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Chemists Ponder the Origin of Life

The American Chemical Society recently dedicated a whole issue of Accounts of Chemical Research to the puzzle of life's chemical origins. The issue does a thorough job of bringing together some of the latest theories and research in the field, and several of the articles address fundamental problems in certain models of origin-of-life research. For example, a paper by Benner et al. points out that the RNA-world model is unattractive because the chemical bonds involved are unstable and the reaction requirements are too specific and unlikely for an early Earth environment.

Another article addresses a possible solution to nature's preference for left-handed amino acids and right-handed sugars (also known as homochirality).

A couple of papers try to explain why DNA is composed of the particular bases A, T, C, and G. Several others discuss self-replicating systems. Another paper discusses how proto-cells may have been formed from lipid micelles. And still others assume an "RNA-first" world, while a few prefer a "metabolism-first" world.

Indeed, this collection offers some of the latest research in the field. We will address a sampling of the research papers. If you want some background on origin-of-life research, see Casey Luskin's recent article "Top Five Problems with Current Origin-of-Life Theories."

Let's first address the editors' introduction, which makes use of some remarkably convoluted rhetoric.

The editors define chemical evolution as including "the capture, mutation, and propagation of molecular information and can be manifested as coordinated chemical networks that adapt to environmental change." In this type of system, one in which information-carrying molecules must be made and propagated, the editors concede that building life from the bottom up requires some aspect of molecular intelligence:

These diverse approaches to deconvolution and reintegration of the origins of the cell, projected in collaboration through the lens of chemical evolution, suggest a remarkable degree of intrinsic molecular intelligence that guide the bottom-up emergence of living matter.
The term "molecular intelligence" is not typically used in origin-of-life research, despite the authors' statement that it is not a new concept: in their view, Darwin's own theory of life beginning in a chemically rich "warm pond" is an example of molecular intelligence. While there are several ways to describe molecular behavior, from statistical mechanics to Brownian motion to self-assembly, making molecules the intelligent actor in the origin of life ascribes a property to molecules that we have yet to prove. They are information-carrying. They are self-replicating. But to say they have intelligence implies that molecules are capable assembling themselves into meaningful structures, something that usually requires knowledge of the end product. This is akin to saying a Lego model of the Millennium Falcon was built by the Legos themselves which (who?) are endowed with an intrinsic "construction intelligence." (Actually, this analogy would be more accurate if the Legos built a working model of the Millennium Falcon that can conduct self-repairs and can self-replicate.)

Let's try to unpack the final paragraph of the editors' introduction:

While our objective is to decipher the evolutionary rules that directed the transition from inanimate matter to life, we recognize that the march of molecular history likely had many pathways.
One of the fundamental research problems in chemical evolution is the transition from non-life to life. This requires more than having the component parts present. In order for this bottom-up, parts-to-whole approach to work, there is some threshold that must be crossed that sets in motion the operations of a cell (or a proto-cell) such that it has the characteristics of a self-sustaining, living organism. That threshold remains a mystery in chemical evolution research.
Accordingly, this issue circumscribes the functional concepts, leveraging Nature's platforms for molecular information, using its existing chemical inventory or libraries, and, with selective and judicious tinkering along the way, elaborates the basic rules of bottom-up self-assembly guided by both digital and analog molecular recognition systems.
This appears to mean that rather than re-inventing the wheel, so to speak, this issue of the journal will focus on deducing the rules for constructing an organism from the bottom-up. The authors will do this by using what we already know about DNA and RNA to construct system using known chemicals and enlisting the help of chemists to guide the reactions where they see fit to do so. But this calls into question just what is meant by "self"-assembly. In materials science, self-assembly is usually regarded as repeated, ordered patterns of specific molecules under the right environmental conditions. The setup for making even a simple self-assembled system (e.g. a self-assembled monolayer) requires quite a bit of forethought and planning on the part of the chemist.
In addition, the diversity in approaches to understanding and employing chemical evolution is as important as the diversity in chemical composition required to promulgate evolution itself and suggests that collaboration among these diverse approaches to gaining insights into chemical evolution and working toward the interfaces among them will be extraordinarily rich with opportunities.
In origin-of-life research, there are, broadly speaking, two camps: The RNA-first world, and the metabolism-first world. There are several nuances to each position, but for brevity's sake, we can think of the RNA-first camp as those who believe the first biomolecules were nucleotides (adenine, uracil, cytosine, and guanine), while the metabolism-first camp believes the first biomolecules were amino acids (e.g., glycine, alanine, thiamine). The RNA-first camp assumes that ribozymes were key players in the formation of the first genetic code. The metabolism-first camp relies on the self-assembly of biomolecules to form the first protein or the first metabolic pathway. (See here for more information on the RNA-world hypothesis.)

These are two fundamentally different approaches to the origin of life. Both have strengths and both have problems. The editors say that there were "multiple pathways" to the origin of life and so perhaps both are right. They assume that collaboration between the camps will lead to greater understanding, but this seems unjustifiably optimistic.

Proposing compromise may seem like a commendable thing -- it's generally a safe way of making yourself appear to be taking the moral high ground. But in this case, the respective approaches have completely different starting assumptions. Each begins with a different set of building blocks, not to mention a different synthetic process. It is also strange to assume that there were many paths to the origin of life yet that somehow these disparate paths came together to form early organisms. How, exactly? More on this later.