For her work with vitamin B-12, Dorothy Crowfoot Hodgkin (1910-1994) was awarded the Nobel Prize in chemistry.
Dorothy Crowfoot Hodgkin
Dorothy Crowfoot Hodgkin employed the technique of X-ray crystallography to determine the molecular structures of several large biochemical molecules. When she received the 1964 Nobel Prize in chemistry for her accomplishments, the committee cited her contribution to the determination of the structure of both penicillin and vitamin B 12.
Hodgkin was born in Egypt on May 12, 1910 to John and Grace (Hood) Crowfoot. She was the first of four daughters. Her mother, although not formally educated beyond finishing school, was an expert on Coptic textiles, and an excellent amateur botanist and nature artist. Hodgkin's father, a British archaeologist and scholar, worked for the Ministry of Education in Cairo at the time of her birth, and her family life was always characterized by world travel. When World War I broke out, Hodgkin and two younger sisters were sent to England for safety, where they were raised for a few years by a nanny and their paternal grandmother. Because of the war, their mother was unable to return to them until 1918, and at that time brought their new baby sister with her. Hodgkin's parents moved around the globe as her father's government career unfolded, and she saw them when they returned to Britain for only a few months every year. Occasionally during her youth she travelled to visit them in such far-flung places as Khartoum in the Sudan, and Palestine.
Hodgkin's interest in chemistry and crystals began early in her youth, and she was encouraged both by her parents as well as by their scientific acquaintances. While still a child, Hodgkin was influenced by a book that described how to grow crystals of alum and copper sulfate and on X rays and crystals. Her parents then introduced her to the soil chemist A. F. Joseph and his colleagues, who gave her a tour of their laboratory and showed her how to pan for gold. Joseph later gave her a box of reagents and minerals which allowed her to set up a home laboratory. Hodgkin was initially educated at home and in a succession of small private schools, but at age eleven began attending the Sir John Leman School in Beccles, England, from which she graduated in 1928. After a period of intensive tutoring to prepare her for the entrance examinations, Hodgkin entered Somerville College for women at Oxford University. Her aunt, Dorothy Hood, paid the tuition to Oxford, and helped to support her financially. For a time, Hodgkin considered specializing in archaeology, but eventually settled on chemistry and crystallography.
Crystallography was a fledgling science at the time Hodgkin began, a combination of mathematics, physics, and chemistry. Max von Laue, William Henry Bragg and William Lawrence Bragg had essentially invented it in the early decades of the century (they had won Nobel Prizes in 1914 and 1915, respectively) when they discovered that the atoms in a crystal deflected X rays. The deflected X rays interacted or interfered with each other. If they constructively interfered with each other, a bright spot could be captured on photographic film. If they destructively interfered with each other, the brightness was cancelled. The pattern of the X-ray spots— diffraction pattern —bore a mathematical relationship to the positions of individual atoms in the crystal. Thus, by shining X rays through a crystal, capturing the pattern on film, and doing mathematical calculations on the distances and relative positions of the spots, the molecular structure of almost any crystalline material could theoretically be worked out. The more complicated the structure, however, the more elaborate and arduous the calculations. Techniques for the practical application of crystallography were few, and organic chemists accustomed to chemical methods of determining structure regarded it as a black art.
After she graduated from Oxford in 1932, Hodgkin's old friend A. F. Joseph steered her toward Cambridge University and the crystallographic work of J. D. Bernal. Bernal already had a reputation in the field, and researchers from many countries sent him crystals for analysis. Hodgkin's first job was as Bernal's assistant. Under his guidance, with the wealth of materials in his laboratory, the young student began demonstrating her particular talent for X-ray studies of large molecules such as sterols and vitamins. In 1934, Bernal took the first X-ray photograph of a protein crystal, pepsin, and Hodgkin did the subsequent analysis to obtain information about its molecular weight and structure. Proteins are much larger and more complicated than other biological molecules because they are polymers—long chains of repeating units—and they exercise their biochemical functions by folding over on themselves and assuming specific three-dimensional shapes. This was not well understood at the time, however, so Hodgkin's results began a new era; crystallography could establish not only the structural layout of atoms in a molecule, even a huge one, but also the overall molecular shape which contributed to biological activity.
In 1934, Hodgkin returned to Oxford as a teacher at Somerville College, continuing her doctoral work on sterols at the same time. (She obtained her doctorate in 1937). It was a difficult decision to move from Cambridge, but she needed the income and jobs were scarce. Somerville's crystallography and laboratory facilities were extremely primitive; one of the features of her lab at Oxford was a rickety circular staircase that she needed to climb several times a day to reach the only window with sufficient light for her polarizing microscope. This was made all the more difficult because Hodgkin suffered most of her adult life from a severe case of rheumatoid arthritis, which didn't respond well to treatment and badly crippled her hands and feet. Additionally, Oxford officially barred her from research meetings of the faculty chemistry club because she was a woman, a far cry from the intellectual comradery and support she had encountered in Bernal's laboratory. Fortunately, her talent and quiet perseverance quickly won over first the students and then the faculty members at Oxford. Sir Robert Robinson helped her get the money to buy better equipment, and the Rockefeller Foundation awarded her a series of small grants. She was asked to speak at the students' chemistry club meetings, which faculty members also began to attend. Graduate students began to sign on to do research with her as their advisor.
An early success for Hodgkin at Oxford was the elucidation of cholesterol iodide's molecular structure, which no less a luminary than W.H. Bragg singled out for praise. During World War II, Hodgkin and her graduate student Barbara Low worked out the structure of penicillin, from some of the first crystals ever made of the vital new drug. Penicillin is not a particularly large molecule, but it has an unusual ring structure, at least four different forms, and crystallizes in different ways, making it a difficult crystallographic problem. Fortunately they were able to use one of the first IBM analog computers to help with the calculations.
In 1948, Hodgkin began work on the structure of vitamin B-12 the deficiency of which causes pernicious anemia. She obtained crystals of the material from Dr. Lester Smith of the Glaxo drug company, and worked with a graduate student, Jenny Glusker, an American team of crystallographers led by Kenneth Trueblood, and later with John White of Princeton University. Trueblood had access to state of the art computer equipment at the University of California at Los Angeles, and they sent results back and forth by mail and telegraph. Hodgkin and White were theoretically affiliated with competing pharmaceutical firms, but they ended up jointly publishing the structure of B-12 in 1957; it turned out to be a porphyrin, a type of molecule related to chlorophyll, but with a single atom of cobalt at the center.
After the war, Hodgkin helped form the International Union of Crystallography, causing Western governments some consternation in the process because she insisted on including crystallographers from behind the Iron Curtain. Always interested in the cause of world peace, Hodgkin signed on with several organizations that admitted Communist party members. Recognition of Hodgkin's work began to increase markedly, however, and whenever she had trouble getting an entry visa to the U.S. because of her affiliation with peace organizations, plenty of scientist friends were available to write letters on her behalf. A restriction on her U.S. visa was finally lifted in 1990 after the Soviet Union disbanded.
In 1947, she was inducted into the Royal Society, Britain's premiere scientific organization. Professor Hinshelwood assisted her efforts to get a dual university/college appointment with a better salary, and her chronic money problems were alleviated. Hodgkin still had to wait until 1957 for a full professorship, however, and it was not until 1958 that she was assigned an actual chemistry laboratory at Oxford. In 1960 she obtained the Wolfson Research Professorship, an endowed chair financed by the Royal Society, and in 1964 received the Nobel Prize in chemistry. One year later, she was awarded Britain's Order of Merit, only the second woman since Florence Nightingale to achieve that honor.
Hodgkin still wasn't done with her research, however. In 1969, after decades of work and waiting for computer technology to catch up with the complexity of the problem, she solved the structure of insulin. She employed some sophisticated techniques in the process, such as substituting atoms in the insulin molecule, and then comparing the altered crystal structure to the original. Protein crystallography was still an evolving field; in 1977 she said, in an interview with Peter Farago in the Journal of Chemical Education, "In the larger molecular structure, such as that of insulin, the way the peptide chains are folded within the molecule and interact with one another in the crystal is very suggestive in relation to the reactions of the molecules. We can often see that individual side chains have more than one conformation in the crystal, interacting with different positions of solvent molecules around them. We can begin to trace the movements of the atoms within the crystals."
In 1937, Dorothy Crowfoot married Thomas Hodgkin, the cousin of an old friend and teacher, Margery Fry, at Somerville College. He was an African Studies scholar and teacher, and, because of his travels and jobs in different parts of the world, they maintained separate residences until 1945 when he finally obtained a position teaching at Oxford. Despite this unusual arrangement, their marriage was a happy and successful one. Although initially worried that her work with X rays might jeopardize their ability to have children, the Hodgkins had three: Luke, born in 1938, Elizabeth, born in 1941, and Toby, born in 1946. The children all took up their parents scholarly, nomadic habits, and at the time of the Nobel Ceremony travelled to Stockholm from as far away as New Delhi and Zambia. Although Hodgkin officially retired in 1977, she continued to travel widely and expanded her lifelong activities on behalf of world peace, working with the Pugwash Conferences on Science and World Affairs. Hodgkin died of a stroke on July 29, 1994, in Shipston-on-Stour, England.
Further Reading on Dorothy Crowfoot Hodgkin
McGrayne, Sharon B., Nobel Prize Women in Science, Carol Publishing Group, 1993.
Opfell, Olga S., The Lady Laureates, Scarecrow Press, 1986.
Journal of Chemical Education, Volume 54, 1977, p. 214.
Nature, May 24, 1984, p. 309.
New Scientist, May 23, 1992, p. 36.