Earlier this week, a biochemist colleague asked me what I would tell students in a biochemistry course about the origin of life (OoL). My mind immediately leapt to specific topics that were salient to origin-of-life research for historical reasons: prebiotic syntheses of building blocks (sparked by the Miller spark-discharge experiments!), ribozyme discovery and manipulation for the RNA World, and my own current interest in proto-metabolism. I rambled some random thoughts, not particularly coherently, and not thinking about how I might relate this to what students are learning in our biochemistry lecture courses.
I’ve since had time to mull over making connections to what students might ponder when they’re taking biochemistry. What is biochemistry? It’s studying the molecules and processes of living systems. Structure and function are intertwined, although the chemist’s reductionist approach tends to impose causality from structure to function. This is useful when you are taking systems apart to study them, but risks throwing out the baby with the bathwater. I’d like students to recognize this conundrum, and remember that life is embedded in a complex system. Thus, the OoL question has to do with how such a system with its myriad inter-relationships could be established.
Experimentally, one can attempt to approach the line between life and death from opposite ends. In the top-down approach, assuming a single cell is the basic unit of life, one could strip out parts until the cell is no longer viable. The challenge is that there are many, many, many ways to kill the cell. And because life is a system, teasing out the ‘fundamental’ part on which everything else depends is nigh impossible because all the parts are interrelated. One might call this ‘irreducible complexity’ although I think the phrase has been hijacked by creationists to argue that evolution cannot lead to a living system. But if complexity is irreducible by definition, this allows us to distinguish the complex from the merely complicated, and free our minds to contemplate the paradoxical cyclical chicken-and-egg relationship of structure and function. As Wicken argues, “the whole is not exactly more than the sum of its parts, since parts are relationally constituted by the wholes in which they evolved…”
That being said, and because our students are required to take two semesters of organic chemistry as a prerequisite to biochemistry, I would want to highlight how O-Chem’s “functional group” thinking allows us to group parts together and see relationships among the parts. I tell students that the way to approach O-Chem (while it does require some memorization in the beginning to build up one’s experiential database) is to look for the patterns and groupings. Biochemically, a rough breakdown of the cell’s building block constituents are carbohydrates, proteins, lipids, nucleic acids, and a bunch of other molecules (co-factors and more), plus ions and water. Could these different molecular groups be synthesized under simpler ‘abiotic’ (or ‘prebiotic’) conditions starting from simpler molecules? The answer is yes, and this is where I would highlight the historical advances made by the prebiotic chemists working in this field – the bottom-up approach to OoL.
But extant living systems only utilize a narrow subset of these molecular groups, while prebiotic syntheses generate a great diversity. Hence a pruning process needs to take place, and the question becomes one of selection. Here is where I would bring up the idea of autocatalysis and how it plays into the growth and pruning of interconnected cycles of reactions. I would need to briefly discuss how a messy diverse milieu of inefficient catalysts would be expected to evolve into a smaller range of more efficient catalysts in such autocatalytic systems. This would also highlight how control and regulation come into play in a related way. One can argue that what drives this is thermodynamics due to the non-equilibrium situation of a potential energy gradient between the sun and the coldness of space, interposed by a suitable planet such as Earth. But I’d want to avoid too much speculation into why life has not arisen on other planets (that we know of) even though students find these ‘alien life’ questions very intriguing.
That’s a lot to squeeze into an hour if I did a class guest-lecture. I’ve left out many interesting stories. The top two on my list would be (1) the discovery and evolution of ribozymes (and the promise and problems of the RNA World theory), and (2) why carbon is uniquely suited as the skeleton for the molecules of life given the environmental conditions experienced by Planet Earth. Other interesting vignettes would be the role of encapsulation and the formation of simple vesicles, the question of homochirality, the iron-sulfur world theory and connections to hydrothermal vents, origins of the genetic code, and my own interests in proto-metabolism. Our first semester biochemistry lecture only covers a bit of metabolism, and much of the focus is on protein structure and enzymes. So I think discussing prebiotic syntheses followed by (auto)catalysis and its evolution fits well with what students would be seeing and thinking about in class.
A negative pessimistic view of biochemistry is that it takes the ‘life’ out of biology with its reductionist approach. I have a more optimistic vision – that reductionistic studies in biochemical systems can help us solve the mystery of the OoL, keeping in mind both its limitations but also using it as guide to how autocatalytic systems prune out the myriad mess of molecular cousins (generated in a bottom-up prebiotic chemical synthesis approach). And the boundary between the living and the non-living is fuzzy, as cryptobiosis bears witness. As someone who worked in heterogeneous (surface science) catalysis last century, I’ve imbibed the view that the edges are where all the interesting action happens. The origin of life is surely the ultimate edge question of what takes place at the edges of biology and chemistry and their increasingly large intersection!
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