Robert Shapiro’s comments

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Based on my experience and background in nucleic acid chemistry, I am convinced that the spontaneous assembly of a functional nucleic acid on the prebiotic Earth would be, as Gerald Joyce and the late Leslie Orgel put it, a near miracle. Such apparent progress as has been claimed in that direction has been due to the direct intervention of the experimentalists. The separate disciplines of abiotic simulation (as practiced in the initial published Miller-Urey experiment) and total organic synthesis (as practiced by the Woodward group and many others) have been utterly confounded.

Because of this conceptual flaw, I would agree with your Question # 14. The origin-of-life field has not progressed in a conceptual point of view since the early experiments of Stanley Miller, though of course much has been learned about Earth history, evolution from the last common ancestor, and molecular biology in general.

From this point of view, Question # 6 ceases to be difficult. The arguments presented in the Premise provide part of the reasons why the prebiotic synthesis of RNA was immensly implausible. I would only disagree with the use of the phrase “bleak”. The established facts point the way to an alternative, satisfactory solution: RNA first appeared through natural selection in living organisms, as the result of an extensive series of events, each of which had its own justification.

The question then arises as to the manner in which life functioned, prior to the appearance of nucleic acids, large proteins and other information-rich macromolecules. The term “metabolism first” has been applied to theories in this area. A diverse group exists, which has been the subject of much discussion, but little experimentation. I have tried to provide a brief overview of this area in my attached article from the Quarterly Review of Biology. In response to your Question # 4, I believe that a cycle, rather than a sequence of reactions was established at the start of life. Further the direction and growth of this cycle was governed not by an array of sequential catalysts, but by its coupling it to an external reaction which permitted a favorable flow of free energy through the system.

The “metabolism-first” point of view, of course, impacts on several of your other questions (5, 8 and 12, for example) , but I have limited myself to three, as you suggested in your overall letter.

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