We’ll never know how we began

[This is the pre-edited text of my Crucible column for the November issue of Chemistry World.]

Oddly, it is easier to explore the origin of the universe than the origin of life on Earth. ‘Easier’ is a relative term here, because the construction of the Large Hardon Collider at CERN in Geneva makes clear the increasing extravagance needed to push back the curtain ever closer to the singularity of the Big Bang. But we can now reconstruct the origin of our universe from about 10**-30 of a second onwards, and the LHC may take us back into the primordial quark-gluon plasma and the symmetry-breaking transition of the Higgs field that created particle masses.

Yet all this is possible precisely because there is so little room for contingency in the first instants of the Big Bang. The further back we go, the less variation we are likely to find between our universe and another one hypothetically sprung from a cosmic singularity – most of what happened then is constrained by physics. So while the LHC might produce some surprises, it could instead simply confirm what we expected.

The origin of life is totally different. There isn’t really any theory that can tell us about it. It might have happened in many different ways, depending on circumstances of which we know rather little. In this sense, it is a genuinely historical event, immune to first-principles deduction in the same way as are the shapes of the early continents or the events of the Hundred Years War. What we know about the former is largely a matter of extrapolating backwards from the present-day situation, and then searching for geological confirmation. We can do the same for the history of life, constructing phylogenetic trees from comparisons of extant organisms and supplementing that with data from the fossil record. But that approach can tell us little about what life was like before it was really life at all.

For the Hundred Years War there is ample documentary evidence. But for life’s origin around 3.8 billion years ago, the geological ‘documents’ tell us very little indeed. Life left its imprint in the rocks once it was fully fledged, but there is no real data on how it got going.

It is a testament to the tenacity and boldness of scientists that they have set out to explore the question anyway. In 1863 Charles Darwin concluded that there was little point in doing so: “It is mere rubbish”, he wrote, “thinking at present on the origin of life.” But he evidently had a change of heart, since eight years later he could be found musing on his “warm little pond” filled with a broth of prebiotic compounds. By the time Alexander Oparin and J. B. S. Haldane speculated about the formation of organic molecules in primitive atmospheres in the 1920s, experimentalists had already shown that substances such as formaldehyde and the amino acid glycine could be cooked up from carbon oxides, ammonia and water.

There was, then, a long tradition behind the ground-breaking experiment of Harold Urey and Stanley Miller at Chicago in 1953. They, however, were the first to use a reducing mixture, and that is why they found such a rich mélange of organics in their brew. Despite geological evidence suggesting that the early terrestrial atmosphere was mildly oxidizing, Miller remained convinced until his recent death that this was the only plausible way life’s building blocks could have been made – some say his stubbornness on this issue ended up hindering progress in the field.

In some ways, the recent study by Paul von Ragué Schleyer of the University of Georgia and his coworkers of the prebiotic synthesis of the nucleic acid base adenine from hydrogen cyanide (D. Roy et al., Proc. Natl Acad. Sci. USA doi:10.1073 pnas.0708434104) is a far cry from Urey and Miller’s makeshift ‘bake and shake’ experiment. It uses state-of-the-art quantum chemical calculations to deduce the mechanism of this reaction, first reported by John Oró and coworkers in Texas in 1960, which produces one of the building blocks of life from five molecules of a single, simple ingredient.

But in another sense, the work might be read as an indication that the field initiated by Urey and Miller is close to having run its course in its present form. The most one could have asked of their approach – and it has amply fulfilled this demand – is that it alleviate George Wald’s objection in 1954 that “one only has to contemplate the magnitude of this task to concede that the spontaneous generation of a living organism is impossible.” There are now more or less plausibly ‘prebiotic’ ways to make most of the key molecular ingredients of proteins, RNA, DNA, carbohydrates and other complex biomolecules. There are ingenious ways of linking them together, in defiance of the deconstructive hydrolysis that dilute solution seems to threaten, ranging from surface catalysis on minerals to the use of electrochemical gradients at hot springs. There are theories of cascading complexification through autocatalytic cycles, and the whole framework of the RNA World (the answer to the chicken-and-egg problem of DNA’s dependence on proteins) seems increasingly well motivated.

And yet there is no more evidence than there was fifty years ago that this is how it all happened. Time has kicked over the tracks. The chemical origin of life has become a discipline of immense experimental and theoretical refinement, as this new paper testifies – and yet it all remains guesswork, barely constrained by hard evidence from the Hadaean eon of our planet. The true history is obliterated, and we may never glimpse it.