John Sulston: a pioneer of genomics

The first of three sections of the John Sulston archive (PP/SUL) is now available. Section A focuses on Sulston’s Nobel Prize-winning work on the nematode worm Caenorhabditis elegans (C. elegans). His findings had a profound impact on genetic and genomic research and his efforts to sequence the worm’s genome became the pilot project for sequencing the human genome.

John Sulston, former director of Sanger Centre, working in a laboratory to purify DNA. Wellcome Image no. C0000661.

Sulston arrived at the Medical Research Council’s Laboratory of Molecular Biology (LMB) in 1969 to work with Sydney Brenner on his research into the genetic inheritance of C. elegans. The accepted wisdom in biology at the time was that a worm was born with all its cells, but Sulston discovered that a worm had in fact only fifteen ventral cord neurons when hatched, yet had fifty-seven by time it had fully matured. After devising a method of keeping the worm reasonably still (giving it plenty of food to munch on), Sulston set to work watching cells divide in order to map the development of the ventral cord and chart the origins of the additional forty-two neurons. He drew what he saw, filling a number of lab notebooks with colour coded circles and lines of descent.

Drawings of C. elegans by John Sulston. Wellcome Library reference: PP/SUL/A/1/3/6/a. Image credit: Wellcome Images.

In 1974 Sulston teamed up with Bob Horvitz to finish what he’d started with the ventral cord and chart the cell lineage of the entire worm. With the help of Judith Kimble, who traced the gonad cell lineage, the work was completed and published in 1977. Sulston was not quite satisfied and in 1979 shut himself away for eighteen months to work solidly on the cell lineage of the embryonic worm. Again, he produced pages of hand drawn diagrams charting the various cell divisions he witnessed and these notebooks form a significant part of Section A of the archive.

In the early 1980s Sulston became interested in genomic mapping and decided to map the C. elegans genome. Work gathered pace in 1983 with the arrival of Alan Coulson, who had been working elsewhere in LMB and then Bob Waterston, who visited on sabbatical and continued the collaboration upon returning to Washington University.

Whereas the cell lineage work required essentially just a microscope and some worms, Sulston realised that mapping the genome would need substantial computer power. Current software did not meet the team’s needs and so Sulston taught himself the programming language Fortran and developed a suit of programs to speed up mapping progress. The archive includes several papers relating to Sulston’s software development work, including computer logs for different programs and annotated data outputs.

Annotated computer log. Wellcome Library reference: PP/SUL/A/1/5/4. Image credit: Wellcome Images.

The genome map was completed in 1989 and the logical step was to move on to sequencing the genome: the process whereby the entire DNA sequence of the C. elegans worm would be determined and documented. Funding was initially gained from the Medical Research Council and the United States National Institutes of Health and then later from the Wellcome Trust as well. Sulston and his team continued to collaborate with Bob Waterston and his laboratory and the final sequence was published in 1998, making C. elegans the first animal to have its entire genome sequenced.

Section A of the archive follows all these developments and documents the research, discussions and experimentation that led to the successful completion of each stage of work. Full details of the archive are available from the Library catalogues under the reference PP/SUL. Section B is currently being catalogued and focuses on Sulston’s involvement as key player in the Human Genome Project and his role as Director of the Sanger Centre.

Author: Victoria Sloyan is Assistant Project Archivist at the Wellcome Library.