sister or something. Lots of people have these premonitions that something terrible has happened to a friend."
},
{
"end_time": 3714.377,
"index": 149,
"start_time": 3685.128,
"text": " I have them as well and every time I have them it never turns out to be true but you know for some people it's true. Is it true? Is it true because it's real or is it true because it statistically is going to be true sometime? I don't know. I've never looked exactly but that's what he was interested in. That's what he was looking for. Communication by radio waves between people at a distance of maybe hundreds of miles and he discovered the EEG instead and it's ironic because"
},
{
"end_time": 3745.196,
"index": 150,
"start_time": 3715.316,
"text": " The key, we're on your ground again here more than my ground, but there's an Israeli scientist who's shown that electron spin, if it's passing through a chiral medium, ends up in the same spin state. So it's been polarized. And a chiral medium includes proteins because proteins are made of amino acids and amino acids are always in the left-handed form."
},
{
"end_time": 3771.749,
"index": 151,
"start_time": 3745.896,
"text": " And so all the current of electrons that flows from hydrogen to oxygen goes through proteins in this membrane and those proteins are chiral and that means that the electrons that are transferred are actually locked in the same spin state and when you lose that spin state that emits a radio signal and that's what leukoturine has detected."
},
{
"end_time": 3796.937,
"index": 152,
"start_time": 3773.166,
"text": " You mentioned something interesting, which is that there's apparently a psychic phenomenon unverified, or maybe it has been, but we don't know. As far as I know, it's unverified. Will people believe they can communicate to one another? One of the reasons why on theories of everything, I don't mind talking to some people who believe they've done studies and they're excluded from academia for whatever reason, I want to find out the validity of those, because I think that there may be something to a certain"
},
{
"end_time": 3826.937,
"index": 153,
"start_time": 3797.278,
"text": " Aspects of what people consider to be paranormal that their explanation for why it works may be incorrect There may be some physical basis like it's that we work obviously communicating right now We don't think that there's any psychic abilities involved because we're just going through the computer But perhaps something similar where radio waves are being transmitted and if it's of a strong enough distress Then perhaps the person feels it. I think that science is intrinsically very conservative And there was a lovely phrase from Peter Meadow who said science is the art of the soluble"
},
{
"end_time": 3854.053,
"index": 154,
"start_time": 3827.244,
"text": " which is to say problems that we can actually solve. So problems that we can't solve because we don't know how to go about it. We tend to put to one side and reject is not science. And that goes for all kinds of things, including ESP and so on. Now, to my mind, there's two questions. Number one is, is it real? And then number two is, well, can we then explain it? And"
},
{
"end_time": 3882.005,
"index": 155,
"start_time": 3854.889,
"text": " I don't think very many scientists get involved in the question of is it real? It's just not part of what science asks because we don't have a way of answering it really, so we don't ask it. So it may be real or may not be real, I don't know. I think there's another factor though which is that"
},
{
"end_time": 3909.821,
"index": 156,
"start_time": 3882.415,
"text": " Occam's razor, which underpins all of science really, which says don't multiply causes, try and find the simplest explanation that explains everything we need to know. It may or may not actually be true, but it is what governs science, which is to say you first of all take the simplest possibility and test that. And if it doesn't work, then try the next simplest one and work your way up until you end up with something mad."
},
{
"end_time": 3938.712,
"index": 157,
"start_time": 3910.026,
"text": " But the problem with anything like ESP is it's almost certainly not the simplest explanation for things. Now, if someone were to show that it's real and that it really is happening, and statistically in some kind of trial, it would have to be with the power of a clinical trial, and then it's going to cost a lot of money, and there's going to be so many comebacks from people who are determined to demonstrate that it's not true, that it would be a very, very difficult thing to do."
},
{
"end_time": 3940.384,
"index": 158,
"start_time": 3939.206,
"text": " and"
},
{
"end_time": 3970.009,
"index": 159,
"start_time": 3942.125,
"text": " Then it boils down to personal experience. I've never really, you know, I don't really believe in ghosts because I've never seen one or I don't see any reason why they would exist. And I've never had any experience with them, but perhaps if I did, then I would change my mind. I don't really believe in ESP because I have these feelings that other people have that says something terrible has happened, but I phoned them up and nothing had happened. It was just a figment of my imagination. Well, you know, there's a simpler explanation, which is just that my brain is active."
},
{
"end_time": 3998.695,
"index": 160,
"start_time": 3970.35,
"text": " You're thinking about someone. Probably for most people, most of the time, that's the real answer. I'm skeptical of these things, but there's a whole lot more out there than we know now. I've been talking about fields and consciousness and so on. That is already pushing the barrel out for most biologists in terms of what are we willing to accept now. I think there's very strong grounds there for accepting those kinds of things."
},
{
"end_time": 4017.756,
"index": 161,
"start_time": 3998.933,
"text": " We can begin to push it into looking at other languages and genes. But if I then start spouting on about ESP or something, then I'll be cold-shouldered by the entire community and I have no desire to go down that path because I have no strong reason to think that exists anyway."
},
{
"end_time": 4040.333,
"index": 162,
"start_time": 4019.411,
"text": " Okay, I don't have a question, but I have a some thoughts. So then I can just take them and then hear what your responses to them. So number one, when it comes to Occam's razor, I always find that a bit tricky, unless someone's speaking about something in physical law, something mathematical, Occam's razor, it's unclear to me what constitutes as an assumption. So for example, in physics, the way that you say that"
},
{
"end_time": 4069.582,
"index": 163,
"start_time": 4040.811,
"text": " a certain model is simpler is that you use less parameters to specify it so it's actually quantifiable how simple the model is and that's one of the reasons why people say string theory is the most beautiful because it can supposedly reduce it all down to one parameter it's still one parameter like there's no yeah there's still some freedom there but it's one as opposed to 26 or so yeah and then so let's say the principle of induction in science is that one assumption or is that two assumptions or three assumptions because it presumes there exists a future and a past and then"
},
{
"end_time": 4098.49,
"index": 164,
"start_time": 4069.991,
"text": " I'm sure you've heard of the problem of induction. The point is, if it's not mathematically stated, then to me, because my brain is so analytical, it's difficult to see, well, what's being assumed and what's not? Like, is God the simplest assumption? Well, then God has the trouble of explaining. Like, you can't predict from that. But God certainly is the most simple assumption. Well, yes. I mean, it depends what... But then it's not simply simplicity. Is God five assumptions? Well, I mean, as soon as you start wondering,"
},
{
"end_time": 4103.268,
"index": 165,
"start_time": 4098.933,
"text": " where God came from. Hear that sound?"
},
{
"end_time": 4130.316,
"index": 166,
"start_time": 4104.206,
"text": " That's the sweet sound of success with Shopify. Shopify is the all-encompassing commerce platform that's with you from the first flicker of an idea to the moment you realize you're running a global enterprise. Whether it's handcrafted jewelry or high-tech gadgets, Shopify supports you at every point of sale, both online and in person. They streamline the process with the Internet's best converting checkout, making it 36% more effective than other leading platforms."
},
{
"end_time": 4150.179,
"index": 167,
"start_time": 4130.316,
"text": " There's also something called Shopify Magic, your AI powered assistant that's like an all-star team member working tirelessly behind the scenes. What I find fascinating about Shopify is how it scales with your ambition. No matter how big you want to grow, Shopify gives you everything you need to take control and take your business to the next level."
},
{
"end_time": 4179.787,
"index": 168,
"start_time": 4150.179,
"text": " Join the ranks of businesses in 175 countries that have made Shopify the backbone of their commerce. Shopify, by the way, powers 10% of all e-commerce in the United States, including huge names like Allbirds, Rothy's, and Brooklynin. If you ever need help, their award-winning support is like having a mentor that's just a click away. Now, are you ready to start your own success story? Sign up for a $1 per month trial period at Shopify.com"
},
{
"end_time": 4190.06,
"index": 169,
"start_time": 4179.787,
"text": " Go to shopify.com."
},
{
"end_time": 4211.084,
"index": 170,
"start_time": 4193.285,
"text": " Razor blades are like diving boards. The longer the board, the more the wobble, the more the wobble, the more nicks, cuts, scrapes. A bad shave isn't a blade problem. It's an extension problem. Henson is a family owned aerospace parts manufacturer that's made parts for the International Space Station and the Mars Rover."
},
{
"end_time": 4239.548,
"index": 171,
"start_time": 4211.084,
"text": " Now they're bringing that precision engineering to your shaving experience. By using aerospace-grade CNC machines, Henson makes razors that extend less than the thickness of a human hair. The razor also has built-in channels that evacuates hair and cream, which make clogging virtually impossible. Henson Shaving wants to produce the best razors, not the best razor business, so that means no plastics, no subscriptions, no proprietary blades, and no planned obsolescence."
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{
"end_time": 4255.913,
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"start_time": 4239.548,
"text": " It's also extremely affordable. The Henson razor works with the standard dual edge blades that give you that old school shave with the benefits of this new school tech. It's time to say no to subscriptions and yes to a razor that'll last you a lifetime. Visit hensonshaving.com slash everything."
},
{
"end_time": 4279.275,
"index": 173,
"start_time": 4255.913,
"text": " If you use that code you'll get two years worth of blades for free. Just make sure to add them to the cart. Plus 100 free blades when you head to h-e-n-s-o-n-s-h-a-v-i-n-g dot com slash everything and use the code everything. You know what what gave rise to cards in the first place there's a lot of assumptions behind that so something is"
},
{
"end_time": 4301.596,
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"text": " As profound and all encompassing as God requires in some way an awful lot of assumptions behind it. But then we know a lot about the world as well. We don't understand it all. But it's definitely four and a half billion years old. There's definitely signs of bacteria from four billion years ago. There was definitely stasis for about two billion years. There was definitely oxygen appearing"
},
{
"end_time": 4328.473,
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"start_time": 4302.176,
"text": " around two billion years ago. There were definitely more complex cells appearing after that. Animals certainly appeared around the time of the Cambrian explosion, 540-50 million years ago. And so, you know, any assumption that God did it would require either a deist God that set it in motion at the beginning and then it follows its own path, or a God that's kind of involved all the way along with every little bit here and there. And there's no"
},
{
"end_time": 4347.995,
"index": 176,
"start_time": 4329.053,
"text": " There's no need for that, as Voltaire said, there's no requirement for God to kind of get involved in this species of bacteria differentiating from that species, you know, that's the level of detail he would have to be involved in. So there's no need for that hypothesis. Deism,"
},
{
"end_time": 4363.285,
"index": 177,
"start_time": 4348.507,
"text": " I think will be very difficult to reject for most scientists who had an open mind. But deism I don't think is something that most people who are religious would be terribly happy about because I think for most people God is"
},
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"start_time": 4363.985,
"text": " communicating with them personally in one way or another. So the idea that there's an aloof God somewhere at the other end of the universe that sets the laws of physics in motion and then steps back and is never seen again is not much of a comforting figure for most people. But frankly, what we know about the world, if it's consistent with any form of God, is more consistent with a deist form of God, I would say, than anything else."
},
{
"end_time": 4418.336,
"index": 179,
"start_time": 4388.882,
"text": " So then there are assumptions and science works on these assumptions and they may or may not be the simplest ones but they underpin everything and one of them is that it's naturalistic, that it's not miracles, that's not science, that's an assumption. We assume that life started and that we can understand the principles that govern the origin of life and the evolution of life and so on"
},
{
"end_time": 4419.548,
"index": 180,
"start_time": 4418.695,
"text": " It may be that..."
},
{
"end_time": 4449.394,
"index": 181,
"start_time": 4419.991,
"text": " There were miracles. It may be that it was delivered from outer space. There's all kinds of things that could have happened, but we make a simplifying assumption that it happened here on Earth and it happened for naturalistic reasons and therefore we don't call on a miracle and that we can understand those naturalistic reasons. These are three huge assumptions that may not be true. There's nothing scientific about them, but all of science is built on those ideas. And the reason that I believe it to be true and most scientists would is that"
},
{
"end_time": 4479.309,
"index": 182,
"start_time": 4449.923,
"text": " Well, everything we know about the world is consistent with that idea. So everything I was saying earlier on about you start with carbon dioxide and hydrogen and you get Krebs cycle intermediates and you have electrical charges on barriers in these hydrothermal, all of this is, is consistent with the naturalistic origin of life. It's a long, long way from proving that that's what happened, but everything I know about it is consistent with it sufficiently that I have some faith"
},
{
"end_time": 4508.831,
"index": 183,
"start_time": 4479.838,
"text": " I'm using the word deliberately, faith that the gaps between the bits that I know a little bit about and this long spectrum of things that I don't know much about can be filled in in due course if we keep on thinking constructively in that way. So I think, you know, science is always based on assumptions and it's always based on some form of faith which most scientists are very reluctant to use the word faith because in a religious sense faith very often means belief in something which"
},
{
"end_time": 4532.91,
"index": 184,
"start_time": 4509.275,
"text": " which is irrational in some way, that it goes against the evidence. Whereas in science, faith is perhaps more about, I have faith that there'll be more of this kind of evidence that will explain the way that the world is. It's a form of faith. It may or may not be true. It may be delusional. Hear that sound?"
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"text": " That's the sweet sound of success with Shopify. Shopify is the all-encompassing commerce platform that's with you from the first flicker of an idea to the moment you realize you're running a global enterprise. Whether it's handcrafted jewelry or high-tech gadgets, Shopify supports you at every point of sale, both online and in person. They streamline the process with the internet's best converting checkout, making it 36% more effective than other leading platforms."
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"text": " There's also something called Shopify Magic, your AI powered assistant that's like an all-star team member working tirelessly behind the scenes. What I find fascinating about Shopify is how it scales with your ambition. No matter how big you want to grow, Shopify gives you everything you need to take control and take your business to the next level. Join the ranks of businesses in 175 countries that have made Shopify the backbone of their commerce. Shopify, by the way,"
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"text": " It's very powerful because it's led to all these scientific advances that we see in the world and that leads people and most people to to begin to believe that science really can explain the world and there really isn't a need for a god to explain the world unless it be a deus god that put these principles in place in the first place and that you know"
},
{
"end_time": 4655.708,
"index": 189,
"start_time": 4646.34,
"text": " That's the way I would see it, but I have a lot of sympathy with people who prefer a religious view of the world. And I certainly couldn't argue against the deists' position."
},
{
"end_time": 4677.927,
"index": 190,
"start_time": 4656.51,
"text": " I wouldn't say that it's a minority, the deist position. Well, when I say minority, I mean, it's a sizable minority if it exists. Because when I was looking at the Pew research data on belief, I believe something like 10 to 20 to 30, let's say 10 to 30% of people believe in a deist God of those who say that they believe in God, that's sizable, because I thought it would be 0.02."
},
{
"end_time": 4703.063,
"index": 191,
"start_time": 4678.353,
"text": " Yes, I would expect it to be smaller as well. Yeah, it's an extreme amount. And then secondly, that there's a sizable portion of people who believe that the definition of God is reality. So by science, one is studying God. And it's not so I used to be the same. I love that as an idea. I have to say, I don't personally believe in God. But the idea"
},
{
"end_time": 4733.66,
"index": 192,
"start_time": 4704.019,
"text": " that people who have tried to understand the world in the past as the world that God put there, I have a huge fellow feeling with them that they were trying to understand the world, they were trying in some way to understand the mind of God. What is nobler in this world than trying to understand these things? And whether or not you put the word God at the end of it, it seems to me almost a trivial distinction"
},
{
"end_time": 4763.473,
"index": 193,
"start_time": 4734.258,
"text": " I remember my grandma saying to me years and years ago that to her God was the voice in her head that told her what was right and what was wrong. It was basically her conscience and I remember saying to her, well I have a voice in my head that tells me what's right and what's wrong and I don't think that it's God and she was shocked and horrified that effectively I was saying I don't believe in God and it hurt her deeply and I've never quite forgiven myself and you know I'm very careful"
},
{
"end_time": 4783.677,
"index": 194,
"start_time": 4763.66,
"text": " To try not to offend people because to me it's not very far away. It's just ways of phrasing things, ways of seeing things and there's no need to be deliberately offensive to people when actually we may both see the glory of the world and want to understand it. Okay, let me get philosophical here for a moment."
},
{
"end_time": 4811.8,
"index": 195,
"start_time": 4784.104,
"text": " I think that was about as philosophical as I can get. I'm agnostic when it comes to this. I'm not coming at this from a religious perspective, just so you know, so you can feel safe to surmise in any direction. What basis so your mother, sorry, your grandmother had a basis to believe in the in the to follow her conscience. If you don't believe that comes from some higher place, what does higher mean? Who knows? For the sake of this, let's just put that aside and assume that we can intuit that. Then why should you follow your conscience?"
},
{
"end_time": 4840.913,
"index": 196,
"start_time": 4813.268,
"text": " Because our conscience has evolved in the context of society, of human societies, of groups, of human groups. To my mind at least, you know, there's all these interesting questions about human evolution. When and why did we develop in the way that we did? When did the human mind take on the ability to be creative, to do art, to believe in gods and what have you?"
},
{
"end_time": 4863.302,
"index": 197,
"start_time": 4841.186,
"text": " the things that we think of as human. And it's not obviously to do with tool use, for example, they often, you know, the use of flints and things and spearheads goes back hundreds of thousands of years, if not more than that, and didn't change very much over a long time."
},
{
"end_time": 4887.619,
"index": 198,
"start_time": 4863.78,
"text": " And things like fire, it's a little difficult to know exactly when was fire invented. And language is another thing that we tend to, as soon as we've got language, then we develop our minds in some way. The one thing that it seems to correlate with most interestingly is population density. This is work that I know of from Mark Thomas, who's a colleague at UCL."
},
{
"end_time": 4909.002,
"index": 199,
"start_time": 4888.422,
"text": " And that corresponds to human migrations, it corresponds to climate change, all kinds of things that we're very familiar with now. But if you have multiple groups of people that are interacting with each other regularly, whether it be through warfare or whether it be, you know, much more congenial interactions,"
},
{
"end_time": 4938.046,
"index": 200,
"start_time": 4909.701,
"text": " Those interactions are forcing creativity and ingenuity and, you know, sense of loyalty or tribalism or whatever it may be. And right and wrong can hardly help, but it has to emerge in that kind of an environment. And it has to be very conflicted. You know, surely anybody knows that the people in the tribe over there that you've been brought up to hate are human beings too and have, you know, have everything that you have."
},
{
"end_time": 4967.005,
"index": 201,
"start_time": 4938.729,
"text": " Why do you hate them? Because your tribe brought you up in some way. You know, we are horribly conflicted and our sense of right and wrong comes from this kind of conflicted feeling of fellow humans and loyalty to groups and whatever else. And no wonder we can't agree about it. It's grounded very deeply in our emotions as individuals in the social context."
},
{
"end_time": 4993.712,
"index": 202,
"start_time": 4967.807,
"text": " Let me stay on this philosophical course for just a few moments longer. So firstly, this assumption, which I believe is a great assumption, but I do believe it to be an assumption that we're all human. The reason why I say that is that, well, human biologically, yes, but human also has a connotation of you being worth a certain amount and having dignity afforded to you and your rights to be the same as mine. That's fairly, fairly new. Genghis Khan, for example, well, many, if you just go back 1000 years or 2000 or 3000 years,"
},
{
"end_time": 5021.203,
"index": 203,
"start_time": 4993.712,
"text": " Human is my tribe. You're not human. You're inhuman. You're subhuman. Yeah, yeah. I mean, I don't know enough history to comment on that. I mean, I find it hard to believe that that we could ever really have felt that way. It seems, I mean, you know, culture and society will tell us that there are differences between people and racism and everything else. You know,"
},
{
"end_time": 5037.022,
"index": 204,
"start_time": 5023.899,
"text": " has stained human history but it's kind of obvious and we know now, you know, genetically and scientifically that there are essentially, we're amazingly similar to each other as humans."
},
{
"end_time": 5065.981,
"index": 205,
"start_time": 5037.517,
"text": " evolutionarily very closely related to each other. We diverged very recently and we have all of these systems for, you know, categorizing people. And I'm part of it in the sense that I work in a university and I, you know, mark exams and things like that. And I'm very conflicted over exams because they, they, they, they mark a certain type of intelligence and they give credit to, and, and, you know, there's so many different types of intelligence that we're not adept to categorizing."
},
{
"end_time": 5090.333,
"index": 206,
"start_time": 5066.681,
"text": " And very often to my mind the people who are the best researchers, they're not necessarily the people who do best in exams, they're the people who think about things in their own way and who are obsessive about the question and who keep on pondering it and don't give up very often. And there are some effortlessly brilliant people but there are also, Darwin himself was probably"
},
{
"end_time": 5118.558,
"index": 207,
"start_time": 5090.742,
"text": " not necessarily the sharpest cookie in the basket, but he asked and kept on asking these questions and ended up coming up with answers that were more important than anybody else's. It is different forms of intelligence. And, you know, Western civilization, Western culture has tried over centuries to categorize and to have a hierarchy and to put the white man at the top of the hierarchy. And it's so patently not true."
},
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"text": " Okay, so then here's some more thoughts."
},
{
"end_time": 5215.026,
"index": 211,
"start_time": 5186.732,
"text": " Again, a few questions, but just thoughts. And then we'll get back to some, well, these are biological questions. So we're saying that, hey, humans are so related to one another. And so it's difficult for you to imagine that other people would think of other people as not being human. But then to me, I was like, okay, well, we have another spectrum issue there, because it's arbitrary, where we define the line as being sufficiently different enough to not call human. And then secondly, it's unclear as to what makes you you is it purely your DNA, but or is it also the culture and the ideas that you"
},
{
"end_time": 5240.503,
"index": 212,
"start_time": 5215.316,
"text": " Of course it's the culture and the ideas. And then if so, well then what we can say is this tribe has a right to say that you're sufficiently different than me unless you convert to me. I mean this is the nature of human history isn't it? It is tribalism and it is generating a sense of difference. I mean you could almost say that culture has gone out of its way to erect differences where they don't exist."
},
{
"end_time": 5268.2,
"index": 213,
"start_time": 5240.811,
"text": " I think individuals will always, if two people from any culture anywhere in the world are left as the only two people left on the world and are forced to talk to each other, they will realize they have everything in common with each other. It was true for practically anybody on earth now and always has been. But this idea of human or non-human, biology is so full of continuum, was a neanderthal of human being."
},
{
"end_time": 5287.875,
"index": 214,
"start_time": 5268.456,
"text": " The last point is that if we agree that tribalism is natural and is almost universal, then what if one's conscience"
},
{
"end_time": 5310.657,
"index": 215,
"start_time": 5288.336,
"text": " led them in the direction of saying hey in order for my genes to survive it's better that my group compete with your group and my conscience is telling me so so this gets back to the question because i was asking yes well why follow your conscience and you were saying well because it developed evolutionarily well what i'm saying is yes yes in other words you're saying is wrong it grew up in the context of tribalism"
},
{
"end_time": 5335.52,
"index": 216,
"start_time": 5311.084,
"text": " and antagonism between different groups of people. Therefore, and I said, you know, the sense of right and wrong is deeply conflicted and probably not a good guide to things. One of the, I think one of the great things about, I suppose, the history of"
},
{
"end_time": 5366.971,
"index": 217,
"start_time": 5337.568,
"text": " From the Renaissance onwards, it's an attempt to break down some of these barriers, to think in broad terms about what human rights are and what are humans. You know, it's been a very, you know, it admitted women for a long time, it admitted different groups for a long time, but it was an attempt to begin to give people rights and see people as"
},
{
"end_time": 5397.483,
"index": 218,
"start_time": 5367.671,
"text": " as equal. And this idea that we're equal is obviously, again, we're not equal. We're not equal genetically. We're all different genetically. We're all unequal almost by definition. That doesn't mean to say someone's better than someone else. It's different. And we come from societal cultural contexts which are different and which condition you to think differently about things. And those are breaking down. And thank God for that. We lose things when they break down."
},
{
"end_time": 5426.971,
"index": 219,
"start_time": 5397.756,
"text": " We lose our culture, our tradition. Groups lose languages. There's a loss to seeing humanity as a single unit, a global family, if you like. There's all the cultural histories that groups have which are wonderful and often different but similar."
},
{
"end_time": 5456.288,
"index": 220,
"start_time": 5427.637,
"text": " they can be engulfed and they can be lost and it's in a way is tragic but at the same time if what we do is cling to the differences and the cultural things that set you apart from everybody else and then look down on other groups I don't think there's anything in biology that says that that's the case. So you know what we need is somewhere"
},
{
"end_time": 5482.91,
"index": 221,
"start_time": 5456.459,
"text": " In the middle where we're proud of our cultures, we're proud of traditions, but we somehow understand other groups as equally human with equally valid and important traditions that we live side by side together. One of the lovely things about living in a place like London is it's often called a melting pot, but different cultures live side by side, I won't say happily, but reasonably happily."
},
{
"end_time": 5499.94,
"index": 222,
"start_time": 5483.404,
"text": " People from countries that are at war elsewhere in the world will rub shoulders together in a place like London and get along together okay and maintain something of their culture and their own sense of identity and self-worth without hating everybody else."
},
{
"end_time": 5524.002,
"index": 223,
"start_time": 5502.466,
"text": " Okay, let's get back to the book. This is a great transition, because you mentioned it would be great if we thought of ourselves as a part of a larger whole. In the beginning of the book, I recall there was an analogy made between a city and a cell and saying, okay, let's zoom out at a helicopter view and look at a city and it looks akin to a cell. Perhaps the cell is well, I think a cell is well, I don't know if that's true, but"
},
{
"end_time": 5538.882,
"index": 224,
"start_time": 5524.275,
"text": " And then there was a line that said, the cell is living, potentially, the cell is living, but"
},
{
"end_time": 5566.186,
"index": 225,
"start_time": 5539.275,
"text": " It's but obviously the city is not something like the obviously yes thinking is it is it obviously that the city is not like what makes something living is it just something that this is obvious that the city is not its own conscious being if if one of our neurons has some proto consciousness but then the collection of them also have a larger consciousness are we a part of a larger consciousness or is it slow transmission speed yeah what you're back to there really is is consciousness an emergent property of a sufficiently complex system"
},
{
"end_time": 5593.473,
"index": 226,
"start_time": 5566.749,
"text": " And what I was arguing earlier on is that it's not. That it is a property of an extremely complex central nervous system. But it wasn't an emergent property from it. It was something which was an integral part of that complex system from the very beginning. I was talking about the language of electrical fields and cells and so on. And this is what has been ramped up. And so the very"
},
{
"end_time": 5623.575,
"index": 227,
"start_time": 5593.899,
"text": " complex feelings and so on that we have now are effectively, they've been through a process of natural selection. They have real meaning for us because they've really been selected. It really does matter if you're starving or if you're dying of thirst or if you are in love or whatever it may be. These feelings are real because they've been through"
},
{
"end_time": 5649.172,
"index": 228,
"start_time": 5624.411,
"text": " Essentially, uncountable generations where they bore some resemblance to what happened to you, to people, to animals, to organisms in their lives. That if you have this overwhelming fear of something and you run away, you will do better. If this overwhelming sense of something"
},
{
"end_time": 5664.531,
"index": 229,
"start_time": 5649.462,
"text": " has a selective value and at the level of single cells it has a selective value just in terms of integrating the cell as a unit as something which can physically go over there rather than have this flagellum firing that way and this one going another way you know what what integrates this system."
},
{
"end_time": 5690.947,
"index": 230,
"start_time": 5664.821,
"text": " So you have a system which is capable of a purpose, if you like, to read too big a word into it. And that has been honed by selection and ends up in a central nervous system. It's not an emergent property, it's something which was built in from the very beginning and has just been kind of raised as part of the edifice. Now, from that point of view, a city"
},
{
"end_time": 5721.886,
"index": 231,
"start_time": 5692.21,
"text": " It hasn't been through generations. It hasn't given rise directly to an offspring city. It hasn't competed. It hasn't died. It doesn't have any of these biological mechanisms of selection. So I think any biologist, and maybe we're very limited here, but any biologist would immediately say a city is not alive as I did. Any physicist would probably say, well, hang on a minute. Are you really so confident that you know what life is that you can say that a city is definitely not alive?"
},
{
"end_time": 5751.408,
"index": 232,
"start_time": 5722.363,
"text": " That boils down, you know, I had a subtitle of an earlier book was why is life the way it is? And the question to me is actually a really serious question, which is, does it have to be this way? Or could it have been a different way? Could we have Fred Hoyle's Black Cloud? Could a city be alive? Can AI become alive? You know, they're very interesting, difficult questions."
},
{
"end_time": 5770.794,
"index": 233,
"start_time": 5752.039,
"text": " And unless we understand, I think there's two ways of going about it. One would be to say, oh, you've got a closed mind and you're a biologist and you're thinking about carbon and you're thinking about cells and open your mind and be open to other possibilities."
},
{
"end_time": 5799.838,
"index": 234,
"start_time": 5771.493,
"text": " Yeah. And the other way of seeing it is to say, well, I don't know. Does life have to be these things? We know the only example of life we know is life here on Earth. And we know that it's carbon-based. We know that it's cellular. We know it thrives in water. So did it have to be that way? Or could it have taken a different turn? Or could we? If we understand why life is carbon-based, then we can begin to say, well, life has to be carbon-based. Or no, it doesn't have to be carbon-based. Or some spectrum in between."
},
{
"end_time": 5825.247,
"index": 235,
"start_time": 5800.708,
"text": " And this is where physicists will very often by temperament and by training split off from biologists because physicists will want to see the universe as almost infinite possibilities with a very small number of laws governing it. And a biologist will want to see"
},
{
"end_time": 5855.589,
"index": 236,
"start_time": 5825.708,
"text": " study the example that we have in front of us realized there are no laws but there are some principles that guide us that you know there are no laws in biology and so it's fuzzy and it's it's uh it's immediately irritating for any self-respecting physicists but that doesn't mean to say that there isn't something to understand from life on earth as we know it and and there's you know this the origin of life field has in a strange way almost tried to ignore what life actually is"
},
{
"end_time": 5880.179,
"index": 237,
"start_time": 5855.913,
"text": " we know about and to my mind if we were to find life on a thousand different planets throughout the Milky Way or something then just because carbon is so good at the chemistry that it does because it's so abundant it's one of the most abundant"
},
{
"end_time": 5899.684,
"index": 238,
"start_time": 5881.101,
"text": " elements in the universe. It's really good at producing molecules that are quite large. Water is also extremely abundant and it does very interesting things with organic molecules. You can have membranes that are not soluble and you can have proteins that are soluble. There's a wealth of possibilities there."
},
{
"end_time": 5927.875,
"index": 239,
"start_time": 5900.367,
"text": " So you take into consideration the abundance and how good it is at doing this chemistry. And then you think, well, is there an important distinction between an outside and an inside? Do you need a compartment? And if you're going to keep your inside different to your outside, stuff has to come and go. Does that give a size? Are there constraints on how large something can be and how active it can be? Obviously, there are. You don't need to really understand exactly what governs those constraints."
},
{
"end_time": 5947.841,
"index": 240,
"start_time": 5928.558,
"text": " So let's talk about life on other planets."
},
{
"end_time": 5966.271,
"index": 241,
"start_time": 5948.029,
"text": " Potential life an interesting phrase that people say when they speak about life is life as we know it I always found it to be interesting life as we know it because again like coming from math You just have the definitions you just say here are the necessary and sufficient conditions and then that's it to say some so-and-so as we know it is"
},
{
"end_time": 5989.514,
"index": 242,
"start_time": 5967.039,
"text": " implies that there could be something else why by what basis will we have to call that life as if we have an intuitive feeling as to what life is and we point to certain examples and say this is living this is not living we haven't quite captured it with our explicit language but it's there implicitly that's the only way that i can make sense of life as we know it but i mean i think i think there's an emotional charge to that phrase life as we know it says"
},
{
"end_time": 6018.336,
"index": 243,
"start_time": 5989.957,
"text": " out there there is life as we don't know it or there may be life as we don't know it and our little limited experience is really just a tiny kind of bit of the universal possibilities. I think we all as human beings thrill to the idea that there could be something majestic out there, life as we don't know it, something much bigger than the human mind to consider and you know God would probably fall into that category but that's kind of make-believe in some sense"
},
{
"end_time": 6037.483,
"index": 244,
"start_time": 6019.121,
"text": " Because it doesn't ask the question, so what would it be like then? What are the principles that govern life as we know it and are they binding principles or are they loose and could it be many other different kinds of ways?"
},
{
"end_time": 6066.049,
"index": 245,
"start_time": 6038.131,
"text": " I think one of the most powerful ideas in biology is natural selection. And again, a lot of physicists have a problem with natural selection because it's just so damn simple and easy. And it's hard to believe that something as trivial as that can be as profound as that. But it becomes amazingly complex. It becomes the stuff that can be explained by"
},
{
"end_time": 6084.309,
"index": 246,
"start_time": 6066.408,
"text": " by how selection works is genuinely astonishing. It's so rich as an idea. I mean, you're talking about ideas in physics that the fewer parameters you can boil it down to. I mean, natural selection gets it down to very few parameters with enormous possibilities and reach."
},
{
"end_time": 6110.486,
"index": 247,
"start_time": 6084.684,
"text": " And biology as a discipline has spent, you know, 100 years or more thinking about, well, how does selection actually work? What are the units of selection is acting on genes, on cells, on organisms, on groups and so on. And I would say we have a fairly decent understanding of a lot of it. And it's it's, you know, it's it's capable of"
},
{
"end_time": 6142.995,
"index": 248,
"start_time": 6113.029,
"text": " It's capable of amazing feats, but the actual processes underlying it are quite simple and rely in the end on forms of copying. And Richard Dawkins has talked about memes and so on. And yes, they can copy and cultural evolution can happen, but it requires the units of living people underneath it with a central nervous system, which is capable of propagating a meme and so on, or a computer, which is capable of, in the end, making copies of itself. So, you know, AI can come alive. I have no real"
},
{
"end_time": 6161.596,
"index": 249,
"start_time": 6143.609,
"text": " I don't think that a planet can bootstrap itself up from nothing to give AI without the intermediary of humans along the way, or at least complex animals, because I don't think that silicon"
},
{
"end_time": 6184.002,
"index": 250,
"start_time": 6162.346,
"text": " as a tool is ever going to get beyond sand on a planetary scale. Carbon is so much better at what it does. It may be limited compared to silicon in the end in terms of processing power, but in terms of how do you start? What you have with carbon is a Lego brick. You have CO2. It sits there in the atmosphere. You pluck it out of the atmosphere and you build your other amazing Lego kits, which is life."
},
{
"end_time": 6200.333,
"index": 251,
"start_time": 6184.411,
"text": " When I was younger and I was watching the Discovery Channel,"
},
{
"end_time": 6222.09,
"index": 252,
"start_time": 6200.93,
"text": " There was, I remember hearing this phrase that, hey, if life exists on other planets, maybe it's silicon based because silicon serves the same purpose as carbon. I don't know. I was too young to understand what that meant. I haven't followed up on that since you just reminded me of it right now. So is that indeed true or not? That silicon is just as versatile? No, it's not nearly as versatile. And that's the problem. I mean, carbon forms much stronger bonds."
},
{
"end_time": 6252.073,
"index": 253,
"start_time": 6222.483,
"text": " than silicon does. It's capable of forming much more interesting molecules than silicon ever can and silicon for the most part forms silicon oxides which are sand and they're basically giant macromolecules that a single grain of sand is an enormous number of atoms in it and it's just a repeating pattern of those atoms. It's a giant crystal. It's not a building block. A single CO2 is a building block. It's like a brick. It's your Lego brick. Whereas"
},
{
"end_time": 6278.882,
"index": 254,
"start_time": 6252.688,
"text": " You know, I suppose trying to build from silicon would be like trying to build from enormous piles of Lego and try to put two piles together and fashion it into some kind of unit. I recall you saying that fact that bacteria are limited in size on Earth, at least has some implication for life in the universe. I don't remember the line of reasoning. So please, if you know what I'm referring to, can you expound on that? Yes. I mean, it's really an observation."
},
{
"end_time": 6304.804,
"index": 255,
"start_time": 6279.138,
"text": " on earth that bacteria are, they're not always tiny but they're mostly, to a first approximation, they're small. They're a couple of micrometers long and that's it. And when you look at them under a conventional microscope you don't see very much going on. Now in terms of their biochemistry, in terms of the molecular machines and all of these things, they're enormously sophisticated. In terms of their"
},
{
"end_time": 6335.026,
"index": 256,
"start_time": 6305.964,
"text": " Genomes, they've got a different structure to their genome. So a single E. coli cell might have about 4,000 genes and we have about 20,000 genes. But an E. coli has what's called a metagenome, which is to say other E. coli have different genomes and they swap genes among themselves. So an E. coli might have a kind of access to a genome with 30,000 genes, which gives it a lot more scope for changing, for evolving, for switching about."
},
{
"end_time": 6361.852,
"index": 257,
"start_time": 6335.503,
"text": " But it means that no two E. coli are exactly identical to each other and they all have a small genome and that tends to mean that if you try and build a multicellular organism from cells that are genetically different to each other then what you end up with is a fight basically that would put fights between different human groups where we're basically genetically close to identical to each other in the shade. What we're dealing with cells that are"
},
{
"end_time": 6391.886,
"index": 258,
"start_time": 6362.346,
"text": " It's huge differences. You put them together and you're never going to make anything as complex as a flea out of bacterial cells because they don't have a large enough genome. What we do is we have a large genome and we switch these genes on in the brain and we switch those genes on in the kidneys and these genes in the heart and so on. We're all genetically identical but we switch off different genes in different"
},
{
"end_time": 6417.483,
"index": 259,
"start_time": 6392.261,
"text": " Now to get a genome that's that big requires I think the kind of radical restructuring of genomes and the reason for that is that any giant bacteria that we see and there are a few around they always have thousands of copies of their complete genome dotted right next to the membrane and it seems that they're there because they they need to control this electrical charge on the membrane which is"
},
{
"end_time": 6446.971,
"index": 260,
"start_time": 6417.892,
"text": " Which is the charge, which is I'm saying is responsible for consciousness, but it's responsible for driving CO2 fixation and for making energy the currency, the ATP currency of life and so on. It's used for pretty much everything and it's a charge which is enormously strong. So if you shrink yourself down to a size of a molecule again and the electrical field strength that you would experience if you're sitting next to that membrane is 30 million volts per meter, which is equivalent to a bolt of lightning."
},
{
"end_time": 6472.142,
"index": 261,
"start_time": 6447.517,
"text": " So we're dealing with a membrane which is five millionths of a meter thick, five nanometers thick, five millionths of a millimeter, sorry, thick, so 10 to the minus nine of a meter. So it's enormously thin and the charge across it is about 100 millivolts or 150 millivolts or something like that, but there's a field strength that's very high."
},
{
"end_time": 6501.032,
"index": 262,
"start_time": 6472.978,
"text": " You need genes to control that. They need to be next to it. And the problem with bacteria is if they try and just expand up, you end up with this enormous cost of having all of these genomes sitting next to that. Now what we have with mitochondria, we have the same what's called extreme polyploidy. We've got thousands of copies of the mitochondrial genome, but they've been whittled down to almost nothing. There's only, I mean, there's, I think,"
},
{
"end_time": 6525.981,
"index": 263,
"start_time": 6501.527,
"text": " 38 genes in the mitochondria left in humans and they only are encoding the machinery and the proteins that are doing respiration, that's it. So they're basically, you could think of them as the same power as a bacterium to generate energy but without all the overhead costs that a normal bacterium would have. So we've got multi-bacterial power, like multi-horsepower or something."
},
{
"end_time": 6547.056,
"index": 264,
"start_time": 6526.578,
"text": " And what that allows us is to have a swollen nuclear genome with 20,000 genes and lots of regulatory capacity and lots of energy for expressing those genes so that we can make tens of thousands of copies of the protein rather than just a thousand copies or something. So we can scale up in a way that is basically impossible for bacteria."
},
{
"end_time": 6574.155,
"index": 265,
"start_time": 6547.517,
"text": " And that came about as a result of an endosymbiosis, which is to say one cell gets inside another cell, which is pretty rare in itself, and it has to survive there and, you know, they have to get along. So the whole history of complex life on Earth is a history of antagonism and cooperation and eventually overcoming the obstacles and the hurdles and becoming integrated as a functional unit."
},
{
"end_time": 6600.742,
"index": 266,
"start_time": 6574.804,
"text": " I didn't realize that there were only 38 genes in the mitochondria. That's not so tiny. It's very few. And for that reason, they're mostly ignored. So the people who work on the human genome, 20,000 genes, sequence the genome, look to see which genes are responsible for diseases. People do what are called GWAS studies, which is a genome wide association studies. So you look for"
},
{
"end_time": 6629.718,
"index": 267,
"start_time": 6600.742,
"text": " this this single letter change here or that one there is associated with epilepsy or Alzheimer's disease or whatever it may be and maybe there's maybe there's a few hundred of these or maybe there's thousands or millions of them but a few hundred may may kind of crop up and you say ah people who've got that letter change there are slightly higher risk of Alzheimer's disease and if they've got this one as well it's a little bit more and people ignore the mitochondria but the mitochondria are what makes us alive it's the difference between just information"
},
{
"end_time": 6654.309,
"index": 268,
"start_time": 6630.162,
"text": " And a living system where it's growing, where it's capable of powering all the work that cells need to do. You get anything wrong with those genes or they don't work properly with a nuclear background and you've compromised the entire living system. So there's not many of them, but they are the most important genes for making us who we are, you may say."
},
{
"end_time": 6681.766,
"index": 269,
"start_time": 6654.906,
"text": " making us alive for being for being here at all. And mitochondria, they have DNA or RNA. They have DNA. Yeah, they have RNA as well. But the genome is made of DNA. The blob of DNA in the nucleus is that called nuclear DNA? Yes. Okay, so there's mitochondrial DNA, there's nuclear DNA. Yes. All right. All right. And they better work together."
},
{
"end_time": 6707.022,
"index": 270,
"start_time": 6682.176,
"text": " Right, right, right. I read that there was some, in your book, that there was some compatibility condition between the mitochondrial DNA and the nuclear DNA. And I think Doug Wallace was investigating this and he took my DNA and put it into Hamster. Yeah, that was quite a long time. Lots of people have done similar work since then. But even within, so some of my own work is on Drosophila, different groups of Drosophila."
},
{
"end_time": 6737.415,
"index": 271,
"start_time": 6707.432,
"text": " We're all within the same species, but if you kind of mismatch their mitochondrial DNA to the nuclear background, then it increases the risk of all kinds. I mean, basically the rate at which some flies age compared to others or how fertile they are. There's various kind of phenotypes and exactly the same principles should apply to humans as well. And somehow this is a driving force or at least is proposed to be a driving force behind speciation. And I don't recall how that line of"
},
{
"end_time": 6767.073,
"index": 272,
"start_time": 6737.858,
"text": " reasoning went? Do you know what I'm referring to? Yes. So the idea, and this is, I won't say it's a speculative idea, but there's not very much evidence that it's really true, but it's a very interesting idea. So in effect, because mitochondrial genes evolve much faster than genes in the nucleus, about 10 times faster on average, maybe more, maybe 50 times faster, we don't actually really know."
},
{
"end_time": 6796.834,
"index": 273,
"start_time": 6767.449,
"text": " But they're changing very quickly. Now there's this selection happening in the female germline. So whenever new oocytes, egg cells are being made, there's a process of effectively winnowing out the bad mitochondria and bringing the better mitochondria together. And an egg cell has as many as half a million mitochondria and copies of mitochondrial DNA in that egg cell."
},
{
"end_time": 6818.848,
"index": 274,
"start_time": 6797.449,
"text": " And they're all as close to a clone as it's possible to make them without killing yourself in the process. And these genes are evolving very quickly and can effectively fail to interact properly with the genes in the nucleus. So if you imagine two populations that are diverging,"
},
{
"end_time": 6830.93,
"index": 275,
"start_time": 6819.445,
"text": " standard idea of speciation. There's two populations on different sides of a mountain and they don't mix for thousands of generations or something."
},
{
"end_time": 6856.237,
"index": 276,
"start_time": 6831.527,
"text": " And then they come back together again and they mix. And so which genes are going to be involved? Sometimes they'll intermix perfectly well and other times there will be some kind of, it's called hybrid breakdown. Basically the offspring, the standard biological definition of a species is if you can't produce viable offspring, if the offspring are sterile or don't develop properly."
},
{
"end_time": 6879.974,
"index": 277,
"start_time": 6856.544,
"text": " then you've got two different species. Very often different species can interbreed perfectly well. This is a very bad definition of a species. It's another example in biology where there isn't a firm definition. They're just separate. Now the genes that are evolving the fastest and changing the fastest, the mitochondrial genes, are the ones that are most likely to cause trouble."
},
{
"end_time": 6909.599,
"index": 278,
"start_time": 6880.179,
"text": " those circumstances. They're the ones most likely to not work well with the nuclear background of the other population from the other side of the mountain. This is the idea. And so incipient speciation may be driven by the rate of change of the mitochondria, which may, you know, if these guys live in a hot climate and these guys live in a cold climate, then maybe the mitochondria specialize to different tasks and that can drive these differences. What we found with flies, interestingly enough, is"
},
{
"end_time": 6923.609,
"index": 279,
"start_time": 6910.111,
"text": " You can end up with 50 or 60 different letter changes in mitochondrial DNA, which is quite a lot. Whether or not you have"
},
{
"end_time": 6952.619,
"index": 280,
"start_time": 6924.701,
"text": " observable problems, for example, not developing properly or aging very quickly or not, doesn't depend on the number of the differences. You might expect there to be a correlation. If you've got 50 letters different, then it's more likely to go wrong than if you've only got five letters different. And that's not the case. What we actually find is it's an absolute flat line that if you've got five letters or one letter difference, it can cause some catastrophic problems if they're bad letters."
},
{
"end_time": 6982.705,
"index": 281,
"start_time": 6953.012,
"text": " And if you've got 50 letters difference, then it can be catastrophically bad, or it can be fine. There is not necessarily any worse. And these are the levels of differences that we see across humans as well. There is a possibility that different human races could interbreed and then produce offspring that were not functional. No one's ever seen it, but it's a theoretical possibility that this work seems to say, no way, that's not going to happen."
},
{
"end_time": 7000.333,
"index": 282,
"start_time": 6983.097,
"text": " Because we can see individuals who have a problem because there's an unfortunate mismatch and incompatibility that we've always known about these things to people just don't work together for whatever reason. But it's nothing to do with races or with speciation."
},
{
"end_time": 7030.247,
"index": 283,
"start_time": 7000.862,
"text": " Once you've got really deep divergence, say between a mouse and a rat or something between a chimpanzee and a human being, then you would see then you would see. So now we're dealing with thousands of thousands of letters, changes, difference. And then you begin to see that there really is some kind of breakdown. But within within populations that are basically homogeneous, as the human populations are, we don't see those changes. Think Verizon, the best 5G network is expensive. Think again. Bring in your AT&T or T-Mobile bill to a Verizon store today."
},
{
"end_time": 7058.865,
"index": 284,
"start_time": 7034.633,
"text": " How many letters make up the mitochondrial DNA? Do you know approximately?"
},
{
"end_time": 7079.206,
"index": 285,
"start_time": 7059.65,
"text": " It's about 18,000. Oh, wow. Great, great, great, great memory. Okay. And then DNA is drastically more sorry, nuclear DNA is far more. We're dealing with about 3 billion then. Okay. Why is it so strange that certain mutations so certain letter changes in the mitochondrial DNA produce"
},
{
"end_time": 7109.411,
"index": 286,
"start_time": 7079.753,
"text": " Well, that troubled me a lot and I didn't understand it. It's not what I expected. And I actually find it quite welcome in a strange way, but it took me a long time to understand why, what's going on there. And I think the reason is that there has to be quite a lot of tolerance for different types of mitochondrial function."
},
{
"end_time": 7139.838,
"index": 287,
"start_time": 7110.708,
"text": " So women and men are different in dietary needs, in outputs of one sort or another, in metabolic rate. On average, men have about 20% higher metabolic rate than women do. So there are all these differences. And the mitochondria, we inherit them from our mothers only. And that means in principle that they adapt to being in the female line,"
},
{
"end_time": 7163.643,
"index": 288,
"start_time": 7140.384,
"text": " And, you know, your mitochondria, my mitochondria, they're going nowhere. If you have kids, then they're not going to get your mitochondria, your mitochondria going in the bin. And that means that they can never really be fashioned to work, to be adapted to being in men. Now, the nuclear background can kind of fashion them to work in men."
},
{
"end_time": 7188.933,
"index": 289,
"start_time": 7164.292,
"text": " the Y chromosome for example can control genes that upregulates those that make female mitochondria effectively work better in men. So there are biological ways around this but the bottom line is there are different requirements on the system in men and women but there are different requirements as well depending on is it in the brain where"
},
{
"end_time": 7219.309,
"index": 290,
"start_time": 7189.514,
"text": " The genes that are expressed in the nucleus is a completely different set of genes compared to those in the kidney where the mitochondria have a different task and the same genes in the mitochondria have to work with a different set of nuclear genes with different requirements. So basically they've got to be generalists. They've got to have a lot of slack that they can operate well enough in completely different tissues, completely different diets. You know, different human groups have very different diets and different"
},
{
"end_time": 7240.964,
"index": 291,
"start_time": 7219.77,
"text": " You know, fat intake or calorie intake or whatever it may be that puts pressures on mitochondrial functions, which can be very different, different temperatures that you're operating at. And especially that was even even worse with things like flies that are cold blooded. And if you change the temperature, then the whole body temperature changes."
},
{
"end_time": 7269.65,
"index": 292,
"start_time": 7241.374,
"text": " So basically they have to be generalists, and that means that they can tolerate a fair amount of change, and most of the changes that happen are tolerated, but some of them are not. And if you're unlucky enough to have a change that is not tolerated, then it affects all of the organs, it affects both the sexes, it affects absolutely everything. And so then you've got a problem."
},
{
"end_time": 7298.609,
"index": 293,
"start_time": 7270.828,
"text": " Because it's so fundamental just to the process of living. I believe there's a concept called mother's curse, which is about okay. So firstly, if you don't mind saying what that is, and then also, why can't we follow the same logic of mother's curse and say that men should have drastically shorter lifespans or be far worse off? I mean, it may be this what may be a why question. Well, men do have men do have shorter lifespans by about five or six years, I think, on average, something of that order."
},
{
"end_time": 7328.251,
"index": 294,
"start_time": 7298.899,
"text": " So mother's curse, I've actually kind of already described this in a way, it's basically because the mitochondria pass down the female line, so they're inherited from mother to daughter to daughter to daughter and so on, they become, any mutation which is bad for the daughter would be selected against"
},
{
"end_time": 7358.677,
"index": 295,
"start_time": 7329.616,
"text": " Whereas any mutation that is fine for the daughter, but bad for the son is not necessarily going to be selected against because the son's mitochondria are not going anywhere. They're a dead end. So there's no direct selection. There can be indirect selection. They can be, you know, if all your sons die, then they can be, you know, indirect forms of selection, but there's no direct selection on them. And so mutations that are effectively, if there are differences between females and males in metabolic requirements, and there are,"
},
{
"end_time": 7385.572,
"index": 296,
"start_time": 7359.343,
"text": " and the mitochondria pass down the female line only, which they do, and some mutations may be harmless or even beneficial to women, but detrimental to men, then selection will select for the ones which are harmless or detrimental in women, and the harmful ones to men will tend to accumulate. There's no mechanism of selecting against them, no direct mechanism of selecting against them. So that's mother's curse. And"
},
{
"end_time": 7407.381,
"index": 297,
"start_time": 7386.169,
"text": " A lot of mitochondrial diseases, for example, are two or three times more common in men than in women. A lot of diseases that have a mitochondrial aspect to them, like Parkinson's disease, are twice as common in men than in women. And men age more quickly and die earlier than women. And all of these things have a mitochondrial component."
},
{
"end_time": 7432.261,
"index": 298,
"start_time": 7407.654,
"text": " and may be linked in some way to mother's curse. So it's real, but I use the word direct selection on several occasions. The genes in the nucleus can compensate. And so for the most part, most men don't have mitochondrial diseases and men live almost as long as women and so on. So mostly,"
},
{
"end_time": 7461.169,
"index": 299,
"start_time": 7432.773,
"text": " The fact that we inherit mitochondria that could be riddled with mutations that are not good for men are compensated for by genes in the nucleus that are specifically male, which effectively offset those disadvantages. And this is where the problem, if you then go and breed with a completely different population that doesn't have those compensating genes in the nucleus, that's where this speciation effect can potentially come in."
},
{
"end_time": 7486.817,
"index": 300,
"start_time": 7462.261,
"text": " These compensating genes in the nucleus, they don't detrimentally affect women? Are they relegated to the Y chromosome, for example? Yes. There are differences in what's called gene expression between men and women, which is to say the Y chromosome controls it, but there's only a handful of genes on the Y chromosome, but those genes"
},
{
"end_time": 7515.981,
"index": 301,
"start_time": 7487.261,
"text": " Say you, you, you, you, you, you, you, you make your proteins, you, you make proteins, you shut down. Um, and so, you know, it's, it's biology is not about which genes you have so much as which genes are active now and a specific stage of development and so on. Um, and so there are, you know, in men, the, the, the genes which are expressed at a certain time, uh, can be very different."
},
{
"end_time": 7544.548,
"index": 302,
"start_time": 7516.903,
"text": " Yeah, geez, it's staggering, staggering, staggering. The complexity does your head in. There's no question. Yeah. So okay, now let's talk about what's not complex. Well, maybe it's complex, but you made an analogy between a cell and the planet, because one is charged on the inside. Okay, can you talk about that? That's interesting. And then I wondered, how far does that analogy go? Does it go to the galaxy? I mean, yes, I mean, no, I don't think we'd go to the galaxy level, but it and it is an analogy. It's, it's not"
},
{
"end_time": 7572.227,
"index": 303,
"start_time": 7546.305,
"text": " I mean I think you will be unwise to take it too far but it's a kind of a beautiful analogy and there's definitely some truth in it. I mean a cell is in effect, this electrical charge on the membrane that I keep talking about, on the inside it's basically saturated in electrons. We've got organic molecules have taken CO2 and they've added hydrogen on and hydrogen is an electron and a proton basically."
},
{
"end_time": 7602.312,
"index": 304,
"start_time": 7572.671,
"text": " And so in making organic molecules, we've taken electrons from the outside and put them inside. And so it's reduced. It's more reduced inside than it is outside. That's the technical term. And reduced is one of those terms that, you know, anybody who's not a chemist backs away from immediately tries to escape from the room. So oxidized and reduced. But in effect, there's more electrons inside than outside. And there's more protons."
},
{
"end_time": 7628.66,
"index": 305,
"start_time": 7602.807,
"text": " It's more negative inside, yes. And so it's relatively positive outside. And there are protons outside that's partly what makes it more positive outside. And we've got this charge on the membrane, which is basically relatively positive outside, relatively negative inside, and the membrane itself is extremely thin. And so we have a charge on it. Now, the planet is basically the same."
},
{
"end_time": 7656.869,
"index": 306,
"start_time": 7629.377,
"text": " Iron, raw iron is electron dense, you might say. When iron rusts, it's effectively losing electrons to oxygen. Oxygen is stripping those electrons from it and you end up with three positive charges on the iron. The iron atom itself ends up with three positive charges and the oxygen gets the electrons and that has a negative charge and you have iron hydroxides and oxides and so on and that's what rust is."
},
{
"end_time": 7684.889,
"index": 307,
"start_time": 7657.415,
"text": " Now, the core of the planet is not rusty at all. There's no oxygen down there. It's got all these electrons sitting on the iron. And so it's relatively negative inside. And the outside, the atmosphere and the oceans and so on, because the gases that are coming from volcanoes and so on are such a high temperature, they tend to have lost their electrons and think you get gases like carbon dioxide."
},
{
"end_time": 7704.172,
"index": 308,
"start_time": 7685.401,
"text": " Coming coming out and the sun will also tend to oxidize the surface the planet will would tend to for example, you can the sun would split water. Water is H2O and it can be split in effect into hydrogen and oxygen and the hydrogen is light enough to escape into space."
},
{
"end_time": 7734.445,
"index": 309,
"start_time": 7704.599,
"text": " And the oxygen will react with rocks like iron and you get rusty rocks. And this is more or less what happened on Mars. That's why it's the red planet. The oxygen that was formed from spitting water reacted with iron in the rocks, turning the rusty red color. And the hydrogen escaped to space. A lot of the oceans were lost that way on Mars. And so you end up with a relatively positive charge in the atmosphere and this relatively negative charge inside, which is basically the same structure as a cell."
},
{
"end_time": 7758.08,
"index": 310,
"start_time": 7734.872,
"text": " And just as a cell membrane has proteins that sit in it where you have movement between the inside and the outside, hydrothermal vents are the equivalent conductance between the negative charge of the interior and the positive charge of the exterior. You have movement going through vents, connecting it up."
},
{
"end_time": 7783.558,
"index": 311,
"start_time": 7758.507,
"text": " And within these vents, the pores inside the vents have got the same structure as well. They're effectively inside, they're filled with the material that came from inside the Earth and the outside, they're surrounded by the material that came from the oceans. And so again, we have a negative charge inside, positive charge outside, relative to each other. It's not that there's an actual charge, it's just that the electrons want to move from here to there."
},
{
"end_time": 7814.428,
"index": 312,
"start_time": 7784.48,
"text": " Now, do you believe this to be a coincidence or that life is somehow mimicking cellular life is somehow? No, I don't think it's a coincidence at all. I think this is exactly how cells work. And what this is doing is effectively there's an electrical charge on the Earth between the inside and the outside. There's an electrical charge in the pores in these hydrothermal vents between the inside and the outside. There's electrical charge on cells between the inside and the outside. They're all equivalent topology because they've all been formed"
},
{
"end_time": 7843.353,
"index": 313,
"start_time": 7814.718,
"text": " from the same processes you might say because the hydrothermal vents is where there is the mixing zone between the inside and the outside so it naturally forms pores where we have this the same charges forming and those charges are more or less necessary to drive the reaction between hydrogen and carbon dioxide to make the organic molecules that make up life at all. So I find it a beautiful conception it doesn't mean it's true but I find it beautiful that the the planet has the same"
},
{
"end_time": 7873.643,
"index": 314,
"start_time": 7843.865,
"text": " basic topological structure as a cell. Cells emerged from the mixing zone between the inside and the outside, effectively part of the circuit, and are driving copies of themselves by making more miniature Earths, if you like, by reacting the hydrogen from the inside with the CO2 from the outside to make organic molecules. It's a planetary scale and it's a beautiful conception. Something I love about you,"
},
{
"end_time": 7899.753,
"index": 315,
"start_time": 7873.951,
"text": " is firstly, you write beautifully. And secondly, you are not afraid to ask why. And you mentioned that you're the most biologists don't like to ask the why question, perhaps because it teeters too much on the religious side, and they would like to stay away. Or for whatever reason, physicists don't like to as well. There's a famous or an infamous video of Feynman, who is castigating a fairly, at least in my opinion, well intentioned interviewer for asking why question you recall that"
},
{
"end_time": 7927.449,
"index": 316,
"start_time": 7900.572,
"text": " I don't remember that one, no. I mean, I love listening to Feynman, but yes, he could castigate people. I thought it was a perfectly reasonable question. And Feynman said, yeah, but you shouldn't ask why, because so-and-so. So why is it that you don't mind asking why? And simultaneously, why do others not like asking why? To be honest, I don't really know. I mean, it's partly I'm just confused, and I can't tell the difference between how and why."
},
{
"end_time": 7953.285,
"index": 317,
"start_time": 7927.841,
"text": " And I think most biochemists are happy asking how, how does this system work? And I can't quite distinguish that from why, why is it working this way rather than a different way? That's kind of almost another way of saying how. And I think why is one of the most human questions. And it's a childlike question. Children always want to know why."
},
{
"end_time": 7983.422,
"index": 318,
"start_time": 7953.677,
"text": " And I think it's the motivation for many people to go into science. And one of the things about science is it tries to stop you from being too naive and tries to impose a method on you to be objective and to not ask questions that are unanswerable in some way, to stick to the, as I mentioned, the art of the soluble before. We'll never know why, but we can't help asking why. And as I say, I can't tell the difference between why and how anyway. So it's very exciting asking why."
},
{
"end_time": 8009.189,
"index": 319,
"start_time": 7984.002,
"text": " And perhaps it's more forgiven in books than it is in papers and you know the more scientific literature. Books I think are a good place to ask why and maybe that's why I write books in part because it gives me this outlet to wonder about things, to wonder about the world and in the end that is what science is. It's about how do we explain"
},
{
"end_time": 8037.978,
"index": 320,
"start_time": 8009.77,
"text": " the world, which is to say, why is the world this way, when it could have been so many other ways? I think why is it is in fact, you know, it's a question in physics, why are the cosmological constants that way, rather than some other way, that's the theory of everything supposed to explain that. It's a why question to me, you could say, how did it come to be that way? I see the strengths of science as being what you mentioned, the focusing on what's soluble, and then the weakness is also that to"
},
{
"end_time": 8065.589,
"index": 321,
"start_time": 8038.558,
"text": " The reason why I say that, but I don't know how to solve this. So I'm just going to pose this as a question. If one was to go into a PhD program, but produce no papers in four years or produced papers with all negative results, then you would likely not be hired. And so, yes, when you're a young person, when you're at your most creative, you're disincentivized for pursuing wild ideas that because most likely they won't work, but they may also lead to breakthroughs."
},
{
"end_time": 8093.012,
"index": 322,
"start_time": 8066.561,
"text": " No, there's a bit of a tragedy about that. It means that we prioritize certain incremental progress versus these substantial. I completely agree. My lab mostly works on the origin of life and I have PhD students and postdocs and so on and I face this problem every day that most of the results we get are negative. What are we going to do? How do I"
},
{
"end_time": 8122.278,
"index": 323,
"start_time": 8093.695,
"text": " I don't want my students to all fail to publish any papers, fail to get any positive results and finish their careers. That's the last thing I want for them. So you've got to juggle. You've got to aim for the lowest hanging fruit. You've got to keep the big picture at the back of your mind and try to think of experiments that will work in one way or another."
},
{
"end_time": 8152.568,
"index": 324,
"start_time": 8122.944,
"text": " And you've got to not forget about the bigger questions behind this and keep on trying them. So I think you have to move people around so that if something starts working and one student's had two years of getting nothing, then you've got to give them something where they're going to get something now. It's difficult and it's difficult not because of the scientific questions so much because of the human aspect of people's careers that they need to be able to come out of it with"
},
{
"end_time": 8178.695,
"index": 325,
"start_time": 8153.148,
"text": " with, you know, a career ahead of them, something to look forward to. Why do you think it is that negative results aren't seen as worthy as or as worthy as positive results? Because to me, just as an outsider, I see this as data, even if you were to say so and so it doesn't work. Great. Now we know so and so it doesn't work. There's the replication crisis in psychology, particularly because people are incentivized to find affirming or new results rather than disconfirming."
},
{
"end_time": 8209.428,
"index": 326,
"start_time": 8180.879,
"text": " I think it's, I mean, we've got a paper coming up. It's probably going to be under embargo, but it's actually out there as a preprint anyway. So I'll tell you about it anyway. This is about how ATP is formed. Now we've found this is Silvana Pinner, who did her PhD with me and she finished a while ago. And this is her big paper from this."
},
{
"end_time": 8237.517,
"index": 327,
"start_time": 8209.855,
"text": " What she found was actually what she did was was effectively repeat some earlier work from a Japanese group from 20 years ago and they had found by chance that a corroding iron electrode when they got ADP in solution around that electrode actually formed some ATP and they looked into it and it turned out that ferric iron which is a iron with three positive charges on it"
},
{
"end_time": 8262.619,
"index": 328,
"start_time": 8237.79,
"text": " will catalyze the formation, this had to be in the presence of something called acetyl phosphate, which is just a two carbon compound, that would catalyze the phosphorylation of ADP to ATP, which is what our mitochondria are doing all the time. But instead of having all this molecular machinery like the ATP synthase, it's just happening in water with ferric iron as the only catalyst. So that's pretty amazing."
},
{
"end_time": 8292.517,
"index": 329,
"start_time": 8264.292,
"text": " So she repeated this, it took a while to figure out exactly how they'd done it and this is very often the case and for a period I remember we were concerned that it would not be possible to replicate it and then she succeeded in replicating it and I find that increasingly pleasing just simply to replicate other people's work because of this problem that sometimes it's made up, sometimes"
},
{
"end_time": 8309.411,
"index": 330,
"start_time": 8293.234,
"text": " Sometimes it's not as cynical as that, but it's for whatever reason, there was some aspect of chance that allowed it to be able to replicate science, I think is the perhaps the single most important thing in science. And so it's very pleasing when you succeed in doing it."
},
{
"end_time": 8339.343,
"index": 331,
"start_time": 8309.77,
"text": " Now, she is probably the single most careful scientist that I've ever met. She really is amazingly precise. You could never see her error bars, because the repeats were so similar to each other that there really wasn't one. But all the rest of her data was negative, which was very interesting. So it worked with ferric iron, but she tried with about 10 other different metal ions. And none of the other metal ions worked."
},
{
"end_time": 8369.428,
"index": 332,
"start_time": 8339.906,
"text": " And she tried with about seven or eight different phosphorylating agents instead of acetyl phosphate. And none of those worked. And she tried with the other bases. So instead of ADP, she tried with GDP and CDP. So the other letters in RNA and UDP and so on. None of those worked either. So this is a paper made up entirely of negative data apart from one result, which had actually been done by someone else 20 years earlier and replicated by Sylvana. Now, this is where negative data really comes into its own."
},
{
"end_time": 8395.043,
"index": 333,
"start_time": 8369.94,
"text": " Because it basically says there is something favored about ADP compared to the other bases and about acetal phosphate compared to the other phosphorylating agents and about this metal ion compared to those other metal ions. This is favored chemistry. Why is it favored? We could come up with a mechanism for it and so on. But there the negative data is effectively saying there's a limited number of ways that this will happen."
},
{
"end_time": 8420.691,
"index": 334,
"start_time": 8395.418,
"text": " And here's one way where it does. Maybe there are other ways that does as well, and we just look at those, some other metal ion that was not in our panel. You know, you can have huge combinatorial panels, but we looked at all the metal ions that seem to have any relevance to life or any relevance to geochemistry, and this ferric ion was the only one that worked. Now, the problem there"
},
{
"end_time": 8448.08,
"index": 335,
"start_time": 8421.084,
"text": " is that imagine that ferric iron didn't work either. Then you would have a paper where everything was negative. Let's just say that she didn't know about that paper and that she never tried ferric iron and that she tried all the others. What she would have had would have been a completely negative set of data which would be unpublishable because nothing worked. Now maybe if she tried some other irons then it would have worked like ferric iron did."
},
{
"end_time": 8477.346,
"index": 336,
"start_time": 8448.439,
"text": " But if you don't happen to choose that one, then you'll never know. And so you can never rule something out. If all your data is negative, it doesn't mean it can't work. It just means that everything we tried under the conditions that we tried it, it never did work. And at that point, we decided to pull the project because this poor PhD student is never going to get a paper out of it. So we explored it as well as we could. But the reality is we've got to move on. And so you've never disproved it, but you've kind of just given up trying to prove it now."
},
{
"end_time": 8506.22,
"index": 337,
"start_time": 8477.858,
"text": " Whereas the fact that someone had done it before meant that that was the one that she tried first which meant that when the paper comes now we have something which is really exciting which is to say the reason that ATP is the universal energy currency is precisely that it works as prebiotic chemistry in water all by itself just with one metal ion as a catalyst and that works and nothing else does work and that's why it's this way. So suddenly you've got a very sexy message which in the end is based on the fact that someone else had found"
},
{
"end_time": 8533.251,
"index": 338,
"start_time": 8506.698,
"text": " out something 20 years ago that was really a serendipitous discovery that they were not applying to the origin of life or anything else it's just you know and science is built this way science is built on it's kind of network of the efforts of different people doing different things for different reasons and you try and put it together and you've got to you know juggle what works what doesn't work when do you give up and and very rarely can you ever disprove anything formally in a way that a physicist would understand disprove"
},
{
"end_time": 8555.077,
"index": 339,
"start_time": 8533.729,
"text": " That's why the positive results are important because they give you something to say, whereas the negative results don't give you anything to say. They just say, everything we tried didn't work. It's possible that something else would have worked, but we don't know because we didn't do that. So that's not going to sell any papers."
},
{
"end_time": 8583.507,
"index": 340,
"start_time": 8556.459,
"text": " I'm not entirely sure about that. Well, you would know in your domain, but in physics, there's something called no-go theorems. So for example, there's the no-go theorem, which says that you can't have a graviton in 4D quantum field theory. And then you're like, well, what's the hope for gravity? And then that's one of the reasons why people think that there's ADS-CFT correspondence of the holographic principle. Because, okay, there was a hidden assumption that wasn't stated by Witten, actually, and he's a careful person, which is that"
},
{
"end_time": 8607.739,
"index": 341,
"start_time": 8584.053,
"text": " You can't have a graviton in your same three plus one quantum field theory, but you can in a different quantum field theory. So you can have, that's why you have this universe within another border. Okay. But anyway, so a negative result can still lead to breakthroughs. Like it leads to whole there's ADS, CFT is like almost a whole field in and of itself. The way that when I hear this, what I'm wondering is, hmm, why is it not the case that studies in different fields,"
},
{
"end_time": 8635.828,
"index": 342,
"start_time": 8608.063,
"text": " I think a lot of clinical trials pre-register in that sense. So a clinical trial that is negative and there is often funded by a pharmaceutical company or something you have some interest in not publishing negative data, but the regulators or it's in the public interest that it should be published. And so this idea of pre-registering is a good one, but there's a kind of a big difference."
},
{
"end_time": 8663.473,
"index": 343,
"start_time": 8636.203,
"text": " The big clinical trials are very expensive to set up. They're very constrained in the way in which they're set up. They're being set up so statistically they can demonstrate a difference between a different treatment or no treatment or whatever it may be."
},
{
"end_time": 8689.718,
"index": 344,
"start_time": 8664.804,
"text": " They come up with an outcome and the chances are it's going to be about as reliable a statement as you can make. But it's very unwieldy. It might take five years to do it. It might cost 20 million pounds or something. Whereas a lot of smaller scale science is much more maneuverable. No PhD student would ever"
},
{
"end_time": 8720.367,
"index": 345,
"start_time": 8691.357,
"text": " No, and I mean, there's also this competitive side in science as well. Whereas if you told everybody what you were doing, then they would do it quicker than you could. So there's, you know, there's some element in which people don't want to say what they're doing necessarily. I'm not sure that that's a good thing, but it is the reality. Basically, what I was saying, what I was thinking is that, hey, the negative results themselves, maybe there were 30 other people across the history of biology that have tried to formulate ATP"
},
{
"end_time": 8728.951,
"index": 346,
"start_time": 8720.725,
"text": " using those metals that didn't work. But Sylvana, your assistant couldn't sorry, your PhD student, correct? Yes. Yes, your PhD student couldn't"
},
{
"end_time": 8754.957,
"index": 347,
"start_time": 8729.599,
"text": " didn't see the literature because everyone else said no and so then she wasted her time too and those 29 other people wasted their time and i was thinking well then if you publish negative results does that just bloat all the journals or like is there another reason to not well i mean the journal the journals are already bloated i i actually think that reading too much of the journals is not good for you which is to say"
},
{
"end_time": 8782.278,
"index": 348,
"start_time": 8755.589,
"text": " When I have new students starting, very often they're encouraged to do a literature review and they'll often get bogged down because literature is overwhelming. There's so much of it out there and it's written in such a way as to imply that the results that they did were decisive in some way. And you'll come out with the feeling that everything's been done and there's really nothing left to do here and well, you might as well despair at that point."
},
{
"end_time": 8808.643,
"index": 349,
"start_time": 8782.824,
"text": " So it's actually much more productive not to know about any of that, to be deliberately ignorant and to just blunder around for a while until you begin to see something and then at that point is the time to access the literature. So have other people done this before? And the answer is often yes they have but we did this bit different and we did that bit different and they did this but we did that and so on and so on and so"
},
{
"end_time": 8835.503,
"index": 350,
"start_time": 8809.565,
"text": " You often end up getting different results to what they got. And you realize that, well, if we'd just taken for granted what they said and didn't do anything, we would never have found that. And if you find exactly the same as them, then that's kind of nice to know as well. And you'll probably try and drop it into a paper somewhere just to make it clear that you have successfully replicated someone else's work. It's worth saying that you've done that. But very often,"
},
{
"end_time": 8858.933,
"index": 351,
"start_time": 8836.015,
"text": " You know, a paper may close down an area by saying this is not possible. And in fact, they were wrong because they did the wrong experiment. And there's so many possible experiments you can do that is so long as you don't close yourself down by believing them, then you'll go on and find something new. So I would sing the praises of blundering around in ignorance and the scientific undergrowth, because it's the way to make progress."
},
{
"end_time": 8887.415,
"index": 352,
"start_time": 8860.452,
"text": " Let's wrap. I just got to use the washroom once more. And I would be remiss if I didn't ask you Carl Friston's questions. He sent me some to ask you. Oh, I see. Right. Yeah. Is that all right? Of course it is. Yes. With TD Early Pay, you get your paycheck up to two business days early, which means you can grab last second movie tickets in 5D Premium Ultra with popcorn, extra large popcorn,"
},
{
"end_time": 8920.026,
"index": 353,
"start_time": 8891.015,
"text": " Now this question comes from Carl Friston, number one. Is the increase in diversity and complexity of phenotypic forms a universal feature of evolution? And if so, is there any principled explanation for this?"
},
{
"end_time": 8946.937,
"index": 354,
"start_time": 8920.998,
"text": " I mean, the simple answer is yes. And I suppose the reason is simply mutations, which leads to diversity. So mutations are almost impossible. I mean, all of evolution is based on mutations. And they have an enormous power. The standard way of seeing"
},
{
"end_time": 8973.541,
"index": 355,
"start_time": 8947.858,
"text": " natural selection from a population genetics point of view. So I'm not a population geneticist, but I'm in a department of genetics and I work with some population geneticists who, you know, worked with some of the founding fathers of the field, people like JBS Haldane and John Maynard Smith and so on. And that field kind of only lets itself see"
},
{
"end_time": 9002.824,
"index": 356,
"start_time": 8973.968,
"text": " detrimental mutations which is to say mutations that are bad for you in one way or another. Now we know that there are neutral mutations, most mutations are neutral, don't make really much of a difference, and there are a few beneficial mutations but the ones that are effectively bad, detrimental, are the ones that the field of population genetics has historically really focused on because they are the ones that are most likely to be selected against"
},
{
"end_time": 9032.858,
"index": 357,
"start_time": 9003.592,
"text": " So neutral ones will be ignored by selection or almost ignored. Beneficial ones are very rare in comparison and detrimental mutations are very common. And I find this quite difficult to get used to because I want to think positively about beneficial mutations. But I've become used to thinking in this framework and I'm shocked at how much power it has. So we have a paper out just recently with another PhD student of mine who's a physicist by training, Marco Colnaghi."
},
{
"end_time": 9060.981,
"index": 358,
"start_time": 9033.37,
"text": " And this is asking about bacteria. I mentioned earlier on, bacteria have this metagenome where an E. coli might have 4,000 genes but access to 30,000 genes from out there somewhere. And they do what's called lateral or horizontal gene transfer, which is they pick up bits of DNA from the environment and they bind it into themselves. And various people have shown that this"
},
{
"end_time": 9090.043,
"index": 359,
"start_time": 9061.442,
"text": " It's a little bit equivalent to sex, which is to say it's doing recombination. It's changing the gene set that you've got. And even if on average you pick up genes that are worse than the ones you've got, on average you'll benefit from it because you're generating variation that selection can act on. And if selection sees differences between individuals, then it will select against the ones with the detrimental mutations and the ones that don't have them will flourish and so on."
},
{
"end_time": 9120.179,
"index": 360,
"start_time": 9090.623,
"text": " So basically selection is all about the differences between individuals and mutations generate differences between individuals, but moving genes around bilateral gene transfer amplifies those differences. And sex is an extraordinary machine for generating differences between individuals. And it uses the same machinery that bacteria use, but it organizes it completely different. And so there's this question, why? And the answer, I think we've found part of the answer at least,"
},
{
"end_time": 9148.746,
"index": 361,
"start_time": 9120.555,
"text": " I mentioned mitochondria before that mitochondria allow you to have a much larger genome and having a very large genome gives you a problem with preventing it from being degraded by mutations and the way that bacteria prevent the genomes being degraded by mutations is picking up bits of DNA from around the place and patching it in and it works for a bacterial sized genome but if you have a much larger genome and let's say five times larger"
},
{
"end_time": 9156.493,
"index": 362,
"start_time": 9148.968,
"text": " And you pick up a random bit of DNA from the environment. In effect, the chances of you getting the right bit is much lower."
},
{
"end_time": 9185.486,
"index": 363,
"start_time": 9157.073,
"text": " And really the only way around it is to pick up large chunks of DNA from the environment. And then there's a problem that if you've got any sequences that match somewhere else in your genome, and this is more like the larger your genome, the more likely to have repeat sequences you are, the more likely to delete information you are when you bring this bit in and throw away your bit. So you end up with a system which is only set up to"
},
{
"end_time": 9202.21,
"index": 364,
"start_time": 9186.425,
"text": " eliminate detrimental mutations can account for the transition from bacterial lateral gene transfer to what's called meiosis and sex where you bring two cells together, they fuse together, they line up the chromosomes and so on."
},
{
"end_time": 9223.37,
"index": 365,
"start_time": 9202.858,
"text": " So the whole thing is based on generating differences between individuals so that selection can act. So to come back around in a long circle to Karl Friston's question about divergence between things is driven by mutations and it's basically inevitable and it will be a property of any biological system that's got information at the base of it."
},
{
"end_time": 9254.155,
"index": 366,
"start_time": 9224.445,
"text": " All right, he has a second question. It's right. Carl Friston says, What is the role of sequestration and isolation and evolution at the molecular or cellular scale? sequestration? Yeah, sequestration. So I'm not quite sure what he specifically had in mind there. I just want to message once more over chat. Yeah. So"
},
{
"end_time": 9285.691,
"index": 367,
"start_time": 9255.964,
"text": " Yes, I mean, what I immediately think of when I read sequestration is sequestration within cells, which is to say you have compartments, you sequester the machinery for respiration within the compartment of mitochondria, for example. Now, I don't know if that's actually what he had in mind, but there's a lovely point about bacteria, which is that they are essentially indivisible. They don't have any sequestrated bits."
},
{
"end_time": 9304.462,
"index": 368,
"start_time": 9286.271,
"text": " So there isn't a compartment which is responsible for respiration. There isn't a compartment which is responsible for, you know, putting the genes in for protecting genes and so on. It's a single open system with a mem- no, it's well, it's not a super, they have to go quite a lot of structure."
},
{
"end_time": 9317.517,
"index": 369,
"start_time": 9305.026,
"text": " There's a lot of interest these days in phase separations between effectively liquid-liquid phase separations and the genes in a bacterial cell are phase separated from the cytosol."
},
{
"end_time": 9347.756,
"index": 370,
"start_time": 9317.824,
"text": " And there's no membrane between the two of them. So the compartment is not a complete compartment in the same way. Whereas the mitochondria have got a membrane around them and it sequestrates the inside of the mitochondria from the rest of the cell. And that allows you to have enormously more power. It allows you to charge up those membranes from the inside. Let me just give one example to do with with with with sequestration and mitochondria."
},
{
"end_time": 9374.138,
"index": 371,
"start_time": 9349.428,
"text": " When anybody thinks of mitochondria, they'll tend to think of a kind of sausage-shaped thing with membranes inside the cell, and there are all these sausage-shaped things in there, and that's not really how they are at all. They will actually fuse together. They're very dynamic, they're moving around, they fuse together, they're fishing apart, they separate out, but a lot of the time they're fused together into a giant network"
},
{
"end_time": 9400.077,
"index": 372,
"start_time": 9374.548,
"text": " which fills up the volume of the cell as a branching network in there. You can think of it as power cables. This is a much more efficient way of generating energy because the charge is distributed across the entire surface of this network and is much better for distributing oxygen around because it dissolves better in the fatty membranes than it does in aqueous solution."
},
{
"end_time": 9416.903,
"index": 373,
"start_time": 9400.555,
"text": " And so it's probably the more efficient way of structuring a network to generate power. You can think of it as a power grid. But if you prevent it from splintering up again, then the cell would generate and die."
},
{
"end_time": 9440.947,
"index": 374,
"start_time": 9418.012,
"text": " It seems that it's important for mitochondria to go back to being little independent sausage shaped things. If you stop them from doing that, then the system doesn't work. So why? Well, because with this independent sausage shaped thing, you can sequester a copy of the mitochondrial DNA. So now what we have is a little sausage with a genome of its own."
},
{
"end_time": 9461.886,
"index": 375,
"start_time": 9441.408,
"text": " And that genome is responsible for making sure respiration works in that mitochondrial. So it generates an electrical charge on the membrane in its own little sausage thing. So now we have a relationship between a genotype and a phenotype. The genotype is that mitochondrial genome, the phenotype is the membrane potential, the electrical charge on this membrane."
},
{
"end_time": 9474.497,
"index": 376,
"start_time": 9462.363,
"text": " And if this mitochondrial DNA is damaged, it's mutated and it can't generate membrane potential, then the cell machinery can see that and kill it at that point. So it's a quality control mechanism."
},
{
"end_time": 9501.067,
"index": 377,
"start_time": 9475.213,
"text": " And if what you have is an open network with, let's say, 500 copies of mitochondrial DNA in there, and one of them has got mutations, selection can never see it because its effect is hidden by the 499 other ones that are all contributing to the shared common phenotype of the electrical charge across this entire network. So you'll never notice it. So you can't get rid of it. So more mutations can happen."
},
{
"end_time": 9531.254,
"index": 378,
"start_time": 9501.664,
"text": " So the very fact that we all have mitochondria which are still functional after two billion years of evolution is because of selection on the mitochondrial DNA which is because of sequestration of the mitochondria within the eukaryotic cell and that is the difference between lots of E. coli between a planet full of bacteria that basically can never get beyond bacteria and the planet full of eukaryotic life, plants and animals and everything else. That's the result of sequestration"
},
{
"end_time": 9541.049,
"index": 379,
"start_time": 9531.596,
"text": " bacteria inside other cells with their own DNA. Now I don't know if that's what he had in mind but that's what comes to my mind when you ask me about that."
},
{
"end_time": 9562.722,
"index": 380,
"start_time": 9541.749,
"text": " Sure, and now a near final question comes from a user rh0d3z, which says, this is much more of a technical question. What are profilanes views on mitochondrial risperosomes slash super complexes in disease? This may be particularly important, seeing that they can omit complex two and bypass Krebs cycle pathways."
},
{
"end_time": 9582.961,
"index": 381,
"start_time": 9563.507,
"text": " Yes, very interesting question. There are actually some recently there's one super complex has been discovered with complex two in it, but mostly whoever asked the question is quite right, complex two is not normally part of it. So for people who don't know,"
},
{
"end_time": 9610.111,
"index": 382,
"start_time": 9583.268,
"text": " The super complexes, normally what you have or normally how we're taught and what we imagine is that we have four or five complexes from complex one, complex two, complex three, complex four and the electrons pass from one to the next one to the next one and so on. Complex two is always a little bit on the side in that sense. They go from complex one to complex three and then to complex four then to oxygen. Now"
},
{
"end_time": 9632.244,
"index": 383,
"start_time": 9611.357,
"text": " The respirosome or the super complexes are where these complexes are brought together very often with a specific stoichiometry so you might have two complex ones and one complex three and one complex four or various other stoichiometries of these things where you have fixed numbers of these things they fit together in snug ways and until about 10 years ago"
},
{
"end_time": 9661.715,
"index": 384,
"start_time": 9632.705,
"text": " It was, their existence was kind of denied almost. It was quite difficult to demonstrate that they really do exist, that they're really real. Now it's generally established that they are, and there's a lot of cryo-electron microscopy shows that these things are real, but there's a lot that's still not known about them. Do they really speed up respiration, for example? Seems that they do, but there's, you know, it's early days in this field. Now the specific bit about complex two,"
},
{
"end_time": 9685.913,
"index": 385,
"start_time": 9662.381,
"text": " part of the Krebs cycle. It's the only enzyme in the Krebs cycle which is anchored into the membrane itself and which is effectively passing electrons directly but is excluded from these super complexes. How that works I don't know. I think it's"
},
{
"end_time": 9707.244,
"index": 386,
"start_time": 9686.903,
"text": " I mean, there's some very strange factors here. So complex one is the only one that oxidizes NADH. I don't want to get too technical here, but it's the only one which is really capable of spinning the whole Krebs cycle. So if complex one is deficient or broken, then the Krebs cycle can't work properly."
},
{
"end_time": 9737.79,
"index": 387,
"start_time": 9708.302,
"text": " If it's part of a respirosome, it's likely to be operating at a faster rate, and it's likely to spin the Krebs cycle faster than it would otherwise be able to spin. But it also depends on the structure of the Christi and all kinds of other factors. So there's a kind of macromolecular scale of organization of mitochondria that we don't know a lot about yet. And it's definitely important. I mentioned fission and fusion of mitochondrial networks, and all of this is linked. It's a very dynamic system."
},
{
"end_time": 9763.473,
"index": 388,
"start_time": 9738.695,
"text": " The interesting thing about complex two is it pumps fewer protons than complex one. If you put electrons into complex two and then they go into three and then four, you can pump a total of six protons. Whereas if you put them into complex one, they can pump a total of 10 protons. So you may think then that there's more power, if you like, but it's actually it's not power so much as gearing."
},
{
"end_time": 9790.538,
"index": 389,
"start_time": 9763.951,
"text": " So it's like being, if you're using complex one, it's like being in a high gear on a bike. You can be in 10th gear or something and you can coast very easily along a flat road, but if you get onto a hill and you want to go down to a lower gear. And a lower gear in the mitochondria, if you're putting electrons into complex two, effectively you've got almost the same amount of power, which is to say the"
},
{
"end_time": 9814.189,
"index": 390,
"start_time": 9790.862,
"text": " Energy that's released when the electrons that go into complex two get through to oxygen is not quite as much as when it's coming from an adh but it's nearly the same but that total energy amount is only pumping six protons rather than 10 protons so you've got nearly the same energy pumping fewer protons and that means you can pump them against a higher potential. You can go uphill now, you can effectively"
},
{
"end_time": 9844.445,
"index": 391,
"start_time": 9814.445,
"text": " switch down to, you know, second or third gear or something and keep on going. Now how all of this works itself out in terms of super complexes and Christie structure and everything else, I don't really know. It will have a feedback effect on the Krebs cycle because the Krebs cycle needs to go through this step if it's not going to increase succinate levels which leak out and that's an epigenetic switch which switches genes on and off. This is, it's hardly been"
},
{
"end_time": 9870.503,
"index": 392,
"start_time": 9845.572,
"text": " explored. I mean this is a fantastic thing about science, in some ways we seem to know so much and in other ways there's this kind of jungle of dynamic mitochondria that are changing shape, that are forming Christies, that have got an organization, they're probably generating electromagnetic fields, that are forming super complexes, that have, you know, if you've got a closed Christy structure and you're pumping protons into it, there's a, you know, the limit that"
},
{
"end_time": 9884.787,
"index": 393,
"start_time": 9871.271,
"text": " Hear that sound?"
},
{
"end_time": 9911.834,
"index": 394,
"start_time": 9885.742,
"text": " That's the sweet sound of success with Shopify. Shopify is the all-encompassing commerce platform that's with you from the first flicker of an idea to the moment you realize you're running a global enterprise. Whether it's handcrafted jewelry or high-tech gadgets, Shopify supports you at every point of sale, both online and in person. They streamline the process with the Internet's best converting checkout, making it 36% more effective than other leading platforms."
},
{
"end_time": 9940.367,
"index": 395,
"start_time": 9911.834,
"text": " There's also something called Shopify Magic, your AI powered assistant that's like an all-star team member working tirelessly behind the scenes. What I find fascinating about Shopify is how it scales with your ambition. No matter how big you want to grow, Shopify gives you everything you need to take control and take your business to the next level. Join the ranks of businesses in 175 countries that have made Shopify the backbone of their commerce. Shopify, by the way,"
},
{
"end_time": 9969.275,
"index": 396,
"start_time": 9940.367,
"text": " powers 10% of all e-commerce in the United States, including huge names like Allbirds, Rothies, and Brooklynin. If you ever need help, their award-winning support is like having a mentor that's just a click away. Now, are you ready to start your own success story? Sign up for a $1 per month trial period at shopify.com slash theories, all lowercase. Go to shopify.com slash theories now to grow your business no matter what stage you're in."
},
{
"end_time": 9995.282,
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"start_time": 9969.48,
"text": " The differences in membrane potential is only hardly been touched on between one Christie and another Christie. If you've got a super complex or you don't have super complex as if complex two is part of it or not part of it. You know, there's a world out there that we've barely discovered and it's a world frankly of physics. This is"
},
{
"end_time": 10019.991,
"index": 398,
"start_time": 9995.862,
"text": " This is about charge, and it's about pushing against charge, and it's the power, and it's the energetics of the whole thing. So it's not conventional biology, but this is, to my mind, where biology needs to go. Thank you, Professor, and we didn't get to talk. Maybe next time we can talk about, if I'm so blessed as to be with you, again, thank you, to talk about the reverse Krebs cycle and aging."
},
{
"end_time": 10047.09,
"index": 399,
"start_time": 10020.35,
"text": " It will be a pleasure to come back. That was a lot of fun. Thank you. Yeah. Do you mind ending by reading the poem from the last chapter or the last bit of your book? I believe it's a short poem. If you have it near you. I'm happy to do that. Do I have a copy of the book anywhere near? I have to go and get one. Just give me a moment. I don't know that this will make sense to anybody who hasn't read the book, but it's a beautiful poem anyway. I don't know how much sense it would make"
},
{
"end_time": 10076.22,
"index": 400,
"start_time": 10048.251,
"text": " Even without the context of the book, yes. So this is Like Most Revelations by Richard Howard. It is the movement that incites the form, discovered as a downward rapture. Yes, it is the movement that delights the form, sustained by its own velocity. And yet, it is the movement that delays the form, while darkness slows and encumbers. In fact, it is the movement that betrays the form,"
},
{
"end_time": 10105.52,
"index": 401,
"start_time": 10076.664,
"text": " Well, thank you."
},
{
"end_time": 10133.097,
"index": 402,
"start_time": 10105.998,
"text": " Thank you, Professor, for being with me, with the Toe audience for so long. Thank you for having me on. It's been a pleasure. Okay, all right. Thank you. Thank you for sticking around for two and a half hours, maybe longer. I appreciate that. I hope that it was enjoyable to you. Again, there's the website theoriesofeverything.org. That's a place that you can go to support Toe if you're interested in that. Like I mentioned in the intro, there are several benefits. You get an ad-free audio version. You get that"
},
{
"end_time": 10158.422,
"index": 403,
"start_time": 10133.507,
"text": " sometimes 12 to 48 hours to a few days prior to premiering on YouTube. You get discounts to the live events when we finally do have them. Sometimes those tickets may even be free. So for instance, I'm looking into doing something with John Vervecky and Ian McGilchrist in person. This is all extremely tentative right now, but this is a plan to do in the future. Carl Friston in London live in front of an audience is another example. There will be exclusive merch and so on. There's"
},
{
"end_time": 10173.08,
"index": 404,
"start_time": 10158.422,
"text": " quite a few benefits you can text me if you like there's a number at least we're testing that for about one week or one month or so again that's theoriesofeverything.org thank you all for watching it's great to see you in the live chat i appreciate all of the love thank you thank you so much"
},
{
"end_time": 10188.916,
"index": 405,
"start_time": 10175.964,
"text": " The podcast is now finished. If you'd like to support conversations like this, then do consider going to theories of everything.org. It's support from the patrons and from the sponsors that allow me to do this full time. Every dollar helps tremendously. Thank you."
}
]
}No transcript available.