Nick Lane – Life as we know it is chemically inevitable

**Dwarkesh** (0:00)
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 four 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 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?

**Nick Lane** (0:31)
Well, first, thanks for having me here. This is fun. I love talking about this kind of thing. 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 larger in 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 all those kind of machinery cell membranes and things. So there's just basically a lot of kit 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 have been multiple origins, but there's no evidence for that. If there was, it disappeared without trace. So we've got this kind of singularity, which happened about 2 billion years ago, about 2 billion years into the history of life on earth. And this thing happens once that gives rise to all complex life on earth. And the one thing which I guess you could conclude from that is bacteria and archaea. In terms of their genetic repertoire, 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 of bacterial cell that overall, they've kind of explored genetic sequence space. They had 4 billion years to have a go at that, and they never came up with a trick which says it's not in the genes, it's not about information, there's something else which is controlling it. And that's something I think is the acquisition of these power packs in our cells called mitochondria.

**Dwarkesh** (2:18)
Now let's go to the origins of life. And you have this really compelling story where you imagine that the first life forms were continuous with Earth's geochemistry.
If you can recapitulate this story a little bit.

**Nick Lane** (2:36)
I mean, I'll tell you how I got there first, because I started out working on mitochondria, and that took me into the evolution of eukaryotes. And eukaryotes acquire these endosymbiotes that become mitochondria, and they change the potential of evolution. It doesn't change everything immediately, but it changes where the endpoints can be. Yeah. And it allows the evolution of these large complex cells and eventually multicellular organisms and us. So what are mitochondria actually doing? Well, what they're actually doing is respiration. They're generating energy for cells. They're doing plenty of other things as well, but the main thing we can think about is they're the energy producers.
And they're derived from bacteria, and bacteria produce their energy in exactly the same way. They're generating energy by generating an electrical charge on the membrane. And that charge, it's small, but the membrane is really thin. So the charge is about 150 to 200 millivolts, but the membrane is 5 nanometers in thickness, so that's 5 millionths of a millimetre. So if you shrank yourself down to the size of a molecule or stood next to that membrane, you would experience 30 million volts per meter.
Which is equivalent to a bolt of lightning. So that's the strength of the force of the voltage across the membrane, which is colossal. And it's generated by really sophisticated proteins that pump protons across the membrane. And then it's ATP synthase, which is again pretty much universal, and it's a rotating nanomotor that sits in the membrane. This is colossally complex, interesting machinery, and it's universally conserved. It's as conserved as say a ribosome, the protein building factor is pretty much everywhere across life. So you wonder, how on earth did life come to be that way? And if it's conserved universally across life, it looks like it goes right back to the common ancestors of all cells. And so there's the question, how did it arise in the first place? And that was actually for me tremendously thrilling because it's a way in as a researcher to the origin of life. It says, how did these energy-generating systems arise in the first place? And my way in was really, the gates were opened by Bill Martin and Mike Russell, who around the early 2000s were publishing some amazing papers together where they were saying that in this deep sea hydrothermal vent, rather than it being like a black smoker with a chimney with smoke belching out of the top, it's like a mineralized sponge with lots of pores that are cell-like in their structure. And you've got an acidic early ocean, and you've got alkaline fluids coming out of these, and you've got mixing going on in this whole system. And so you could at least imagine that you've got a pore in here, which is a bit like a cell in terms of its size and its shape, and on the outside, you've got acid ocean waters percolating in, and on the inside, you've got these hydrothermal fluids. So you've got a barrier, you've got an inside and an outside, and you've got more protons outside coming in, potentially driving work. So it's very much like a cell is structured. And the other thing is, what are these minerals? You've got these mineralized sponges that pours with minerals. Well, the minerals we think on the early Earth would have been a lot of metals in there. So things like iron sulfide or nickel sulfide and things like that. Now, the reason that's important is that what plant cells do, but also what autotrophic bacteria do, is they take CO2 and they take hydrogen and they react them together to basically make all the building blocks of life. Now plants get the hydrogen from water, H2O. They take the H2 out of water and throw away the oxygen and that collects in the atmosphere. But what bacteria very often do is they've got hydrogen bubbling out of a hydrothermal vent. They just take the hydrogen stream's gas and they react it with CO2 and they make all the building blocks of life. So what are the enzymes that they use to do that? Well, they're very often using these same metals that you would have found in the early oceans, nickel and iron and so on. And how are they powering the reaction between hydrogen and CO2? Well, they're using this membrane potential, the electrical potential, the difference in protons between the outside and the inside to drive that work. So effectively to power the reaction between hydrogen and CO2 to make organics and drive growth. So this was all kind of in place before I came along. This was coming from Mike Russell and Bill Martin.