20th century / Science

Dorothy Crowfoot Hodgkin and the Crystallography Quest

By Navaratnarajah Kuganathan

Dorothy Hodgkin

With a career spanning six decades British chemist Dorothy Crowfoot Hodgkin had a huge impact in the world of science and beyond. Her determination by X-ray techniques of the structures of important biochemical substances won her the Nobel Prize in Chemistry and earned her a place in history as one of the most eminent scientists of her time.

Born Dorothy Mary Crowfoot in Cairo in 1910, she was sent to England for her education where she became interested in chemistry and crystals at a young age. Her enthusiasm was encouraged during subsequent visits to her parents, then working in the Sudan, by Dr A. F. Joseph, a government soil chemist and family friend, who showed her how to analyse simple minerals. By the end of her school career, Crowfoot had decided to study chemistry at University and undertook her degree at Somerville College, Oxford.

Dorothy Crowfoot began her crystallographic research career in 1932 with H.M. Powell by elucidating the structure of thallium diakyl halides for her Master’s project, earning her a publication in the renowned scientific journal ‘Nature’. Following this Crowfoot moved to Cambridge University to read for a DPhil where she began work with crystallographer John Bernal. Bernal had recently been appointed to research the study of crystals by X-ray diffraction and had begun to look at biologically interesting molecules, a field which greatly appealed to Crowfoot.

Dorothy Hodgkin

During her time in Cambridge, Crowfoot carried out research on many significant biological compounds and, with Bernal, made the first X-ray diffraction studies of the protein pepsin marking the beginning of a new field of biochemical science. It was upon on her return to Oxford in 1934 that she began work with C. H. Carlisle, and correctly analysed cholesterol iodide; the first complex organic molecule to be determined completely by X-ray crystallography.

In 1936 Crowfoot became a tutor and fellow of Somerville College and in 1937, married Thomas Hodgkin, a left-wing historian who focussed upon the history and politics of the African and Arab world but was also involved in adult education. At the age of just twenty-eight, Dorothy Hodgkin began to suffer from rheumatoid arthritis, a severely painful condition that began to twist and deform her hands. In spite of this crippling illness, she continued to carry out the delicate manipulations necessary for her work.

Early in the Second World War, Howard Florey and his team in Oxford extracted penicillin and showed, by a series of tests upon bacterially infected mice, that it had remarkable ability to combat bacterial disease. This led to an urgent call to determine the chemical structure of penicillin which was being hailed as a ‘miracle drug’ by virtue of its apparent ability to affect resurrection-like cures of patients on their death-beds. As such penicillin was crucial in the fight against septic bacterial infections incurred on the front line. By understanding the structure, the production of penicillin could be increased, its mode of action elucidated and other antibiotics developed to target specific diseases.

Debate over the structure of penicillin had been raging in scientific circles, with one of the Medical Research Council’s researchers John Cornforth stating that if the ‘beta-lactam’ structure was correct he would give up chemistry and grow mushrooms instead. Hodgkin and her co-workers revealed the structure of penicillin in three years; at that time the largest molecular structure to be determined by X-ray techniques. With her results Hodgkin proved that penicillin does indeed contain a ring known as a ‘beta lactam’ and hence laid the foundations of huge developments in antibiotic design.

Following her election as a Fellow of the Royal Society in 1947, Hodgkin began work on the X-ray analysis of vitamin B12, the substance central to the prevention of a disease called pernicious anaemia. The analysis lasted nearly ten years during which Hodgkin made use of new computer technology to aid the lengthy and painstaking task of assimilating the data. Vitamin B12 proved to have a highly complex architecture and is the only biomolecule known to have a stable carbon-metal bond. The discovery of this structure led to further work by other research groups who were able to synthesise the vitamin and demonstrate its role in many processes occurring in the body.

Dorothy Hodgkin

After the success of the vitamin B12 work, Hodgkin returned to the studies of what she later believed to be her greatest scientific achievement; namely solving the crystal structure of insulin. Insulin is the hormone which is essential for blood-sugar regulation; a failure in its production leads to the disease diabetes. Hodgkin had first begun work on insulin in 1935 when she took the first X-ray photographs of insulin crystals, but it was not until 1969, after the development of many crystallographic procedures and advances in computer technology, that she was finally able to announce its structure.

For her work on the structures of important biochemical substances, Hodgkin was awarded the Nobel Prize in 1964. Her other honours are numerous, one of the most notable being the Order of Merit, making her only the second woman ever to receive the award; the first was Florence Nightingale. Hodgkin was instrumental in the founding of the International Union of Crystallography and, later in her life, she became president of the Pugwash Conferences on Science and World Affairs, an organisation dedicated to bringing together influential scholars to seek solutions to enable world peace.

Dorothy Hodgkin was a remarkable scientist who managed to combine a tireless quest for knowledge with her responsibilities as a wife and mother; a significant achievement in itself given the attitude often encountered in the male dominated scientific arena. Her work in scientific fields and beyond has lead to huge breakthroughs in structural and medicinal chemistry- the fantastic legacy of an extraordinary woman.

References:
Ferry. G, Dorothy Hodgkin: A Life (1999)
Farago. P, ‘Interview with Dorothy Crowfoot Hodgkin’, Journal of Chemical Education 54 (4): 214-216.
Bertsch McGrayne. S, Nobel Prize Women in Science: Their Lives, Struggles and Momentous Discoveries (1998)

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