Dorothy Crowfoot Hodgkin (1910–1994): X-ray Crystallography and the Intricacy of Molecular Maps

The men returned from the countryside with gold. Dorothy Hodgkin was a girl at the time, living with her parents in Anglo-Egyptian Sudan, and the men had been part of a British geological expedition outside Khartoum. “Three or four little pellets of gold which had been got from this expanse of streams,” Hodgkin said in an interview with the Biochemical Society (1). Hodgkin began to pan in a stream that flowed through their back garden. Instead of gold, she found a shiny, black mineral. A family friend helped to identify it—ilmenite. “[It was] much later found on the surface of the moon,” she said, “which gave me a lot of pleasure.”

When Hodgkin was moving through the British primary school system in the 1920s, the standard thinking was that boys took chemistry, girls took needlework (2). However, her firsthand experiences gave Hodgkin an early interest in science. Born in Cairo to a pair of English archeologists, Hodgkin spent her childhood bouncing between the U.K., North Africa, and the Middle East (3). Much of her early education came from her mother, who encouraged her to study natural history. Around age 10, she received a gift from the same family friend who helped her identify ilmenite: a box of chemicals with which to conduct her own experiments in the attic (2).

Hodgkin enrolled in Somerville College, Oxford, in 1928 to earn her degree in chemistry. There, she decided to focus on crystallography, the study of molecular shapes, on the advice of her tutor (3). “I became captivated by the edifices chemists had raised through experiment and imagination, but still I had a lurking question,” she would later write in her 1964 Nobel Lecture (4). “Would it not be better if one could really ‘see’ whether molecules as complicated as the sterols or strychnine were just as experiment suggested?”

She accepted a postgraduate position at Cambridge University, where she began her work with X-ray crystallography, the technique of calculating the molecular structure of a crystal based on how X-rays are photographed when diffracting. While she was earning her PhD, her laboratory became the first to photograph an X-ray of a protein crystal, proving that organic molecules could, in fact, crystallize (5).

During this time, Hodgkin was also diagnosed with ulna deviation, a condition caused by swelling in the knuckles (6). While she would wrestle with joint pain throughout her life, it never affected her success.

After earning her doctorate, Hodgkin returned to Oxford, where she remained for most of her career. With new knowledge about the crystallization of organic molecules, she began to study the structure of insulin. “Our hope,” she wrote in her Nobel Lecture (4), “is that a complete knowledge of the molecular geometry, how the peptide chains fit together within the molecule and the molecules within crystals, may make it possible for us to understand and control its behavior.”

Hodgin would eventually, in 1969, create a detailed map of insulin, but her initial work soon took a backseat to what was considered a more pressing need. “We were encouraged to try our operations on penicillin,” she wrote in her Nobel Lecture (4). “I grew crystals for X-ray analysis from 3 mg of the sodium salt flown over during the war.” With 17 atoms, penicillin took 4 years to map (5). The project was completed in 1945, just as World War II came to an end.

Hodgkin’s next breakthrough was with B12, mapping the vitamin’s 181 atoms. Other proteins followed. Then, after 34 years of work, Hodgkin finally completed her work with insulin, mapping its 788 atoms (5).

“The quite interesting thing was the zinc in the middle. There were two zincs because there are six molecules . . . two groups of three, one above the other,” she said in her interview with the Biochemical Society (1). “The first three-dimensional maps of insulin . . . [featured] this very pretty hexameric group of molecules fitting together.”

This completion of her work with insulin came late in her career. By then, Hodgkin had already won the Nobel Prize in Chemistry in 1964. Her research expanded the scientific understanding of what could be accomplished through X-ray crystallography and made it easier to manufacture life-saving drugs. Throughout her career, Hodgin encouraged scientific cooperation for the betterment of humankind. She fought for the inclusion of Soviet and Chinese scientists in the International Union of Crystallography during the Cold War and later served as president of the Pugwash Conferences on Science and World Affairs, a scientific collective established to diminish the threat of nuclear weapons (5).

The American Diabetes Association is celebrating the contributions of female scientists like Dorothy Hodgkin. The cover of Diabetes Care features the artwork of Rachel Ignotofsky, a New York Times best-selling author and illustrator known for her work in promoting scientific literacy and addressing the gender gap in STEM. Ignotofsky also created an interactive, collaborative mural for the American Diabetes Association’s 84th Scientific Sessions that featured Hodgkin alongside two other prominent scientists who advanced diabetes research. Conference participants were invited to actively engage with the mural by coloring it in, creating an interactive tribute to these trailblazing women in science.