The worm that turned…..into the human genome project

Judyth Sassoon

December 2000

 

John Sulston is the nice guy of human genome science. The Guardian duly reported that he wears old leather sandals, drives a second hand car and is married to a former Greenham Common anti-missile protestor. In keeping with this right-on image of service to mankind, he is now Director of the publicly funded Sanger Centre, Cambridge, UK. With their worldwide collaborators, the Sanger Centre made steps to sequence the entire human genome and generously made each new sequence available to the public as it was decoded, free of charge. Opposite the socially aware Sulston stands the American upstart entrepreneur, Craig Venter, who claims that his company Celera were the first to decode the human genome, but released nothing though their results are now available to subscribers. The battle of the gene-genies has been much talked and written about and provides a very interesting insight into the realities of scientific research.

On the 27th November 2000, Sulston received the Albert Wander Prize offered by the University of Berne, Switzerland for outstanding contributions to biomedical research and subsequently gave the "Wander Memorial Lecture". The title was "Society and the Human Genome", a lecture which he has given repeatedly to promote and justify the human genome project (HGP). Sulston positively exuded political correctness as he spoke about the HGP as something that belongs to all mankind. This time he did not rail against his rival Venter, saying instead that the time for bickering was over and that the next phase must be debate and collaboration between the public sector and Celera. After all, the ultimate goal was the "complete understanding of life" - a fine ideal unworthy of petty rivalry. With beneficence oozing from every pore, Sulston announced that the HGP "belongs to no-one and everyone".

John Sulston has had a fascinating research career. For many years prior to the HGP he studied the Nematode worm, Caenorhabditis elegans. This 1 mm long creature is, in terms of gene sequencing, the predecessor of the human. It was the first multicellular organism to be fully sequenced and the results were published in Science (11 Dec. 1998 Vol. 282) and are available on the world wide web, URL http://elegans.swmed.edu/genome.shtml .   It was the culmination of an 8 year effort, during which the 97 million bases of the genome were sequenced, and a technological milestone as it helped pave the way for the sequencing of the 3 billion bases that make up the human genome. It was the first time that all the genes necessary for an animal to function were mapped.

C. elegans develops from egg to adult in about 3.5 days, at which time it possesses about 1,000 somatic cells. It is transparent making observation easy, and its development has been followed on a cell by cell basis from egg to adult. The history of each cell is now known from birth to death, largely thanks to the work of Sulston and Sydney Brenner of the MRC Laboratory of Molecular Biology in Cambridge. Sulston, originally an organic chemist, was recruited by Brenner to study the worm and by 1983 he produced a lineage map, which traced the fate of each cell during growth from a single cell to a full-sized C. elegans. After this breakthrough the Cambridge group decided that the next obvious step was to track down the genes involved in controlling cell fates. So from a developmental map they started to make a physical map of the worm genome and when that was done, they made the giant leap towards mapping the human genome.

The early success of worm sequencing was instrumental in convincing researchers and funding agencies of the value and feasibility of large-scale sequencing projects. It is interesting, however, that even at this late stage, with the human genome virtually finished, Sulston still feels obliged to justify the question "why sequence whole genomes". During his lecture he presented a much used slide listing reasons such as "it provides complete information and an archive for the future; it provides new material for biologists to work on; it provides information on genome structure and history and is useful for evolutionary studies". While the slide showed the official line, Sulston himself admitted to having a liking for "grandiose, meaningless projects".

At the end of the lecture, someone from the audience asked how many expressed genes there were in the human genome. Sulston answered that the exact number is still not established but that estimates oscillate between a minimum of 20 000 and maximum of 50 000. It is worth noting that the nematode worm has 19,000 genes-very close to the lower estimate. Is it possible that the human being and the worm both express a comparable number of genes? One wit from the audience expressed his concern about this estimate and suggested that, following the example of the American Presidential elections, we should have a recount.

 

Dr. Judyth Sassoon
Dept. of Chemistry and Biochemistry
University of Berne
Freiestrasse 3
CH-3012 Berne
Switzerland
Tel: +41 31 631 4324
Fax: +41 31 631 4887
Email: sassoon@izb.unibe.ch

 

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