On John Sulston’s death

journal.pgen.0020225.g002

Photograph of Sir John Sulston taken in 2006 by Jane Gitschier and originally published as part of the article, ‘Knight in Common Armor: An Interview with Sir John Sulston’ in PLOS Genetics, doi: https://doi.org/10.1371/journal.pgen.0020225. Reproduced here under Creative Commons Attribution License.

John Sulston, one of the driving forces behind the development of the strategy of the Human Genome Project as it evolved in the mid-1990s, died in March. As the head of what is now known as the Wellcome Sanger Institute, he was the public face of the project in the UK, and was deeply influential in steering the public and charity funded effort in three ways. Firstly, in favour of having a small number of centres sequencing vast volumes of the human genome. Secondly, in ensuring that the data produced would be publicly and freely available in open access databases. Thirdly, in tackling the private sector competition spearheaded by J. Craig Venter head on.

At the time, the competition, often depicted as a race, captured the media’s attention. In the manner of parents wanting to keep the peace between feuding siblings, a formal tie was announced at a White House declaration in 2000, at which the head of the US National Human Genome Research Institute Francis Collins played nice with Venter. The tie was declared before the finish line was breached, however, the publications heralding the completed genome sequence only appearing in 2003. The appearance of the separate private and public project publications on the same day was also a negotiated draw, and the definition of completeness somewhat fudged to ensure the announcement of a ‘final draft’ on the 50th anniversary of the discovery of the structure of DNA.

The obituaries of Sulston reflect on the race, but also the openness agenda which at the time was presented as a victory for public access over private control. In some respects, this was the case, and it set an important precedent for the sequencing of other organisms. The free and open access to sequence data undercut the business models of many burgeoning biotechnology companies, while providing a massive informational subsidy to the pharmaceutical industry. In addition, it quickly became apparent that an understanding of the biology of organisms and the ability to intervene in it required far more than sequence data.

The popular press inevitably concentrated on Sulston as a scientific politician, emphasising his socialist beliefs and connecting them to his promotion of openness and advocacy of the public project. Scientific publications gave more prominence to his scientific rather than administrative achievements, most notably his work at the Laboratory of Molecular Biology under Sydney Brenner, mapping out the cell lineage of the nematode worm C. elegans and then undertaking the mapping and then sequencing of the worm’s genome.

The distinction between his scientific and managerial efforts are less distinct when one views them in turns of outcomes. Not only did both projects constitute gigantic efforts to produce resources for use by a wider scientific community, they also helped constitute a community of users in the first place. Brenner’s insight to develop C. elegans as a tool for genetic and developmental biology research and the work done by Sulston and others to make it so enabled a new community to be formed to further develop and use the model.

Similarly, the acceleration and scaling-up of genomics that Sulston pushed, even before the public-private competition became salient, shaped the nascent field of genomics. He, along with National Institutes of Health policies, helped to centralise sequencing, and in so doing shifted the economics and geography of it, and how other scientists interacted with it. The rapid availability of sequence data undermined the economics and rationale for many small groups or individual scientists to sequence. Sequencing work in humans therefore largely (though far from completely) transferred from those who had a direct interest in the functional implications of the sequence data of a genome region of interest towards mass high-throughput sequencing conducted according to strict divisions of labour in large-scale sequencing centres. There was nothing inevitable in this shift; Sulston’s influence in shaping the organisation of this area of biological research was considerable.

The legacy he leaves biology in terms of the particular forms of openness he successfully advocated and the organisation of sequencing is undoubted, but the consequences are not quite as clear cut as his understandably laudatory obituaries suggest.

 

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