In the Beginning Was the Worm: Finding the Secrets of Life in a Tiny Hermaphrodite
by Andrew Brown
244pp, Simon & Schuster, £15.99
Within 15 years of the discovery of the structure of DNA in 1953 and the birth of molecular biology, the most creative researchers in the field were beginning to chafe. Somehow the fun had gone out of it; it seemed the most important scientific questions had been answered and what was left was merely to fill in the details. That's when Francis Crick began his mutation into a neuroscientist and when his brilliant and closest colleague, Sydney Brenner, began what some of us at the time referred to sceptically as the most expensive wiring diagram in scientific history, now revisited in Andrew Brown's timely book.
Virtually all the work that led to the cracking of the genetic code had been done with the gut bacterium Escherichia coli. But, as the joke ran, was what was true for E coli true also for E lephant? The challenge was to find a multi-cellular animal as amenable to genetic studies as E coli. Brenner chose Caenorhabditis elegans, a nematode worm half a millimetre long, possessed of just 902 cells, a genome containing perhaps 20,000 genes and a voracious, if hermaphroditic, rate of sexual activity. The goal was optimistically simple: if an organism is nothing but the inexorable reading out of its DNA, then identifying the individual genes and their functions would be enough to "compute" it.
The initial task was formidable enough: to map the genes and track the cell lineages - the sequence through which the fertilised C elegans egg divided and its progeny cells migrated to form the adult organism. Gene mutations would result in observable differences - in cell patterns or in simple forms of behaviour, such as moving, eating, excreting or mating - and more or less linear relationships between genes and phenotype (the form of an organism) could be established.
Small wonder that many regarded Brenner's project as at best misguided. But the force of his charismatic personality and the distinctly laid-back and flexible management of the famous Laboratory of Molecular Biology in Cambridge made it possible for him to recruit a small team of dedicated microscopists and geneticists. For several years there was no apparent output. Much more glamorous work seemed to be going on down the other corridors of the LMB.
But the momentum gradually increased. Brown describes the most recent worm meeting in the US, where more than 2,000 papers were presented. Worm research has become an industry. What caused the change was the recognition, primarily by John Sulston, that the worm's genes could be sequenced and matched to the map of their functions. This was the programme, beginning in the 90s, that provided the groundwork for the international human gene sequencing project Sulston went on to spearhead.
Brown's book traces the worm project from its inception, as fascinating for the obsessive, almost nerd-like quality of the researchers as for the unravelling of the worm's wormliness. He notes the overwhelming maleness of the scientists, working 15-hour days and neglectful of family responsibilities, yet routinely sustained by female technicians. He contrasts their apparent naivety and openness with the frenetic and money-driven "race" into which some were co-opted when the human sequencing project began. By the end of Brown's account, one feels he has become almost as worm-centred as his human cast of characters - but it is inexcusable of his publishers not to include photographs or even diagrams; not to have a single picture of the star of the show, even on the cover, is ridiculous.
The culmination of the worm project was last year's Nobel award to Brenner, Sulston and their American colleague, Bob Horvitz. But as to "computing" the worm, predicting its behaviour from its genes - well, even Brenner now doubts whether that is possible in any straightforward way. It was recently shown (though it is not mentioned by Brown) that worms show social behaviour; put them together in a colony and they go in for synchronised swimming, for instance. Celegans still has surprises in store.
· A new edition of Steven Rose's prizewinning book The Making of Memory will be published by Jonathan Cape later this year.