🎤 Eric Smith: Origins of Life

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Here’s my raw, copy-pasted outtakes from a segment of the conversation Eric Smith had with Jim Rutt on Jim’s podcast.

I felt it was extremely lucid - same as Jessica Flack’s appearance on the show. It put the book The Origin and Nature of Life on Earth (The Emergence of the Fourth Geosphere)

Everything below is direct quotes from Eric: my expertise in this subject is not deep enough to attempt a synthesis. If you’re missing context you can find the original here.


Phase transition are a big broad ranging idea of 20th century physics in science, even more than quantum mechanics and general relativity

In the events before you have something recognizable as fully integrated life, you have increasingly organized states of geochemistry.

Organized states of geochemistry are organized around paths of least resistance.

What we want in understanding the origin of life is how those paths of least resistance sort of set a template for biochemistry and then that template was strong enough and simple enough that it allowed control structures, like genes and the central dogma to come into existence

We should view the biosphere the same way we view any of the other geo spheres. It’s a new state of matter. It’s dynamically defined. The rules in it are different and distinctive from those of the atmosphere or the hydrosphere or the lithosphere.

The biosphere is more tied together by the integration of its processes than the exchanges that it makes with any of the other components of the planet

Subsurface water alteration zones are a very, very good place to do planetary chemistry. In fact, since life is driven by  electron transfer under sort of voltage differences, it’s very difficult to find any other place within the planet, where you have so many conditions that are good for providing those electron transfer potentials and also, the catalytic environments to make use of them.

A planet like the Earth is a battery. All of the materials from which it formed, the iron and the hydrogen of the early stellar atmosphere, those are very electron donating materials, but once you separate into an atmosphere and ocean and a rocky bulk, the water tends to "boil off" the top of the atmosphere.

That’s not quite the right way to say it. The right way to say it is that the ultraviolet and the x-rays from the Sun split the water and the hydrogen escapes, leaving oxygen behind. That drives the atmosphere away from electrical equilibrium with the deep bulk and you start to get an electron transfer out of the bulk into the atmosphere from which the electrons are then transported off the top as we lose our ocean to stellar breakdown.

There’s a net electron flow in this battery out of the deep bulk into the atmosphere and then, out into space. If you look at where that electron flow occurs, it dominantly occurs at the spreading centers that are underneath the ocean basins at this time. This is where new crust is being formed from rock that came out of the bulk and was not recently in contact with the oxidizing atmosphere.

The important thing about low energy chemistry is that if you don’t have catalysts, nothing happens at all.

If we’re looking for an [[origin of life]] at rock water interfaces, where new crust is formed, we really need to understand the catalytic environment to be able to predict anything at all.

Cellular Respiration: Everything in biochemistry that’s formed comes through a small system of only 11 organic acids. The biggest of them only has six carbon atoms. This is called the citric acid cycle.

On Earth today, the citric acid cycle exists as a carbon fixation cycle, but even in the organisms that don’t use it to fix carbon, it still is the starting point to synthesize everything. If you were looking for a foundation for all of biochemistry, I think there’s no better evidence of a place to look than the evidence in modern biology for the citric acid cycle.

It’s really funny, if you want to ask, “In all of this big planet, is there one molecule that is the center of metabolism and the center of carbon fixation?” It’s acedic acid, it’s vinegar. That is the central molecule for the deepest part of the biosphere. I think it’s really fascinating is that I’ve been looking more recently at the organization and the amino acids sort of continuing our interest in the genetic code.

You could say, “Okay, if acetic acid is the core molecule for fixing carbon and the start of biochemistry, is there a central molecule for the beginning of everything complicated?” The answer to that looks like yes too. That central molecule is pyruvic acid. Biology is full of these little core linchpins. We look at these as the circumstantial evidence for where to put the search light to do small molecule chemistry.

Biochemistry is full of autocatalytic cycles and those are the things that allow biochemistry to remain integrated and purified in an environment, where things are constantly falling apart.

The difference between Stu’s (Steward Kaufmann) approach and ours is that Stu starts from a very unstructured flat kind of a combinatorial medium. It can be boolean networks. It can be abstracted models for gene regulatory networks. He wants the laws of large numbers to give him feedbacks in those large networks. That can be a good thing to do if you’re looking at for instance gene regulation.

If we look at biochemistry, the important thing about biochemistry that’s new in science is that chemistry itself is a very structured medium.

In physics, we have only understood collective and cooperative effects and phase transitions in systems that have a lot of symmetry.

When you get down into the dynamics of chemistry, you have systems that have a lot of structure. The leading edge is going to be to understand what collective and cooperative effects look like and how one searches for the natural feedbacks in autocatalysis in a highly structured system like organic chemistry.

In thermodynamics, energy is one of the quantities that tells you how much of your state space is available to you. Other quantities are what are you made of, how much of each chemical do you have, how much of each element, but also volume, are you partitioned, how much space can you take up?

In equilibrium, the internal energy you have in your system is essentially set. The volume you have, your material composition is set. The part of your state space you can explore is fixed.

Energy flow in the Prigogine sense remains important because the more information you provide about the boundary conditions, the less freedom your system has to explore, another way to say that is that the more ordered the system can be. A driven system always has more information in the boundary conditions than one that’s not driven because if I’m at equilibrium, all of my energetic boundaries have to be in equilibrium with each other.

I can go away from equilibrium in many ways. It’s kind of like Tolstoy, all equilibrium systems are more or less alike. Every disequilibrium system is disequilibrium in its own fashion.

“The flow of energy through a system tends to organize the system.” - Harold Morowitz

What’s the state of origin of life research right now? It’s a bunch of little islands, where we have repositories of information and about those, we can hope to say a lot. Then, there are these big areas, where you don’t even hear good ideas being floated. I mentioned the core biochemistry, the carbon fixation pathways, the chemistry surrounding the citric acid cycle, the reactions that tend to get used and how they’re used.

We have lots of recorded information there and probably, it’s not even recorded. Probably, this is actually an extension of the periodic table that is being expressed by the rigidity of our biosphere. You go up a level and look at the ribosome and all of a sudden, you have an extraordinary repository of history about RNA and early peptides and the emergence of translation.

We don’t know what process that history froze into place and yet, we know an amazing amount about what it froze into place. We’ve been given the answer to a final exam, but we don’t know what the questions on that exam were. That’s another place, where we have a streetlamp giving us tremendous light. A place where these two intersect is the genetic code.

Traditionally, the genetic code has been viewed as a problem of assignment or shuffling, where people take the amino acids as somehow given and they take RNA and the translation system as somehow given. Then, they look for how many ways you could assign amino acids to codons in the translation system. Eric: I think that’s a wrong view. I think it’s not nearly dynamic enough because I don’t think the amino acids were given. I think the process of becoming biotic was integrated with the process of becoming energetically active and discovering how to fold.

I think that when we understand the origin of the translation system in the genetic code, we’re going to realize that regularities of deep biochemistry, fundamental physical regularities of the problem of folding and how easy or hard that problem was different for peptides than for RNA kind of bootstrapped themselves up. What we see recorded in the genetic code is the way each system got as far as it could and then, hit a wall and a discovery in one of the other systems that right now looks like it’s a different system opened a door for the next innovations. They jointly went through that door. I think we have these little islands that have information, but where our own disciplinary boundaries have kept us from seeing what that information is about.

Simon has a set of classic arguments about the architecture of complex systems, where he says, “Kind of like politics, all error correction is local.” That’s not an incidental actually. This is true for any distributed system and this is where decentralized banking came from in England. If you have a complex control problem, the higher order systems that are your controllers are often made by assembling building blocks at a smaller scale, but that means that they’re coarser and the information bandwidth through the interfaces is too small to keep up with all the things that can go wrong internally to the building blocks.

Herb Simon used to argue that if you see a complex system in the world, the only plausible mechanism to have created that system is one that has integral error correction in the subsystems along the way that creates sort of stable intermediate states of assembly, which then provide platforms to explore from for later assembly. Eric: Herb Simon uses the analogy of watch assembly. You don’t put a thousand pieces in a watch together, holding them all in place and then, put a screw on the top. Instead, you assemble components of 10, put each on the shelf. You put 10 of those together to make assemblies of 100. Put them on the shelf. Put 10 of those together and that’s your assembled watch. If you were never interrupted, it wouldn’t matter that you do those things, but in a world where you really are interrupted, it does matter.

He used also the example of the Alexandrian Empire, where Alexander’s Empire was only possible in a relatively sophisticated state system, where the states could be left to manage their own internal affairs. In looking at the origin of life, we are looking for where in chemistry the [inaudible 00:35:35] of least resistance tend to regress toward their own central tendencies, so that your control systems don’t have to constantly herd them back in those directions. The control systems can provide low bandwidth signals to sort of make the major switches between the stable or metastable domains of the traction.

Catalysis by proteins is obtained by first making a fold architecture and then, putting the side chains of a bunch of amino acids in very particular configuration. That’s a hard thing to do because you don’t get catalysis until you have a lot of supporting machinery. If you want to understand how you could ever have had the catalysis the proteins enable, you would first say, “Is there any catalysis by small molecules that’s doing much of the job within a small assembly that doesn’t require this sequence coordination to happen?” The fascinating thing is that if you look at the reactions that involve RNA and DNA, they often involve what’s called substrate assisted catalysis. What that means from the technical side is that the RNA molecule or the DNA molecule itself is defining most of the catalytic contexts. The surrounding catalysts only needs to kind of orient the components. It doesn’t usually need to have its fingers in the transition state of the reaction, which means that a much simpler surrounding environment can be catalytic for those kinds of reactions. Eric: It’s fascinating that RNA and DNA would be the place, where those substrate assisted catalytic processes are most common because those are exactly the sorts of chemistry that would need to have been in place to enable the memory systems to get more complicated protein catalysis.

Jim: Very good. What do you see as right on the frontier that we need to learn next in the origin of life? Eric: We need to learn how to explore chemistry. Jim: Could you unpack that a little bit? Eric: Yeah, chemistry is a combinatorial system that is so big that we don’t know most of what’s in it. We don’t know what happens. We don’t have a system for searching systematically and as a consequence, we don’t have the ability to reason about it the way we reason about any mature science, which is in most mature sciences, we start with a hypothesis. We get up to a point, where we get stuck and then, we have the ability to figure out what we don’t know and to backtrack to the last place where we needed something and take a different path. In spaces that are so big, we don’t know how to search them. What we do instead is we sort of ad-hoc based on the expertise that any given person or community has, we explore some region. Then, if it doesn’t have what we want, we just kind of go back to exploring, so we’re taking potshots. This is not to denigrate people’s expertise. The expertise of chemists is everything we have to go from and it’s extraordinary what they know and how they can reason. The space of everything dynamical that can happen in chemistry is so much bigger than anything we have understood before in science that it just requires new methods that have not existed before and need to be created.