Monday, May 24, 2010

Creation myths

Artificial life? Don’t ask me guv, I was too busy last week building sandcastles in Lyme Regis. However, now making up for lost time… I have a Muse on Nature’s news site (the pre-edited text of which is below – they always remove the historical quotes), and a piece on the Prospect blog. The Venter work may, if it survives the editor’s shears, also be briefly discussed on an episode of Radio 4’s Moments of Genius that I’ve also just recorded with Patricia Fara, due to be broadcast this Sunday (30th May).

Claims of ‘synthetic life’ have been made throughout history. And each time, they are best regarded as mirroring what we think life is.

The recent ‘chemical synthesis of a living organism’ by Craig Venter and his colleagues at the J. Craig Venter Institute [1] sits within in a very long tradition. Claims of this sort have been made throughout history. That’s not to cast aspersions on the new results: while one can challenge the notion that this new bacterium, whose genome is closely modelled on that of Mycoplasma mycoides, stands apart from Darwinian evolution, the work is nonetheless an unprecedented triumph of biotechnological ingenuity. But when set in historical context, the work reflects our changing conception of what life is and how it might be made. What has been done here is arguably not so much a ‘synthesis of life’ as a (semi-)synthetic recreation of what we currently deem life to be. And as with previous efforts, it should leave us questioning the adequacy of that view.

To see that the new results reiterate a perennial theme, consider the headline of the Boston Herald in 1899: ‘Creation of Life. Lower Animals Produced by Chemical Means.’ The article described how the German biologist Jacques Loeb had caused an unfertilized sea-urchin egg to divide by treating it with salts. It was a kind of artificial parthenogenesis, and needless to say, very far from a chemical synthesis of life from scratch.

But Loeb himself was then talking in earnest about ‘the artificial production of living matter’, and he was not alone in blending his discovery with speculations about the de novo creation of life. In 1912 the physiologist Edward Albert Schäfer alluded to Loeb’s results in his presidential address to the British Association, under the rubric ‘the possibility of the synthesis of living matter.’ Schäfer was optimistic: ‘The [cell] nucleus – which may be said indeed to represent the quintessence of cell-life – possesses a chemical constitution of no very great complexity; so that we may even hope some day to see the material which composes it prepared synthetically.’

Such claims are commonly seen to imply that artificial human life is next on the agenda. It was a sign of the times that the New York Times credulously reported in 1910 that ‘Prof. Herrera, a Mexican scientist, has succeeded in forming a human embryo by chemical combination.’ It is surely no coincidence that many media reports have compared Venter to Frankenstein, or that the British Observer newspaper mistakenly suggested he has ‘succeeded in ‘creating’ human life for the first time’.
What is life?

Beliefs about the feasibility of making artificial organisms have been governed by the prevailing view of what life is. While the universe was seen as an intrinsically fecund matrix, permitting bees and vermin to emerge from rotten flesh by spontaneous generation, it seemed natural to imagine that sentient beings might body forth from insensate matter. The mechanical models of biology developed in the seventeenth century by René Descartes and others fostered the notion that a ‘spark of life’ – after the discovery of electricity, literally that – might animate a suitably arranged assembly of organic parts. The blossoming of chemistry and evolutionary theory spurred a conviction that it was all about getting the recipe right, so that nature’s diverse grandeur sprung from primordial colloidal jelly, called protoplasm, which Thomas Henry Huxley regarded as the ‘physical basis of life’.

Yet each apparent leap forward in this endeavour more or less coincided with a realization that the problem is not so simple. Protoplasm appeared as organic chemists were beginning on the one hand to erode the concept of vitalism and on the other to appreciate the full and baffling complexity of organic matter. The claims of Loeb and Schäfer came just before tools for visualizing the sub-cellular world, such as X-ray crystallography and the electron microscope, began to show life’s microstructure in all its complication. As H. G. Wells, his son George, and Julian Huxley explained in The Science of Life (1929-30), ‘To be impatient with the biochemists because they are not producing artificial microbes is to reveal no small ignorance of the problems involved.’

The next big splash in ‘making life’ came in 1953 when Harold Urey and Stanley Miller announced their celebrated ‘prebiotic soup’ experiment, conjuring amino acids from simple inorganic raw materials [3]. This too was obviously a very far cry from a synthesis of life, but some press reports were little troubled by the distinction: the result was regarded as a new genesis in principle if not in practice. ‘If their apparatus had been as big as the ocean, and if it had worked for a million years, instead of one week’, said Time, ‘it might have created something like the first living molecule.’ Yet that same year saw the discovery of life’s informational basis – the source of much of the ‘organization’ of organic matter that had so puzzled earlier generations – in the work of Crick and Watson. Now life was not so much about molecules at all, but about cracking, and perhaps then rewriting, the code.

Burning the book

Which brings us to Venter et al. Now that the field of genomics has fostered the belief that in sequencing genomes we are reading a ‘book of life’, whose algorithmic instructions need only be rejigged to produce new organisms, it’s easy to see why the creation of a wholly synthetic genome and its ‘booting up’ in a unicellular host should be popularly deemed a synthesis of life itself. Here the membranes, the cytoplasm, everything in fact except the genes, are mere peripherals to the hard drive of life. (The shift to a new realm of metaphor tells its own story.)

But what this latest work really implies is that it is time to lay aside the very concepts of an ‘artificial organism’ and a ‘synthesis of life’. Life is not a thing one makes, nor is it even a process that arises or is set in motion. It is a property we may choose to bestow, more or less colloquially, on certain organizations of matter. ‘Life’ in biology, rather like ‘force’ in physics, is a term carried over from a time when scientists thought quite differently, where it served as a makeshift bridge over the inexplicable.

More important than such semantics, the achievement by Venter et al. is a timely reminder that anything laying claim to the function we might call life resides not in a string of genes but in the interactions between them. Efforts to make de novo organisms of any complexity – for example, ones that can manufacture new pharmaceuticals and biofuels under demanding environmental constraints – seem likely to highlight how sketchily we understanding how those interactions operate and, most importantly, what their generic principles are. The euphoria engendered by rapid whole-genome sequencing techniques is already giving way to humility (even humiliation) about the difficulty of squaring genotype with phenotype. Yet again, our ideas of where the real business of life resides are shifting again: away from a linear ‘code’ and towards something altogether more abstract, emergent and entangled. In this regard at least, the latest ‘synthesis of life’ does indeed seem likely to repeat the historical template.

 1. D. G. Gibson et al. Science doi:10.1126/science.1190719 (2010)
2. E. A. Schafer, Nature 90, 7-19 (1912)
3. S. Miller, Science 117, 528 (1953)

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