Literature

Gerald Joyce wrote of Leslie Orgel, the veteran origin-of-life researcher:

"Although Orgel was a theoretician, he always demanded that theory be subject to rigorous experimental validation. This, he felt, was especially true in the field of the origins of life, where "theories are a dime a dozen and facts are in short supply"."

"If pigs could fly" hypothetical chemistry is thriving in OOL research

These words are dramatically illustrated by Orgel's block-buster of a paper critiquing the metabolic cycle route for the origin of life (OOL), published posthumously in PLoS Biology. Metabolic cycles have been proposed as an alternative (or as a precursor) to the RNA World OOL scenarios. These cycles involve sustained chemical reactions to synthesise biologically interesting molecules. For example: "The proposal that the reverse citric acid cycle operated nonenzymatically on the primitive Earth has been a prominent feature of some scenarios for the origin of life." If advocates have the freedom to argue the case for viable prebiotic chemistry scenarios, there can be no complaint when critics point out their implausibility. Orgel wrote as someone starting out with an open mind and with a commitment to follow the evidence wherever it leads:

"If a complex system of evolvable nonenzymatic cycles that did not depend on residue-by-residue replication could be shown to be feasible, it would mark a breakthrough in origin-of-life studies. What is essential, therefore, is a reasonably detailed description, hopefully supported by experimental evidence, of how an evolvable family of cycles might operate. The scheme should not make unreasonable demands on the efficiency and specificity of the various external and internally generated catalysts that are supposed to be involved. Without such a description, 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."

Orgel set out to answer the question: "Could prebiotic molecules and catalysts plausibly have the attributes that must be assigned to them in order to make the self-organization of the cycles possible?" So thorough is the argumentation, it is difficult to provide a summary in a paragraph or two. The Conclusions section, however, highlights two points very nicely.

First, advocates of metabolic cycles need catalysts for their reactions, but they face the problem that familiar and relevant catalysts are enzymes, which are highly complex structures needing (at least) the RNA World as a prerequisite. So nonenzymatic catalysts have been explored. This is where Orgel puts his finger on the fundamental problem of specificity. Without this, there can be no cycles.

"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."

Second, there is an embedded tension in all the proposals of hypothetical metabolic cycles leading to replication.

"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."

Orgel's essay contains many other detailed critiques of metabolic cycle research, including numerous valuable comments on methodology (for more about this, go here). Clearly, he thought that there has not been enough testing of hypotheses by empirical work. This prompted his concluding remark:

"However, solutions offered by supporters of geneticist or metabolist scenarios that are dependent on "if pigs could fly" hypothetical chemistry are unlikely to help."

Orgel has bequeathed us a valuable legacy. His essay deserved respect. The main message concerns, not the various detailed critiques, but his commitment to "detailed examination and criticism", his call for claims to be supported "from experimental or theoretical chemistry", and his rejection of the argument that theories can be "justified by the inadequacy of competing theories". Although he was no ally of Intelligent Design, his arguments so closely parallel those of ID scientists that we have to regard his critique as a remarkable example of convergent evolution!

The Implausibility of Metabolic Cycles on the Prebiotic Earth
Leslie E. Orgel
Public Library of Science: Biology, 6(1): e18, Jan 22, 2008, doi:10.1371/journal.pbio.0060018.

First paragraph: Cycles occur widely in all branches of chemistry. The definition of a catalyst as an agent that facilitates the conversion of reactants to products without itself being changed almost guarantees that a catalyst can initiate successive "cycles" of the same reaction. Metabolic cycles are different. Strictly, they are by definition restricted to biochemistry. Like catalytic cycles, they too result in repeated conversions of substrates into products, but they involve much more complex sequences of chemical reactions. As far as I am aware, the formose reaction, which converts formaldehyde to a complicated mixture of products, including various sugars, is the only known nonenzymatic reaction sequence that is at all similar to a metabolic cycle, although the existence of one or two much simpler cycles has been established or made probable in the literature of prebiotic chemistry. The possibility that reactions of hydrogen cyanide (HCN) might form the basis for a complex cyclic organization has been proposed, but there is as yet no experimental evidence to support this proposal.

See also:

Coppedge, D.F. Leslie Orgel's Last Testament: Pigs Don't Fly, and Life Doesn't Just Happen, Creation-Evolution Headlines, 01/26/2008

Joyce, G.F. Obituary: Leslie Orgel (1927-2007), Nature 450, 627 (29 November 2007) | doi:10.1038/450627a