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62 | Chemistry World | July 2010 www.chemistryworld.org Cracking crystal codes Cholesterol, , B12 …? Mike Sutton completes the list and explains the connection

The final item is and the link analysing more complex patterns in shorter wavelengths than visible is , the English the future. In short light – might be similarly scattered who unravelled their Among the books which  Dorothy Hodgkin by atoms inside crystals. Two of his molecular structures. Outside the encouraged Dorothy’s enthusiasm for was a pioneer of x-ray assistants beamed x-rays at a crystal lab, she was a committed political science were two volumes based on , a and successfully photographed the activist who raised three children Sir William Bragg’s structural elucidation resulting diffraction pattern. – often in the absence of a busy lectures for children. They alerted technique still widely The Braggs refined this technique husband – despite being increasingly her to the x-ray crystallographic used today and calculated the arrangement handicapped by arthritis from her discoveries which earned Bragg and  She cracked the of atoms in simple crystals such as late 20s onwards. The very model of his son Lawrence the 1915 structure of many sodium chloride. During the 1920s a modern multitasking mother, she in physics. While seeking a research medically important more complex substances were was the calm centre of her bustling project for the final year of her degree, molecules, earning her a investigated – Dame Kathleen world, and her many acts of kindness Dorothy learned that Oxford had Nobel prize in 1964 Lonsdale, for example, showed that were fondly remembered by former acquired an x-ray laboratory and a  Outside of chemistry, benzene rings were flat. students and colleagues. crystallographer – Herbert Powell she is remembered as a But although the basic physical She was born Dorothy Mary – capable of using it. She became warm friend and mother, principles were straightforward, Crowfoot on 12 May 1910 in , Powell’s first student, working in and a committed political deducing the positions of atoms in , where her father was conditions that would horrify a activist a crystal from the pattern of spots serving in the British imperial modern safety inspector. on an x-ray photograph (or from administration. After retiring as readings on an x-ray spectrometer) assistant director of education for X-raying history was a complex task. the Sudan, he became a full time The symmetry of crystals – from It was often done backwards archaeologist. Dorothy’s mother gemstones to salt and sugar – has – researchers first proposed a was a qualified midwife who had fascinated humankind for centuries. structure and calculated how considered becoming a missionary Philosophers and scientists often it would scatter x-rays. Then before her marriage. In Egypt, speculated that the geometry of a they aimed x-rays at crystals and she helped make modern medical crystal must be determined by its compared the result with their techniques available to local women. internal structure. But it was not calculations. This worked on simple During school holidays until 1895 that Wilhelm Röntgen’s salts, but for larger molecules Dorothy travelled widely with discovery of x-rays offered a means Dorothy Hodgkin has the chances of success were slim. her parents, but she saw them of confirming this. featured on several UK infrequently while being educated Diffraction – the scattering of light postage stamps in . Nominally in the care to produce colourful interference of relatives, she grew used to taking patterns – is now an everyday sight responsibility for herself and on compact disks and holograms, but her younger sisters. After being the phenomenon was noticed long accepted by Somerville College (at ago in naturally occurring objects, the ) to read from bird feathers to oily films on chemistry in 1928, Dorothy spent puddles. In the 19th century, Thomas the summer vacation on her parents’ Young and Augustin Fresnel showed archaeological dig at Jerash, in how diffraction was explained what is now Jordan. Recording the by the wave theory of light, and geometrical designs of a Byzantine in 1912 Max von Laue suggested mosaic floor there prepared her for that Röntgen’s x-rays – which had www.chemistryworld.org Chemistry World | July 2010 | 63 Historical profile

With organic compounds, even obtaining stable crystals was often problematic. Dorothy later remarked: ‘I should not like to leave an impression that all structural problems can be settled by x-ray analysis or that all crystal structures are easy to solve. I seem to have spent much more of my life not solving structures than solving them.’

Dorothy takes to the stage The first molecules Dorothy tackled were dimethylthallium halides like Th(CH3)2Br, and with Powell’s guidance she confirmed their expected configuration. After graduating with first class honours, she moved on to Desmond Bernal’s University of lab, then a leading centre for x-ray crystallography. Soon after arriving in 1932 she became his most valued assistant, co-authoring 12 of his

published papers between 1933 and LIBRARY PHOTO SCIENCE / MEADOWS MATT 1936 while working on her own PhD. Their x-ray work could not intuition were tested by prolonged determine complete structures number crunching, which sometimes for organic compounds, but it gave approximate answers capable of sometimes revealed enough further refinement, and sometimes to decide between alternative didn’t. structures suggested by the In 1934, a sophisticated form of Hodgkin worked out the was Oxford through and through . However, their most Fourier analysis was developed complete structure of – his grandfather had been master notable success was demonstrating by Arthur Lindo Patterson, a New penicillin by spring 1945 of Balliol College, his father was a for the first time that a Zealand-born crystallographer – but the results were not history don at Queen’s College, and he () had a regular molecular working at Massachusetts Institute of published until 1949 himself had won first class honours in structure – though they were unable Technology in the US. It enabled him classics. When Dorothy met him he to give a detailed picture of it. to calculate electron density maps for had already abandoned two jobs (first Bernal was unable to find Dorothy some organic molecules, and infer in archaeology, then in government a permanent job at Cambridge. So molecular structures from them. He service in the Middle East), and was when Somerville College offered her showed that if a heavy atom could be beginning what eventually became a a fellowship in 1934 she returned substituted into the molecule without successful career in adult education. to Oxford, successfully completing disrupting it, then the position of that They were both politically radical, her Cambridge PhD under Bernal’s atom could usually be established and in 1938 campaigned together supervision in 1936. Encouraged by with confidence. This made it (despite Dorothy’s pregnancy) for the of organic chemistry, easier to confirm or reject possible the anti-appeasement candidate in Sir Robert Robinson (see Chemistry molecular structures. Oxford’s controversial parliamentary World, April 2010, p54), she At Oxford, Dorothy began by-election. continued applying x-ray analysis creating Patterson maps of organic When appeasement failed and war to numerous organic compounds, molecules. The work was slow began, chemists at the University using a new interpretative method and resource intensive, but grants of Oxford prioritised research on a

V&A IMAGES/VICTORIA AND ALBERT MUSEUM ALBERT AND IMAGES/VICTORIA V&A involving Fourier transforms which from ICI and the Rockefeller new wonder drug. At first Dorothy provided more details of their foundation gradually helped her couldn’t help much, because molecular structures. establish better facilities. With her penicillin wouldn’t crystallise. But Fourier analysis is a mathematical graduate student Harry Carlisle, she its breakdown products did (more technique for converting a finally confirmed the 3D molecular or less), so she worked on them with complicated periodic function structure of cholesterol iodide by . She wrote to Thomas: into several simpler ones. During x-ray analysis in 1942. It was the first ‘I’ve spent my whole day looking the 1920s crystallographers used time this had been achieved with down a microscope teasing things it to relate the regular patterns a biologically significant molecule with a pin.’ (Not easy with Dorothy’s of spots on an x-ray diffraction – but celebrations were muted, as already arthritic hands.) Then, US photograph to the molecular more urgent tasks awaited her. researchers managed to crystallise structure which generated them. the sodium salt of benzyl penicillin Unfortunately, some terms in the Getting personal A wallpaper design based – ‘Penicillin II’ – and Dorothy got Fourier series could not be deduced Marriage in 1937, motherhood in 1938, on Hodgkin’s initial a tiny sample to yield diffraction from diffraction patterns, and had and war in 1939 had not inhibited structure of insulin was photographs. Interpreting them to be estimated by indirect means. Dorothy’s research. Her husband, created for the 1951 remained problematic throughout Structures based on chemical Thomas Hodgkin, understood. He 1944. 64 | Chemistry World | July 2010 www.chemistryworld.org Eventually the ‘heavy atom’ molecule she wanted to crack. In the technique enabled Dorothy to 1930s she had found insulin too large confirm the molecule’s 2D structure and complex to resolve. However, by comparing Patterson maps for by 1955 had penicillin’s potassium and rubidium discovered its sequence, salts. After she gained access to better and in 1959 Dorothy resumed the computing facilities (a punched-card search for its 3D structure. machine used for tracking ships’ By now severely afflicted with cargoes), the Fourier calculations arthritis, she was helped by talented sped up allowing her to pursue a young co-workers like Marjorie 3D molecular model. By the spring Harding, Sivaraj Ramaseshan, Guy of 1945 Dorothy and her assistants Dodson, Mamannamana Vijayan

PUGWASH CONFERENCES ON SCIENCE AND WORLD AFFAIRS WORLD AND SCIENCE ON CONFERENCES PUGWASH had got the complete structure. and . Their efforts Frustratingly, the publication of a full were essential to the project’s account of this triumph was delayed success, but it was Dorothy who – first by security restrictions, then by co-ordinated them all, and her vision commercial ones – until 1949. and enthusiasm that sustained them By then Dorothy was a through many disappointments to of the UK’s Royal Society, and ultimate triumph in 1969. stalking bigger molecules. It had Dorothy continued working on been known since the 1920s that insulin until 1988, locating its atoms pernicious anaemia was caused by with ever greater precision, but a diet deficient in , but was increasingly in demand outside the pure compound was not isolated the laboratory. As chancellor of until 1948. Lester Smith of Glaxo gave from 1970 she did Dorothy some crystals, and having far more than the usual ceremonial learned that it contained cobalt – duties. In 1975 she became president another useful heavy atom – she of the Pugwash Conferences on started investigating. of Ghana.) In the family tradition, Hodgkin with the Science and World Affairs, whose aim Thanks to Ken Trueblood at the their children were scattered structure of insulin, is ‘to bring together, from around the University of California, Los Angeles around the globe – Luke lecturing which she finally cracked world, influential scholars and public in the US, Dorothy had access to at an Algerian university, Elizabeth in 1969 figures concerned with reducing the much greater computing power for school-teaching in Zambia, and Toby danger of armed conflict and seeking the Fourier syntheses. Nevertheless, spending a gap year in India – but cooperative solutions for global the structure of this large and most of the family managed to attend problems’. And despite their political complex molecule remained the prize giving celebrations in differences, her advice on scientific unresolved until 1954. Many Stockholm, Sweden. issues was occasionally requested by individuals and several institutions Thereafter, Dorothy could easily Vitamin B12 – one of the one of her former chemistry students, contributed essential pieces to the have become a scientific bureaucrat, structure elucidations , who became the puzzle, but everyone (except some dispensing advice and funds to rising that won her the 1964 UK’s first female prime minister in chemists) youngsters. But there was another 1979. acknowledged Dorothy as the Dorothy died in 1994, 12 years driving force behind its completion. after her husband, and was fondly Meanwhile, her Oxford lab became a remembered by all who knew her. finishing school for promising young Another Nobel prize-winning crystallographers from all over the crystallographer, , world. recalled, ‘there was magic about her Dorothy’s peripatetic childhood person. She had no enemies, not had made her an internationalist. even among those whose scientific (She visited the theories she demolished or whose – the precursor for the UN – in political views she opposed. It was 1925 and admired its ideals, if not marvellous to have her drop in on you its achievements.) After becoming in your lab, like the spring.’ a prominent figure in the global

SCIENCE AND SOCIETY PICTURE LIBRARY - SCIENCE MUSEUM SCIENCE - LIBRARY PICTURE SOCIETY AND SCIENCE scientific community, she tried to Mike Sutton is a visiting fellow in use her influence in the interests the department of humanities of of peace and justice whenever she Northumbria University, UK could. But this was the era of the Cold war, and some of her actions aroused Further reading suspicion in the US, where she was G Dodson, Dorothy Mary Crowfoot Hodgkin in refused an entry visa for several years. Biographical Memoirs of of the Royal Society, 2002, 48, p179-219 G Ferry, Dorothy Hodgkin: a life, Granta Publica- Nobel intentions tions, London, UK, 1998 News that she had won the 1964 G Ferry, lecture on x-ray crystallography in Well- Nobel prize in chemistry reached come collection www.wellcomecollection.org/ Dorothy and her husband while they explore/education/topics/how-science-works/ video.aspx?view=georgina-ferry were in Africa. (In 1961, Thomas had D Hodgkin, Nobel lecture 11 December 1964 become director of the Institute of http://nobelprize.org/nobel_prizes/chemistry/ African Studies at the University laureates/1964/hodgkin-lecture.html

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