It is inevitable that the origins of life on Earth will be forever shrouded in mystery, says Philip Ball

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 Hadron Collider at Cern in Geneva makes clear the increasing extravagance needed to peer back in time ever closer to the Big Bang. But we can now reconstruct the origin of our universe from about 10-30 seconds 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 particles’ masses.  

This is possible because there is so little room for contingency in the first instants of the Big Bang. The further we go back, the less variation we are likely to find between our universe and any other that might have hypothetically sprung from a cosmic singularity. 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.  

In that latter case, it’s possible to extrapolate backwards from the present-day map of the world, and search for geological confirmation of our hypothesis. We can do the same for the history of life, constructing family trees of species by comparing today’s living organisms and supplementing that with data from the fossil record. But geological evidence from 3.8 billion years ago tells us very little about life’s origins - 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.  

This was the 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 oxidising, 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. 

Refined guesswork 

The latest attempt to peer into the prebiotic broth is a far cry from Urey and Miller’s makeshift ‘shake and bake’ experiment. Paul von Ragué Schleyer of the University of Georgia, Athens, and his coworkers, have used state-of-the-art quantum chemical calculations to deduce the mechanism of the reaction that forms the nucleic acid base adenine from hydrogen cyanide.1 First reported by John Oró and coworkers in Texas in 1960, the reaction 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 alleviates 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 also 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 that account for increasing complexity 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 (see Chemistry World, August 2006, p42). 

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 von Ragué Schleyer’s new paper testifies - but it all remains guesswork. Our true history has been obliterated, and we may never glimpse it.