Dorothy Hodgkin (1910-94)

NEWS AND VIEWS

10 utions to biological problems and the example of this is found in the Picornavir RNA . Indeed, like many really useful relative simplicity of the fusion mechan idae which, in spite of possessing no lipid biological engines, this one pops up in ism in influenza virus suggest that other and hence having no need of membrane disparate contexts, for instance in what is systems may employ different tactics. On fusion to get their genetic material into the perhaps the most dramatic irreversible the other, the strategy of using proteolytic cell, appear to drive infection in an analo structural rearrangement yet seen among cleavage to set a molecular trap seems to gous way. In this case, cleavage of the eukaryotic protein molecules, the serpin 11 have found more general application. polypeptide chains during maturation of family of protease inhibitors . D Thus many viruses produce precursor the capsid seems to prime the virus for polyproteins which are cleaved to form pH- or receptor-mediated extrusion of a David Stuart is in the Laboratory of Molecu• the mature polypeptides, often with sub hydrophobic structure into the host cell lar Biophysics, Rex Richards Building, stantial separation of the freed ends. An membrane, initiating release of the viral South Parks Road, Oxford OX1 3QU, UK. OBITUARY------, Dorothy Hodgkin (1910-94)

DOROTHY Hodgkin died on 29 July, thirty The next challenge was vitamin B12, rendered the determination of heavy years after her receipt of the Nobel Prize which contains more than four times as atom positions needed for isomorphous for Chemistry "for her determination by many atoms as penicillin. But in 1948, replacement extremely difficult. Dorothy X-ray techniques of the structures of when Dorothy took the first X-ray pic• was delighted when, in 1988, a genetical· biologically important molecules". Each tures, even its molecular weight was ly modified human insulin promised an of her structures extended X-ray crystal· unknown. She records that "the discov- improved treatment for diabetes. This lography to molecules of greater com· could not have been designed without the plexity than any previously analysed. She ~ structure on which she had laboured for established it as one of the fastest most of her active life. methods of finding the chemical con· Dorothy Hodgkin radiated love: for stitution of natural products; nuclear science, her family, her friends, her stu· magnetic resonance has since become dents and her crystals. That love was the other. combined with a brilliant mind and an In 1943, Dorothy solved her first struc· iron will to succeed. Her uncanny knack ture, that of cholesterol iodide. She of solving structures owed much to her assumed that the scattering contribu· wide knowledge of stereochemistry (she tions of the heavy iodine atoms out· used to write the chapters on crystal weighed the combined ones of all the structures for the Annual Reports of the light atoms and hence determined the Chemical Society and kept all their phases; but because the two iodines in stereochemistry in her head). She and the unit cell are related by a centre of her students had to solve their structures symmetry, and the molecule contains laboriously by taking series of Weissen· chiral centres, this gave the right struc• berg photographs with weak X-rays from ture superimposed on its mirror image. sealed tubes, by estimating the intensi· Undeterred, she devised an ingenious ties of hundreds or even thousands of way of distinguishing the correct from Dorothy Hodgkin- a brilliant mind and an spots visually, and by calculating struc· the spurious peaks in the electron densi· iron will to succeed. ture factors and initially even Fouriers on ty map, and the structure fell out. She was manually operated calculators. Any of disappointed when it added merely a few ery of the cobalt atom ... first stimulated these structures could now be solved in a stereochemical details to the formula of us to attempt a detailed investigation". few days by feeding X-ray data collected cholesterol already elucidated by the Dorothy solved its structure and discov· on computer-controlled diffractometers chemists. ered its remarkable chemical constitu· into other computers programmed to Penicillin, first isolated in 1942 by tion by her imaginative, bold interpreta• find atomic positions automatically by Ernst Chain a stone's throw away from tion of three-dimensional Patterson tunc· direct methods. Even Dorothy's favourite Dorothy's Oxford laboratory, presented a tions and of blurred electron-density molecule, insulin, with a molecular greater challenge because its chemical maps phased on the cobalt atom alone, weight of 5,n8, is now beginning to yield constitution was then still unknown. In· ingeniously picking out the significant to direct methods, and may also soon be itially the crystals proved useless, and peaks from a jungle of spurious ones. To solved automatically. She would have she had to wait until February 1944 when succeed, she had to shed the obvious rejoiced at that phenomenal progress of the first good ones arrived from the assumption that the groups surrounding X-ray analysis. United States. Fourier projections of the the cobalt were pyrrole rings as in por• Science apart, Dorothy's life was de· sodium salt phased by the heavy atom phyrins and discovered the quite novel voted to many good causes. But I thought method, and of the rubidium and potas· ring structure which she named corrin. that in this memoir I should concentrate sium salts phased by isomorphous re· In 1935, at the very start of her career, on her research rather than her work for placement, gave only the vaguest out• Dorothy had prepared her first crystals peace, for the Third World, or the stu· lines of the molecule. Again, Dorothy of insulin and discovered their rich X-ray dents of Somerville College and of Bristol refused to be discouraged. By a remark· diffraction pattern which made her de· University of which she was Chancellor. able piece of chemical intuition, she termined to solve its structure. She per• In Nature she would have wanted to be inferred the right answer and proved it by severed with her attempts in parallel with remembered above all as the superb an elegant three-dimensional Fourier all her other work. To her disappoint· scientist she was. Max Perutz synthesis which revealed the complete ment, however, insulin did not yield until stereochemistry, including the very un· 1969, mainly because it crystallized in Max Perutz is in the MRC Laboratory of usual f3·1actam ring proposed a few the rhombohedral space group R3 which Molecular Biology, Hills Road, Cambridge weeks earlier by E. P. Abraham. lacks centrosymmetric projections and CB2 2QH, UK.