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A most remarkable researcher

I took a photograph at the 1988 American Crystallographic Association meeting in Philadelphia of six elderly people smiling for a phalanx of camera-wielding admirers (Figure 1). You wouldn’t guess that there was anything special about these people, unless you recognized the weathered faces and knew that each had won a Nobel Prize for chemical research in which crystallography played a significant role. It may have been the last time this group was assembled together (in this life, anyway).

I was fresh out of grad school, having spent 4¹/₂ years studying inorganic crystallography. I knew the work of Pauling, Hauptman, and Karle, but the other three were less familiar. Dorothy Crowfoot Hodgkin (1910–1994) was introduced as “the woman who solved the insulin structure”, and that was that. After reading Dorothy Hodgkin: A Life by Georgina Ferry, I now know what an understatement that was.

Called on Dorothy Crowfoot at the Museum. . . . C. is Mrs. Hodgkin and admits that she has been married 8 years and has 3 children, one of them quite recent. All this to show that if the research urge is there it will go on even in women. . . . She looks astonishingly like Jeanette MacDonald! — Gerard Pomerat, assistant director of the Natural Sciences Division, the Rockefeller Foundation (1946)

Not only that, “C.” was one of the first women on the science faculty at Oxford University (a position she attained after years of temporary assignments)—a dedicated mentor who wasn’t averse to pulling strings to see that her students got the necessary visas, funding, and laboratory facilities. Later in her career, she was an active advocate of scientific research in China, India, and the Soviet Union (a pursuit that caused her many bureaucratic headaches whenever she wanted to visit the United States).

Figure 1. Six winners of the Nobel Prize in chemistry who used crystallography in their research. From left, Herbert Hauptman (1985), Linus Pauling (1954), William Lipscomb (1976), Sir John Kendrew (1962), Dorothy Hodgkin (1964), Jerome Karle (1985).

Hodgkin’s unusual accomplishments sprang from an unusual childhood. Her father, John Crowfoot, served in the British-sponsored government education service in Khartoum, Sudan, and later, in Cairo. Her mother, Molly, was a midwife who brought medical care to women who were prohibited by purdah restrictions from seeking care from male doctors. Molly Crowfoot’s career-mindedness and political activism made their imprint on Dorothy (but more on that later).

Georgina Ferry captures Hodgkin’s understated, matter-of-fact attitude in her narrative of Hodgkin’s unusual upbringing, education, and early career. Rather than bemoaning the obstacles in her way, Hodgkin went around them or persevered her way through them. At the same time Hodgkin struggled for funding, lab space and equipment, and students, she was also facing health problems (her own and her husband’s) and raising three children (with help from nannies, friends, and family members).

Hodgkin’s 1964 Nobel Prize citation notes “her determinations by X-ray techniques of the structures of important biochemical substances” (1). One of these “important biochemical substances” was penicillin. The outbreak of World War II dried up research funding for many projects. Penicillin research, however, took on an added urgency as researchers strove to synthesize the antibiotic in sufficient quantities to save the lives of wounded soldiers.

Solutions to crystal structures involve mind-numbing amounts of mathematical calculations. Hodgkin recalled, “All we had to do Fouriers were Beevers–Lipson strips and an electronic calculator that literally went ker-plunk, and so it took a long time.”

Things improved somewhat when her student Barbara Low and the Scientific Computing Service’s George Hey took their boxes of punch cards to Cirencester, where they had access to an American Hollerith machine that was used to track ships’ cargoes. According to Low, “The first night . . . what came out was absolute garbage. . . . We then invented a ship and did something so they could treat this Fourier as though it were a ship’s cargo. We gave it a new title, and it went through perfectly.”

In 1945, on VE Day, Hodgkin was confident enough in her penicillin structure to present a little model made of wires and corks to her colleagues; she presented her work to the scientific community in autumn 1945 at the Royal Society’s celebration of the 50th anniversary of Röntgen’s discovery of X-rays.

After the war, Hodgkin tackled the problem of vitamin B₁₂. X-ray crystallography was still a difficult enterprise, requiring inventiveness, imagination, and persistence to make sense of the blurry patches on the sheets of photographic film. John Robertson, a member of Hodgkin’s research group, observed,

When shown an oscillation photo, still wet, of some brand new crystal, she was capable, after an apparently casual glance, of gaily pronouncing what the space group must be, to the consternation (even humiliation) of the young man who had just developed the picture . . . really, it was the product of her phenomenal knowledge of relevant chemistry and physics, her long experience, her marvellous memory for detail and her tirelessly active mind.

The vitamin B₁₂ work fueled speculation among Hodgkin’s colleagues that she might soon win a Nobel Prize. She would have to wait in the wings, however, for another 8 years, enduring several near misses, but she confided her disappointment only to members of her immediate family. Finally, on October 29, 1964, the headlines in the Daily Telegraph announced, “British woman wins Nobel Prize—£18,750 award to mother of three.”

When the award was announced, Hodgkin and her husband, Thomas, were at the University of Ghana. She received the news from a couple of young reporters from the Ghana Times. They weren’t sure what a Nobel Prize was, but they had been sent to cover the story. Meanwhile, the telegram with the official announcement was making a three-month trip to Africa via sea mail, having been forwarded from England by a frugal niece.

The insulin structure, however, was Hodgkin’s Holy Grail. She had been fascinated by crystals since childhood, when her mother bought her the published versions of two lecture series for children by Sir William Bragg, a pioneer of X-ray crystal structure analysis. She saw in Bragg’s technique a means of answering questions about biological materials that had not been answered in her chemistry courses at school. The discovery of insulin in the early 1920s caused quite a stir in the scientific community, but no one imagined that the fledgling X-ray diffraction methods could map the structure of such a complex molecule. In 1934, Dorothy Crowfoot received a 10-mg sample of insulin crystals that a colleague had obtained from the Boots Pure Drug Company. It took several months before she was able to make a zinc heavy-atom analogue and crystals that were large enough for X-ray photography.

It would be another 34 years before computers, X-ray diffraction equipment, and crystal synthesis techniques would be advanced enough to produce an electron density map that could be interpreted, and from which a structure could be derived. Hodgkin published her last paper on insulin in 1988, when she was 78 years old. The paper was 87 pages long, had 10 co-authors, and described the insulin structure, complete with water molecules, to a resolution of 1.5 Å.

To her credit, Hodgkin was enthusiastic in her support of a Chinese research group that was working on the insulin structure at the same time as her own group. The Chinese Academy of Sciences launched a major effort at solving the structure, and Tang Youqi was asked to head it. He was somewhat reluctant to compete with Hodgkin’s group. “That decision was made by the authorities,” he explained. “I knew that Dorothy was working on [insulin], and she was not an enemy.” Hodgkin cooperated fully with the Chinese group, visiting when she could to compare notes on the analogues they were working with, and celebrating when the structure they obtained in 1971 matched closely with the structure her group had solved two years before.

Hodgkin’s last years were spent traveling the world as an advocate of scientific research and education, and as an active proponent of world peace. She served as president of the Pugwash Conferences on Science and World Affairs, an international group inspired by Bertrand Russell that advocated nuclear disarmament.

Not all of Hodgkin’s efforts turned out to her satisfaction. She recalled one student in particular who turned out to be something of a disappointment. Margaret Roberts worked for one year on the antibiotic gramicidin S, before obtaining a second-class degree (a kind of bachelor’s degree) and giving up chemistry for law. Miss Roberts eventually married Denis Thatcher and took up residence on Downing Street in London, where she pursued a career in government work.

Georgina Ferry, a freelance science writer, a broadcaster, and the science editor of Oxford Today, has written an understated and affectionate biography of this most remarkable woman. Dorothy Hodgkin left behind fragments of an autobiography at the time of her death in 1994, but she was wary of others’ “attempts on her life”. Her daughter Elizabeth and other members of her family encouraged Ferry to complete the tale, and friends and colleagues were happy to contribute. The result is a portrait of a highly intelligent, determined researcher who was also a dedicated wife and mother, and a mentor to an impressive number of young scientists who would go on to become known in their own rights.

Dorothy Hodgkin: A Life by Georgina Ferry; Granta Books: London; 423 pp, 1998 (first edition), 1999 (paperback edition, £9.99); ISBN 1-86207-285-X; U.S. distribution Cold Spring Harbor Laboratory Press: Cold Spring Harbor, NY, 2000; hardcover edition Sept 1, 2000; ISBN: 0879695900; $25; paperback edition October 2000; ISBN: 0879695943; $20.

Reference

1. www.almaz.com/nobel/chemistry/1964a.html (accessed July 2001).

Nancy K. McGuire is associate editor for Chemical Innovation.