The pilot project for the Human Genome Project: C. elegans

The C. elegans genome project was a critical milestone in genetic research.

John Sulston, a British biologist, and Bob Waterston, an American biologist who moved to the UK on a sabbatical, both had a very specific interest in the nematode worm C. elegans. Their work together, mapping and sequencing the genome of the worm, acted as a test project for the Human Genome Project. It provided an opportunity to perfect many of the techniques and technologies that would be used to sequence a human genome. The C. elegans genome project was a critical milestone in genetic research.

Playing a significant role in the Human Genome Project was not the initial intention of the C. elegans genome project. Originally, they just wanted to investigate the genetics of the worm to see if it revealed any secrets about its development they may help them to understand how humans develop.

John Sulston talks about sequencing the nematode worm C. elegans, his role in the Human Genome Project and the importance of sharing data.

Mapping allows researchers to piece together genome sequences and locate important sections, such as individual genes.

Their first job in the quest to de-mystify the genome of the worm was to ‘map’ its genome. Mapping allows researchers to piece together genome sequences and locate important sections, such as individual genes. Genome mapping is vital for sequencing because it allows scientists to navigate round large genomes and piece them together.

This was the first time that the genome of an animal had been sequenced.

By the end of the 1980s, John, Bob and their colleagues had completed mapping the genome of the worm and with one of the first Human Genome Project grants, the team” progressed to sequencing it. Although DNA sequencing had been carried out before to decode the genomes of smaller organisms such as viruses, this was the first time that the genome of an animal had been sequenced.

As the sequencing of the worm progressed, John and Bob’s skills were in high demand, particularly from individuals with commercial interests in genetics. John was keen to remain in Cambridge to continue his work on C. elegans, however funding and space to complete the worm project were in limited supply.

It took John and his team” over 12 years to map and sequence the nematode genome.

John therefore applied to the Wellcome Trust and Medical Research Council for a new institute to be built which could sequence the genome of C. elegans and contribute to the international effort to sequence the human genome. His application was successful and so in the summer of 1992, with a grant of £46.5 million from the Wellcome Trust, the Sanger Centre was born.

It took John and his team” over 12 years to map and sequence the nematode genome, but the sequence was finally published in 1998 in the journal Science.

Although C. elegans was already commonly used as a model organism in the lab, by sequencing its genome John and Bob provided an invaluable resource and short cut to gene discovery.

John and Bob were committed to the free release of scientific information and made the genome sequence of C. elegans openly accessible to everyone.

With the worm they were able to demonstrate the use of the high-throughput, low-cost techniques that, when scaled up, would be suitable for the Human Genome Project. This helped to convince many who doubted the feasibility of a project to sequence a human genome, that it could be done.

Both John and Bob were also committed to the free release of scientific information and made the genome sequence of C. elegans openly accessible to everyone online. These values continued during the Human Genome Project and made a huge difference to the progress made during the project. However, open access to information was also a topic of major contention as the Human Genome Project went forward.