Dorothy Hodgkin

Dorothy Mary Crowfoot Hodgkin was an English chemist who advanced the technique of X-ray crystallography to determine the structure of biomolecules, which became essential for structural biology. She received the 1964 Nobel Prize in Chemistry, and is the only British woman scientist to have been awarded a Nobel Prize.
Among her most influential discoveries are the confirmation of the structure of penicillin as previously surmised by Edward Abraham and Ernst Boris Chain; and mapping the structure of vitamin B₁₂, for which in 1964 she became the third woman to win the Nobel Prize in Chemistry. Hodgkin also elucidated the structure of insulin in 1969 after 35 years of work.
Hodgkin used the name "Dorothy Crowfoot" until twelve years after marrying Thomas Lionel Hodgkin, when she began using "Dorothy Crowfoot Hodgkin". Hodgkin is referred to as "Dorothy Hodgkin" by the Royal Society, and by Somerville College. The National Archives of the United Kingdom refer to her as "Dorothy Mary Crowfoot Hodgkin".

Early life

Dorothy Mary Crowfoot was born in Cairo, Egypt, the oldest of the four daughters whose parents worked in North Africa and the middle East in the colonial administration and later as archaeologists. Dorothy came from a distinguished family of archaeologists. Her parents were John Winter Crowfoot, working for the country's Ministry of Education, and his wife Grace Mary , known to friends and family as Molly. The family lived in Cairo during the winter months, returning to England each year to avoid the hotter part of the season in Egypt.
In 1914, Hodgkin's mother left her and her two younger sisters Joan and Elisabeth with their Crowfoot grandparents near Worthing, and returned to her husband in Egypt. They spent much of their childhood apart from their parents, yet they were supportive from afar. Her mother would encourage Dorothy to pursue the interest in crystals first displayed at the age of 10. In 1923, Dorothy and her sister would study pebbles that they had found in nearby streams using portable mineral analysis kit. Their parents then moved south to Sudan where, until 1926, her father was in charge of education and archaeology. Her mother's four brothers were killed in World War I and as a result she became an ardent supporter of the new League of Nations.
In 1921 Hodgkin's father entered her in the Sir John Leman Grammar School in Beccles, England, where she was one of two girls allowed to study chemistry. Only once, when she was 13, did she make an extended visit to her parents, then living in Khartoum, the capital of Sudan, where her father was Principal of Gordon College. When she was 14, her distant cousin, the chemist Charles Harington, recommended D. S. Parsons' Fundamentals of Biochemistry. Resuming the pre-war pattern, her parents lived and worked abroad for part of the year, returning to England and their children for several months every summer. In 1926, on his retirement from the Sudan Civil Service, her father took the post of Director of the British School of Archaeology in Jerusalem, where he and her mother remained until 1935.
In 1928, Hodgkin joined her parents at the archaeological site of Jerash, in present-day Jordan, where she documented the patterns of mosaics from multiple Byzantine-era Churches dated to the 5th–6th centuries. She spent more than a year finishing the drawings as she started her studies in Oxford, while also conducting chemical analyses of glass tesserae from the same site. Her attention to detail through the creation of precise scale drawings of these mosaics mirrors her subsequent work in recognising and documenting patterns in chemistry. Hodgkin enjoyed the experience of field archaeology so much that she considered giving up chemistry in favour of archaeology. Her drawings are archived by Yale University.
Hodgkin developed a passion for chemistry from a young age, and her mother, a proficient botanist, fostered her interest in the sciences. On her 16th birthday her mother gave her a book by W. H. Bragg on X-ray crystallography, "Concerning the Nature of Things", which helped her decide her future. She was further encouraged by the chemist A.F. Joseph, a family friend who also worked in Sudan.
Her state school education did not include Latin, then required for entrance to Oxbridge. Her Leman School headmaster, George Watson, gave her personal tuition in the subject, enabling her to pass the University of Oxford entrance examination.
When Hodgkin was asked in later life to name her childhood heroes, she named three women: first and foremost, her mother, Molly; the medical missionary Mary Slessor; and Margery Fry, the Principal of Somerville College.

Higher education

In 1928 at age 18 Hodgkin entered Somerville College, Oxford, where she studied chemistry. She graduated in 1932 with a first-class honours degree, the third woman at this institution to achieve this distinction.
In the autumn of that year, she began studying for a PhD at Newnham College, Cambridge, under the supervision of John Desmond Bernal. It was then that she became aware of the potential of X-ray crystallography to determine the structure of proteins. She was working with Bernal on the technique's first application to the analysis of a biological substance, pepsin. The pepsin experiment is largely credited to Hodgkin, however she always made it clear that it was Bernal who initially took the photographs and gave her additional key insights. Her PhD was awarded in 1937 for research on X-ray crystallography and the chemistry of sterols.

Career and discoveries

In 1933 Hodgkin was awarded a research fellowship by Somerville College, and in 1934, she moved back to Oxford. She started teaching chemistry with her own lab equipment. The college appointed her its first fellow and tutor in chemistry in 1936, a post which she held until 1977. In the 1940s, one of her students was Margaret Roberts who, while Prime Minister, hung a portrait of Hodgkin in her office at Downing Street out of respect for her former teacher. Hodgkin was, however a life-long Labour Party supporter.
In April 1953, together with Sydney Brenner, Jack Dunitz, Leslie Orgel, and Beryl M. Oughton, Hodgkin was one of the first people to travel from Oxford to Cambridge to see the model of the double helix structure of DNA, constructed by Francis Crick and James Watson, which was based on data and technique acquired by Maurice Wilkins and Rosalind Franklin. According to the late Dr Beryl Oughton, they drove to Cambridge in two cars after Hodgkin announced that they were off to see the model of the structure of DNA.
Hodgkin became a reader at Oxford in 1955 and she was given a fully modern laboratory the following year. In 1960, Hodgkin was appointed the Royal Society's Wolfson Research Professor, a position she held until 1970. This provided her salary, research expenses and research assistance to continue her work at the University of Oxford. She was a fellow of Wolfson College, Oxford, from 1977 to 1983.

Steroid structure

Hodgkin was particularly noted for discovering three-dimensional biomolecular structures. In 1945, working with C.H. Carlisle, she published the first such structure of a steroid, cholesteryl iodide.

Penicillin structure

In 1945, Hodgkin and her colleagues, including biochemist Barbara Low, solved the structure of penicillin, demonstrating, contrary to scientific opinion at the time, that it contains a β-lactam ring. The work was not published until 1949.

Vitamin B₁₂ structure

In 1948, Hodgkin first encountered vitamin B₁₂, one of the most structurally complex vitamins known, and created new crystals. Vitamin B₁₂ had first been discovered at Merck earlier that year. It had a structure at the time that was almost completely unknown, and when Hodgkin discovered it contained cobalt, she realized the structure actualization could be determined by X-ray crystallography analysis. The large size of the molecule, and the fact that the atoms were largely unaccounted for—aside from cobalt—posed a challenge in structure analysis that had not been previously explored.
From these crystals, she deduced the presence of a ring structure because the crystals were pleochroic, a finding which she later confirmed using X-ray crystallography. The B₁₂ study published by Hodgkin was described by Lawrence Bragg as being as significant "as breaking the sound barrier". Scientists from Merck had previously crystallised B₁₂, but had published only refractive indices of the substance. The final structure of B₁₂, for which Hodgkin was later awarded the Nobel Prize, was published in 1955 and 1956.

Insulin structure

was one of Hodgkin's most extraordinary research projects. It began in 1934 when she was offered a small sample of crystalline insulin by Robert Robinson. The hormone captured her imagination because of the intricate and wide-ranging effect it has in the body. However, at this stage X-ray crystallography had not been developed far enough to cope with the complexity of the insulin molecule. She and others spent many years improving the technique.
It took 35 years after taking her first photograph of an insulin crystal for X-ray crystallography and computing techniques to be able to tackle larger and more complex molecules like insulin. Hodgkin's dream of unlocking the structure of insulin was put on hold until 1969 when she was finally able to work with her team of young, international scientists to uncover the structure for the first time. Hodgkin's work with insulin was instrumental in paving the way for insulin to be mass-produced and used on a large scale for treatment of both type one and type two diabetes. She went on to cooperate with other laboratories active in insulin research, giving advice, and traveling the world giving talks about insulin and its importance for the future of diabetes. Solving the structure of insulin had two important implications for the treatment of diabetes, both making mass production of insulin possible and allowing scientists to alter the structure of insulin to create even better drug options for patients going forward.