🇬🇧Dorothy
Hodgkin

She was eight years old when she first encountered crystals. Dorothy Crowfoot — not yet Hodgkin — found some mineral specimens in Sudan during one of the journeys that punctuated her childhood, and was captivated not just by their visual beauty but by the question behind them: why did matter arrange itself this way? Why did atoms lock into repeating geometries, and what could those geometries reveal about the atoms themselves? The question would organize her entire scientific life. By the time she died at eighty-four, she had determined the three-dimensional atomic structures of some of the most important biological molecules in medicine — structures so complex, using technology so primitive by modern standards, that her contemporaries often considered her targets impossible before she achieved them. They were not impossible. They just required her.

Dorothy Crowfoot was born in Cairo on May 12, 1910, to British parents engaged in archaeological and educational work in Egypt and Sudan. Her childhood was geographically scattered and intellectually rich. She came to chemistry through the soil — literally: she was given a mineral analysis kit as a child and became absorbed in the chemistry of the samples she collected in North Africa. She enrolled at Somerville College, Oxford, in 1928, one of the only colleges at Oxford that admitted women, and read chemistry. Oxford did not grant women full degrees until 1920, barely a decade before she arrived. She performed brilliantly, graduated in 1932, and went to Cambridge to study X-ray crystallography under John Desmond Bernal — one of the most creative and unorthodox scientists of the twentieth century and a decisive influence on her scientific development.

X-ray crystallography works by directing X-ray beams through a crystalline substance and recording the diffraction pattern of the scattered rays on photographic film. From the pattern of dots and arcs, a crystallographer can — in principle — work backward to determine the three-dimensional arrangement of atoms in the crystal. In practice, in the 1930s and 1940s, this required solving a mathematical problem of enormous complexity by hand, with slide rules and graph paper, from data of limited quality. Hodgkin was exceptional at this. She had spatial intuition of a rare kind — she could hold three-dimensional molecular structures in her mind and rotate them, interrogate them, build toward a solution that others could not see. In 1934, she and Bernal obtained the first X-ray diffraction photograph of a crystalline protein — pepsin — demonstrating that it was possible in principle to determine the structures of these complex molecules. The experimental program would take decades.

She returned to Oxford in 1934 and remained there for the rest of her career. She had rheumatoid arthritis in her hands from her mid-twenties — the disease progressively deformed her fingers, making fine laboratory work increasingly difficult — but she adapted her methods and continued. She also married the historian Thomas Hodgkin in 1937, had three children, and sustained a research program of extraordinary productivity throughout. In 1945 she determined the three-dimensional structure of penicillin, solving a problem that had seemed intractable: the molecule was not large by modern standards, but the crystallographic computing required was beyond the capacity of any available calculator. The result — the first complete structure of a biologically active molecule of its complexity — was immediately useful to pharmaceutical chemists designing synthetic routes to the antibiotic.

If penicillin was remarkable, vitamin B12 was extraordinary. B12 is a cobalt-containing compound essential for nerve function and red blood cell formation, and its deficiency causes pernicious anaemia. It was isolated in the late 1940s; its structure was entirely unknown. The molecule has 181 atoms — far larger than anything previously solved by crystallography. Hodgkin began working on it in the late 1940s, in collaboration with colleagues at Oxford and with American crystallographers. The computation involved was so massive that she enlisted one of the first electronic computers — Ferranti MARK 1 — to help calculate the electron density maps. After eight years of work, in 1956, she determined the complete structure of vitamin B12. The Nobel Committee called it one of the most brilliant uses of X-ray analysis ever performed. In 1964, she received the Nobel Prize in Chemistry — the third woman to receive the Nobel in that discipline, after Marie Curie and Irène Joliot-Curie.

She did not stop. Insulin had been her dream target since 1934, when she obtained the first X-ray diffraction images of insulin crystals as a young graduate student. Insulin is a hormone produced by the pancreas that regulates blood sugar, and its structure was crucial to understanding diabetes and developing synthetic insulin. The molecule is far larger than B12: over 800 atoms. Hodgkin and her team worked on it for thirty-five years — across the entire span of her Nobel-prize-winning career — finally solving the complete three-dimensional structure of insulin in 1969. She was fifty-nine. The structure made possible the engineering of modified insulins with improved therapeutic properties. Today, millions of diabetic patients worldwide benefit from synthetic insulin variants designed with knowledge of the structure Dorothy Hodgkin spent three and a half decades determining.