Exactly 50 years ago, a Nobel Prize was awarded which we have much reason to be reminded of today. Max von Laue was awarded the 1914 Nobel Prize for physics for, according to the citation, "his discovery of the diffraction of X-rays by crystals". It is this phenomenon which has formed the basis of the work for which Mrs. Dorothy Crowfoot Hodgkin has been awarded the Nobel Prize for chemistry this year.
Very soon after von Laue's discovery, the two English scientists Bragg, father and son, began to apply X-ray diffraction in order to determine how the atoms of a compound are situated in relation to each other in a crystal. In other words, they tried to find out what is usually known as the "structure" of the compound. Their successes in this field resulted in their being jointly awarded the 1915 Nobel Prize for physics.
Knowledge of a compound's structure is absolutely essential in order to interpret its properties and reactions and to decide how it might be synthetized from simpler compounds. To begin with, only very simple structural problems could be solved by X-ray diffraction, and these problems were taken almost entirely from the field of inorganic chemistry. Organic compounds, compounds containing carbon, usually have more complicated structures, and these presented too many difficulties at this stage. However, even then considerable possibilities existed for determining how the atoms of an organic compound are bonded to each other, by purely chemical methods. These methods were based largely upon the knowledge obtained from the latter half of the nineteenth century concerning the geometry of the bonds directed from a carbon atom. Large molecules were broken down into components whose structures were already known, and when some idea had been obtained of how these components were joined together in the large molecule this could often be confirmed by synthetizing the molecule.
Gradually, however, such large and complicated molecules were reached that these "classical" methods no longer yielded a result. This was particularly so in the case of the structures of many of the molecules which form part of living organisms and participate in the vital processes. In these instances it was necessary to obtain help from the field of physics, and in the first place use was made of X-ray diffraction by crystals of the compound concerned. During the period following the discovery of X-ray diffraction, this method of structure determination had been developed to such a degree that by the 1940's it began to be possible to use it for solving the structures of organic compounds which were insoluble by classical methods.
However, even today structure determination by X-ray methods does not yield a direct route from the experimental data to the structure. In complicated cases the scientist only obtains a result after considerable mental effort, in which chemical knowledge, imagination and intuition play a significant part. In addition, the experimental data often have to be processed using different mathematical treatments, which must be varied according to the circumstances. Add to this the fact that the more complicated the structure, the greater becomes the volume of experimental data which must be amassed and processed. For relatively simply built compounds it was possible to carry out the calculations with pencil and paper. Nowadays it is nearly always necessary to use electronic computers, and their arrival has made an enormous difference to the possibility of carrying out structure determinations. However, it is not usually possible to just feed in the experimental data, and get out the figures which give the final structure; the scientist's ability to handle the data is still of vital importance. It is in this respect that Mrs. Hodgkin has shown such exceptional skill.
Mrs. Hodgkin has carried out a large number of structure determinations, primarily of substances which are of importance biochemically and medically, but two of these substances deserve especial mention. These are penicillin and vitamin B12, whose structures have become completely and definitely known through her efforts.
The use of penicillin in medicine began to be tested about the beginning of the second world war, and its exceptional antibiotic properties meant that the demand increased enormously. It was therefore obviously desirable to find out whether penicillin itself or other related compounds having a similar effect could be prepared by chemical methods. For this purpose it was essential to determine the composition and structure of penicillin, and a large number of chemists and X-ray crystallographers in both England and the U.S.A. were put on to this problem. Mrs. Hodgkin was to play a leading part in the X-ray crystallographic work, and it was chiefly her efforts which brought it to a satisfactory conclusion. The work was begun in 1942 and the structure was elucidated after four years' intensive work. This was marked by close cooperation between organic chemists, X-ray crystallographers and scientists in other branches of physical chemistry and physics. A number of X-ray crystallographic methods were also used here for the first time.
Mrs. Hodgkin's determination of the structure of penicillin bears evidence of exceptional skill and great perseverance. The difficulties were considerable, but this was not because the molecule was particularly large. However, it possessed some unknown features, which meant that the chemical properties did not give sufficient guidance.
In 1948 Mrs. Hodgkin began her attempts to determine the structure of vitamin B12, which had been isolated in the same year. This vitamin can be synthetized by certain bacteria and fungi, of which some play an active part in the digestive processes of animals. The production of B12 is most pronounced in the ruminants, who seem to require this vitamin in particularly large amounts. In most of the other higher animals, for example in man, the production of B12 is small, and their food must therefore contain sufficient quantities of ready-made B12. Lack of B12 in the diet, or a reduced ability to absorb this vitamin via the walls of the alimentary canal, leads in man to the fatal blood condition of pernicious anaemia. The illness can always be arrested by injections of B12 which is only needed in very small quantities. It is still not clear how B12 functions in the metabolic processes, but in order to begin to come to grips with this problem it is essential to know the structure in detail.
In 1956, after eight years' work, Mrs. Hodgkin and her collaborators had clarified the B12 structure. Never before had it been possible to determine the exact structure of so large a molecule, and the result has been seen as a triumph for X-ray crystallographic techniques. It was also, however, a triumph for Mrs. Hodgkin. It is certain that the goal would never have been reached at this stage without her skill and exceptional intuition.
There is reason to hope that the detailed knowledge of the B12 structure, revealed as a result of this work, will make it possible both to understand how this vitamin assists in the body's metabolism and to synthetize it. For the time being it has to be produced via bacterial fermentation.
Dorothy Crowfoot was born in Cairo on May 12th, 1910 where her father, John Winter Crowfoot, was working in the Egyptian Education Service. He moved soon afterwards to the Sudan, where he later became both Director of Education and of Antiquities; Dorothy visited the Sudan as a girl in 1923, and acquired a strong affection for the country. After his retirement from the Sudan in 1926, her father gave most of his time to archaeology, working for some years as Director of the British School of Archaeology in Jerusalem and carrying out excavations on Mount Ophel, at Jerash, Bosra and Samaria.
Her mother, Grace Mary Crowfoot (born Hood) was actively involved in all her father's work, and became an authority in her own right on early weaving techniques. She was also a very good botanist and drew in her spare time the illustrations to the official Flora of the Sudan. Dorothy Crowfoot spent one season between school and university with her parents, excavating at Jerash and drawing mosaic pavements, and she enjoyed the experience so much, that she seriously considered giving up chemistry for archaeology.
She became interested in chemistry and in crystals at about the age of 10, and this interest was encouraged by Dr. A.F. Joseph, a friend of her parents in the Sudan, who gave her chemicals and helped her during her stay there to analyse ilmenite. Most of her childhood she spent with her sisters at Geldeston in Norfolk, from where she went by day to the Sir John Leman School, Beccles, from 1921-28. One other girl, Norah Pusey, and Dorothy Crowfoot were allowed to join the boys doing chemistry at school, with Miss Deeley as their teacher; by the end of her school career, she had decided to study chemistry and possibly biochemistry at university.
She went to Oxford and Somerville College from 1928-32 and became devoted to Margery Fry, then Principal of the College. For a brief time during her first year, she combined archaeology and chemistry, analysing glass tesserae from Jerash with E.G.J. Hartley. She attended the special course in crystallography and decided, following strong advice from F.M. Brewer, who was then her tutor, to do research in X-ray crystallography. This she began for part II Chemistry, working with H.M. Powell, as his first research student on thallium dialkyl halides, after a brief summer visit to Professor Victor Goldschmidt's laboratory in Heidelberg.
Her going to Cambridge from Oxford to work with J.D. Bernal followed from a chance meeting in a train between Dr. A.F. Joseph and Professor Lowry. Dorothy Crowfoot was very pleased with the idea; she had heard Bernal lecture on metals in Oxford and became, as a result, for a time, unexpectedly interested in metals; the fact that in 1932 he was turning towards sterols, settled her course.
She spent two happy years in Cambridge, making many friends and exploring with Bernal a variety of problems. She was financed by her aunt, Dorothy Hood, who had paid all her college bills, and by a ?75 scholarship from Somerville. In 1933, Somerville, gave her a research fellowship, to be held for one year at Cambridge and the second at Oxford. She returned to Somerville and Oxford in 1934 and she has remained there, except for brief intervals, ever since. Most of her working life, she spent as Official Fellow and Tutor in Natural Science at Somerville, responsible mainly for teaching chemistry for the women's colleges. She became a University lecturer and demonstrator in 1946, University Reader in X-ray Crystallography in 1956 and Wolfson Research Professor of the Royal Society in 1960. She worked at first in the Department of Mineralogy and Crystallography where H.L. Bowman was professor. In 1944 the department was divided and Dr. Crowfoot continued in the subdepartment of Chemical Crystallography, with H.M. Powell as Reader under Professor C.N. Hinshelwood.
When she returned to Oxford in 1934, she started to collect money for X-ray apparatus with the help of Sir Robert Robinson. Later she received much research assistance from the Rockefeller and Nuffield Foundations. She continued the research that was begun at Cambridge with Bernal on the sterols and on other biologically interesting molecules, including insulin, at first with one or two research students only. They were housed until 1958 in scattered rooms in the University museum. Their researches on penicillin began in 1942 during the war, and on vitamin B12 in 1948. Her research group grew slowly and has always been a somewhat casual organisation of students and visitors from various universities, working principally on the X-ray analysis of natural products.
Dorothy Hodgkin took part in the meetings in 1946 which led to the foundation of the International Union of Crystallography and she has visited for scientific purposes many countries, including China, the USA and the USSR. She was elected a Fellow of the Royal Society in 1947, a foreign member of the Royal Netherlands Academy of Sciences in 1956, and of the American Academy of Arts and Sciences (Boston) in 1958.
In 1937 she married Thomas Hodgkin, son of one historian and grandson of two others, whose main field of interest has been the history and politics of Africa and the Arab world, and who is at present Director of the Institute of African Studies at the University of Ghana, where part of her own working life is also spent. They have three children and three grandchildren. Their elder son is a mathematician, now teaching for a year at the University of Algiers, before taking up a permanent post at the new University of Warwick. Their daughter (like many of her ancestors) is an historian-teaching at girls' secondary school in Zambia. Their younger son has spent a pre-University year in India before going to Newcastle to study Botany, and eventually Agriculture. So at the present moment they are a somewhat dispersed family.
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