What do we know for certain? Scientists have learned that abundant organic molecules must have been synthesized, and must have accumulated, in a host of prebiotic environments. They have also demonstrated many processes by which biomolecular systems—including lipid membranes and genetic polymers—might have formed on mineral surfaces. As molecular complexity increased, it seems plausible that simple metabolic cycles of self-replicating molecules emerged, as did self-replicating genetic molecules.

So we’ve learned a lot, but what we know about the origin of life is dwarfed by what we don’t know. It’s as if we were trying to assemble a giant jigsaw puzzle. A few pieces clump together here and there, but most of the pieces are missing and we don’t even have the box to see what the complete picture is supposed to look like.

The greatest mystery of life’s origin lies in the unknown transition from a more-or-less static geochemical world with lots of interesting organic molecules to an evolving biochemical world in which collections of molecules self-replicate, compete, and thereby evolve. How that transition occurred seems to boil down to a choice among three possible scenarios.

1. Life began with metabolism, and genetic molecules were incorporated later: Following Günter Wächtershäuser’s hypothesis, life began autotrophically. Life’s first building blocks were the simplest of molecules, while minerals provided chemical energy. In this scenario, a

self-replicating chemical cycle akin to the reverse citric acid cycle became established on a mineral surface (perhaps coated with a protective lipid layer). All subsequent chemical complexities, including genetic mechanisms and encapsulation into a cell-like structure, emerged through natural selection, as variants of the cycle competed for resources and the system became more efficient and more complex. In this version, life first emerged as an evolving chemical coating on rocks.

The true test of this origin scenario rests on chemical synthesis experiments. Starting with simple molecules and common minerals subjected to plausible prebiotic conditions, researchers must discover a way to jump-start a self-replicating cycle of molecules that mimics the core citric acid metabolism of modern life-forms. We’re close, and several of the essential steps have been accomplished. A key missing experiment is the synthesis of 4-carbon oxaloacetate from 3-carbon pyruvate, perhaps using sulfur analogs in an environment rich in hydrogen sulfide. If that step can be demonstrated, and a self-sustaining cycle of reactions maintained, then metabolism-first will be the model to beat.

2. Life began with self-replicating genetic molecules, and metabolism was incorporated later: According to the RNA World hypothesis, life began heterotrophically and relied on an abundance of molecules already present in the environment. Organic molecules in the prebiotic soup, perhaps aided by clays or PAHs or some other template, self-organized into information-rich polymers. Eventually, one of these polymers (possibly surrounded by a lipid membrane) acquired the ability to self-replicate. All subsequent chemical complexities, including metabolic cycles, arose through natural selection, as variants of the genetic polymer became more efficient at self-replication. In this version, life first emerged as an evolving polymer with a functional genetic sequence.

This scenario, with its appealing reliance on the multiple ancient roles of RNA, lacks only the crucial support of an experiment that demonstrates the plausible prebiotic synthesis of a genetic polymer—RNA or its precursor. If an experiment successfully demonstrates the facile synthesis of such a polymer from prebiotic building blocks, then the biggest gap in our understanding of life’s origin will have been filled. In that case, many experts will conclude that the problem of life’s chemical origin has been solved.

3. Life began as a cooperative chemical phenomenon arising between metabolism and genetics: A third scenario rests on the possibility that neither protometabolic cycles (which lack the means of faithful self-replication) nor protogenetic molecules (which are not very stable and lack a reliable source of chemical energy) could have progressed far by themselves. If, however, a crudely self-replicating genetic molecule became attached to a crudely functioning surface-bound metabolic coating, then a kind of cooperative chemistry might have kicked in. The genetic molecule might have used chemical energy produced by metabolites to make copies of itself, while protecting itself by binding to the surface. Any subsequent variations of the genetic molecules that fortuitously offered protection for themselves or for the metabolites, or improved the chemical efficiency of the system, would have been preserved preferentially. Gradually, both the genetic and metabolic components would have become more efficient and more interdependent.

Such a “dual origins” model might at first seem to introduce a needless complication (not to mention sounding like a wishy-washy compromise). Nevertheless, exactly this kind of symbiotic coupling of metabolism and genetics is now thought to have occurred early in the history of cellular life. Crucial features of our own cells suggest an ancient cooperative merging of early, more primitive cells. If experiments establish easy synthetic pathways to both a simple metabolic cycle and to an RNA-like genetic polymer, then such a symbiosis may provide the most attractive origin scenario of all.

We don’t yet know the answer, but we’re poised to find out. Each day, new experiments expose more of the truth and winnow the possibilities. Each day, we get closer to understanding. And whatever the correct scenario, of one thing we can be sure: Ultimately, competition began to drive the emergence of ever more elaborate chemical cycles by the process of natural selection. Inexorably, life emerged, never to relinquish its foothold on Earth.

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