John Sulston: Hands-on at the Sanger 28/2/01. By Georgina Ferry Under the leadership of Sir John Sulston, the Wellcome Trust Sanger Institute became one of the world's largest contributors to the Human Genome Project.

John Sulston says that he became Director of the Sanger Center, spearheading the UK's contribution to large-scale human genome sequencing, only because he couldn't see how else he would get the funding to finish his real life's work, the genome sequence of the nematode worm.

Dr Sulston originally trained as an organic chemist. In 1969 he joined Sydney Brenner at the MRC's Laboratory of Molecular Biology (LMB). Dr Brenner was attempting to link genes, development and behaviour through the study of a very simple organism, the tiny nematode worm Caenorhabditis elegans. Dr Sulston's first major contribution was to document the lineage of every cell in the adult worm, right back to the fertilised egg.

This global approach led him inexorably to think about describing a whole organism at the level of the genome. With Alan Coulson at the LMB and Bob Waterston at Washington University in St Louis, he went on to make a complete physical map of the worm's six chromosomes.

By 1989 the map was complete, and with James Watson's backing the team obtained funding from the National Institutes of Health and the MRC to begin to sequence the worm clones. Three years later they had been so successful that sequencing the human genome suddenly seemed a real possibility. The Wellcome Trust saw the opportunity to establish a world-class genome sequencing centre in the UK, using the high-throughput approach that the worm project had pioneered. In 1992 they founded the Sanger Centre jointly with the MRC, and invited John Sulston to be its first Director.

It meant, among other things, that he could get the worm finished, and in December 1998 he and his colleagues published the complete sequence, the first of a multicellular organism.

"I was not personally going for the human genome," he says. "It was more a question of wanting to get genomics going, and then more specifically to study the genome of the worm. But I also believed very strongly that the UK should become involved in large-scale genomics, and so when the opportunity came to head the Sanger Centre and help to make a serious attempt on the human, I was ready for it."

Collaboration and competition

Many features of the worm sequencing project are very much in evidence in the way Dr Sulston and his colleagues have managed their contribution to the human project. A prime example is the continued partnership with Bob Waterston's lab in St Louis, now called the Genome Sequencing Center (GSC). Another is the 'strong, principled view of data release' that the worm project pioneered. All sequence data produced at the Sanger Centre, the GSC and the other partners in the publicly funded project are made freely available to other researchers every day. "It was totally agreed between Bob and me that this was the right way to do things," says Dr Sulston.

The entry of a private competitor, Celera Genomics, into the genome sequencing arena catapulted John Sulston unexpectedly into the limelight. Having previously had very little public recognition, he found himself regularly speaking up for the project on Newsnight and the Today programme, while the Observer placed him among the UK's 100 most powerful people.

"The perceived 'race' with Celera exposed us to the attention of reporters competing for soundbites in a way that distorted the science," he says. "But having gained people's attention, we can now capitalise on it by emphasising the great benefits the project will bring."

He believes that this kind of confrontation will become a thing of the past as the science moves forward from data gathering to data analysis. "There's huge room for speciation in the post-genomic era," he says. "With groups undertaking their own, hypothesis-driven research, there'll be much less of the head-to-head competition of genomics." For his own part, having helped to steer the report on the working draft of the human genome through to publication, he plans to return to doing what he always wanted – solving the final few problems that remain in the genome of the nematode worm.

Caption

Between 1992-2000, Sir John Sulston was Director of the Sanger Centre and led the UK’s involvement in the Human Genome Project.