COMMENT OBITUARY John Sulston (1942-2018) Nobel-prizewinning champion of the Human Genome Project and open data.

he principle that genomic data should sequencing of the human genome was not be universally shared without com- impossible. In 1992, the UK Wellcome Trust mercial involvement owes its wide- invited Sulston to head its new sequencing Tspread acceptance largely to John Sulston. facility, the Sanger Centre (now the Sanger As leader of the British contribution to the Institute), in Hinxton.

international Human Genome Project, Leading the Sanger as part of an interna- BARBOUR/GETTY SCOTT Sulston persuaded funders and colleagues of tional consortium, Sulston had a key role in the crucial importance of making a complete, establishing the principles of data release and high-quality sequence freely available to the open access. When, in 1998, a private initia- global scientific community. His commit- tive led by Craig Venter of Celera Genomics ment stemmed from a moral certainty that announced its intent to sequence the human profit as a motive had no place in science. genome first, and for commercial profit, In 2002, he shared the Nobel Prize in Sulston defended the principle of open data. Physiology or Medicine for his contribu- He became, with Francis Collins — then head tion to understanding how genes control the of the US National Human Genome Research fate of cells in the developing roundworm Institute — a leading voice in persuading both Caenorhabditis elegans. In his work on the the US National Institutes of Health and the worm cell lineage and, later, genome sequenc- Wellcome Trust to commit to the project’s ing, Sulston promoted the idea that invest- completion. The human genome sequence, ing in large-scale data collection without a finished to a standard of 99.99% accuracy, specific hypothesis has long-term benefits. was published in Nature on 21 October 2004 Sulston, who died on 6 March, was the (International Human Genome Sequencing son of an English clergyman and a teacher. Consortium Nature 431, 931–945; 2004). He took to heart his parents’ indifference to As Sulston predicted, the availability of the material wealth and their desire to work for differential-interference contrast microscope, complete human genome drove research, the common good. Mechanics fascinated to visualize cell nuclei in living worm larvae both academic and commercial, worldwide. him from an early age and, by dissecting and, later, in the more challenging embryos. The work is slowly delivering clinical appli- dead animals, he began to see living things, He observed and recorded the invariant cations, especially in areas such as cancer, too, as machines. He won a scholarship to sequence of cell divisions that build an adult where genetic mutations determine whether study natural sciences at the University of worm. His work provided a foundation for a tumour will be sensitive to a therapy. Mean- Cambridge, UK. future worm biologists to answer questions while, technology has advanced and costs His PhD, also at Cambridge, was on the about development that have implications for dropped such that whole-genome sequencing synthesis of oligonucleotides — the building other species, including our own. of individuals might soon be routine. blocks of nucleic acids such as DNA and RNA. Sulston spotted that certain cells are elimi- Sulston was hands-on in the lab, person- His flair as an experimentalist secured him a nated during development. He began to ally preparing the worm-clone library for the position as a postdoc with organic chemist explore the genetics of this process with US mapping project, and decrypting the early Leslie Orgel at the Salk Institute for Biological postdoc, Robert Horvitz. On his return home sequencing machines so that the electronic Studies in La Jolla, California, investigating to the Massachusetts Institute of Technology data could be analysed directly. But he always the origins of life. Sulston arrived in 1966 to in Cambridge, Horvitz discovered genes that valued collaborators with skills different from study the replication of nucleic acids, and, for regulate programmed cell death. Later, muta- his own, and co-managed the Sanger on a the first time he understood the evolutionary tions in these genes proved instrumental to board of seven people. When he asked me to context of his work in chemistry. understanding the uncontrolled multipli- co-author a book on the battle for the human There, too, Sulston met Francis Crick, co- cation of cancer cells. Sulston, Horvitz and genome, The Common Thread, he insisted discover of the DNA’s double helix; Crick Brenner shared the 2002 Nobel prize “for that we work as equal partners. recommended him for a post at the Medical their discoveries concerning genetic regula- After the human sequence was published, Research Council’s Laboratory of Molecular tion of organ development and programmed Sulston devoted himself to writing and speak- Biology back in Cambridge. In 1969, Sulston cell death”. ing in support of open access and, more joined a small group headed by geneticist From 1983, Sulston set out to map and broadly, on the relationship between science Sydney Brenner. Looking for a model organ- sequence the 100-million-base-pair genome and society. Warm and articulate, he won over ism in which to explore the interactions of of the worm. His lab worked in partnership audiences with his humility and passion. ■ genes, development and behaviour, Brenner and friendly competition with that of Robert chose C. elegans. The tiny worm has only 959 Waterston, then at the University of Wash- Georgina Ferry is a science writer and cells as an adult, yet it has a gut, a nervous ington in St. Louis. In 1989, their collective biographer in Oxford, UK. She and Sulston system, gonads and a repertoire of behav- drive motivated Jim Watson, then head of the co-authored The Common Thread: A Story iours to move, feed and reproduce. Human Genome Project, to fund their pilot of Science, Politics, Ethics and the Human It is also transparent. Sulston used what sequencing initiative. The worm project dem- Genome (Bantam Press, 2002). became his favourite tool, the Nomarski onstrated that automated, high-throughput e-mail: [email protected]

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