About the author

Dan Rhoads

Dan is a postdoc working at the University of Cyprus in developmental biology. He has a BSc in molecular biology and a PhD pharmacology and biochemistry.

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One of the several popular views regarding the origin of life stems from thermodynamics. Harold Morowitz refers to it as “Metabolism recapitulates biogenesis”.

In PLoS Biology there’s an interesting essay that was submitted posthumously by the chemist Leslie Orgel on this subject – The Implausibility of Metabolic Cycles on the Prebiotic Earth. Orgel takes a hearty dose of skepticism to contemporary hypotheses presented by W?¤chtersh?¤user and Morowitz^3,4, including the reverse citric acid cycle in particular. For clarification: the reverse citric acid cycle has been proposed to have operated nonenzymatically, not only fixing carbon but (in a chaotic soup-like mixture of inorganic catalysts) also producing metabolic intermediates for many of the amino acids, nucleotides, etc., required for the later RNA world.

The core of this and related metabolic explanations for biogenesis, is that life can presumably be reduced to two minimal properties: reductive fixation of energy, and reproductive or catalytic cycles. These may have begun near natural sources of reductive chemistry, adjacent to or within aqueous compartments (primitive membranes). While the logic is sound, Orgel notes that “It must be recognized that assessment of the feasibility of any particular proposed prebiotic cycle must depend on arguments about chemical plausibility, rather than on a decision about logical possibility.”

So Orgel called for the demonstration of the existence of a complex, nonenzymatic metabolic cycle, such as the reverse citric acid. That would put the logic of metabolism-first over the top of genes-first theories of biogenesis, which have received more experimental support, even if they remain noticeably incomplete.

I’m thoroughly sold on the logic of metabolism-first, but Orgel’s criticism of it is dead-on. No theory can be bought into so readily without experimental testing (falsificationism). And that just hasn’t been done. The experimental schemes to do so, however, will take decades at least. His closing paragraph says it so well, and with a hint of humor:

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.

1. Morowitz HJ (1992), Beginnings of Cellular Life: Metabolism Recapitulates Biogenesis, Yale University Press. isbn:0300102100
2. Orgel LE (2008) The Implausibility of Metabolic Cycles on the Prebiotic Earth, PLoS Biology. doi:10.1371/journal.pbio.0060018
3. W?¤chtersh?¤user G (1988) Before enzymes and templates: theory of surface metabolism. Microbiol Rev 52: 452–484. pubmed:3070320
4. Morowitz HJ, Kostelnik JD, Yang J, Cody GD (2000) The origin of intermediary metabolism. Proc Natl Acad Sci USA 97: 7704–7708. pubmed:10859347