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The Curious Wavefunction

The Curious Wavefunction

Musings on chemistry and the history and philosophy of science

Why chemists should study the origin of life

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A white smoker hydrothermal vent, a potential origin-of-life location that teems with interesting chemical questions (Image: Wikipedia Commons)

Physicists have their Big Bang, biologists have evolution by natural selection… and chemists have the origin of life. The question of life’s primordial beginnings – one of those existential questions that humans have pondered since antiquity – belongs squarely in the domain of chemistry. The origin of life is chemists’ “big idea”, a platter of interdisciplinary treats that addresses both important chemical conundrums as well as philosophical profundities. Darwin answered the question, “How did life get underway?” and left the possibly thornier question “How did life begin?” for chemists to answer.

But from a professional standpoint chemists could well ask what’s in it for them. Most academic chemists don’t study a problem because it’s of overwhelming philosophical significance. Most chemists, just like scientists in other fields, study something because they find it interesting. They study it because it promises to enrich basic knowledge of their field. Seen this way, it’s pertinent to ask why professional chemists should study the origin of life (OOL)?

Here are a few potential benefits:

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 known for decades, but it was only recently that the concrete connection to OOL was made. In fact unlike what we knew fifty years ago, we now have a good idea of the kinds of chemical reactions that could have formed life’s basic components. The main challenge is in simulating these reactions in a test tube and using them to guide the construction of a self-reproducing system that promises to yield itself to natural selection. 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 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 from the vast OOL domain 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.

Life is built from a handful of molecular components – for instance the four bases that make up DNA’s elegant rungs – that seem to be invariant across every known species and organism. There are some variations for sure, but the basic plan is pretty much constant as it should be based on what we know about evolution and common descent.

Questions pertaining to the nature of these building blocks can run very deep. For instance, why are the pKa values of amino acids what they are? What would happen if they were different? Or another famous question; why did nature choose phosphates (found in DNA and ATP, the energy currency of the cell), 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 (rather than beta amino acids)? Why ribose and deoxyribose? 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 calculations. This leads us from not knowing anything to fine-tuning our understanding and knowing something. As an ancillary benefit, this information can lead us to well-informed criticism in the face of fanciful and unrealistic speculation.

These basic questions about molecular origins are similar to questions of fine-tuning asked by physicists: Why do Planck’s constant and the speed of light have their specific values and not others? Why is the strength of the strong force what it is? We know (or at least we think) that life would not have existed if there were even a slight variation in the value of these fundamental constants. Does a similar scenario exist for the fundamental building blocks of chemistry? How much variation do they allow? The great advantage of chemistry over physics however is that through its creative and synthetic capabilities it can actually vary the fundamental properties of life's molecules and ask what the consequences should be. The culmination of this capability is the exciting science of synthetic biology whose practitioners are already investigating the effects of expanded genetic codes and non-standard amino acids on biological function. This is unlike the fictitious discipline of "synthetic astronomy" where it's not really possible to explore the effects of varying the gravitational constant on the evolution of the universe.

3. OOL forces us to understand self-assembly.

From a practical standpoint this may be the greatest benefit of OOL research. Self-assembly is the process by which molecules come together and form supramolecular systems which demonstrate interesting and often emergent structures and properties that are not evident from those of the original building blocks. Self-assembly is 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 architectures for solar energy research. The workhorse in self-assembly is our cherished friend the hydrogen bond, a remarkably pliable type of chemical interaction that allows biological molecules like proteins to fold, unfold, wiggle and stretch, grasp and release demand. Hydrogen bonding is the molecular glue that holds the components of life together. 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 have 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 novel materials like thermostable proteins, new eco-friendly catalysts and responsive polymers. 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 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.

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 time. 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” that tosses out fundamental questions for us to discuss, debate and research. OOL like few other conundrums in science promises an infinity of riches.

What more could we want?

This is an updated and revised version of a post published on The Curious Wavefunction.

The views expressed are those of the author and are not necessarily those of Scientific American.

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