Biography: John Sulston
Nobel Prize in Medicine

John Edward Sulston was born in England, and grew up in Hertfordshire, where he attended the York House preparatory school in Croxley Greene. His father, an Anglican priest, was an administrator with the Society for the Propagation of the Gospel, a missionary organization. His mother had taught English at a local grammar school, but chose to stay home while young John and his sister Muriel were growing up.

From an early age, John Sulston took an interest in the natural world and scientific phenomena, particularly electricity. He was an enthusiastic hobbyist and tinkerer. He did well in school and won a scholarship to attend a prestigious boys school, Merchant Taylors in Northwood, Middlesex. He enjoyed his science courses, particularly work in the laboratory, and looked forward to studying science in university.

After graduating from Merchant Taylors, he received a scholarship to study Natural Sciences at Pembroke College, Cambridge. He had surprised his teachers at Merchant Taylors by choosing to concentrate on biology, rather than the more expected math-based course of study. A more difficult development was his gradual loss of faith in the religion that meant so much to his parents. Although he left the Church of England, he believes the moral teachings and ethical example of his parents had a lasting influence on his view of the world.

At Cambridge, Sulston became bored with the book-based biology curriculum, and after a detour into the lighting crew of the university's dramatic club, decided to concentrate on organic chemistry. He completed his undergraduate chemistry degree in 1963. He remained at Cambridge for graduate school, working in the laboratory of Professor Colin Reese, who assigned him to a project studying oligonucleotide synthesis. The laboratory work suited Sulston far better than his undergraduate reading had. He loved the work and resolved to spend the rest of his life in scientific research. In graduate school he met a fellow research student, Daphne Bate, and they soon became a couple. In 1966, as Sulston neared completion of his doctoral dissertation on the chemical synthesis of DNA, Professor Reese suggested he undertake postdoctoral research with Leslie Orgel at the Salk Institute in La Jolla, California.

John and Daphne married before embarking for California, where their first child, Ingrid, was born within the year. The Salk Institute proved a highly congenial setting for John Sulston. Dr. Orgel's research area was prebiotic chemistry, the study of the chemical origins of life, and Sulston was pleased to find himself returning to the study of biology. While at the Salk Institute, Sulston learned the technique of employing formaldehyde to induce fluorescence in catecholamines. These organic compounds function as neurotransmitters, and making them fluorescent enabled scientists to observe them in specimens of frozen tissue. Sulston would find this technique invaluable in his later work. Dr. Orgel made a point of introducing Sulston to the distinguished scientists who passed through La Jolla, including Sir Francis Crick, the co-discoverer of DNA. Crick, in turn, introduced Sulston to the Cambridge neurobiologist Sydney Brenner, who was conducting research with the minuscule nematode worm Caenorhabditis elegans. Approximately a millimeter long, the worm is a common soil organism with relatively simple organ structures, but its very simplicity made it an ideal subject, Brenner maintained, for studying the life of an organism at the cellular level.

Brenner saw profound research potential in the nematode, but few of his colleagues shared his view. Sulston was intrigued, and although Orgel was eager to keep him at La Jolla, Sulston chose to join Brenner's group back in England. In 1969, Sulston returned to England, along with Daphne and Ingrid, and became a junior staff member at the Cell Biology Division of the Medical Research Council's Laboratory of Molecular Biology (LMB) in Cambridge. Daphne would also find work at Cambridge, as librarian at the Department of Applied Mathematics and Theoretical Physics. Their children Adrian and Madeleine were born after their return to England.

Sulston's first years at the LMB were spent studying the neurochemistry of C. elegans. Applying the formaldehyde-induced fluorescence method he had learned in the United States, he produced a complete map of the worm's neurons. Turning his attention to the worm's DNA, he determined that its genome was 20 times greater than that of the bacterium E. coli. Existing research suggested that the worm's cell lineage was established in embryo, but as he traced the cell lineages of the worm's nervous system, he found only 15 neurons in the ventral cord of the larva, 57 in the adult worm. By presenting the worm with a narrow strip of bacteria to feed on, he kept the worm stationary on its slide, and in the course of a single weekend, was able to observe the origin of the 42 additional neurons in the adult ventral cord.

From the worm's nervous system, Sulston moved on to the rest of its anatomy and made a surprising discovery. Certain cells were apparently programmed to die at a particular time during the differentiation of the worm's embryonic cells. At LMB, Sulston mentored an American postdoctoral student, H. Robert Horvitz. After returning to the U.S., Horvitz continued to study programmed cell death, or apoptosis, in C. elegans at MIT. A growing community of scientists turned their attention to the nematode worm; Brenner, Sulston, Horvitz and others were able share their work in a series of international conferences devoted to the subject.

By 1983, Sulston's group had tracked the process of cell division in C. elegans, from the fertilized egg to the 959 somatic cells of the adult worm. Sulston observed and reported the stages of apoptosis, and identified the specific gene mutations involved. These historic results were published in 1983, the first such study to be performed in any animal. By then, Sulston and his team had set out to map the entire C. elegans genome. In the middle of this work, Sulston's discoveries were recognized with admission to Britain's prestigious Royal Society in 1986. The map of the C. elegans genome was complete in 1990, and the work of sequencing began. Sulston's progress in this venture spurred an international effort to decode the human genome. In 1992 the Wellcome Trust established the Sanger Centre in Cambridge, as a home for research in the genome of worms, mice, humans and other species. John Sulston was chosen to direct the center, the British component of an international consortium, the Human Genome Project. On the U.S. side, the project was led by James Watson and Francis Collins, with a substantial contribution by Eric Lander of MIT; on the UK side, by John Sulston and the Sanger Centre.

Leadership of a large research facility was a novel experience for Sulston, who had always seen himself as a laboratory scientist, not an administrator, but he remained at his post for eight years. Sulston proved to be an able administrator and fundraiser, and the center grew from a staff of 15 in temporary facilities, to a workforce of 600 in buildings designed to house the revolutionary research. In 1997, Sulston and company had completed the sequencing of the nematode C. elegans, the first creature to have its entire genome sequenced. The results were published the following year, and progress on the human genome surged forward. In 1999, a private firm, Celera, announced its intention to complete the human genome independently, patent the most lucrative genes, and profit from its discoveries. Sulston emerged as a vigorous international spokesman for public ownership of the human genome research. The controversy grew quite heated, with investors taking an interest in the commercial potential of the human genome. Sulston rallied mass media and financial backing for the public project. The private effort ran aground, and in 2000, the International Human Genome Project published its first rough draft of the human genome.

Sulston stepped down as Director of the Sanger Centre in 2000, and the following year was knighted by Queen Elizabeth II for his services to science. Sir John wrote an account of the "public vs. private" genome controversy in collaboration with Georgina Ferry, published in 2002 as The Common Thread: A Story of Science, Politics, Ethics and the Human Genome. Sulston's experience with the genome controversy caused him to consider more thoroughly the implications of the profit motive in science, and the ultimate purposes of scientific research. He would take these concerns to the international stage after he was awarded the 2002 Nobel Prize in Medicine, along with his old mentor Sydney Brenner and his colleague Robert Horvitz, "for their discoveries concerning genetic regulation of organ development and programmed cell death" in the nematode worm. Since receiving the Nobel Prize, Sulston has returned to his research, and continues to speak out on questions of science, ethics and the public interest.