Nick Lane on Dwarkesh Patel: Why Alkaline Vents Birthed Life

1. 0:00 – 8:26

   The singularity that unlocked complex life

   1. NLNick Lane0:00

      (instrumental music plays) If you've got a thousand planets with life on, maybe life is gonna be the same way 999 out of 1,000 times, 'cause it's gonna be carbon-based, it's gonna be water, it's gonna be cells, it's gonna be charges, it's gonna be hydrogen and CO2, and you're gonna face the same constraints.

   2. DPDwarkesh Patel0:13

      If life is not only abundant, but almost inevitable, the bottleneck to not seeing aliens everywhere-

   3. NLNick Lane0:20

      Well, there's probably more than one bottleneck, but eukaryotes is, in my own mind-

   4. DPDwarkesh Patel0:23

      Right.

   5. NLNick Lane0:24

      ... the big one.

   6. DPDwarkesh Patel0:24

      You could have had, imagine there's like Frankenstein-like moment where a thing zaps alive.

   7. NLNick Lane0:29

      Hmm, I hate, I hate that as an idea.

   8. DPDwarkesh Patel0:32

      If I was a God-fearing person-

   9. NLNick Lane0:34

      Mm-hmm.

   10. DPDwarkesh Patel0:34

       ... I would hear this and I'd be like, "Wow, this is a vindication of intelligent design."

   11. NLNick Lane0:38

       I mean, I agree with you. It- it- I find it a little, uh, almost disturbing.

   12. DPDwarkesh Patel0:44

       Today, I'm chatting with Nick Lane, who is an evolutionary biochemist at University College London, and he has many books and papers which help us reconceptualize life's 4 billion years in terms of energy flow, and helps explain everything from how life came to be in the first place to the origin of eukaryotes to many, uh, contingencies we see today in how life works. So, Nick, maybe a good place to start would be, why are eukaryotes so significant in your worldview of why life is the way it is?

   13. NLNick Lane1:15

       Well, first, thanks for having me here.

   14. DPDwarkesh Patel1:17

       (laughs)

   15. NLNick Lane1:17

       This is- this is fun. Uh, I- I love talking about this kinda thing. So- so eukaryotes, what's a eukaryote? It's basically the cells that make us up, but also make up plants and make up things like amoeba or fungi, algae. So basically, everything that's large and complex that you can see is composed of this one cell type called the eukaryotic cell. And we have a nucleus where all the DNA is, where all the genes are, and then a- all this kind of machinery, cell membranes and things. There's just basically a lot of kit in- in- in these cells. And the weirdness is, if you look inside a plant cell or a fungal cell, it looks exactly the same under an electron microscope as one of our cells. But they have a completely different lifestyle. So why would they have all the same kit if they evolved to be a single-celled alga living in an ocean, doing photosynthesis? It's still got the same kit that our cells have. So, we know that because they share all of these things, they arose once in the whole history of life on Earth. There could've been multiple origins, but there's no evidence for that, that, you know, if there was, it disappeared without trace. So we've got this kind of singularity-

   16. DPDwarkesh Patel2:18

       Mm.

   17. NLNick Lane2:18

       ... which happened about two billion years ago, about two billion years into the history of life on Earth, and this thing happens once that gives rise to all complex life on Earth.

   18. DPDwarkesh Patel2:27

       Mm-hmm.

   19. NLNick Lane2:27

       A- and the one thing which I- I- I guess you could conclude from that is, bacteria and archaea, in terms of their genetic repertoire, they're actually, th- they've got a lot more genes, a lot more versatility than eukaryotes do. It's just that a single bacterial cell has much less in it, but there's so many different types-

   20. DPDwarkesh Patel2:44

       Mm-hmm.

   21. NLNick Lane2:44

       ... of bacterial cell, that overall, they've kind of explored genetic sequence space.

   22. DPDwarkesh Patel2:49

       Right.

   23. NLNick Lane2:49

       They had four billion years to have a go at that, and they never came up with the trick, which says it's not in the genes, it's not about information, there's something else which is- which is controlling it. And that something, I think, is the acquisition of these power packs in our cells called mitochondria.

   24. DPDwarkesh Patel3:03

       Now let's go to the origins of life, and you have this really c- compelling story where you imagine that the first life forms were continuous with Earth's geochemistry. And if-

   25. NLNick Lane3:18

       Yeah, yeah.

   26. DPDwarkesh Patel3:18

       ... you can recapitulate the story a little bit, and then I wanna ask some questions about it.

   27. NLNick Lane3:21

       Yeah, I- I mean, I'll tell you how I got there first-

   28. DPDwarkesh Patel3:23

       Yeah.

   29. NLNick Lane3:23

       ... because, uh, I- I started out working on mitochondria-

   30. DPDwarkesh Patel3:27

       Mm-hmm.
2. 8:26 – 23:36

   Early life continuous with Earth's geochemistry

   1. NLNick Lane8:26

      and now you've, you're free to become large and more complex. So, so, so you've gone from, you know, thinking about a puzzle about why eukaryotes are special to thinking about planetary systems and thinking about, uh, the origin of life and what are the forces that are going to give rise to life, and how would that constrain life, and would we see the same things on other planets or something different? Uh, what are, what are the fundamental reasons that it works this way? So it becomes astrobiology, really, and, and, and, uh, it's, uh, it's a thrilling change of perspective, uh, to come from... Uh, my, my own background was to do with mitochondrial biology-

   2. DPDwarkesh Patel9:02

      Yeah.

   3. NLNick Lane9:02

      ... actually in organ transplantation once upon a time. Uh, and, and spinning on a pinhead, you end up working on the origin of life. It's fantastic.

   4. DPDwarkesh Patel9:09

      Yeah.

   5. NLNick Lane9:09

      (laughs)

   6. DPDwarkesh Patel9:10

      I mean, it's, it's so fascinating. So just to recapitulate for my own understanding and the audience's, um, let, let's just break down what we have here. So you have the analog of a cell in these pores. You have something which concentrates the buildup of these organics so that they don't just all diffuse in some l- big primordial soup. And so this is why you think, like, some primordial lake is not where this happened. It had to be concentrated in some entity. Then you've got a chemiosmotic gradient, a proton gradient, which drives work, and specifically, it favors the fixation of, uh, carbon dioxide and to, you know, to d- drive the reaction with hydrogen gas to make organics.

   7. NLNick Lane9:53

      Yeah, yeah.

   8. DPDwarkesh Patel9:53

      And then you've got... Along this membrane, you've got catalysts, which are basically early enzymes. So you've got enzymes, you've got the cell, you've got the proton gradient, and then the story is basically that you make simp- very simple organics with CO2 and H2, and then those simple organics are then re-catalyzed to make more and more complex organics and like, basically TL;DR metabolism, and like-

   9. NLNick Lane10:19

      Yeah.

   10. DPDwarkesh Patel10:19

       ... fatty acids and nucleotides, everything else.

   11. NLNick Lane10:21

       Yes, yeah. That's basically it, yeah.

   12. DPDwarkesh Patel10:22

       Yeah.

   13. NLNick Lane10:22

       Um, so, so, so what do you get if you react hydrogen and CO2? What you get are what are called Krebs cycle intermediates or carboxylic acids, small molecules made only of carbon, hydrogen, and oxygen, with this organic acid group at the end, which can be-

   14. DPDwarkesh Patel10:36

       Yeah.

   15. NLNick Lane10:36

       ... two, three, four, five carbon units in the chain. And this is your basic building blocks. You, you add on ammonia to this, and you, you get an amino acid. You add more hydrogen on, and you're going to get a sugar. Um, you react amino acids with sugars, and you're going to get nucleotides. You know, it, it... There's lots of steps along here, but this is, these, this is the basic kind of starting point for all of biosynthesis in biochemistry today.

   16. DPDwarkesh Patel11:00

       And then it's, it's... Then you make, if you make fatty acids, they will sort of spontaneously, because of the hydrophilic nature of, uh, their different sides, they will spontaneously form the membrane if they're-

   17. NLNick Lane11:09

       Yeah, so, so-

   18. DPDwarkesh Patel11:10

       ... if they're created.

   19. NLNick Lane11:10

       ... so, so what I say is, you know, Krebs cycle intermediates are short chain carboxylic acids-

   20. DPDwarkesh Patel11:14

       Right.

   21. NLNick Lane11:14

       ... and fatty acids is long chain.

   22. DPDwarkesh Patel11:16

       Yeah.

   23. NLNick Lane11:16

       So, you know, your 10, 12, 15 carbons in the chain instead of four or five.

   24. DPDwarkesh Patel11:20

       Yeah.

   25. NLNick Lane11:21

       And they will spontaneously, not just alone usually, but if you've got other long chain hydrocarbons mixed up with them, then you will form a bilayer membrane spontaneously, and we've done this-

   26. DPDwarkesh Patel11:31

       Yeah.

   27. NLNick Lane11:31

       ... in the lab.

   28. DPDwarkesh Patel11:31

       Yeah.

   29. NLNick Lane11:32

       Uh, and it's pretty robust to, you know, you can, you can make these things at 70 degrees, 90 degrees centigrade, uh, across a range of pH, from around about pH 7 up to about pH 12, um, a- and in the presence of ions like calcium and magnesium and other salts and so on. So you can... Uh, and you make a, a vesicle with a bilayer membrane around it, which is the, basically the same as a cell membrane.

   30. DPDwarkesh Patel11:54

       Yeah.
3. 23:36 – 42:16

   Eukaryotes are the great filter for intelligent life

   1. NLNick Lane23:36

      set the laws of the universe in motion.

   2. DPDwarkesh Patel23:38

      Right.

   3. NLNick Lane23:38

      And they, they're left to play out. Now, you know, this is kind of Einstein's God really. Um, in terms of what most people understand by God, I think most people look for comfort in God and are looking for something which is meaningful to them and who's been involved in humanity. And, um, so this is a very cold kind of... (laughs) God is thermodynamics, uh, sets the laws of the universe in motion-

   4. DPDwarkesh Patel24:05

      Yeah.

   5. NLNick Lane24:05

      ... reproducibly gives rise to the same kinds of things. Yes, you could interpret it in a kind of theistic, natural theistic way, but I don't think many people would get that much comfort or meaning from that way of seeing the world.

   6. DPDwarkesh Patel24:20

      Right, yeah. Okay, so, uh, very basic question but...If life is not only abundant, but almost inevitable in all these rocky planets, then the bottleneck to not seeing aliens everywhere presumably is eukaryotes which lead to complexity.

   7. NLNick Lane24:38

      Yeah. Well, there's probably one, more than one bottleneck, but eukaryotes is, in my own mind-

   8. DPDwarkesh Patel24:42

      Right.

   9. NLNick Lane24:42

      ... the big one, yes.

   10. DPDwarkesh Patel24:43

       So it would have to be the case that out of billions of potential planets where, that could give rise to eukaryotes, only on Earth does this chance occurrence happen.

   11. NLNick Lane24:55

       I wouldn't argue that.

   12. DPDwarkesh Patel24:56

       Okay.

   13. NLNick Lane24:57

       I mean, only on Earth. No, I don't think so.

   14. DPDwarkesh Patel24:59

       Sure, sure.

   15. NLNick Lane24:59

       But, but is, is there... Uh, I suppose what I would dig my heels in a little bit is, is, is there's a kind of Carl Sagan co- cosmological view that, uh, that once you've got, you know... Uh, we're talking about the inevitability almost of life arising-

   16. DPDwarkesh Patel25:14

       Yeah.

   17. NLNick Lane25:14

       ... according to these laws of chemistry and thermodynamics and so on, and you, you get life. And, and then is it gonna roll on and inevitably give rise to complex life-

   18. DPDwarkesh Patel25:22

       Yeah.

   19. NLNick Lane25:22

       ... and to humans and to, to, to intelligence? Um, I, it's a, it's a beautiful thought. It would be lovely if that was how the universe worked.

   20. DPDwarkesh Patel25:32

       Mm-hmm.

   21. NLNick Lane25:32

       But what we ha- what we know on Earth is that you have two billion years of stasis where you'd... And, and then, and then this apparent u- singular event where eukaryotes arose, and then another long gap before you get to animals. And then if, you know, if you roll back the clock two million years, there aren't any humans around either, so-

   22. DPDwarkesh Patel25:47

       That's right, yeah.

   23. NLNick Lane25:47

       ... you know, it, it, we're just, we're just the, the, the, the, the icing.

   24. DPDwarkesh Patel25:51

       Why is it supposedly this hard to have this, uh, successful endosymbiotic event?

   25. NLNick Lane25:59

       Well, there's, there's multiple reasons.

   26. DPDwarkesh Patel26:01

       Yeah.

   27. NLNick Lane26:01

       Um, I mean, one of them is that the, the prokaryotes, uh, we should say archaea and bacteria, well, they're pretty small things. So just having another cell inside you is already a difficult thing to do. It's not... Uh, and there are no... There are occasional phagocytes in bacteria that can engulf other cells.

   28. DPDwarkesh Patel26:18

       Mm-hmm.

   29. NLNick Lane26:18

       But that's pretty uncommon. And once you've got these cells inside you, you know, it may have, that may have happened s- scores of occasions. There's some tentative evidence that suggests that, that archaea... I mean, there's one nice example where, uh, the haloarchaea seem to have acquired more than 1,000 bacterial genes from the same source, implying perhaps they had got a, an endosymbiont that they then lost later on. So the question is, h- how often would it go wrong and, and you lose your endosymbiont? And I, I guess that would be the more likely outcome is that you pick up a bunch of genes and you lose your endosymbiont. It, it simply doesn't work out. Uh, so, so it's, it's hard to know exactly what are all the bottlenecks here.

   30. DPDwarkesh Patel26:57

       Yeah.
4. 42:16 – 1:08:12

   Mitochondria are the reason we have sex

   1. NLNick Lane42:16

      to- to do almost anything.

   2. DPDwarkesh Patel42:17

      Yeah.

   3. NLNick Lane42:18

      If you've got naked bits of RNA, what tends to happen is they- they- they're selected for their replication speed, they- they- they just go on making copies of themselves. They don't become more complex, they don't start encoding metabolism, they just go on copying themselves and- and it's a dead end.

   4. DPDwarkesh Patel42:33

      Yeah.

   5. NLNick Lane42:33

      Um, if you're trapping them inside growing proto-cells, then effectively they're sharing the same fate, and if some of them are capable of making that proto-cell grow faster, uh, then- then they will get more copies of themselves because they're inside this proto-cell. The proto-cell is growing faster, it makes a copy of itself and it's still associated. So- so you've got actually selection as we know it in cells today, whereas where the replicator are the genes, but the system which is being reproduced is the cell.

   6. DPDwarkesh Patel43:01

      So, uh, your sort of mitochondria first viewpoint helps explain why there's two sexes. Maybe you can recapitulate that argument, but I'm curious if, um, if there was a world where prokaryotes had evolved sex, do you think that they would've likely evolved just one sex?

   7. NLNick Lane43:16

      Uh, I, I'm gonna unpack that a little bit.

   8. DPDwarkesh Patel43:18

      Yes.

   9. NLNick Lane43:18

      Because the, so, so, so, so what have mitochondria got to do with sexes?

   10. DPDwarkesh Patel43:22

       Yeah.

   11. NLNick Lane43:22

       So what they have to do with sexes is, uh, effectively, the female sex, and this goes even for single cells things that don't have any, you know, obvious differences between gametes, which is to say they don't have, uh, oocytes and sperm or anything like that. You know, they produce little motile gametes that look more like sperm than anything else. Both sexes would do that.

   12. DPDwarkesh Patel43:41

       Mm-hmm.

   13. NLNick Lane43:41

       But by definition, the female sex passes on the mitochondria-

   14. DPDwarkesh Patel43:45

       Hmm.

   15. NLNick Lane43:45

       ... and the male does not. Uh, and that's a kind of, that's a, that's an approximation. It's not always true. There's, there's exceptions to that rule, but it's a kind of a rule of thumb in biology that the females pass on, uh, the mitochondrial DNA. Um, so why would that happen? With sex, what you're doing is you're increasing the variance in the g- in the nuclear genome, and you're subjecting that to selection, and the, the winners are coming through that. And, and, and everything which is worse than it would've been gets eliminated by selection. So you're effectively, you're increasing variance on nuclear genes, uh, the genomes, and, and then, and then, and, and then selecting for what works.

   16. DPDwarkesh Patel44:21

       Mm-hmm.

   17. NLNick Lane44:22

       With the mitochondria, they're not doing, they're not, they're, they're passing on asexually down the generations. Uh, there's a very small genome, but there's multiple copies of it. Um, and so the question is, well, how do you keep that clean? How do you prevent that from degrading and degenerating over time? Because if you've got, let's say if you've got 100 copies of mitochondrial DNA and two of them acquire mutations, but you've still got 98 which are doing their job fine, what's the penalty for those two mutations? It's not very much. You'll hardly notice them.

   18. DPDwarkesh Patel44:51

       Yeah.

   19. NLNick Lane44:52

       S- so, so now you acquire another couple of mutations, and you, you can degenerate over time. It's a process called Muller's ratchet, but it's basically, it's, it's, uh, uh, these mutations are kind of somewhat screened from selection by being compensated for by clean copies that you have-

   20. DPDwarkesh Patel45:06

       Mm-hmm.

   21. NLNick Lane45:06

       ... of oth- other copies. So how do you get rid of those mutations that are building up over time? Well, the answer is you, what you need to do is increase variance of mitochondrial genes. What you need to do is effectively segregate into these cells all the mutants, and into those ones, all the wild type ones.

   22. DPDwarkesh Patel45:22

       Yeah.

   23. NLNick Lane45:23

       So you can do that by, by multiple rounds of cell division, but it helps if you've got two sexes that effectively only one sex passes on the mitochondria. So you're already sampling. So you're already increasing the variance, um, and, and you're increasing visibility to selection. So you're basically, it's about s- it's about the quality of mitochondrial genes.

   24. DPDwarkesh Patel45:42

       C- Can you help me understand why it's okay, so uniparental inheritance of mitochondria helps increase variance?

   25. NLNick Lane45:47

       Because s- uh, so, so, so we're talking about variance between cells.

   26. DPDwarkesh Patel45:51

       Yeah.

   27. NLNick Lane45:51

       So if you imagine that you have 100, 100 cells, um, and y- you, y- they all come from the same parent, let's say.

   28. DPDwarkesh Patel45:59

       Yeah.

   29. NLNick Lane45:59

       And you randomly give each cell-

   30. DPDwarkesh Patel46:02

       Yeah.
5. 1:08:12 – 1:12:34

   Are bioelectric fields linked to consciousness?

   1. NLNick Lane1:08:12

      some years. There are big crux points like making purine nucleotides where there's 12 steps in this synthetic pathway and it, and all the intermediates are unstable and break down easily. It c- it's been done in things like methanol, so not in water. In water, stuff breaks down. So, we're trying to do it. It's difficult. Uh, so, we'll, I, I, I believe, I think we'll get there, which is why we're trying to do it. But maybe we won't, in which case, again, the hypothesis is wrong. We- you've got to wake up every morning and think, you know, "The hypothesis could be wrong." It's, it's beautiful, it might, it makes sense, but, uh, you know, there's so many beautiful ideas killed by ugly facts.

   2. NANarrator1:08:50

      Yeah.

   3. NLNick Lane1:08:50

      So, there's no good believing that you're right. You've got to believe you're probably wrong and keep going anyway. And then the other, the other thing which I'm excited about at the moment is, is, is work on anesthetics and mitochondria. It turns out, I heard this from, from a guy called Luca Turin, a few years ago now, um, who pointed out to me that anesthetics affect mitochondria. I had no idea that anesthetics affect mitochondria. Well, they do. We've been doing experiments on it. And, and, and it seems we've not fully established this yet, but it does seem as if their main effect is mitochondria. And, and anesthetics work on all kinds of things including things like amoeba. So, it's already saying, this doesn't prove anything, but it's beginning to say, well, if you can make an amoeba unconscious, then is it con- was it conscious before? Well, not as we understand consciousness. But the way we would understand consciousness is really about neural nets.

   4. NANarrator1:09:42

      Yeah.

   5. NLNick Lane1:09:42

      And, and nervous system, and, and all the complexity of human consciousness. That's what we primarily think about. But there's a deep problem, uh, which, which goes back, I, I mean, it's the, it's the mind-body problem.

   6. NANarrator1:09:53

      Mm-hmm.

   7. NLNick Lane1:09:53

      But, but it was, it was framed by David Chalmers as the hard problem of consciousness-

   8. NANarrator1:09:59

      Right.

   9. NLNick Lane1:09:59

      ... which boils down as my understanding of this, is more or less, we don't know what a feeling is in physical terms. So, you can understand the information processing of a neural network but what actually if you feel miserable, when you feel pain, uh, or you feel love, or whatever it may be, what actually is that in the chemistry of a system? And, and, and I suppose the problem is that you have all of these neural nets firing and some of them are conscious. We're aware that (laughs) of, of what we're thinking about. And others, which seem to have all the same properties-

   10. NANarrator1:10:31

       Mm.

   11. NLNick Lane1:10:31

       ... in terms of their neurons, they have synapses, they have neurotransmitters, they depolarize, they pass on an action potential, but we're not conscious of it. It's, it's, it's non-conscious information processing. So, so there's this question, okay, so if, if anesthetics affect things that don't have neural nets, uh, and, and, and feelings are something that we can't define in terms of a neural net, could it be that feelings are somehow linked more broadly to, to life? Um, so why would they be? What would it f- uh, so, so, so again, the way I think about this is as an evolutionary biologist. So, the first question is, would we think that, uh, that, that, that feelings are real? I would say yes. Uh, do we think that they evolved? I would say yes. I think any evolutionary biologist would say yes to those, those questions. Um, if it's r- if it's real and it evolved, then natural selection must be able to see it and act on it in some way. In other words, there's something physical about it that can be selected for. Again, I don't think there's anything controversial about that statement.

   12. NANarrator1:11:38

       Mm-hmm.

   13. NLNick Lane1:11:39

       So, but then if it's physical and real and has been selected on, you, you know, the implication is we should be able to measure it. Uh, there should be... I- it has to offer an advantage for selection to act on and, uh, and if it's a physical process, it should be measurable but we don't really know what we're trying to measure here. So, I then kind of revert back to thinking, okay, what, what would a bacterial cell need to do? And this is just, just kind of back of the envelope thinking. A- and I immediately think about metabolism. What's the difference between the inside of a bacterial cell and the outside world? It's basically, you know, the inside is, is, is metabolically alive. It's doing stuff with its chemistry all the time and it's at a colossal rate. A bacterial cell will have about a billion reactions every second in, in this metabolism. So, I'm immediately left wondering how is it all controlled. How do you have, how do you, how do you get this cell to have a coherent behavior so it decides I'm going to crawl over there?

Episode duration: 1:20:53