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Guest Blogger James Le Fanu: The Last Days of the Façade of Knowing

The philosopher Thomas Nagel in a memorable phrase laments 'the ludicrous overuse of evolutionary biology to explain everything about life' -- where there is nothing too sensational, extraordinary or bizarre about the living world that cannot be accounted for as having evolved to be that way over billions of years by the same known materialistic process of natural selection acting on random genetic mutation.

This façade of knowing cannot last, of course, and 20 years or so hence historians and commentators will rightly wonder how science could conceivably have endorsed so simplistic a theory to explain the billion fold complexities of the living world -- and for so long.

The impetus for that disillusionment can only come from within science itself, where it is probable that the current baffling perverse findings of genomic science will, in retrospect, be seen to have played the decisive role. To clarify.

For the best part of 60 years science has been seduced by the elegant simplicity of the Double Helix into supposing that the 'secret of life' might be knowable -- were it possible to decode the genetic instructions strung out along its intertwined strands and understand the programme that makes an organism.

And from the mid 1970s onwards the massive onslaught of the techniques of modern genetics promised to do just that, culminating in 2001 in the 'stunning achievement,' as the journal Science described it, of spelling out the full sequence of human genes, the Human Genome Project, with its potential to 'unlock the secrets of our genetic inheritance and our place alongside the other participants in the adventure of life'. Since then the techniques of gene sequencing have become faster and cheaper by orders of magnitude, ushering in the age of genomic science where the major research centres generating megabytes of basic biological data every week have sequenced hundreds of genomes encompassing the full range of the diversity of life; dozens of bacteria, fourteen types of fungi, nine different types of plant (soya bean, barley, cassava, rice and wheat); insects (mosquito, honey bee and fly); fish (fugu and zebrafish); several types of worm, the sea urchin and chicken and a whole menagerie of our fellow mammals -- mice and rat, cat and dog, pig, sheep and cow and our closest cousin, the chimpanzee, with many more to come.

We should thus, by rights, as the journal Science anticipated a decade ago, be vastly more knowledgeable about those 'secrets of genetic inheritance' and particularly how the instructions encoded in those chemical genes strung out along the Double Helix give rise to that vast diversity of form and attributes that so readily distinguish bacteria from fungi, plants from fish, mice from chimps and from ourselves. Further, the opportunity to compare one genome with another should also have identified the myriad of small random genetic mutations that, as required by prevailing theory, provide the raw material for evolutionary transformation.

But that is not how it has turned out. Indeed perversely after a decade of genetic science we now know vastly less about such matters than might ever have seemed possible. And exponentially so, for every newly sequenced genome only compounds that 'puzzling question', as Steven Salzberg of the Institute of Genomic Research describes it, of the source of those 'huge differences in physical and behavioural characteristics' that so readily distinguish one form of life from another.

The most obvious of those 'puzzling questions' that he cites is the 'gene number dilemma' epitomized by the most astonishing revelation of the Human Genome Project -- that we have roughly the same number of genes, a modest 20,000, as the millimeter long worm, C.elegans -- that is fashioned from just 1,000 cells (compared to our 60 trillion) in all, has neither a circulatory system nor internal skeleton and a life expectancy of just two weeks. Since then every newly sequenced genome has added its own further twist to this surprising lack of any correspondence between gene numbers and organismic complexity -- where flies and chickens, it emerges have a third fewer genes than the diminutive C.elegans while, at the other extreme, plants such as rice and soya bean have twice as many.

The further yet more 'puzzling question' is the revelation of the interchangeability of the master or homeotic genes across diverse species, where for example, the same gene that orchestrates the fly's distinctive compound type eye does so for the very different mammalian camera type eye. That interchangeability across species reaches its apotheosis with the finding that we share 99% of our genes with a mouse. How so trivial a genetic difference can generate such diversity of form defies all explanation, other than to suppose it must be 'something to do' with gene regulation, 'the turning on and off of genes at different times and places in the course of development'.

The implications are clear enough. Biologists could in theory sequence every living creature on the face of the planet, but this would only confirm they all share the same core set of genes that account for the nuts and bolts of the proteins and enzymes of the cell of which all living things are made. But beyond that the really interesting question -- that of 'form' -- what it is that so readily distinguishes the elephant from the octopus, fireflies from foxes would remain as elusive as ever.

The genetic instructions must be there of course because otherwise the tens of millions of our fellow species would not replicate themselves with such fidelity from generation to generation. But we are compelled in the light of these extraordinary findings of the recent past that we have no conception of why we should become so different from a worm or fly.

And the same applies though more significantly still to Darwin's proposed mechanism of evolutionary transformation. There is, to be sure, persuasive evidence of a shared or common ancestry in the interchangeability of, for example, our genome with that of a mouse and our primate cousin -- but beyond that the myriad of random genetic mutations that would provide a basis for the transformation of one form of life into another are nowhere to be found. "We cannot see in this why we are so different from chimpanzees", observed Svante Paabo Chairman of the Chimpanzee Genome Project on its publication in 2005 -- "part of the secret is hidden in there, but we don't understand it". Nothing has subsequently emerged to challenge that conclusion.

The standard scientific response to these anomalies and perplexities is to concede that 'it' has turned out to be much more complex than originally contemplated -- which is certainly true. But nonetheless, the argument goes, the accumulation of yet more biological data, the sequencing of yet more genomes must eventually, like a bulldozer, drive a causeway through current perplexities. Perhaps, but more certainly, the reverse for the more that science progresses, the more genomes that are sequenced, the more striking the irresoluble discrepancy between the similarity of the genetic instructions and the diversity of the living world.
 
It might seem futile to enquire why this might be so, but the explanation must lie in that simple elegance of the Double Helix that for so long has held out the promise that the phenomena of life might be knowable. The simple elegance of its structure, on reflection, cannot be because it is simple but because it has to be simple -- if it is to replicate the genetic instructions every time the cell divides.

And that obligation to be simple requires the Double Helix to condense within the one dimensional sequence of chemical genes strung out along its intertwined strands, those biological complexities that determine the unique three dimensional form and attributes that so readily distinguish flies from ourselves and the tens of millions of species living and long since extinct. The Double Helix's semblance of simplicity then becomes a measure of its inscrutable profundity or, as Phillip Gell, Professor of Genetics of the University of Birmingham anticipated so presciently 20 years ago, "the gap in our knowledge is not merely unbridged, but in principle unbridgeable, and our ignorance will remain ineluctable".

There is in all this the powerful impression that science has been looking in the wrong place for explanations that somehow must lie outside its domain -- some potent force that might conjure the richness of the living world from that monotonous sequence of chemical genes strung out along the Double Helix.

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James Le Fanu's most recent book, Why Us?: How Science Rediscovered the Mystery of Ourselves, is published by Vintage ($16.00).