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origin-of-life
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The RNA world hypothesis, in which RNA both stored information and catalyzed reactions, is the leading framework. Prebiotic chemistry has made nucleotides under plausible early-Earth conditions. No one has yet made a self-sustaining, evolving system from simple starting materials, which is the clear verifier for this problem.
What would settle it
A self-replicating chemical system built from prebiotic starting materials