[Book Review] "The Vital Question" by Nick Lane

by lsusr10 min read27th Sep 202121 comments

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Book ReviewsBiologyExtraterrestrial LifeChemistryEvolution
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There is a singularity at the beginning of biology. We know what happened before biology―that's just physics. We know what happened after the first cells: evolution. But we don't know how the first cells formed out of nonliving matter.

The most popular theory is called "primordial soup". The basic idea is that organic molecules (which just means chemical compounds with carbon-hydrogen bones) formed from natural physical processes and then some of those organic molecules randomly organized themselves into RNA and then that RNA built itself a cell. Bam.

The primordial soup theory is implausible from a physics perspective due to thermodynamics.

Living cells are at disequilibrium with their environment. They must harvest negentropy from an external source in order to stay alive. This isn't a property life happens to have. It's the essence of what life is. Life that isn't harvesting negentropy isn't alive.

For life to exist it needs a barrier between its ordered self and its chaotic environment. Life on Earth uses a cell wall composed of a lipid membrane. Since the inside of the cell is ordered and the outside is chaotic, there is an entropy gradient across the cell wall.

Here's where the primordial soup theory becomes implausible. A primordial soup is at chemical equilibrium. A cell is at chemical disequilibrium. Could a primordial soup form a cell? Sure, in the same sense that all the atoms in my body could quantum teleport themselves to the Restaurant at the End of the Universe. "Things randomly happened to violate thermodynamics" is so statistically unlikely it should be the last resort we fall back upon after every conceivable hypotheses fails.

The Vital Question by Nick Lane provide a theory of the origin of life that is physically plausible.

Proton Gradients

Cellular biology textbooks spend a lot of time on:

  1. Metabolism via mechanisms like the Krebs cycle.
  2. Channels which pump chemicals in and out of the cell.

I can imagine life without DNA. I can imagine life without mitochondria and without chloroplasts. (Most organisms don't have them.) I cannot imagine life without metabolism. Sustained metabolism requires a cell to pump chemicals in and out of an organism.

The most important chemical reaction is the synthesis of ATP. It would not be an exaggeration to say ATP powers life. ATP is manufactured by harvesting energy from a proton gradient across a membrane.

Membrane Bioenergetics

There are three domains of life: bacteria, archaea and eukaryotes. The first eukaryote formed when an archaea formed a symbiotic relationship with a bacterium. If the primordial soup theory is correct then there is must be a single origin of life. Bacteria or archaea must have a common ancestor. We call it LUCA (Last Universal Common Ancestor).

But there are some mysteries. Membranes are made of lipids. Part of a lipid is made of glycerol. All archaea/bacteria use their respective lipids and their respective glycerol. Evolution is messy. It never replaces something that thoroughly. If one was replaced by the other then we should see some intermediate organisms. The fact that we don't is is evidence archaea/bacteria lipids and glycerol were never replaced. If the membranes they were never replaced then bacteria membranes arose independently from archaea membranes.

But if one type of lipid was not physically replaced with another, then what kind of membrane did the common ancestor actually possess? It must have been very different from all modern membranes. Why?…Even putting aside the question of what type of membrane it was, there is again the issue of disturbing early sophistication. In modern cells, chemiosmotic coupling only works if the membrane is almost impermeable to protons. But all experiments with plausible early membranes suggests that they would have been highly permeable to protons. It's extremely difficult to keep [protons] out…it's a classic chicken and egg problem. What's the point of learning to pump protons if you have no way to tap the gradient? And what's the point of learning to tap a gradient, if you have no way of generating one?

This chicken and egg problem is the core of Nick Lane's argument. Either proton gradients arose first or proton pumps arose first. Proton gradients can form by ordinary nonliving physical processes. Proton pumps cannot. Nick Lane concludes proton gradients must have come first.

Starting with proton gradients solves the chemical disequilibrium problem too.

Geothermal Vents

You know those black smokers with the anemones, tube worms and the giant clams? They rely on photosynthesis. Not directly, of course. No sunlight makes it down to the bottom of the ocean. Instead, they react hydrogen sulphide (H₂S) with oxygen (O₂). That oxygen comes from photosynthesis.

Nick Lane proposes instead that life originated a different kind of ocean vent called a white smoker.

They are not superheated, but warm, with temperatures of 60 to 90°C. They are not open chimneys, venting directly into the sea, but riddled with a labyrinth of interconnected micropores.

Thermal currents through microporous labrynths have a remarkable capacity to concentrate organic molecules (including amino acids, fatty acids and nucleotides) to extreme levels, thousands or even millions of times the starting concentration, by way of a process known as thermophoresis. This is a little like the tendency of small items of laundry to accumulate inside a duvet cover in the washing machine. It all depends on kinetic energy. At higher temperatures, small molecules (and small items of laundry) dance around, with some freedom to move in all directions. As the hydrothermal fluids mix and cool, the kinetic energy of the organic molecules falls, and their freedom to dance around diminishes (which is what happens to socks inside the duvet cover). That means they are less likely to leave again, and so they accumulate in these regions of lower kinetic energy.

So that's why my laundry accumulates in the duvet cover!

Lipids self-assemble into membranes. These membranes naturally form inside the tiny pores like soapy water on a bubble blower. One side of the membrane is exposed to water in contact with the alkali ovaline rock. The other side is exposed to the water. This creates a proton gradient behind which there are concentrated organic molecules.

There's no oxygen yet. Instead of reacting hydrogen sulfide with oxygen, proto-life could react hydrogen (H₂) with carbon dioxide (CO₂) to form methane (CH₄). At any given pH, it's impossible to for life reduce CO₂ with H₂. But a membrane doesn't have just a single pH. It has a different one on each side of the membrane.

Nick Lane proposes that LUCA was a membrane capped pore in an olavine rock. Nick Lane even makes specific predictions about which biological machinery LUCA did and din't have.

LUCA really was chemiosmotic, with an ATP synthase, but really did not have a modern membrane, or any of the large respiratory complexes that modern cells use to pump protons. She really did have DNA, and the universal genetic code, transcription, translation and ribosomes, but really had not evolved a modern method of DNA replication.

Early Evolution

Nick Lane practices epistemic rigor by not speculating beyond his area of expertise.

I am not concerned in this book with the details of primordial biochemistry: where the genetic code came from, and other equally difficult problems. These are real problems, and there are ingenious researchers addressing them. We don't yet know the answers. But all these ideas assume a plentiful supply of reactive precursors.

We now have LUCA established over a proton gradient. But we still have the chicken-and-egg problem of proton-impermeable membranes and hydrogen pumps. Which came first? Nick Lane guesses it was a Na⁺/H⁺ antiporter.

An antiporter is like a turnstile to a building which lets exactly one person into a building for every person which leaves except instead of people it operates on ions. A Na⁺/H⁺ antiporter lets in one sodium ion for every hydrogen ion it lets out and one hydrogen ion in for every sodium ion it lets in. If there is more hydrogen on one side of the membrane, a Na⁺/H⁺ antiporter acts as a hydrogen-powered sodium pump[1]. Sodium is much bigger than hydrogen. It's easy to evolve a sodium-impermeable membrane. The sodium gradient can drive metabolic reactions. Once you have all this machinery set up, a proton-impermeable membrane evolving naturally.

The Na⁺/H⁺ antiporter theory predicts that our oldest enzymes (those found in both bacteria and archaea which make DNA and RNA work) will be optimized to work at low sodium concentration even though the oceans have been high in sodium since life originated―and this is exactly how modern biochemistry works.

LUCA still replies on an inorganic proton gradient. It can't pop free of the rock until it has proton pumps. But we finally have proton-impermeable membranes! Proton-impermeable membranes let us evolve proton pumps. Proton pumps are an alternative to geologic proton gradients. With proton pumps and proton-impermeable membranes, a vesicle can separate from LUCA to form a proper cell.

Bacteria and Archaea

Methanogens are archaea. Acetogens are bacteria. They have different acetyl CoA pathways going all the way back to LUCA. Nick Lane proposes they evolved proton pumps independently. To cut to the chase, one of them pumps H⁺ into the cell for one biochemical reason; the other pumps H⁺ out of the cell for another biochemical reason[2]. This has various downstream effects―some random (like the handedness of glycerol), others logical.

We end up with two kinds of cells descended from LUCA: bacteria and archaea. They both rely on DNA but their membranes, cell walls and DNA replication are very different.

Eukaryotes

The book goes downhill[3] from there. The rest of the book isn't bad. In fact, it's a pretty great introduction to cellular biochemistry approachable to laypeople even though it's full of of technical detail. This post-eukaryote evolutionary theory is neither new nor controversial so I'll just give a quick summary.

Eukaryotes formed when an archaeon consumed a bacterium, forming a symbiotic relationship. The symbiotic organism is called an eukaryote and the bacteria inside it are is called mitochondria.

Mitochondria provide a eukaryote's ATP. Why shouldn't a eukaryote create its own ATP? Nick Lane thinks the reason is because genes have to be close to a cell membrane in order to make ATP. The square-cube law means that a cell's membrane grows slower than its volume. A big archaeon is limited in how much ATP it can create which limits how many genes it can have which limits its complexity.

Among the three domains of life, eukaryotes are the most complex. By offloading ATP production to mitochondria, they get around the square-cube law limiting ATP production. They can have more genes which enables more complexity.

Once you have eukaryotes, sex becomes very important. Nick Lane has a chapter on sex too. It's interesting and if it was written in any other book I'd say "this is top-tier science writing" but Nick Lane sets the bar of so impossibly high by proposing a fascinating new theory to one of the most important questions in all science that merely "top-tier science writing" is a step down. He gives a testable hypothesis about "what causes ageing" backed up by diagrams and evolutionary theory. For most science writers, that would be the entire book. To Nick Lane, it's ancillary.

The coolest thing about The Vital Question is it makes precise predictions about what life on other planets might look like. We may not ever get to test this theory ourselves but―perhaps―eons from now, some descent of humankind will stumble across infant alien life, load this book from its Most Ancient Archives and find out whether Nick Lane was right.

Credits

This post was funded by Less Wrong. Thank you!

Photos

  • The black smoker image from from NEPTUNE Canada. It is of the Juan de Fuca Rige.
  • The White smoker comes from the Center for Marine Environment Sciences, University of Bremen.

  1. A Na⁺/H⁺ antiporter is mechanically possible because H⁺ rarely exists in isolation. It binds to Hydrogen forming H₃O⁺ which has a radius similar to Na⁺. ↩︎

  2. Nick Lane does explain the reasons. I'm skipping them . ↩︎

  3. This is a physics joke. Entropy and energy always flow downhill. Life is the harnessing of energy flowing downhill. Life without energy flowing downhill is not alive. In the context of biophysics, saying Nick Lane's argument "goes downhill" means the argument flows logically from one idea to the next. ↩︎

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I'm glad you wrote this review, now I don't have to :-)

(I agree that it's an excellent book and heartily endorse it.)

Nick Lane thinks the reason is because genes have to be close to a cell membrane in order to make ATP. The square-cube law means that a cell's membrane grows slower than its volume. A big archaeon is limited in how much ATP it can create which limits how many genes it can have which limits its complexity.

Among the three domains of life, eukaryotes are the most complex. By offloading ATP production to mitochondria, they get around the square-cube law limiting ATP production. They can have more genes which enables more complexity.

The way I remember his argument is a bit different, and not involving the square-cube law: (1) if some little section of a membrane is producing ATP, it needs a nearby copy of all the genes for ATP production; (2) if there's a big complicated cell doing lots of stuff, it needs a lot of surface area for producing ATP; (3) It follows from (1) + (2) that if there's a big complicated cell doing lots of stuff, it needs a gazillion copies of its genome per cell; (4) if the genome is really huge, then it's prohibitively expensive to make a gazillion copies of it per cell; (5) therefore genomes can't be huge; (6) therefore cells can't be too complicated.

The reason eukaryotes avoid this dilemma is that they have two genomes. One genome is tiny, and has just the genes for ATP production, and there are gazillion copies of that genome per cell. The other genome is huge, with massive numbers of genes, but it's OK because there's only one copy of that genome per cell.

So the way I remember the story, it doesn't involve the square-cube law. Can't a bacteria increase the effective surface area by, say, putting ATP production machinery onto a vesicle? It's been a while since I read the book, I could be misremembering. :-)

I'm glad you didn't write this review, now I got to instead :-)

I could be wrong and I would like to be corrected if I am. From your writings and from having met you, I would not be surprised if you know far more biology than I do.

(3) It follows from (1) + (2) that if there's a big complicated cell doing lots of stuff, it needs a gazillion copies of its genome per cell;

Why can't bacterium/archaeon just have many copies of the same ATP gene on a single genome? Duplicating a DNA segment is not an uncommon mutation.

On the other hand, packaging ATP genes in mitochondria lets a cell create more or less of them on demand, something it can't do with a repeated sequence in DNA.

Can't a bacteria increase the effective surface area by, say, putting ATP production machinery onto a vesicle?

If I understand correctly, mitochondria use cristae for this purpose instead of vesicles. Cristae are what gives mitochondria membranes their characteristic shape.

I think the "nearby" part is important ... I thought his claim was basically that if I'm an ATP production machine, I need the genome to be really close to me distance-wise (like within X nanometers, for some number X that I don't know), so that if I have a broken part then a replacement can be quickly manufactured on demand in the right location. So having 100 copies of the gene that are physically attached to each other doesn't help at all towards solving the problem, and in fact makes the problem worse.

I really don't know much biology, I'm just going off my memory of the book :-)

He definitely did say something to that effect and it definitely is easier to have the genome near the cell wall of a small cell than a large cell.

You say "the genome" but note that one bacterium (i.e. one cell) can have more than one copy of its entire genome inside it, e.g. "many bacteria harbor multiple copies of their genome per cell", "Enormous bacterium uses thousands of genome copies to its advantage", etc. That's what I was (implicitly) referring to. :-)

I did not realize that. Whoops.

I was also halfway through a review of this book. Since I've only met one other person who'd read it I thought it was unlikely anyone else would! I guess LWers have more similar interests than I would have predicted.

I suppose I'll review another book instead!

I’d love to see two reviews of the book if you feel like it!

Me too. I'd hate to find out Jemist's work has gone to waste. A second review could add to what I have here. I skimmed at least half the book including sex, biochemistry and why eukaryotes appeared exactly once. I came to this book with my own perspective. Someone with a different perspective could draw different main ideas from it. Besides, I like the idea of more biological content on LW.

Thanks for this review. I particularly appreciated the explanation of why the transition from primordial soup to cell is hard to explain. Do you know how Lane's book has been received by other biochemists? 

Thanks.

Do you know how Lane's book has been received by other biochemists?

No idea.

There would be quite a long period of time between the initial formation of these micro-pore membranes and the point in time where they could form free floating cells. In that time, they would need to evolve all the machinery to exist unsupported: better membranes, RNA, maybe even DNA, and some method of generating their own proton gradient. And to evolve at all, they would need to reproduce.

The problem is that these creatures are stuck in their respective pores. In order to evolve beyond a stage where they could barely even be considered alive at all, these things would need a way of colonizing other pores. I'm not sure if Lane discusses the question at all, but it seems like a difficult problem. The process would initially have to be so simple it could happen naturally without any molecular machinery.

I am not any sort of chemist, let alone a biochemist, so this is all fanciful speculation.

I also haven't read the book, but I don't read the review as suggesting "creatures" at all. Just collections of compounds near membranes, in a positive feedback loop where the presence of those compounds makes it more likely that those compounds are produced from the other stuff in the environment.

In that sort of picture, it seems somewhat plausible that initially such feedback loops and diffusion could stand in for reproduction within the environment of a single smoker. Greater or lesser variations in the environment might provide selection effects toward robustness of feedback loops.

I can imagine some intermediate stage between free-floating chemicals near membranes and a fully formed cell: forming an extra membrane when conditions change in some direction, such as increased temperature. This could prevent diffusion and mixing of any more harmful environment with the mixture. When the conditions return to normal, the extra membrane dissolves and the chemicals start diffusing and catalysing their own production again.

Here's where the primordial soup theory becomes implausible. A primordial soup is at chemical equilibrium. A cell is at chemical disequilibrium. Could a primordial soup form a cell? Sure, in the same sense that all the atoms in my body could quantum teleport themselves to the Restaurant at the End of the Universe. "Things randomly happened to violate thermodynamics" is so statistically unlikely it should be the last resort we fall back upon after every conceivable hypotheses fails.

Not if we already believe the world is Big. (And indeed one conclusion we could draw from all this is that the world is probably Big.) In a big world -- say, one of infinite spatial or temporal extent -- everything that can happen does happen infinitely often, no matter how unlikely it is to happen in any particular place. Indeed, given that we don't see any aliens in the sky, there must be some sort of Great Filter, and so why don't we just conclude that this is probably it? Solve two mysteries at once! (why we don't see aliens & the Vital Question).

Relatedly, for a project I'm working on, it would be great to know precisely how unlikely it would be for a given puddle of primordial soup to spontaneously originate life in a given second. Are we talking 1/2^100, or 1/2^10000, or what?

One thing is: we're in a universe where there are in fact geochemical features that concentrate reactive precursors. For example, the white smokers (a.k.a. alkaline hydrothermal vents) discussed here are expected to exist on lots of planets (IIRC, at least according to Nick Lane—I think he said white smoker = water + olivine, and those are both super common on planets).

So, if geochemical features that concentrate reactive precursors do in fact exist all over the place, and if such features make it × more likely (or whatever) for life to arise, then the question of whether life could arise even in the absence of such features would appear to be an irrelevant question, right?

Anyway, if you want the emergence of life to be the great filter (as opposed to the emergence of eukaryotes, for example, which did in fact take longer on earth), you can still have that in an alkaline hydrothermal vent. For example, maybe it has to be just the right sub-sub-type of alkaline hydrothermal vent, a sub-sub-type which can only form on certain types of very young planets, or whatever. Or maybe you have to win the lottery with the reactive precursors coming together into just the right configuration (although I guess the speed that it happened on earth would vote against that one).

BTW the book has a good discussion of why the emergence of eukaryotes would be plausibly "hard"—like all the things that needed to go right in the first few generations after the merge. It seems to have happened only once in earth's history, despite there being a gazillion coexisting archaea and bacteria, all around the planet, all the time.

I'm confused by this - even if everything happens infinitely many times, there are still different sizes of infinity and we select the biggest as the most likely. How does a big world shift this perspective?

What do you mean by different sizes of infinity here? Your ultimate claim is that a hypothesis in which life appears on every 10^40th planet is more probable than a hypothesis in which life appears on every 10^400th planet, even if both hypotheses have infinitely many instances of life appearing. (Perhaps you are using SIA, instead of SSA? SIA rewards hypotheses that have larger population sizes.)

If this claim is true, wouldn't it also be true that a hypothesis in which life appears on every planet is more probable than a hypothesis in which life appears on every 10^40th planet? Shouldn't we be looking hard to find an explanation for why aliens might be hiding from us, since it's so improbable that aliens just don't exist?

I was speaking to the probability of life appearing in different parts of the (finite) ocean, so possibly I misunderstood what you were addressing. But since the reasoning should generalize:

I mean different sizes of infinity like these:

  • the set-of-all-sets is infinite, but the set-of-all-sets-including-that-set is one set larger, and so on
  • given an infinite length, 1/2 the length is still infinite, and so is 1/3 the length, but the 1/2 length is larger than the 1/3 length
  • an infinite tube of soap foam and an infinite rod of steel of the same diameter both contain infinitely many atoms, but there are more atoms in the steel, because it is much more dense
  • there are infinitely many numbers between 0 and 1. But there are twice as many numbers between 0 and 2.
  • More germane to the life example, if process 1 generates life at 1 per unit time, and process 2 generates life at 2 per unit time, as the arrow of time extends infinitely, both process 1 and 2 will generate life infinitely many times, but process 2 genesis is twice as large as process 1 genesis.

I'm not familiar enough with either SSA or SIA to apply them, and my grasp of anthropic reasoning is shaky in the extreme, but the idea of not rewarding population sizes baffles me. Do you have a preferred breakdown for this point I should check out, or will google serve me well enough?

If this claim is true, wouldn't it also be true that a hypothesis in which life appears on every planet is more probable than a hypothesis in which life appears on every 10^40th planet?

If planets and stars lasted infinitely long, and were sufficiently constrained in their composition, then I would say yes. But this chain of reasoning ignores the local information we have about the problem. Returning to the primordial soup quote you were responding to, the argument is that what we know of thermodynamics doesn't allow a causal mechanism to work. By contrast, the white-smoker vent hypothesis does allow a causal mechanism to work; therefore we should prefer it as the explanation for the origin of life (as we know it).

When I try running the intuition of your example of different frequencies of planetary genesis in reverse, and on primordial soup:

We should keep primordial soup on the table because a big world predicts this will still work an infinite number of times, then surely we must also keep a less-complex primordial soup (say, a primordial cocktail) on the table for the same reason; and then bare rock, with no soup at all; and then a complex cell springing into existence with no causal history; etc. This may be true, but doesn't really seem helpful in terms of what to expect.

An alternative framing: would it be fair to say that under a big world, every prediction happens an infinite number of times? If I accept that all infinities should be treated the same, that still leaves us with the ability to compare the number of infinities, which should lead us to favor the hypotheses according to how many predictions they allow us to make.

Regarding the appearance of aliens, have you checked out the grabby aliens post yet? I recommend it.

If density/population size is so important, you may not like the conclusions you end up with! In particular, you probably end up concluding that this whole world is a simulation run on a different substrate, and that different substrate is infinite in extent and also extremely densely packed with life. I think...

SSA vs. SIA: I don't have a favorite link, sorry. It's been a while since I thought about this stuff. I remember liking Katja Grace's posts on the subject, and Bostrom's Anthropic Bias. Plus googling and the philosophy literature should work pretty well. Also some Stuart Armstrong posts but that's more advanced.

Yeah, thinking about grabby aliens is the thing I need to know the probability number for. :)

Before seeing any evidence, we should indeed expect that life has high density in the universe. We just have enough data to rule that out. More generally I think UDASSA is probably the best framework for approaching problems like this, and it would hold that, in situations where our existence is contingent on an anthropically-selected unlikely event, we should still expect that this event is as likely as possible while being consistent with the evidence. So 10^-40 likelihood origination events more probably than 10^-400 likelihood events.

Also, primordial soups don't necessarily have to be in chemical equilibrium. If the soup is sitting in sunlight, then it could very easily be out of chemical equilibrium, and probably would be. (Soups could be out of equilibrium for a variety of other reasons too, like a consistent influx of chemicals coming out of the ground.) Sunlight comes from a surface with a temperature of 5700K. Compared to a puddle with a temperature of 300K sitting on the Earth's surface, those photons are absurdly energetic, and could easily bump up the prevalence of some molecules that would otherwise have too much free-energy to exist.

Once you have excess free energy, copying information becomes possible, and it becomes conceivable that you could have self-copying information, aka life.