Citation: Orgel LE (2008) The Implausibility of Metabolic Cycles on the Prebiotic Earth. PLoS Biol 6(1): e18 doi:10.1371/journal.pbio.0060018

Published: January 22, 2008


The demonstration of the existence of a complex, nonenzymatic metabolic cycle, such as the reverse citric acid, would be a major step in research on the origin of life, while demonstration of an evolving family of such cycles would transform the subject. In view of the importance of the topic, it is essential to subject metabolist proposals to the same kind of detailed examination and criticism that has rightly been applied to genetic theories. In the case of these latter theories, an appraisal of their plausibility can be based on a substantial body of experimental work. In the case of the former, because little experimental work has been attempted, appraisal must be based on chemical plausibility.

Almost all proposals of hypothetical metabolic cycles have recognized that each of the steps involved must occur rapidly enough for the cycle to be useful in the time available for its operation. It is always assumed that this condition is met, but in no case have persuasive supporting arguments been presented. Why should one believe that an ensemble of minerals that are capable of catalyzing each of the many steps of the reverse citric acid cycle was present anywhere on the primitive Earth, or that the cycle mysteriously organized itself topographically on a metal sulfide surface? The lack of a supporting background in chemistry is even more evident in proposals that metabolic cycles can evolve to “life-like” complexity. The most serious challenge to proponents of metabolic cycle theories-the problems presented by the lack of specificity of most nonenzymatic catalysts-has, in general, not been appreciated. If it has, it has been ignored. Theories of the origin of life based on metabolic cycles cannot be justified by the inadequacy of competing theories: they must stand on their own…

The prebiotic syntheses that have been investigated experimentally almost always lead to the formation of complex mixtures. Proposed polymer replication schemes are unlikely to succeed except with reasonably pure input monomers. No solution of the origin-of-life problem will be possible until the gap between the two kinds of chemistry is closed. Simplification of product mixtures through the self-organization of organic reaction sequences, whether cyclic or not, would help enormously, as would the discovery of very simple replicating polymers. However, solutions offered by supporters of geneticist or metabolist scenarios that are dependent on “if pigs could fly” hypothetical chemistry are unlikely to help.

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