Dorothy Hodgkin

Dorothy Hodgkin a British chemist and crystallographer (1910-1994) who determined the structures of some of the most important biological molecules of the twentieth century. She was awarded the Nobel Prize in Chemistry in 1964 for her work on the structures of penicillin and vitamin B12, and she remains the only British woman to have won a Nobel Prize in the sciences.

Early Life and Education

Dorothy Crowfoot was born in 1910 in Cairo, where her father worked in the education service of the British administration, and she grew up between Egypt, Sudan and England. She was drawn to chemistry as a schoolgirl, and with her parents' encouragement she pursued the subject at Sir John Leman School and then at Somerville College, Oxford, where she graduated in 1932.

At Oxford she was one of the few women studying chemistry, and she became interested in the new technique of X-ray crystallography, by which the arrangement of atoms in a crystal can be deduced from the pattern formed when X-rays are scattered by it. She went to Cambridge for her doctorate and worked under J. D. Bernal, a pioneer of the method, on the structures of organic and biological molecules.

In Bernal's laboratory she took part in the first X-ray photograph of a protein, a milestone that showed that the complex molecules of living things could be studied by crystallographic means. The experience determined the direction of her career, and she returned to Oxford in 1934 with a fellowship that allowed her to set up her own research.

Penicillin and Vitamin B12

During the Second World War Hodgkin turned to the structure of penicillin, the newly discovered antibiotic whose chemistry was unknown and whose production was of urgent importance. The molecule proved more complicated than had been expected, and it took years of painstaking analysis of crystalline derivatives before she and her collaborators established its structure in 1945.

She then undertook the structure of vitamin B12, one of the most complex molecules known at the time and one that contains a cobalt atom at its centre. The work demanded the measurement of thousands of X-ray reflections and the development of new methods of computation, and it took years to complete. When the structure was announced in 1956 it was hailed as a triumph of the method.

The vitamin B12 analysis established three-dimensional crystallography as a practical tool for chemistry and biology. It also convinced Hodgkin that the technique could be applied to the proteins and other macromolecules whose structures hold the secret of biological function, and she began to plan the work that would occupy her for the rest of her career.

Protein Structures and Insulin

Hodgkin's greatest single achievement was the determination of the structure of insulin, a protein hormone that regulates the level of sugar in the blood and that is essential to the treatment of diabetes. She began work on it in the 1930s, and the task required decades of refinement, the collection of enormous numbers of X-ray measurements and the solution of the phase problem, the central difficulty of protein crystallography.

The structure was finally solved in 1969, when she and her team were able to build an accurate three-dimensional model of the molecule and to see for the first time how its atoms are arranged. The result explained how insulin is stored in the body and how it can be modified, and it was the first determination of the structure of a protein hormone.

She also worked on the structures of other biologically important substances, including vitamin D, the antibiotic gramicidin and various sterols, and she contributed to the understanding of the relation between molecular shape and biological activity. Her laboratory at Oxford became one of the world centres of crystallography and trained a large number of distinguished scientists.

Method, Patience and the Craft of Crystallography

Hodgkin's method depended on patience, accuracy and a willingness to compute for years without certainty of success. Before electronic computers were available she and her colleagues performed their calculations with mechanical machines and by hand, and she was tireless in checking and rechecking the results. She was known for the careful preparation of crystals and for the long exposures needed to record faint diffraction patterns.

She insisted that the structure of a molecule should be determined directly from the data rather than assumed from chemical analogy, and she was cautious about publishing until the evidence was secure. Her approach combined the rigour of physics with the practical judgement of a chemist, and it required a temperament suited to slow and cumulative work.

She was also a generous and encouraging teacher. Her laboratory attracted visitors and students from around the world, and she gave her time freely to their problems. Women and men worked side by side in her group at a time when science was still largely a male preserve, and several of her students went on to win distinction in their own right.

Recognition, Politics and Legacy

Hodgkin received the Nobel Prize in Chemistry in 1964 for her determinations by X-ray techniques of the structures of important biochemical substances, only the third woman to win a Nobel Prize in science. She was awarded the Order of Merit in 1965 and the Copley Medal of the Royal Society, and she held the honorary degree of many universities. She also led the Pugwash movement for the peaceful use of science and disarmament.

She worked to the end of her life, publishing the structure of a further form of insulin in the year of her death. She was a committed Quaker and a lifelong advocate of international scientific cooperation, and she used her standing to support scientists in countries with repressive governments and to promote understanding across political divisions.

She died in 1994 in Warwickshire. Her legacy lies in the structures she solved, in the methods she helped to develop, and in the demonstration that crystallography could reveal the architecture of the molecules of life. Her work laid the foundation for much of modern structural biology and for the rational design of drugs.

See also

• X-ray crystallography
• Penicillin
• Insulin
• Vitamin B12