John Sulston on Limitations of the Sanger Sequencing Method
  John Sulston     Biography    
Recorded: 15 Jun 2005

Fred Sanger and his collaborators, Aaron Klug and Alan Coulson, had devised a way of rapid gene sequencing, but it was relatively rapid, so you could sequence a few thousand bases, and that meant that once you had your gene, you were in a very powerful position, you could quite quickly sequence it. What we could not do was to sequence a hundred million bases of the worm genome at that time. It was just too much. So it was still the bottleneck to actually isolate the genes. What it means to isolate a gene in practice is to somehow snip out the relevant bit of the whole genome, get it into a bacterium, so that you can clone it in that way, and then you could have indefinite amounts of this particular bit as those bacteria grew.

John Sulston was born in Buckinghamshire on 24 March 1942, the son of a Church of England minister and a schoolteacher. A childhood obsession with how things worked – whether animate or inanimate – led to a degree in Natural Sciences at the University of Cambridge, specialising in organic chemistry. He stayed on to do a PhD in the synthesis of oligonucleotides, short stretches of RNA. It was a postdoctoral position at the Salk Institute in California that opened Sulston's eyes to the uncharted frontiers where biology and chemistry meet. He worked with Leslie Orgel, a British theoretical chemist who had become absorbed in the problem of how life began. On Orgel's recommendation, Francis Crick then recruited Sulston for the Medical Research Council's Laboratory of Molecular Biology in Cambridge.

He arrived there in 1969, and joined the laboratory of Sydney Brenner. Brenner had set out to understand the sequence of events from gene to whole, living, behaving organism by studying the tiny nematode worm Caenorhabditis elegans.

For more than 20 years Sulston worked on the worm, charting for the first time the sequence of cell divisions that lead from a fertilised egg to an adult worm, identifying genetic mutations that interfere with normal development, and then going on to map and sequence the 100 million letters of DNA code that make up the worm genome.

The success of this last project, carried out jointly with Bob Waterston of Washington University in St Louis, led the Wellcome Trust to put Sulston at the head of the Sanger Centre, established in 1993 to make a major contribution to the international Human Genome Project. There he led a team of several hundred scientists who completed the sequencing of one third of the 3-billion-letter human genome, together with the genomes of many important pathogens such as the tuberculosis and leprosy bacilli.

As the leader of one of the four principal sequencing centres in the world, Sulston was a major influence on the Human Genome Project as a whole, particularly in establishing the principle that the information in the genome should be freely released so that all could benefit.

In 2000 Sulston resigned as director of the Sanger Centre (now the Wellcome Trust Sanger Institute), though he retained an office there for a few more years, continuing to work on the Human Genome Project publications and on outstanding problems with the worm genome.

Anxious to promote his views on free release and global inequality, he published his own account of the 'science, politics and ethics' of the Human Genome Project*, while adding his voice to influential bodies such as the Human Genetics Commission and an advisory group on intellectual property set up by the Royal Society. The same year he gave the Royal Institution Christmas Lectures for children on the topic 'The secrets of life'.

In 2002, John Sulston was awarded the Nobel Prize for Physiology or Medicine jointly with Sydney Brenner and Bob Horvitz, for the work they had done in understanding the development of the worm and particularly the role of programmed cell death.

The Common Thread by John Sulston and Georgina Ferry, Bantam Press 2002.

Taken from: http://genome.wellcome.ac.uk/doc_WTD021047.html 9/2/09 - AC Written by: Georgina Ferry John Sulston-Biography