Friday, January 24, 2025

Dorothy Crowfoot Hodgkin, chemist, crystallographer, Nobel laureate, mother, arthritis patient, peace and disarmament activist

Dorothy Crowfoot Hodgkin, linocut print, 11" x 14", by Ele Willoughby, 2025
Dorothy Crowfoot Hodgkin, linocut print, 11" x 14", by Ele Willoughby, 2025

The next prompt for PrinterSolstice is cobalt, an element animals including humans require for their metabolism, in the form of vitamin B12. So I made the portrait of English chemist and x-ray crystallographer Dorothy Mary Crowfoot Hodgkin (née Crowfoot, 1910-1994) won the Nobel Prize in chemistry for her models of biomolecules like penicillin, vitamin B12 and insulin, which were essential to structural biology.

The eldest of four daughters of English parents who were in the colonial administration of North Africa and the Middle East, and later, archeologists, Dorothy was born in Cairo, Egypt. The family escaped the heat of the summers by returning to England. When Dorothy was 4, her mother left her and her sisters Joan (2) and Elizabeth (7 months) with her Crowfoot grandparents near Worthing and returned to her husband and life in Egypt. The girls grew up with grandparents in England with parental support from afar. Dorothy became interested in chemistry as early as 4 and interested in crystals by age 10; "captured for life by chemistry and crystals," she later wrote. Her mother, a proficient botanist, encouraged her interests. She found a dark rock when visiting her parents in north Africa and asked a family friend, soil scientist A.F. Joseph if she could analyse it; he gave her a surveyor's box of reagents and minerals to encourage her.  She and her sisters would use a portable mineral kit to analyse pebbles they found in the stream.  During WWI, Dorothy lost four uncles on her mother's side influencing her to become an ardent supporter of the League of Nation and later a peace and disarmament activist. Her parents moved to Sudan where her father was in charge of eduction and archeology until 1926. In 1921, she entered Sir John Leman Grammar School, one of two girls allowed to study chemistry rather than domestic science usually assigned to girls.  She had one extended trip to spend time with her parents in Khartoum when she was 13.  A distant cousin who was a chemist, Charles Harrington (later Sir Charles) recommended D.S. Parsons' 'Fundamentals of Biochemistry' to her at age 14. She set up a a small lab in her attic, using chemicals she got from the local pharmacist. On her 16th birthday her mother gave her W.H. Bragg's 'Concerning the Nature of Things' about x-ray crystallography, which used the scatter pattern of x-rays through crystals at different angles, recorded on photographic plates to image crystals and use mathematics to then deduce their structure from these patterns. As Latin, required for entry to Oxford, was not on her school curriculum, the headmaster personally tutored her so she was able to pass the entrance exam. 

Post-WWI her parents eventually returned to their habit of summering in England to spend time with their children and escape the heat while working abroad. After retiring from the Sudan Civil Service in 1926, her father took job as Director of the British School of Archeology in Jerusalem and her parents lived there until 1935.

Dorothy joined her parents at the archeological site Jerash (present day Jordan) and documented patterns of mosaics of several 5th to 6th century Byzantine era churches, taking a year to finish her drawing just as she entered Oxford to study chemistry. There she also performed chemical analyses of glass tesserae from these sites. Her precise and meticulous drawings are now housed at Yale. She so enjoyed field archeology she considered switching her field of study. Her attention to detail in documenting patterns would later serve her well as a chemist. She graduated Oxford with a first class degree in chemistry in 1932.

She entered the PhD programme at Cambridge later that year studying with John Desmond Bernal and became interested in the use of x-ray crystallography to study the structure of proteins. She worked with Bernal on the first application of the method to image a biomolecule, pepsin. Previously, the method had only been used for inorganic crystals. Bernal believed in equal opportunities for women in chemistry and helped make x-ray crystallography one of the few fields with significant representation from women scientists. He followed in the example of William Bragg himself, who had 11 women amongst his 18 students. In 1933 she was awarded a research fellowship at Somerville College and returned to Oxford in 1934  to teach with her own lab equipment. She missed the day Bernal made the first photo of an x-ray of a protein crystal for health reasons. She was only 24 when she began experiencing pain in her hand which was diagnosed as chronic rheumatoid arthritis. She went to a clinic in Bruton for thermal baths and gold treatments before returning to work. The disease caused her hands to swell and become distorted; she had to add a special lever to the allow her to continue to use the main switch on the x-ray equipment. The disease is progressive and caused increasingly debilitating pain, problems and deformities in her hands and feet. She was appointed the college's first fellow and tutor in chemistry in 1936, a roll she held until 1977. She earned her PhD in 1937 on the x-ray crystallography and chemistry of sterols. In 1945 with C.H. Carlisle, she published the first structure of a steroid, chloresterol iodide. From 1941 through 45, she worked with colleagues including Barbara Low, on solving the structure of penicillin. She made her calculations manually with a set of specially printed paper strips and with her team plotted 108,00 points in the molecule to make two-dimensional contours of electron densities. With help from her sister, she drew the contour sheets on perspex so these 2D slices could be stacked to visualize the molecule in three dimensions. Only then could she make the traditional ball and stick model (like I have shown in my portrait); she surrounded hers with 2D contour plots of electron density. Country to scientific opinion, they found that penicillin contained a β-lactam ring. She was doing all this intense work while Thomas was teaching in Newcastle; she had to send him a telegram to alert him the arrival of their second child was imminent. The research was characterized as a wartime secret. She sent Thomas a postcard, 'Think we really have found out something for certain about P. Am extremely cheerful.' They completed the work on VE day in 1945. She became a Fellow of the Royal Society in 1947. They published their penicillin results in 1949; she bowed to social pressure at this point and added Hodgkin to her name, though she had up to this point published as Dorothy Crowfoot.

In 1948, Merck discovered vitamin B12, one of the most complex vitamins then known, and Hodgkin created some new crystals. Merck only published its refractive indices. When she realized it contained cobalt, she knew the almost completely unknown structure could be established with x-ray crystallography, but its size and largely unidentified atomic components would make it a challenge. Since the crystals were pleochroic, that is, they displayed different colours at different angles, she deduced the presence of a ring structure, confirmed by x-ray crystallography. Her 1954 published study was described by Nobel Laureate Lawrence Bragg as being as significant as "breaking the sound barrier." She published the final structure in 1955 and 56. 

In 1953, she, Sydney Brenner, Jack Dunitz, Leslie Orgel, and Beryl Oughton (later Rimmer), were the first people to drive from Oxford to Cambridge in two cars to see the model of the double helix of DNA built by James Watson and Francis Crick, informed by x-ray crystallography by Maurice Wilkins and Rosalind Franklin and their student Gosling. 

In 1957 the Royal Society awarded her the Royal Medal and she became a reader at Oxford, gaining a full, modern laboratory in 1958. She was appointed the Royal Society's Wolfs Research Professor in 1960 through 1970 which provided salary, research expenses and assistance and she was a fellow of Wolfson College, Oxford from 1977 to 1983. 

Insulin, illustrated by Dorothy Crowfoot Hodgkin
Insulin, illustrated by Dorothy Crowfoot Hodgkin. This drawing was presented to crystallographer Dr. Helen Megan who was organizing the Festival Pattern Group in Britain in 1951. Hodgkin refused a fee or to copyright an image found in nature. Megaw organized an exhibit of the wonders of scientific patterns applied in design as part of the Festival of Britain. I decided life is too short to try and make a relief print of a molecule this complex!

One of her most important and celebrated studies was the longest lasting. She first received a sample of insulin in 1934. The size and complexity of the molecule was too great to explore with x-ray crystallography at that time, but the importance of the hormone captured her imagination. She had paused this research to work on the structure of penicillin, which contains 17 atoms, and vitamin B12, which contains 181 atoms, but returned to it later. By 1969, 35 years later, she was finally able to work with an international team of young scientists to reveal the structure of insulin. Insulin contains 788 atoms! It's hard to overstate the size of the task and the sheer number of calculations involved. This work was instrumental in our ability to mass-produce insulin and treat diabetes and also to allow scientists to alter the structure of the molecule to create even better drug options. She remained active in collaborating on insulin production and drug development to better treat diabetes. 

Sample of insulin wallpaper design made for the Festival of Britain
Sample of insulin wallpaper design made for the Festival of Britain. This simplified and stylized insulin design inspired the blouse she's wearing in my portrait.

Soft-spoken and gentle but determined and hardworking, Hodgkin inspired her students, whom she encouraged to address her simply as Dorothy. Her most famous student moved on from chemistry to politics; conservative UK PM Margaret Thatcher (née Roberts), hung Hodgkin's portrait in her office, out of respect for her former tutor, the livelong Labour supporter, sometime Communist Party of Britain member and pacifist Hodgkin. Hodgkin's politics were greatly influenced by her mentor Bernal, an open and vocal communist and supporter of the Soviet regime until it invaded Hungary in 1956. She always called him "Sage" and they briefly had a relationship (unconventionally, Bernal had an open marriage) before she met Thomas Hodgkin. Thomas was teaching adult education classes in northern English mining and industrial communities, after resigning from the Colonial Office. Intermittently a member of the Communist Party, he later wrote several works on African politics and history and lectured at Balliol College, Oxford. The two married in 1937 and had three children, Luke (1938-2020), Elizabeth (1941), and Toby (1946). Thomas spent a much time in west Africa, supporting and chronicling emerging postcolonial states. A lifelong advocate for peace, Dorothy campaigned against nuclear arms and the Vietnam war. Because of Dorothy's political activities and her husband's communist party membership she was banned from entering the US in 1953, and subsequently not allowed in without CIA waiver. 

She was in Ghana, where her husband was an advisor to president in 1964 when she learned she had been awarded the Nobel Prize for Chemistry her work on the structure of biomolecules. She served as President of the International Union of Crystallography, an organization she helped found, from 1972 to 1975 and worked to foster international collaboration. She worked to include Chinese and Soviet scientists through the Cold War. In 1976 she won the prestigious Copley Medal, the first woman to do so (the second wasn't until Jocelyn Bell Burnell in 2021). Concerned about social inequities and preventing war and in 1976 she became the longest-serving president of the international Pugwash Conference on Science and World Affairs, which brings scientists and public figures to work together to reduce the risk of armed conflict and seek solutions to global security threats. She stepped down in 1988 after the signing of the Intermediate-Range Nuclear Forces Treaty ban on short and long-range nuclear weapons. She accepted the Lenin Peace Prize from the Soviet government in 1987 for her peace and disarmament work. Fellow chemist, peace activist and Nobel laureate Linus Pauling had recommended her for the award.

In later years she spent a great deal of time in a wheelchair because of the progress of the rheumatoid arthritis, but she was able to remain an active scientist. She skipped the 1987 Congress of the International Union of Crystallography in Australia, but attended the 1993 Congress in Beijing. She died by stroke in 1994 in her husband's village of Ilmington. 

The Royal Society now awards the Dorothy Hodgkin Award in her honour to outstanding early career scientists requiring flexible work due to caring or health reasons. The Council offices in Hackney, university buildings at the universities of York, Bristol and Keele and the science block at her old school Sir John Leman High School are named in her honour. Oxford International Women's Festival presents the annual Dorothy Hodgkin Memorial Lecture in her honour.

Her work helped in the rapid production of penicillin, considered a miracle drug at the time, mapping vitamin B12 helped the fight against pernicious anemia and her structure of insulin greatly improved our ability to treat diabetes. She left her mark on science and society both.

References,

All or Nothing,  Back From the Dead exhibit website from The Museum of the History of Science, 2021

Alman, Margaret. Art in the Atoms: Chemist Dorothy Crowfoot Hodgkin, blog post, February 3, 2010.

Cole, Rupert. Happy Birthday Dorothy Hodgkin. Science Museum blog. May 11, 2018

Dorothy Crowfoot Hodgkin, Nobel Prize website, accessed January, 2025

Dorothy Hodgkin, Wikipedia, accessed January, 2024

Hodgkin, Dorothy Mary Crowfoot, Jennifer Kamper, June Lindsey, Maureen F. Mackay, Jenny Pickworth, John H. Robertson, Clara Brink Shoemaker, J. G. White, R. J. Prosen and Kenneth N. Trueblood. “The structure of vitamin B12. I. An outline of the crystallographic investigation of vitamin B12.” Proceedings of the Royal Society of London. Series A. Mathematical and Physical Sciences 242 (1957): 228 - 263.



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