A Biochemist’s View of Life’s Origin Reframes Cancer and Aging | Quanta Magazine

Your book argues that the flow of energy and matter structures the evolution of life and is how metabolism conjures genes into existence. What’s the most compelling reason to think metabolism, not genetic information, evolved first?

The purist view of “information first” is the RNA world, where some process in the environment makes nucleotides, and the nucleotides go through a process that makes them link up into polymer chains. Then we have a population of RNAs, and they invent everything, because they’re capable of both catalyzing reactions and copying themselves. But then how did the RNAs invent all of metabolism, cells, spatial structure and so on? Genes don’t actually do that even today. Cells come from cells, and genes go along for the ride. So why would genes do it at the very beginning?

And how would they do it? Let’s say there are 10 steps in a biochemical pathway, and any one step by itself is not of much use. Every product in a pathway would have to be useful for it to evolve, which is not the case. It just looks so difficult to evolve even a single pathway.

What’s the alternative?

The alternative is that these things happen spontaneously under favorable conditions, and that you get very small amounts of interconversion from one intermediate into the next intermediate all the way down that whole pathway. It wouldn’t be very much, and it wouldn’t be very fast compared to enzyme-catalyzed reactions, but it would be there. Then when a gene arises at some later stage, it can catalyze any of those steps, which will tend to speed up the whole pathway.

That makes the problem much easier. But it also makes this unnerving prediction that all of the chemistry in this pathway has to be favored. And then you say that for another pathway and another, and it becomes an increasingly scary proposition that the core of biochemistry just happens to be thermodynamically favored in the absence of genes.

Six or seven years ago, this was not a position easy to sustain, because there was no evidence for it, really. But since then, at least three or four of these pathways have been demonstrated to happen spontaneously and at low levels in the lab. Not all the pathways are complete, but intermediate steps occur. It begins to look as if it’s not an unreasonable position to say genes came into existence in a world where we already had some quite sophisticated proto-metabolism.

Let’s talk about how the proto-metabolism could have evolved in deep-sea hydrothermal vents. What is it about the vent environment that makes you think it favored the beginnings of what we call the Krebs cycle, the metabolic process that derives energy from carbohydrates, fats and proteins?

Let’s start with what life is starting with: hydrogen and carbon dioxide, which don’t react very easily. How does life make them react? As we see in mitochondria and in certain bacteria, life uses an electrical charge on the membrane to transfer electrons from hydrogen onto iron sulfur proteins like ferredoxin. These tiny clusters of iron ions and sulfur ions at the heart of ancient proteins are like little minerals. You get these minerals in hydrothermal vents, and you also get carbon dioxide and hydrogen, and there are even thin barriers in the porous rock with an electrical charge on them.

The question is: Does this structure at the vents effectively drive the reaction between carbon dioxide and hydrogen? And the answer we’re finding in the last year or two in the lab is yes, it really does. We don’t get a lot, but we’re getting more as we begin to optimize our process, and what we’re seeing produced is Krebs cycle intermediates. And if you put some nitrogen in, you get the same amino acids that life is using.

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