I saw an excellent lecture by George Whitesides of Harvard yesterday. His official status as god-of-chemistry – and the fact that his talk was tantalisingly entitled ‘Questions about questions about the origins of life’ – meant that the small hall was packed to overflowing.

Whitesides put a health warning on the talk – there were very few facts, a lot of speculation, and no answers. Nevertheless, in forty minutes he set out a research agenda that could allow chemistry to answer one of the most fundamental questions – how life began. 

Unlike the ‘puzzles’ that trouble most chemists (projects such as total synthesis of a natural product, where much of the intellectual satisfaction is in the journey, rather than the destination; where its possible to frame the question absolutely; and where its clear that there is an answer to be found), this is a true ‘problem’, he argues – it’s really not clear what questions need to be answered, or if there is even an end-point to be reached.

There has been fifty years of research into how simple biological molecules could have formed from the prebiotic components available on Earth some 3.8 billion years ago. Likewise, progress towards defining the ‘RNA world’, where that molecule acted as both information carrier and catalyst before DNA arrived on the scene, is pretty good. 

But there is a hug gap to bridge between the two, says Whitesides, and chemists are best place to build it. So if you want to get started on a problem which he predicts will take generations to crack, here are a few of his suggestions:

– Work out the organic chemistry of black smokers, the underground geothermal chimneys that spew out a hot, fertile mixture of organics and inorganics

– Figure out what kind of chemistry is possible in deep space

– Work out how ‘primitive co-factors’ – enzymes that contain clunky inorganic bits, such as the nickel-dependant urease – which are common to most forms of life could form.

– Discover how ion gradients (potassium inside the cell, sodium outside the cell) can form from natural processes. ‘People ask me where life comes from,’ says Whitesides, only half-joking, ‘and I say Alberta’. He’s specifically referring to an evaporated salt sea that would have concentrated these ions in its shrinking pools.

– Likewise, how did the triphosphate energy-carrying group arise?

Interestingly, he thinks that the search for the origins of chirality doesn’t fall into this catalogue of life’s fundamental aspects. Organic chemists love chirality, which is why so much effort is expended on figuring out life’s preference for left-handed amino acids, he says – but ultimately it’s a distraction. ‘It’s a real Rorschach test for people,’ he told me. ‘Either you think it’s really important, or not important at all’. Hmmm – Ron Breslow is clearly in the former category, and indeed so am I. On the other hand, it’s a brave man that bets against Whitesides. 

He argues that it’ll take new ways of thinking about chemistry to tackle the origin of life problem – and trying to reconstruct these complex networks will take a lot of hard maths (so the biologists are no use, he adds). So – anyone up for the challenge?

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