Field of Science

Why should chemists study the origin of life?

In the past we have alluded to the fact that the origin of life (OOL) is a quintessentially chemical problem. But from a professional standpoint, what's in it for chemists and why should they care? Some thoughts:

1. OOL is the ultimate interdisciplinary playing field: No matter what kind of chemist you are, OOL provides an opportunity for you to flex your intellectual muscles. Organic chemists can of course contribute directly to OOL research by speculating on and studying the kinds of reactions that would have been important in molecular origins. Some reactions such as the Strecker reaction (for amino acid synthesis) and the formose reaction (for carbohydrate synthesis) have already been proposed as the frontrunners for the genesis of life's molecules. Both reactions have been around for decades, but it was only recently that the concrete connection to OOL was made. What other reactions in the organic chemist's bag of tricks are applicable to OOL? The question should tickle organic chemists' brain cells like no other.

Other kinds of chemists also have a lot of potential contributions to make. The connection to biochemistry is obvious; for instance, how did the crucial watershed event of membrane formation come about and how did the earliest enzymes form? Inorganic chemists have made new inroads into OOL research, especially through pioneering research implicating metal sulfides in deep sea hydrothermal vents as precursors to organic life and inorganic surfaces (such as clays) as templates for primitive evolution and polymerization. Analytical chemists can bring their impressive phalanx of instrumentation like mass spectrometry and chromatography to bear on the problem. And theoretical and computational chemists can contribute to OOL by performing calculations on the forces operating in the processes of self-assembly that must have been key during the early moments of molecular organization. Of course, none of these areas is insular and every problem stated above demands the attention of every conceivable kind of chemist. Thus, there is a slice of pie in OOL for every chemist who dares to dream and the field guarantees an unlimited number of interdisciplinary collaborations.

2. OOL is a proving ground for basic chemical concepts: Just like organic synthesis is supposed to provide the ultimate training laboratory for fundamentals like spectroscopy, mechanism, and physical organic chemistry, OOL provides an opportunity to review and probe every basic chemical concept we can imagine in every chemical field. For instance, why are the pKa values of amino acids what they are? What would happen if they are different? Or the famous question; why did nature choose phosphates, a question which leads us to basic discussions of nucleophilicity, pKa, steric effects, thermodynamics, kinetics, atomic sizes and myriad other fundamental concepts. Other questions may include: Why alpha amino acids? Why ribose? Why these twenty amino acids and not others? We will never know the ultimate answers to these questions (since there was a fair element of chance involved), but simply asking them forces us to re-evaluate fundamental concepts of chemistry, an exercise that can be enormously rewarding and informative. OOL has involved fundamental research on chirality, self-assembly (more on this in the next point) and free energy calculation. This leads us from not knowing anything to fine-tuning our understanding and knowing something. As a side-benefit, then when there are some fanciful-sounding announcements, we can count on this knowledge to provide answers and level informed criticism.

3. OOL forces us to understand self-assembly: From a practical standpoint this may be the greatest benefit of OOL research. Self-assembly is undoubtedly the single-most important process in life's beginnings, and it also turns out to be of paramount importance in understanding everything else, from how Alzheimer's disease proteins fold to how surfactants sequester dirt to how we can construct supramolecular architectures for solar energy research. The workhorse in self-assembly is our cherished friend the hydrogen bond. Understanding the hydrogen bond thus opens the door to understanding self-assembly. In the past few years we have gained extremely valuable insights into hydrogen bonding, partly obtained through OOL research. For instance, studies of hydrogen bonding in DNA base pairing has revealed the subtle interplay between thermodynamics and electrostatics that stabilizes nucleic acids. Similar effects naturally operate in protein folding. The knowledge gained from such studies can help in the design of everything from novel proteins to supramolecular arrays. The same kind of self-assembly leads to insights into OOL questions addressing fundamental issues such as the formation of the first cell. The practical applications of self-assembly and OOL are thus two ends of a cycle which feed into each other, contributing and utilizing important insights that would fuel both basic and applied research. Understand self-assembly and you will not only inch closer to understanding origins but will also be able to harvest knowledge from the field toward practical ends.

4. OOL is the ultimate open-ended problem: Technically most problems in science are open-ended, but OOL is literally a problem without end. There is no conceivable way in which we will hit on the single, unique solution that jump-started life at a molecular level. We can inch tantalizingly closer to the plausible, but there is still a gigantic leap between the plausible and the certain. Should we despair? Absolutely not. If science can be defined as the "endless frontier", then OOL is the poster child for this definition. OOL will promise us an unending string of questions and plausible explanations until the end of the human species. This will bring us a proliferation of riches in basic chemical understanding. As scientists in general and chemists in particular, we should be ecstatic that OOL has given us a perpetual question machine to do research, discuss, debate and do more research. OOL like few other questions in science promises an infinitude of moments for reveling in the pleasure of finding things out.

And ultimately of course, OOL will help us take one more modest step in answering the question which human beings have asked since eternity- "Where do we come from?"

What more could we want?

6 comments:

  1. OoL is one of the (few?) problems in chemistry that can compete with cool problems in other scientific disciplines for the capitivation/imagination of the general public.

    The greatest factors holding back the growth of OoL chemistry are the lack of constraints applied to the field and the machismo of "hardcore" chemists who believe progress is measured by how far one drills into the ground, even if the water coming out has long since slowed to a trickle.

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  2. Allow me to amend that from "the greatest factors" to "two signficant factors"

    No need for untenable hyperbole this early on a Monday morning.

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  3. Indeed! Selling OOL as a chemical problem which is cool as the origin of the universe problem in cosmology will be exciting and challenging. We need to find ways to convince the public that the problem really belongs to chemistry and not to biology as most believe.

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  4. Yes, by the time you get to stuff that resembles biology, the OoL "problem" has long since been solved. OoL is a *chemical* problem.

    While I think "RNA/DNA-first" work is interesting with respect to OoL chemistry, my interest in the problem lies much earlier in the game. DNA and RNA would have encountered massive problems with hydrolysis, unless early life had developed some way to protect these compounds.

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  5. True. There are three avenues of research that I personally find most exciting; one is the clay-based OOL research pioneered by A G Graham Cairns-Smith and others, the second one is the whole hydrothermal vent OOL debate and then there's Jack Szostak's very interesting work on vesicles and membranes (which partly addresses the nucleic acid instability problem you were referring to). He has written a very nice review on this in a recent Annual Reviews issue.

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