Leslie Orgel: Metabolic Origin of Life “Unlikely”; Complexity Requires “A Skilled Synthetic Chemist”

Last year I blogged about Robert Shapiro’s excellent article in Scientific American that gave cogent critiques of many standard models of the chemical origin of life. Shapiro critiqued the view that a primordial soup existed on the early earth that ultimately gave birth to a self-replicating molecule, which eventually evolved into RNA and then DNA. After critiquing this standard model, Shapiro gave his alternative explanation, proposing that life evolved from metabolic pathways that naturally occurred on the early earth. As I wrote at that time , Shapiro “gives scant explanation for how these life-like metabolic networks can come into existence naturally, and he gives no details as to how these thermodynamic states produce real life—life as we know it today.”

Now Leslie Orgel, the eminent and late origin of life chemist has published (posthumously) a direct critique of Shapiro-like hypotheses which claim that life arose through metabolic pathways.

Orgel is no proponent of intelligent design. In fact, the purpose of his paper is to offer sage advice to those seeking to explain the origin of life via evolving metabolic pathways. As this 2-part blog series will show, Orgel clearly states that many new breakthroughs must be necessary before such origin of life theories are to be plausible.

Orgel recounts many obstacles to the spontaneous formation of metabolic pathways (also called “cycles”) on the early earth. He observes that such cycles “must be evaluated in terms of the efficiencies and specificities that would be required of its hypothetical catalysts in order for the cycle to persist.” In other words, Orgel inherently assumes there are irreducible thresholds of reactivity and numbers of catalysts that must be crossed in order for these metabolic pathways to exist.

But even according to Orgel, simply having such metabolic pathways is not enough, for “the identification of a cycle of plausible prebiotic reactions is a necessary but not a sufficient step toward the formulation of a plausible self-organizing prebiotic cycle. The next, and more difficult step, is justifying the exclusion of side reactions that would disrupt the cycle.” Again, Orgel essentially assumes that cyclic metabolic pathways are irreducibly complex systems that require a large number of parts in order to function—including parts that allow them to avoid many side pathways that will disrupt the cycle. In Orgel’s view, it is not plausible to contend that such complex systems, with all of their numerous required components, would simultaneously come into existence:

At the very least, six different catalytic activities would have been needed to complete the reverse citric acid cycle. It could be argued, but with questionable plausibility, that different sites on the primitive Earth offered an enormous combinatorial library of mineral assemblies, and that among them a collection of the six or more required catalysts could have coexisted.

(Leslie E. Orgel, ” The Implausibility of Metabolic Cycles on the Prebiotic Earth ,” PLOS Biology (January 2008, Volume 6(1):e18).)

Finally, Orgel observes that catalysts often react with more than one substrate, and that these enzymes would require sufficient specificity to be able to discriminate between different substrates so as not to react with the wrong component of the cycle. Orgel writes that such specificity is not produced naturally, and normally requires “a skilled synthetic chemist”: It is likely that such catalysts could be constructed by a skilled synthetic chemist, but questionable that they could be found among naturally occurring minerals or prebiotic organic molecules. … It is not completely impossible that sufficiently specific mineral catalysts exist for each of the reactions of the reverse citric acid cycle, but the chance of a full set of such catalysts occurring at a single locality on the primitive Earth in the absence of catalysts for disruptive side reactions seems remote in the extreme. Lack of specificity rather than inadequate efficiency may be the predominant barrier to the existence of complex autocatalytic cycles of almost any kind. So what is going on here? The multiple specificities required could be constructed by “a skilled synthetic chemist” but are highly unlikely to exist in nature. Just like the case of the ribosome, the evidence shows that the complexity of life requires an intelligent cause.

According to Orgel, metabolic pathways have little apparent reason to evolve into genetic molecules, because they “d[o] not seem capable of evolving in any interesting way without becoming more complex” and the proposed explanations fail to “explai[n] how a complex interconnected family of cycles capable of evolution could arise or why it should be stable.” The problems faced by evolving multiple metabolic pathways are the same as the problems faced by those trying to evolve a single metabolic pathway: Given the difficulty of finding an ensemble of catalysts that are sufficiently specific to enable the original cycle, it is hard to see how one could hope to find an ensemble capable of enabling two or more. Orgel goes on to explain that until there is empirical evidence that a family of metabolic cycles could evolve—systems that do not require highly specific or efficient catalysts—”acceptance of the possibility of complex nonenzymatic cyclic organizations that are capable of evolution can only be based on faith, a notoriously dangerous route to scientific progress.” He concludes his article with a call to provide more detail about how metabolic origins of life scenarios took place: 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 ability to create an information-carrying genetic molecule is not resolved According to Orgel, “solutions offered by supporters of geneticist or metabolist scenarios that are dependent on ‘if pigs could fly’ hypothetical chemistry are unlikely to help.”

At the beginning of this series I recounted that last year, Robert Shapiro, critiqued various origin of life scenarios, but proposed metabolic pathways as an alternative explanation of the source of life. Now the eminent origin of life theorist Leslie Orgel has posthumously shown that such explanations are presently found wanting. Different hypotheses are being tossed about by different scientists, but scientists are finding great deficiencies with each of these various hypotheses. In my view, perhaps the problem for all of these hypotheses is that life did not originate via blind chemical processes, because the language-based specified and complex information contained in DNA is precisely the type of code or language that, Stephen C. Meyer recognizes, “invariably originate[s] from an intelligent source, from a mind or personal agent.”

source 1, source 2