In 2002 the biologist John Sulston, who has died of stomach cancer aged 75, shared a Nobel prize for physiology. He won it for elucidating the entire sequence in which the daughters of a single cell divide and sometimes disappear as an embryo grows into an adult in the tiny roundworm Caenorhabditis elegans. However, he is much better known for leading the British team that sequenced a third of the human genome, and for the fierce integrity with which he successfully argued that all genomic data should be openly accessible to the scientific community without commercial involvement.
Previously content to pursue his work out of the public eye, in 1998 Sulston found himself catapulted on to the front pages as the publicly funded Human Genome Project (HGP) faced competition from a rival, private genome-sequencing project launched by the American geneticist Craig Venter’s Celera Genomics. Sulston took every opportunity to challenge, on both ethical and scientific grounds, a model in which access to the data would be controlled by commercial licence agreements.
His arguments helped to persuade the HGP’s principal funders, the National Institutes of Health in the US and the Wellcome Trust in the UK, to increase their support for the International Human Genome Sequencing Consortium, which carried it out, even though Venter claimed Celera would do the job more cheaply and in half the time.
The different methods used by the two teams made it difficult to judge any claim to be “winning the race”, but Venter’s intervention stimulated the HGP to increase its output. The outcome became politically charged, and in June 2000, at press conferences addressed by Bill Clinton and Tony Blair, the result was declared a draw as both sides announced the completion of a “draft” sequence.
The international consortium finally published the complete, high-quality sequence in 2003, on the 50th anniversary of James Watson and Francis Crick’s discovery of the double helix structure of DNA. The sequence, freely available as Sulston urged, has provided a reference for all subsequent research into the way human biology is controlled at the molecular level: it has enabled scientists to pinpoint genetic mutations that cause disease and to design more targeted therapies for cancer.
Sulston recognised that he was not the kind of scientist who dreamed up hypotheses of potentially explanatory force and put them to the test. Instead he saw his science as principally Baconian, or, more unflatteringly, ignorance-driven: comprehensive collection of data, which then provides a resource for others to test their own hypotheses. His work on the worm-cell lineage first introduced him to the power of this approach. The lineage provided a road map for others to follow as they studied genetic mutations that disrupted normal development. Sulston’s colleague Bob Horvitz shared the Nobel prize for revealing how genes control developmental processes such as cell death, a universal mechanism critically relevant to cancer research.
It also provided the first illustration of the tenacity with which Sulston would pursue projects he had embarked on, whatever the obstacles in his way. From the mid-1970s until 1982, he sat over a microscope in the Medical Research Council’s Laboratory of Molecular Biology (LMB) in Cambridge and watched cells dividing, first in the worm larva with Horvitz and then in the embryo on his own, day after day until they had the whole lineage from one to 959 cells. A brilliant practical experimentalist, he developed a method of freezing worms without killing them, so that he could leave them overnight and continue the next day.
The same tenacity characterised his decision in 1983 to embark on mapping the worm genome, putting identified lengths of DNA known as clones into order as an aid to finding genes. While the lineage was largely a solo operation, he undertook the mapping in partnership with Alan Coulson at the LMB, and later also with Bob Waterston at the University of Washington in St Louis. He liked partnerships and was a wonderful collaborator, as I had the privilege of discovering myself when we wrote a book together (The Common Thread, 2002).
The map opened the way to sequencing. Reading off the 100 million As, Cs, Gs and Ts (the initials of the four types of bases of a DNA molecule) of the worm genome seemed an impossible task to many, but with funding from the HGP – then led by Watson – Sulston and Waterston got started. By 1992 the worm sequencing project was going so well that the Wellcome Trust asked Sulston to head a new sequencing institute that would not only finish the worm sequence but also contribute substantially to the human genome sequence of 3bn “letters”.
He felt “swept along like a leaf on the stream”. Managing teams of people was not something he relished, but he accepted it as the price he would have to pay for getting the worm sequence done. The Sanger Centre (now the Sanger Institute) opened in 1993 near Cambridge, initially as an automated factory for producing sequence data, with Sulston as its director.
Similar sequencing centres were being established elsewhere in the world as the Human Genome Project formally got under way, some with an eye to the commercial possibilities of patenting newly discovered genes. With the support of the Wellcome Trust, Sulston convened the first of a number of international strategy meetings in Bermuda in February 1996. It clarified who were likely to be the major players in the human genome effort and sorted out competing claims to sequence individual chromosomes.
However, its most significant outcome was the set of Bermuda principles, hammered out under Sulston’s chairmanship, that all sequencing data would be released immediately and for public benefit. This was what Sulston and his colleagues had always done with the worm data, a practice that had massively increased opportunities for scientists around the world to answer biological questions using the worm as a model. Keeping the genome sequence in the public domain became for him a moral duty against threats such as that posed by Celera two years later.
Born in Fulmer, Buckinghamshire, John was the son of the Rev Canon Ted Sulston and his wife, Muriel (nee Blocksidge); he had a sister, Madeleine. His father, a former army chaplain, worked as overseas secretary to the Society for the Propagation of the Gospel and his mother was an English teacher. “From them both I gained a sense that there is not, or need not be, any clear distinction between work and play,” John wrote, “and that one has a duty both to serve others and to do the best one can in everything.”
He spent his childhood taking apart and rebuilding radios or dissecting dead animals, anything to satisfy his curiosity about how things worked. By his teens he had decided that his father’s religious faith made no sense to him, and, as his scientific studies progressed, he began to feel “a sudden overwhelming sense of the power of the human mind”.
The family was not well off, but they found the money to send John to a private preparatory school. He won a scholarship to the academically ambitious Merchant Taylors’ school for boys, a few miles from his home in Rickmansworth, in south-west Hertfordshire, and then another to Pembroke College, Cambridge, to study natural sciences. Bored with book-learning and temporarily diverted by an interest in stage lighting for student drama productions, he failed to obtain a first-class degree; but the professor of organic chemistry, the Nobel prizewinner Alexander Todd, accepted him to study for a doctorate. With his supervisor, Colin Reese, he worked on the synthesis of oligonucleotides, the building blocks of DNA.
From that moment Sulston realised that the laboratory was his natural habitat.
On obtaining his doctorate in 1966 he married Daphne Bate, a research assistant in the Cambridge geophysics department, and went to California to work with Leslie Orgel at the Salk Institute on the molecular origins of life. With their daughter, Ingrid, on the way, he and Daphne rented a wooden house five miles from the campus and saved money by growing their own vegetables.
Invited by Crick, Sulston returned to Cambridge in 1969 to work at the LMB: his son, Adrian, was born soon afterwards. He joined the small team led by Sydney Brenner (who also shared the 2002 Nobel prize), who had seized on the worm C elegans as a model to develop a complete understanding of the genetic control of development and behaviour. Generous resources for equipment (though little space), a non-hierarchical approach to management and a commitment to the science characterised the LMB ethos, which Sulston subsequently tried to replicate as director of the Sanger Centre.
When the sequence of the worm genome, which Sulston regarded as his true life’s work, was published in 1998, he handed in his notice as director. But he did not finally step down until his successor was appointed in 2000, and remained fully engaged with the HGP until the publication of the finished human sequence in 2003.
Thereafter he devoted his time to causes related to open access and human well-being. In 2008 he became founding co-chair, with the bioethicist John Harris, of the Institute for Science, Ethics and Innovation at the University of Manchester, retiring in 2013. He chaired a Royal Society commission on People and the Planet, which reported in 2012.
Recently he had devoted more time to his favourite pastimes, hill walking and gardening, and supported local voluntary organisations such as Cambridge Past, Present and Future.
A lifelong Guardian-reading, beard-and-sandals socialist, Sulston lived by his own principles: he never did anything for money and much of what he received he quietly gave away.
The frugal cheese sandwich that he made for his lunch each day was a source of amusement to his colleagues at the Sanger. But he was anything but hairshirted – he loved nothing better than an evening with friends over a few pints or a meal with his family.
Offered a knighthood in 2001, he hesitated before accepting the honour as a recognition not of himself but of the whole sequencing team, and because he recognised, correctly, that the title would give him a platform to promote his ideas. In June last year he was made a Companion of Honour.
He faced his illness, diagnosed only a month before his death, with his customary stoicism.
John is survived by Daphne, his children, Ingrid and Adrian, his grandchildren, Micah and Kira, and by Madeleine.
• John Edward Sulston, biologist, born 27 March 1942; died 6 March 2018
