James (Jim) Watson, LMB Nobel laureate, co-discoverer with Francis Crick of the structure of DNA, has died at the age of 97. The revealing of the double helical structure of DNA in 1953 is hailed as one of the greatest scientific breakthroughs of the 20th century. It started a revolution in the field of molecular genetics and far beyond. The structure immediately suggested answers to the age-old mystery of heredity. The iconic status of the DNA double-helix is evidenced by its prevalence in the arts and popular culture.
Watson was born on 6 April 1928 in Chicago, USA. A boyhood interest in natural history, in particular ornithology, led him in 1943 to study zoology at the University of Chicago. While there he became interested in genetics and for his PhD he joined Salvador Luria’s group at Indiana University, Bloomington. Salvador was looking at bacteriophages and Watson found himself studying the effects of X-rays on bacteriophage multiplication. After receiving his PhD in 1950, Watson headed to Europe, initially to Herman Kalckar’s lab in Copenhagen. He was joined there by Gunther Stent, but they soon realised that their interests were better suited to Ole Maaløe’s research on the transfer of radioactive DNA from phage to their progeny. A year later, after hearing a talk on diffraction from fibres of DNA by Maurice Wilkins in Naples, Watson decided that the structure of DNA could be tackled and found himself heading to the Medical Research Council (MRC) Unit for the Study of the Molecular Structure of Biological Systems (now the LMB), under the leadership of Max Perutz. This was thanks in part to Salvador meeting John Kendrew, also based at the MRC Unit, at a conference in Ann Arbor, and making the arrangements for Watson to go to Cambridge.
In September 1951, Watson arrived at the fledgling MRC Unit, to work with John Kendrew on the structure of myoglobin. The MRC Unit had been established in 1947 primarily to obtain the structure of proteins. There, he met Francis Crick, who shared his interest in solving the structure of DNA to understand the molecular basis of genetics. This formed the key subject of the many discussions between them and they were soon sharing an office and ideas. Following the publication in 1951 of Linus Pauling’s paper proposing the a-helical structure in proteins, Crick began working on the theory of helical diffraction, a move that proved to be essential for the structure of DNA.
Influenced by Linus’ successful model for the a-helix, Watson and Crick started to build models for the structure of DNA by combining various types of data, including X-ray diffraction data being generated at King’s College London in the groups of Rosalind Franklin and Maurice Wilkins. Watson and Crick’s first attempt was hopelessly wrong, as pointed out by Franklin when she was invited to view the model. It was inconsistent with her results: that the phosphate groups are on the outside, not the inside, and that the water content was much higher than shown in the model. After this disastrous error, they were discouraged to continue the work on DNA at Cambridge by Lawrence Bragg, then the Cavendish Professor. But the challenge was impossible to resist, and with several other researchers, including Linus Pauling, working elsewhere on the problem, Watson and Crick soon began model building again. This time they succeeded. Although the model brilliantly synthesised many disparate types of information, some of the key parameters that allowed them to build an accurate model came from the X-ray diffraction of hydrated B-form DNA by Franklin’s group. The structure showed how two chains of DNA are intertwined to form a double helix with each chain consisting of alternating sugars and phosphates. The nitrogen-containing bases protrude from the two halves of the backbone into the centre of the helix and link together in pairs to form a double helix.
Watson made a major breakthrough when he determined how the base pairs connected, since knowing the shape of the four bases was critical for building a realistic model. Watson played around with cardboard cut-outs of the four bases: adenine (A), thymine (T), guanine (G) and cytosine (C) and found that A and T, and G and C could be bonded together to form pairs with similar shapes. This also fitted with Erwin Chargaff’s numerical constancies that the amount of G = C and A = T in DNA. Arranged correctly the bases bridge the gap between the two spiral backbones and join together via hydrogen bonds. This was a connection that no one else had previously made.
The revealing of the structure of DNA immediately suggested the way in which DNA is replicated: the two strands ‘unzip’ to allow the ‘code’ of bases to be copied. It could also be seen that the order of the bases was significant, and in a second paper, Watson and Crick wrote: “It therefore seems likely that the precise sequence of bases is the code which carries the genetical information” (Nature 171, 964-967, 1953). For this work, Jim Watson, Francis Crick and Maurice Wilkins were awarded the 1962 Nobel Prize for physiology or medicine for “their discoveries concerning the molecular structure of nucleic acids and its significance for information transfer in living material”. Rosalind Franklin had died in 1958 so was ineligible for the award.
After Cambridge, Watson returned to the USA. In 1953, he joined Caltech where he pursued the structure of RNA. In 1955, he returned to the MRC Unit for a year to work with Francis Crick and Don Caspar on the general principles of construction of small viruses, and he would return later for a couple of sabbatical visits, including to the new LMB in 1962. In 1956, he became an Assistant Professor in the Biology Department at Harvard, studying the role of RNA in protein synthesis, where his lab made pioneering discoveries on mRNA and the ribosome. From 1968, Watson was appointed Director, then President and finally Chancellor of Cold Spring Harbor Laboratory (CSHL) near New York. Here, he moved his research focus to the study of cancer and made CSHL a world-leading research centre in molecular biology.
From 1988 to 1992, Watson was significantly involved in helping to establish the National Institutes of Health Human Genome Project, whose objective was to complete a detailed map of the whole human genome. He was a founding Director and promoter of the project.
Watson was also widely known for his writing. His 1968 account of the DNA work, The Double Helix, was ground-breaking for its frank and colourful portrayal of the process of science and of scientists. Although a huge bestseller, it has sparked controversy ever since it was published, particularly for Watson’s portrayal of Rosalind Franklin. Francis Crick, Linus Pauling and Sydney Brenner all initially opposed its publication. Watson’s text book, The Molecular Biology of the Gene was more unambiguously successful. First published in 1965, it reinvented the undergraduate science textbook with its clear writing and presentation style, and five editions later is still a huge publishing success. Watson had a unique talent to extrapolate pending scientific discoveries, which contributed to its success.
As well as the Nobel Prize, Watson received many accolades for his work and role in science. He became a member of the National Academy of Sciences (USA) in 1962, was elected a Foreign Member of The Royal Society in 1981, awarded EMBO membership in 1985 and an honorary Knighthood in the New Year Honours in 2002 for “services to the UK-American partnership in the field of genetics and science.”
Watson was both a promoter and critic of science. He was also a controversial figure: from the DNA work, when Watson and Crick were both accused of obtaining data from Rosalind Franklin’s work without her permission or knowledge, from not giving her due credit in their 1953 paper, and for his later 1968 account of the DNA work. In addition, his increasingly brash and outspoken views on gender, race and eugenics have overshadowed his scientific career and diminished his standing in the last part of his life. But he was an enormously influential figure in the development of 20th century molecular biology.
Venki Ramakrishnan, LMB Group Leader and Nobel laureate commented: “Few people have influenced modern molecular biology and genetics as much as Jim Watson. He also trained and nurtured many generations of leading scientists, including some pioneering women in molecular biology such as Joan Steitz and Nancy Hopkins, so it is a pity that his later life was marred by his extreme views on race, gender and genetic determinism. In the end, his contributions will long outlast his prejudices.”
Further references
Molecular structure of nucleic acids: a structure for deoxyribose nucleic acid. Watson, J., Crick, F. Nature 171, 737–738 (1953). This article is behind a paywall
Genetical implications of the structure of deoxyribonucleic acid. Watson, J., Crick, F. Nature 171, 964–967 (1953). This article is behind a paywall
LMB Nobel page
Nobel Prize for physiology or medicine 1962