25 September 2009
UCL and UCLH NHS TrustAppeared in BioNews 527
Genomes and What to Make of Them
Published by University of Chicago Press
ISBN-10: 0226172953, ISBN-13: 978-0226172958
Buy this book from Amazon UK
A feature of science, perhaps a characteristic feature, is that over time some of its better 'ideas' have come increasingly to be seen as actual 'things'. From being (only) conceptual they become physically real with a definite measurable size and a three-dimensional structure. A process of materialisation is in evidence. 'The word became flesh', so to speak. Think of atomic theory; or the transformation of chemistry as merely symbolic and diagrammatic in the 19th Century, into the metric science of the 20th. Structure improves explanatory power. An atom conceived merely as a point or a very small billiard ball has nothing to offer by way of an explanation of how it combines with another.
Before someone rushes to correct me, I realise that this is not universally true. Signally it does not seem to be true of theoretical physics, for instance, which tends to go in the opposite direction. 'As Maxwell's models were developed they became more and more abstract. Forces were replaced by fields, fields by potentials, potentials by Langrangians, and equations of motion by action integrals and modified metrics.' The words are those of astronomer, William Saslaw.
A science where it has certainly been thought to be true, however, is genetics. It is this that provides the theme of Genomes, or at least one of them. Inherited traits came to be explained by the idea of genes. Though abstract as an idea to start with, their behaviour could be studied through their observed effects. In time their structure was realised and with it an explanation of how they 'worked'. 'Genes really did exist', says the book. They were a set of instructions - embodied in a unique length of DNA, a strict sequence of bases - 'telling' a cellhow to make a particular protein. Indeed it was difficult to see that cells were any more (or less) than machines for making proteins. A departure from the strict sequence results in an abnormal or faulty protein which may manifest itself in disease or an observable difference in some physical feature of an organism. It is a scientific parable with extraordinary explanatory power. Unfortunately, as the authors point out, it is not really true.
Once we can 'do' structure more ambitiously, rather than just guess at function, that story becomes not an end of something else's story, that of heredity, but the beginning of a story in its own right. Consider: 'For a start, the contrast made in classical genetics between the normal and the abnormal allele in a pair may become a contrast between thousands of 'normal' DNA sequences and an even larger number of 'abnormal' ones.' From an idea to a thing - the 'thing' has now become a constellation of related things. The 'thingness' is also radically undermined by the realisation that the coding sequence of the 'gene' may be scattered fairly randomly over a large length of DNA and its sequence-encoded message assembled by splicing together the corresponding lengths of mRNA (messenger RNA). And worse than that, the one- to-one relationship between 'gene' and protein begins to evaporate, because what is to stop the lengths of RNA getting spliced in different combinations and permutations to create any number of different proteins? In principle - at least - apparently nothing. Barnes and Dupré give the instance of a 'gene' giving rise to 38,000 proteins through heroically promiscuous splicing.
From genes to genomes; as the 'materialness' of the gene has decreased, that of the genome has increased: '...it began to make sense to say that there really are genomes but not genes.' The genome is not now seen to be defined in the secondary role as a mere linear library of genes strung end to end, but rather as the main player. The genome is the material thing, and which interacts with the rest of the molecular population of the cell in the wonderfully complicated dynamic 'system' - which not merely drives the cell's life-cycle, but in some sense is that cycle. 'Genes' are now seen simply as convenient ways to refer to some of those interactions. From early attempts to explain inherited differences, through the realisation of the genome as an object as physical and three dimensional as the cell it inhabits, genetics has taken up pole position in biology. In biology as opposed to medicine it is the mystery of the detailed working of the cell-cycle and its elucidation that draws attention.
It is the remarkably well told story of the transformation over a century or thereabouts of the idea of inheritable traits to that of the cycling genome that is this book's backbone. It brings home vividly the truth of Georges Canguillhem: 'The history of science is not only science's memory but epistemology's laboratory.' For my part, I am far from certain that this review has done much justice to a book quite as ambitious as this in terms of its reach and grasp of genomics, and what it is, and why it matters.
One reason it matters is because of its influence on what people may think and what they can do. '...whether and how we shall cope with our own ever increasing powers standsamong the great unanswered questions of our times,' say the authors, pointing out that genomics is pre-eminently one of those powers. It is both an instance of and a symbol for the increasing potential and with it the threat of new technologies. 'It is given the role once assigned to nuclear physics'. Think about it.
Buy Genomes and What to Make of Them from Amazon UK.