Re: Autocatalytic sets: less worse than RNA World?

On 12/01/2025 7:36 pm, MarkE wrote:
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Jack Szostak thinks not...
Suzan Mazur: When we met at the Simons Foundation in April, you told me you “don’t believe” in autocatalytic sets. Why is that? Haven’t the Europeans integrated autocatalytic subsystems into their systems science?
Jack Szostak: Autocatalytic sets is one of those concepts where the people who came up with the original idea, like Stuart Kauffman, rather than admit being wrong, kept changing their story until it was basically the same concept everybody was already working on.
The original idea was that there would be large numbers of compounds where one would help another to replicate, and that one would help some other one to replicate, and that somehow, out of this huge population of interacting molecules, autocatalytic replication would emerge.
In my opinion, that was never chemically realistic. Now you see people talking about non-enzymatic RNA replication and calling that “autocatalytic sets.” If that’s what you want to call it, that’s fine. But it seems like the concept has lost all meaning.”
Mazur, Suzan. The Origin of Life Circus: A How To Make Life Extravaganza (pp. 57-58). Kindle Edition.
Or...
Nick Hud: I also have a problem with autocatalytic cycles -- with the chemistry, the utility and the wide range of what people are talking about. There is a long history of people proposing autocatalytic cycles and thinking that such cycles are central to starting life, but then not getting much to work in the lab.
I am a great fan of the idea of cycles, but I mostly think of cycles that are driven externally, such as day-night cycles that are driving chemicals between different states. To me, that seems a lot more reasonable as the type of cycle that could get life started.
When it comes to an autocatalytic cycle where you just put the molecules into a solution and they replicate, they have to be very specialized molecules. Only certain ones will do, and a lot of engineering goes into making these.
Whereas, we have already demonstrated that you can take some very simple molecules and subject them to wet-dry cycles, and you can make polymers. These polymers break apart and they reform. Those are the type of reactions that I think you need to get life going. You can call that a cycle -- a cycle of making and breaking bonds. But you don’t need very special molecules, aside from the fact that they’re stable and they have certain reactive groups that react together at mild enough temperatures.
Mazur, Suzan. The Origin of Life Circus: A How To Make Life Extravaganza (pp. 89-90). Kindle Edition.
One more...
Suzan Mazur: Is autocatalytic sets a somewhat marginalized approach at this point in protocell development?
Matt Powner: I don’t think the idea of autocatalytic sets has been marginalized, but I don’t know if it’s necessary. My understanding of the concept is that autocatalytic sets can in essence themselves evolve purely through change in chemical composition. I’m not sure that’s been demonstrated in a relevant system that doesn’t rapidly degenerate, and I’m not sure that’s the essential step to building what we know as a modern cell. However, if we actually found that autocatalytic
Mazur, Suzan. The Origin of Life Circus: A How To Make Life Extravaganza (p. 242). Kindle Edition.