Prokaryotic vs eukaryotic cells

Well, the source of energy at the origin of life is the reaction between carbon dioxide and hydrogen. And amazingly, most of these reactions are exergonic, which is to say they release energy. If you have hydrogen and CO2, and you put them together in a Falcon tube and you warm it up to, say, 50 degrees centigrade, and you put in a couple of catalysts and you shake it, nothing's going to happen. But thermodynamically that is less stable. Two gases, hydrogen and CO2, is less stable than cells. What should happen is you get cells coming out. Why doesn't that happen is because of the kinetic barriers. That's where you need the spark. The following is a conversation with Nick Lane, a biochemist at University College London, and author of some of my favorite books on biology, science, and life ever written, including his two most recent titles, Transformer: The Deep Chemistry of Life and Death, and The Vital Question: Why Is Life the Way It Is? This is the Lex Fridman Podcast. To support it, please check out our sponsors in the description. And now, dear friends, here's Nick Lane.

Let's start with perhaps the most mysterious, the most interesting question that we little humans can ask of ourselves. How did life originate on earth? You could ask anybody working on the subject, and you'll get a different answer from all of them. They will be pretty passionately held opinions, and they're opinions grounded in science, but they're still really at this point, they're opinions. Because there's so much stuff to know, that all we can ever do is get a small slice of it, and it's the context which matters. So, I can give you my answer. My answer is, from a biologist's point of view, that has been missing from the equation over decades, which is: well, what does life do on earth? Why is it this way? Why is it made of cells? Why is it made of carbon? Why is it powered by electrical charges on membranes? There's all these interesting questions about cells, that if you then look to see: well, is there an environment on earth, on the early earth 4 billion years ago that kind of matches the requirements of cells?

Overgrown ants. Okay. What do you think about the idea of panspermia, the theory that life did not originate on earth and was planted here from outer space or pseudo-panspermia, which is like the basic ingredients, the magic that you mentioned was planted here from elsewhere in space? I don't find them helpful. That's not to say they're wrong. So pseudo-transpermia, the idea that the chemicals, the amino acids, the nucleotides are being delivered from space. Well, we know that happens. It's unequivocal. They're delivered on meteorites, comets and so on. So, what do they do next? That's, to me, the question. Well, what they do is they stock a soup, presumably they land in a pond or in an ocean or wherever they land. And then a best possible case scenario is you end up with a soup of nucleotides and amino acids. And then you have to say, "So now what happens?"

It's so freaking amazing that it happened though. It feels like there's a direction to the thing. Can you try to answer from a framework of: what is life? So, you said there's some order and yet there's complexity, so it's not perfectly ordered, it's not boring. There's still some fun in it. And it also feels like the processes have a direction through the selection mechanism. They seem to be building something, always better, always improving. Maybe it's- That's a perception.

Let's actually go there. Let's go through the inventions. Yeah.

Generally speaking. So another fun invention, us humans seem to utilize it well, but you say it's also very important early on is sex. So what is sex? Just asking for a friend. And when was it invented and how hard was it to invent, just as you were saying, and why was it invented? How hard was it? And when? I have a PhD student who's been working on this-

It's also actually exactly the way I approach dating, but that's probably why I am single. Okay. What about, if we can step back, DNA just mechanism of storing information, RNA, DNA, how big of an invention was that? That seems to be fundamental to something deep within what life is, is the ability, as you said, to kind of store and propagate information. But then you also kind of inferred that with you and your students' work, that there's a deep connection between the chemistry and the ability to have this kind of genetic information. So how big of an invention is it to have a nice representation, a nice hard drive for info to pass on? Huge, I suspect. I mean, but when I was talking about the code, you see the code in RNA as well, and RNA almost certainly came first. And there's been an idea going back decades called the RNA world because RNA in theory can copy itself and can catalyze reactions. So it kind of cuts out this chicken and egg loop.

So what about, you mentioned predatory behavior. Yeah.

Yeah. Yeah. I don't know how you guys do it. The way I run things, it's always life and death. Okay. So it is interesting about humans that there is an inner sense of morality, which begs the question of, how did homo sapiens evolve? If we think about the early invention of sex and early invention of predation, what was the thing invented to make humans? What would you say? I suppose a couple of things I'd say. Number one is you don't have to wind the clock back very far, five, six million years or so, and let it run forwards again, and the chances of humans as we know them is not necessarily that high. Imagine as an alien, you find planet Earth, and it's got everything apart from humans on it. It's an amazing, wonderful, marvelous planet, but nothing that we would recognize as extremely intelligent life, space-faring civilization. So when we think about aliens, we're kind of after something like ourselves or after a space-faring civilization. We're not after zebras and giraffes and lions and things, amazing though they are. But the additional kind of evolutionary steps to go from large, complex mammals, monkeys, let's say, to humans doesn't strike me as that long a distance. It's all about the brain. And where's the brain and morality coming from? It seems to me to be all about groups, human groups and interactions between groups.

Asking for a friend again, what do you think happened to Neanderthals? What did we cheeky humans do to the Neanderthals, homo sapiens? Do you think we murdered them? How do we murder them? How do we out-compete them, or do we out-mate them? I don't know. I think there's unequivocal evidence that we mated with them.

Yeah. The truth might be very painful. What about, if we actually step back, a couple of interesting things that we humans do? One is object manipulation and movement, and of course, movement was something that was done... That was another big invention, being able to move around the environment. And the other one is this sensory mechanism, how we sense the environment. One of the coolest high-definition ones is vision. How big are those inventions in the history of life on Earth? Vision, movement, again, extremely important going back to the origin of animals, the Cambrian explosion, where suddenly you're seeing eyes in the fossil record. And it's not necessarily... Again, lots of people historically have said, "What use is half an eye," and you can go in a series of steps from a light-sensitive spot on a flat piece of tissue to an eyeball with a lens and so on if you assume no more than... I don't remember. This was a specific model that I have in mind, but it was 1% change or half a percent change for each generation how long would it take to evolve an eye as we know it, and the answer is half a million years. It doesn't have to take long. That's not how evolution works. That's not an answer to the question. It just shows you can reconstruct the steps and you can work out roughly how it can work.

Yeah. Simulate all of that, including the social construct, the spread of ideas and the exchange of ideas. I don't know. But those questions are really important to understand as we become more and more digital creatures. It seems like the next step of evolution is us becoming partial... All the same mechanisms we've talked about are becoming more and more plugged in into the machine. We're becoming cyborgs. And there's an interesting interplay between wires and biology, zeroes and ones and the biological systems, and I don't think we'll have the luxury to see humans as disjoint from the technology we've created for much longer. We are, in organisms, that's [inaudible 01:33:56]. Yeah. I agree with you, but we come really with this to consciousness, and is there a distinction there? Because what you are saying, the natural end point says we are indistinguishable, that if you are capable of building an AI, which is sufficiently close and similar, that we merge with it, then to all intents and purposes, that AI is conscious as we know it. And I don't have a strong view, but I have a view, and I wrote about it in the epilogue to my last book.

But how do we get that understanding? It's so incredibly difficult. I mean, you would have to... One promising direction, I'd love to get your opinion on this. I don't know if you're familiar with the work of DeepMind and AlphaFold with protein folding and so on. Do you think it's possible that that will give us some breakthroughs in biology trying to basically simulate and model the behavior of trivial biological systems as they become complex biological systems? I'm sure it will. The interesting thing to me about protein folding is that for a long time, my understanding, this is not what I work on, so I may have got this wrong, but my understanding is that you take the sequence of a protein and you try to fold it, and there are multiple ways in which it can fold. And to come up with the correct confirmation is not a very easy thing because you're doing it from first principles from a string of letters, which specify the string of amino acids. But what actually happens is when a protein is coming out of a ribosome, it's coming out of a charged tunnel and it's in a very specific environment which is going to force this to go there now and then this one to go there and this one to come like that. And so you're forcing a specific conformational set of changes onto it as it comes out of the ribosome.

So the hard leap, the hardest leap, the most important leap is from prokaryotes to eukaryotes. What's the second, if we were ranking? You gave a lot of emphasis on photosynthesis. Yeah, and that would be my second one, I think. But it's not so much... I mean, photosynthesis is part of the problem. It's a difficult thing to do. Again, we know it happened once, we don't know why it happened once, but the fact that it was kind of taken on board completely by plants, and algae, and so on as chloroplasts, and did very well in completely different environments, and then on land and whatever else, seems to suggest that there's no problem with exploring. You could have a separate origin that explored this whole domain over there that the bacteria had never gone into.

The origin of AI is going to have to be in the chemistry of a planet, but that's not a limiting factor. Let me ask the Fermi Paradox question. Let's say we live in this incredibly dark and beautiful world of just billions of planets with bacteria on it and very few intelligent civilizations, and yet there's a few out there. Why haven't we at scale seen them visit us? What's your sense? Is it because they don't exist? It it because- Well, they don't exist in the right part of the universe at the right time. That's the simplest answer for it.

Yeah, it depends the time. You write quite beautifully in Transformers. Once again, I think you opened the book in this way. I don't remember. From space describing Earth, it's such an interesting idea of what Earth is. Hitchhiker's Guide summarizing it as harmless or mostly harmless. It's a beautifully poetic thing. You open Transformers with "From space, it looks gray and crystalline, obliterating the blue-green colors of the living Earth. It is crisscrossed by regular patterns and convergence striations. There's a central amorphous density where these scratches seem lighter. This 'growth' does not look alive, although it has extended out along some lines and there is something grasping and parasitic about it. Across the globe, there are thousands of them varying in shape and detail, but all of them, gray, angular, inorganic, spreading. Yet at night they light up, glowing up the dark sky, suddenly beautiful. Perhaps these cankers on the landscape are in some sense living. There's a controlled flow of energy. There must be information and some form of metabolism, some turnover of materials. Are they alive? No, of course not. They are cities."

There's beauty in darkness. You write about life and death sort of at the biological level. Does the question of suicide, why live? Does the question of why the human mind is capable of depression? Are you able to introspect that from a place of biology? Why our minds, why we humans can go to such dark places? Why can we commit suicide? Why can we go suffer? Suffer, period, but also suffer from a feeling of meaninglessness of going to a dark place that depression can take you? Is this a feature of life or is it a bug? I don't know. If it's a feature of life, then I suppose it would have to be true of other organisms as well. And I don't know. We were talking about dogs earlier on and they can certainly be very sad and upset and may mooch for days after their owner died or something like that. So I suspect in some sense it's a feature of biology. It is probably a feature of mortality. It's probably a... But beyond all of that, I guess there's two ways you could come at it. One of them would be to say, well, you can effectively do the math and come to the conclusion that it's all pointless and that there's really no point in me being here any longer. And maybe that's true in the greater scheme of things. You can justify yourself in terms of society, but society will be gone soon enough as well. And you end up with a very bleak place just by logic.

Amen to that. Let me, on writing in your book, Power, Sex and Suicide. First of all, can I just read off the books you've written, if there's any better titles and topics to be covered, I don't know what they are. It makes me look forward to whatever you're going to write next. I hope there's things you write next. So first you wrote Oxygen: The Molecule that Made the World as we've talked about this idea of the role of oxygen in life on Earth. Then wait for it, Power, Sex, Suicide: Mitochondria and the Meaning of Life. Then Life Ascending: The 10 Great Inventions of Evolution. The Vital Question, the first book I've read of yours, the Vital Question: Why is Life the Way It Is? And the new book Transformer: The Deep Chemistry of Life and Death. In Power, sex and Suicide, you write about writing or about a lot of things, but I have a question about writing. You write in the Hitchhiker's Guide to the Galaxy Ford Prefect spends 15 years researching his revision to the Guide's entry on the Earth, which originally read, "Harmless," by the way, I would also as a side question, I would like to ask you what would be your summary of what Earth is.

Could you give advice to young people in general, folks in high school, folks in college, how to take on some of the big questions you've taken on. Now you've done that in the space of biology and expand it out, how can they have a career they can be proud of or have a life they can be proud of? Gosh, that's a big question.

So the summary from harmless to mostly harmless in Hitchhiker's Guide to the Galaxy, how would you try to summarize Earth? And if you had to summarize the whole thing in a couple of sentences and maybe throw in meaning of life in there, why? Maybe is that a defining thing about humans that we care about the meaning of the whole thing? I wonder if that should be part of the... These creatures seem to be very lost. Yes. They're always asking why. That's my defining question is why. People used to made a joke, I have a small scar on my forehead from a climbing accident years ago, and the guy I was climbing with had dislodged a rock and he shouted something, he shouted, "Below," I think, meaning that the rock was coming down and I hadn't caught what he said. So I looked up and he went smashed straight on my forehead, and everybody around me took the piss saying, "He looked up to ask why."