Women in Crystallography
By Dr Kate Crennell
Crystallography, as a subject can be thought as starting in Australia between the years 1886 and 1909.
Sir William Henry Bragg (above left) OM, KBE, PRS (2 July 1862 – 12 March 1942) was a British physicist, chemist, mathematician and active sportsman who uniquely shared a Nobel Prize with his son William Lawrence Bragg (above right) – the 1915 Nobel Prize in Physics: “for their services in the analysis of crystal structure by means of X-rays”. The mineral Braggite is named after him and his son. He was knighted in 1920.
In 1885, (at the age of 23), Bragg was appointed (Sir Thomas) Elder Professor of Mathematics and Experimental Physics in the University of Adelaide, and started work there early in 1886. Initially he regarded himself as a mathematician but developed an interest in physics, particularly in the field of electromagnetism.
At the end of 1908 Bragg returned to England and occupied the Cavendish chair of physics in the University of Leeds from 1909. He continued his work on X-rays with much success. He invented the X-ray spectrometer and with his son, William Lawrence Bragg, then a research student at Cambridge, founded the new science of X-ray crystallography, the analysis of crystal structure using X-ray diffraction.
In 1915 father and son were jointly awarded the Nobel Prize in Physics for their studies, using the X-ray spectrometer, of X-ray spectra, X-ray diffraction, and of crystal structure. Ten years later, their volume X-Rays and Crystal Structure (1915) had reached a fifth edition.
Sir William Lawrence Bragg CH OBE MC FRS (31 March 1890 – 1 July 1971) was an Australian-born British physicist and X-ray crystallographer, discoverer (1912) of the Bragg law of X-ray diffraction, which is basic for the determination of crystal structure. He was joint winner (with his father, William Henry Bragg) of the Nobel Prize in Physics in 1915: “For their services in the analysis of crystal structure by means of X-ray” an important step in the development of X-ray crystallography.
X-ray spectrometer developed by Bragg
Dame Kathleen Lonsdale, DBE FRS (née Yardley, 28 January 1903 – 1 April 1971) was an Irish crystallographer, who finally proved that the benzene ring was flat by X-ray diffraction methods in 1929. She was the first to use Fourier spectral methods while solving the structure of hexachlorobenzene in 1931. During her career she attained a number of firsts for a woman scientist, including one of the first two women elected a Fellow of the Royal Society in 1945 (along with Marjory Stephenson), first woman tenured professor at University College London, first woman president of the International Union of Crystallography, and first woman president of the British Association for the Advancement of Science.
Kathleen was born on the 28th January 1903 in County Kildare Ireland. At the age of 5 her family re-located to Seven Kings Essex. She first went to Woodford County High school for girls but transferred to Ilford County High school for boys so she could study maths and science, subjects not offered at the girls’ school.
She gained a BSc from Bedford College for women in 192 and gained an MSc in physics from University College London in 1924.
In 1924, she joined the crystallography research team headed by William Henry Bragg at the Royal Institution.
After beginning her research career at the University of Leeds, in 1927 she married Thomas Lonsdale and they went on to have three children. During the early 1930s, she cared for her small children nearly full-time
In 1934, Lonsdale returned to work with Bragg at the Royal Institution as a researcher. She was awarded a DSc from University College London in 1936 while at the Royal Institution. In addition to discovering the structure of benzene and hexachlorobenzene, Lonsdale worked on the synthesis of diamonds. She was a pioneer in the use of X-rays to study crystals. Lonsdale was elected as one of the first two women Fellows of the Royal Society in 1945 (the other was the biochemist Marjory Stephenson).
In 1949, Kathleen became a professor of chemistry and the head of the Department of Crystallography at University College, London. Amongst her students was Karimat El-Sayed who became a Professor of Crystallography in Egypt. On a more personal level El-Sayed credits Lonsdale with demonstrating to her how a career and a family could be balanced. She was the first tenured woman professor at that college, a position she held until 1968 when she was named Professor Emeritus.
In 1956, she was given the title Dame Commander of the Order of the British Empire.
In 1966, she was elected as the first woman president of the International Union of Crystallography.
In 1967, active in encouraging young people to study science, she was elected as the first woman president of the British Association for the Advancement of Science.
A Kathleen Lonsdale Building is named in her honour at both University College London, UK and University of Limerick, Ireland.
In 1969, she was awarded an Honorary Degree (Doctor of Science) by the University of Bath.
Lonsdaleite, an allotrope of carbon, was named in her honour; it is a rare form of diamond found in meteorites.
Kathleen died on the 1st April 1971 from an anaplastic cancer of unknown origin. Her career long exposure to X-Rays is thought to have had a significant impact on her cancer risk.
Helen Dick Megaw (1 June 1907 – 26 February 2002) was an Irish crystallographer who was a pioneer in X-ray crystallography. She made measurements of the cell dimensions of ice and established the Perovskite crystal structure.
Helen was born in Dublin into a high achieving family. Her father was a high court judge and MP for North Antrim, her uncle was the director of the Indian Medical Service, one of her brothers was an engineer specialising in tunnels and another brother became a Lord Justice of appeal. It has been said that when one of Helen’s siblings obtained a second-class degree her father said it was nothing to celebrate.
Helen was educated at Alexandra College, Dublin from 1916 to 1921 and Roedean School (England) from 1922 to 1925. Normally she would have proceeded to Girton College, then the women’s college at Cambridge University, but apparently for financial reasons this was postponed and instead she matriculated at Queen’s University, Belfast, though she remained there one year only; awarded a scholarship she indeed proceeded to Girton to study natural sciences, where she graduated BA in 1930.
For the next four years she was a research student under J. D. Bernal, the outstanding British scientist who was amongst other distinctions a pioneer in X-ray crystallography, and was a rather forceful personality, who encouraged Helen to dedicate herself to this discipline; this was not especially difficult as she had already been developing an interest there, having read William Lawrence Bragg’s X-rays and Crystal Structure, the research on which had led to his being elected a Nobel laureate in 1915 (Helen read the book while still at school).
John Desmond Bernal FRS (10 May 1901 – 15 September 1971) was one of the United Kingdom’s best-known and most controversial scientists. Known as “Sage” to friends, Bernal is considered a pioneer in X-ray crystallography in molecular biology. He published extensively on the history of science.
Helen was awarded her PhD from Cambridge in 1934 and one of her first scientific specialties, the structure of “heavy” and “normal” ice, brought her the distinction of having an Antarctic island named after her.
Helen was in Vienna during 1934 to 1935 on a Hertha Aryton research scholarship which allowed her to study under Professor Hermann Francis Mark, the molecular scientist who occupied the chair in Chemistry at the university there.
Phoebe Sarah Hertha Ayrton (28 April 1854 – 23 August 1923) was an English engineer, mathematician, physicist, and inventor. She was awarded the Hughes Medal by the Royal Society for her work on electric arcs and ripples in sand and water.
Herman Francis Mark (May 3, 1895, Vienna – April 6, 1992, Austin, Texas) was an Austrian-American chemist regarded for his contributions to the development of polymer science.
In 1935 Helen published an article in the Proceedings of the Royal Society”, entitled “The Function of Hydrogen in Intermolecular Forces” published jointly with Bernal and describing their work on hydrogen bonding in metal hydroxides; the so-called Bernal-Megaw model” (to fix the position of hydrogen in trioctahedral layer hydroxides) derived from this influential article.
Helen moved to the Clarendon Laboratory, Oxford, during 1935-1936 where she continued her research under Professor Francis Simon, the outstanding German-born low-temperature physicist.
Sir Francis Simon, (2 July 1893 – 31 October 1956), was a German and later British physical chemist and physicist who devised the method, and confirmed its feasibility, of separating the isotope Uranium-235 and thus made a major contribution to the creation of the atomic bomb.
From 1936 until 1943 Helen worked as a school teacher, first at Bedford High School, then at Bradford Girls’ Grammar School but in 1943 she moved to Philips Lamps Ltd in Mitcham and it was here that she worked out the crystal structure of barium titanate, a significant industrial material: it is a ferroelectric ceramic material which is used to make capacitors found in items such as ultrasound machines; infrared cameras; microphones and other transducers. As a material it crystallises in the so-called perovskite structure, and Helen was the first to identify this; she became particularly renowned for her expertise in this area.
Barium titanate is the inorganic compound with the chemical formula BaTiO3. Barium titanate is a white powder and transparent as larger crystals.
The image below shows the structure of cubic BaTiO3. The red spheres are oxide centres, blue are Ti4+ cations, and the green spheres are Ba2+.
A perovskite is any material with the same type of crystal structure as calcium titanium oxide (CaTiO3), known as the perovskite structure with the oxygen in the face centres. Perovskites take their name from the mineral, which was first discovered in the Ural mountains of Russia by Gustav Rose in 1839 and is named after Russian mineralogist L. A. Perovski (1792–1856).
Ferroelectricity is a property of certain materials that have a spontaneous electric polarization that can be reversed by the application of an external electric field.
A capacitor (originally known as a condenser) is a passive two-terminal electrical component used to store energy electrostatically in an electric field.
In 1945 Helen moved to Birkbeck College, London, where she was able to work with Bernal again, and the following year she took up a post at the Cavendish Laboratory, Cambridge, which would be her last, and longest, appointment; concurrently she was a Fellow and Director of Studies in physical science of her old college, Girton. Moreover, the then Director of the Cavendish Laboratory was none other than WL Bragg, and perhaps the most significant – certainly now the best-known- crystallographers were also working in the Cavendish Laboratory at that time: Francis Crick and James Watson, carrying out their seminal work on the structure of DNA.
http://en.wikipedia.org/wiki/Francis_Crick (below left)
http://en.wikipedia.org/wiki/James_Watson (below right)
Francis Harry Compton Crick, OM, FRS (8 June 1916 – 28 July 2004) was a British molecular biologist, biophysicist, and neuroscientist, most noted for being a co-discoverer of the structure of the DNA molecule in 1953 with James Watson. James Dewey Watson (born April 6, 1928) is an American molecular biologist, geneticist and zoologist.
Helen preferred to stick to mineralogy and inorganic crystals. For example, she provided her own crystal structure diagrams to the Council of Industrial Design, which were then used in the designs for textiles, window glass, ashtrays, and even a tea set used at the Festival of Britain in 1951. In 1957 she published her first book, Ferroelectricity in Crystals, a ground breaking work which became within the discipline its “bible” according to a colleague.
Helen’s supervisor at the Cavendish was WH Taylor, a leading expert on feldspars, a group of minerals which are complicated in structure, but make up the larger part of the earth’s crust and the surface of the moon. With Taylor’s encouragement she continued his work, her major contribution being to in distinguishing between unit cell and lattice disorders. In 1973 came another book, Crystal Structures: a Working Approach, “a fine text that illustrated well her unique approach to describing the structure of crystals” according to AM Glazer, a crystallographer who studied with her.
“…a remarkable person: formidable in some ways, but also very kind and patient. She had a particularly interesting gift: a rare ability to be able to visualize in three dimensions, so that she could take a crystal structure and turn it around in her mind and then sketch it from any perspective. In the days before computer graphics, this was a very useful trick, especially for a crystallographer, who must somehow always be able to appreciate three-dimensional architecture.”
Helen’s academic and professional honours included honorary fellowships, the Roebling Medal of the Mineralogical Society of America and the first woman to be awarded this, and two honorary doctorates, from Cambridge University; and from Queen’s University, Belfast. She retired in 1972 and divided her time between Cambridge, always keeping in touch with colleagues and scientific developments, and Ballycastle, County Antrim where she pursued one of her main non-professional passions, gardening. Other interests she had developed were photography (she had exhibited in the prestigious London Salon of Photography as early as 1943) and winter sports. Of being a woman in the world of science, she remarked that she had rarely if ever experienced any discrimination on this count, which she put down firstly to her parents, and also to Girton College, as those who advised and guided her having had a positive view of equal opportunities.
Dr Megaw, Queen’s University wishes to recognise her contribution to science and the example that she has set to generations of young women and young men. I now call upon the Dean of the Faculty of Engineering to present Helen Megaw for the degree of Doctor of Science, honoris causa.
She died at home in Ballycastle. Among many tributes to her was from Professor Robert E Newnham of Pennsylvania State University: “Along with Kathleen Lonsdale and Dorothy Hodgkin, Helen Megaw is one of the grand old British school of women crystallographers who serve as role models for many of us – men and women alike.”
Dorothy Hodgkin O.M.
Dorothy Mary Hodgkin, OM, FRS (12 May 1910 – 29 July 1994), known professionally as Dorothy Hodgkin, was a British biochemist who developed protein crystallography, for which she won the Nobel Prize in Chemistry in 1964.
Dorothy was born on the 12th may 1910 in Cairo, Egypt as her father was an expert on ancient Egyptian textiles.
Dorothy was sent to England during the First World War but her parents remained in Egypt. She was cared by relatives and friends of the family.
In 1921, she entered the Sir John Leman Grammar School in Beccles.
Dorothy developed a passion for chemistry from a young age, and her mother encouraged her interest in science in general. Her state school education left her without Latin or a further science subject, but she took private tuition in order to enter the University of Oxford entrance examination. At the age of 18 she started studying chemistry at the University of Oxford (Somerville College, Oxford).
She studied for a Doctor of Philosophy at the University of Cambridge under the supervision of John Desmond Bernal, where she became aware of the potential of X-ray crystallography to determine the structure of proteins, working with him on the technique’s first application to the analysis of a biological substance, pepsin. Bernal greatly influenced her life both scientifically and politically. Apart from being a distinguished scientist he was a member of the communist party and an early supporter of the soviet regimes.
In 1933 she was awarded a research fellowship by Somerville College, and in 1934, she moved back to Oxford.
At the age of 24, Hodgkin began experiencing pain in her hands. A visit to a doctor led to a diagnosis of rheumatoid arthritis which would become progressively worse and crippling over time with deformities in both her hands and feet. Eventually, Hodgkin spent a great deal of time in a wheelchair but remained scientifically active despite her disability.
Somerville College appointed her its first fellow and tutor in chemistry in 1936, a post which she held until 1977.
In 1937 Dorothy married Thomas Hodgkin and they had 3 children. Thomas was a well-known Oxford lecturer.
Dorothy was particularly noted for discovering three-dimensional biomolecular structures. In 1945, working with C. H. (Harry) Carlisle, she published the first such structure of a steroid, cholesteryl iodide (having worked with cholesteryls since the days of her doctoral studies). In 1945, she and her colleagues solved the structure of penicillin, demonstrating (contrary to scientific opinion at the time) that it contains a β-lactam ring. However, the work was not published until 1949.
Model of the structure of penicillin, by Dorothy Hodgkin, Oxford, c. 1945 above left and Molecular model of penicillin by Dorothy Hodgkin, c. 1945 above right
In 1947 on the 20th March Dorothy became a fellow of the Royal Society (FRS).
In 1948, Dorothy first encountered vitamin B12, and created new crystals. From these, she deduced the presence of a ring structure because the crystals were pleochroic, a finding which she later confirmed using X-ray crystallography. Scientists from Merck had previously crystallised B12, but had published only refractive indices of the substance. The final structure of B12, for which Hodgkin was later awarded the Nobel Prize, was published in 1955.
Together with Sydney Brenner, Jack Dunitz, Leslie Orgel, and Beryl M. Oughton, Dorothy was one of the first people in April 1953 to travel from Oxford to Cambridge to see the model of the double helix structure of DNA, constructed by Francis Crick and James Watson, based on data acquired by Rosalind Franklin. According to the late Dr. Beryl Oughton, later Rimmer, they all travelled together in two cars once Dorothy Hodgkin announced to them that they were off to Cambridge to see the model of the structure of DNA.
In 1960, Dorothy was appointed the Royal Society’s Wolfson Research Professor, a position she held until 1970. This provided her salary, research expenses and research assistance to continue her work at the University of Oxford.
In 1964 Dorothy was awarded a Nobel Prize for determining the structure of insulin, penicillin and vitamin B12 and in 1965 she was awarded the order of merit, O.M.
Order of Merit medal of Dorothy Hodgkin, displayed in the Royal Society, London
The Order of Merit is a dynastic order recognising distinguished service in the armed forces, science, art, literature, or for the promotion of culture. Established in 1902 by King Edward VII, admission into the order remains the personal gift of the Sovereign.
Insulin was one of Dorothy’s most extraordinary research projects. It began in 1934 when she was offered a small sample of crystalline insulin by Robert Robinson. The hormone captured her imagination because of the intricate and wide-ranging effect it has in the body. However, at this stage X-ray crystallography had not been developed far enough to cope with the complexity of the insulin molecule. She and others spent many years improving the technique. Larger and more complex molecules were being tackled until in 1969 – 35 years later – the structure of insulin was finally resolved. But her quest was not finished then. She cooperated with other laboratories active in insulin research, gave advice, and travelled the world giving talks about insulin and its importance for diabetes.
In 1958, Dorothy was elected a Foreign Honorary Member of the American Academy of Arts and Sciences.
In 1966, Dorothy was awarded the Iota Sigma Pi National Honorary Member for her significant contribution in her field.
Between 1970 and 1988 Dorothy became Chancellor of Bristol University
Dorothy was concerned about social inequalities and stopping conflict. As a consequence she was President of Pugwash from 1976 to 1988. http://en.wikipedia.org/wiki/Pugwash_Conferences_on_Science_and_World_Affairs
The Pugwash Conferences on Science and World Affairs is an international organization that brings together scholars and public figures to work toward reducing the danger of armed conflict and to seek solutions to global security threats.
Dorothy was awarded an Honorary Degree (Doctor of Science) from the University of Bath in 1978.
In 1983, Dorothy received the Austrian Decoration for Science and Art.
In 1991 the BCA arranged a Dorothy Hodgkin triennial lecture; she presented the 1st prize to the lecturer Durward Cruicshank in the year of her 80th birthday
Dorothy died at home in Oxfordshire 29 July 1994
In 1995 the Royal Society set up a post-doctoral fellowship scheme to be known as the ‘Dorothy Hodgkin Fellowships’ initially 10 fellowships were offered for 4 years. The Royal Society has established the Dorothy Hodgkin fellowship for early career stage researchers.
In 1996 Dorothy was one of 5 Women of Achievement on British Postage stamps and on another stamp printed to commemorate the 350th founding of the Royal Society
In 1999 the first Dorothy Hodgkin memorial Lecture was held during the Oxford International Festival for Women, which is held annually in March. This lecture is now sponsored jointly by the Oxford International Festival for Women, AWiSE (Association of Women in Science and Engineering), Somerville College who select the speaker and finance a reception afterwards and the Oxford University Museum of Natural History who donate the lecture room and reception facilities in the Museum. Speaker at the first lecture on the 4th March 1999 was Louise Johnson on the topic “Dorothy Hodgkin and penicillin; 50 years from structure to present day understanding of Biosynthesis and bacterial resistance.”
In 2001 the Royal Society of Chemistry erected a memorial plaque on the building where she worked in Oxford.
•Collected Works of Dorothy Hodgkin (in 3 Volumes) published by the Indian Academy of Sciences, 1996 ISBN 81-7296-020-4, volume III has copies of addresses presented at her funeral and memorial service.
Dorothy Hodgkin and Linus Pauling. A tribute. Talks presented at the Montreal meeting of the ACA 25 July 1995 printed by University of California, Los Angeles, 1996
•Dorothy Hodgkin: A Life biography by Georgina Ferry, reviewed in ‘Crystallography News’ Dec 98 has a useful bibliography.
Rosalind was born on the 25th July in Notting Hill London into an affluent Jewish family. Her father was a merchant banker who also did some teaching.
From an early age Rosalind showed herself to be very clever. At the age of six she went to school at Norland place school. Her aunt said “Rosalind is alarmingly clever – she spends all her time doing arithmetic for pleasure, & invariably gets her sums right.” At the age of nine she entered Lindores School for Young Ladies in Sussex and then when she was eleven she went to St Paul’s Girls’ where she excelled at science, Latin, sports, German, and French. Her only educational weakness was in music, for which the school music director Gustav Holst once called upon her mother to inquire whether she might have suffered from hearing problem or tonsillitis.
In 1938 Rosalind entered Newnham College, Cambridge to study chemistry within the Natural Sciences Tripos. Her teachers included the spectroscopist W.C. Price, who later became one of her senior colleagues at King’s College London. She graduated in 1941 with a second class honours degree.
Rosalind was awarded a research fellowship to join the physical chemistry laboratory of the University of Cambridge to work under Ronald Norrish (winner of the 1967 Nobel Prize in Chemistry), the event described as “without great success.
Resigning from Norrish’s Lab, she fulfilled the requirements of the National Service Act (set up because of the Second World War) and worked as an Assistant Research Officer at the British Coal Utilisation Research Association (BCURA) in 1942. She also became an air raid warden.
Rosalind studied the porosity of coal and compared helium’s density. Through this, she discovered the relationship between the fine constrictions in the pores of coals and the permeability of the porous space. By concluding that substances were expelled in order of molecular size as temperature increased, she helped classify coals and accurately predict their performance for fuel purposes and for production of wartime devices (i.e. gas masks). This work was the basis of her Ph.D. thesis The physical chemistry of solid organic colloids with special reference to coal for which Cambridge University awarded her a Ph.D. in 1945. It was also the basis of several papers.
Through a friend, Adrienne Weill, she met Marcel Mathieu, a director of the Centre National de la Recherche Scientifique (CNRS), the network of institutes that comprise the major part of the scientific research laboratories supported by the French government. This led to her appointment with Jacques Mering at the Laboratoire Central des Services Chimiques de l’Etat in Paris. She joined the labo (as referred to by the staff) of Mering on 14 February 1947 as one of the fifteen chercheurs (researchers).
Mering was an X-ray crystallographer who applied X-ray diffraction to the study of rayon and other amorphous substances, in contrast to the thousands of regular crystals that had been studied by this method for many years. He taught Rosalind the practical aspects of applying X-ray crystallography to amorphous substances. She used X-rays to create images of crystallized solids including complicated structures like biological molecules. This presented new challenges in the conduct of experiments and the interpretation of results. Rosalind applied them to further problems related to coal, in particular the changes to the arrangement of atoms when it is converted to graphite. She published several further papers on this work. It became part of the mainstream of work on the physics and chemistry of coal, covered by a current monograph, the annual and other publications.
In 1950, Franklin was granted a three-year Turner and Newall Fellowship to work at King’s College, London. In January 1951, she started working as a research associate in the Medical Research Council’s (MRC) Biophysics Unit, directed by John Randall. She was originally appointed to work on X-ray diffraction of proteins and lipids in solution, but Randall redirected her work to DNA fibres because of new developments in the field, and she was to be the only experienced experimental diffraction researcher at King’s at the time. Randall made this reassignment, even before she started working at King’s, because of the pioneering work by Maurice Wilkins, the laboratory’s second in command who had already been working on DNA, and Raymond Gosling – a Ph.D. student assigned to help her.
Wilkins and Gosling had been carrying out X-ray diffraction analysis of DNA in the unit since May 1950 and even though their equipment was rather crude, they had obtained an outstanding diffraction picture of DNA which sparked further interest in this molecule.
Randall very rudely had not informed Wilkins and Gosling that he had asked Rosalind to take over both the DNA diffraction work and guidance of Gosling’s thesis. Randall’s lack of communication about this reassignment significantly contributed to the well documented friction that developed between Wilkins and Franklin. What also didn’t help was Wilkins seemed to feel that Rosalind was there to assist his work and behaved as though she were a technical assistant and she suspected that she was ill-received because she was a woman – Kings College still had a tradition of segregation.
Rosalind built up the unit and began working on dioxyribonucleic acid (DNA). Working with Gosling, she started to apply her expertise in X-ray diffraction techniques to the structure of DNA. She used a new fine focus X-ray tube and microcamera ordered by Wilkins, but which she refined, adjusted and focused carefully. Drawing upon her physical chemistry background, she also skillfully manipulated the critical hydration of her specimens. When Wilkins inquired about this improved technique, she replied in terms which offended Wilkins as Rosalind had “an air of cool superiority”. She could be impatient, direct and unnerving and Wilkins was very shy and slowly calculating in speech while he avoided looking anyone directly in the eye. Not a match made in heaven.
In spite of the intense atmosphere, Rosalind and Gosling discovered that there were two forms of DNA: at high humidity (when wet), the DNA fibre became long and thin; when it was dried it became short and fat. These forms were termed DNA “B” and “A” respectively. Because of the intense personality conflict between Franklin and Wilkins, Randall divided the work on DNA. Rosalind chose the data rich A form while Wilkins selected the “B” form because his preliminary pictures had hinted it might be helical. He showed tremendous insight in this assessment of preliminary data. The X-ray diffraction pictures taken by Franklin and Gosling at this time have been called, by J. D. Bernal, as “amongst the most beautiful X-ray photographs of any substance ever taken”
By the end of 1951 it was generally accepted at King’s that the B form of DNA was a helix, but after Rosalind had recorded an asymmetrical image in 1952 May, Franklin became unconvinced that the A form of DNA was helical in structure. In July 1952, as a practical joke on Wilkins (who frequently expressed his view that both forms of DNA were helical), Franklin and Gosling produced a funeral notice regretting the ‘death’ of helical crystalline DNA (A-DNA). During 1952, they worked at applying the Patterson function to the X-ray pictures of DNA they had produced. This was a long and labour-intensive approach but would yield significant insight into the structure of the molecule.
By January 1953, Rosalind had reconciled her conflicting data, concluding that both DNA forms had two helices, and had started to write a series of three draft manuscripts, two of which included a double helical DNA backbone. Her two A form manuscripts reached Acta Crystallographica in Copenhagen on 6 March 1953, one day before Crick and Watson had completed their model on the B DNA. She must have mailed them while the Cambridge team was building their model, and certainly had written them before she knew of their work. On 8 July 1953 she modified one of these “in proof”, Acta articles “in light of recent work” by the King’s and Cambridge research teams.
Francis Crick and James D. Watson of the Cavendish Laboratory in Cambridge University had also been working on DNA.
The third draft paper was on the “B” form of DNA, dated 17 March 1953, which was discovered years later amongst her papers, by Rosalind’s Birkbeck colleague, Aaron Klug. He then published an evaluation of the draft’s close correlation with the third of the original trio of 25 April 1953 Nature DNA articles. Klug designed this paper to complement the first article he had written defending Franklin’s significant contribution to DNA structure. He had written this first article in response to the incomplete picture of Franklin’s work depicted in Watson’s 1968 memoir, The Double Helix.
On the 30th January 1953, Watson travelled to King’s carrying a preprint of Linus Pauling’s incorrect proposal for DNA structure. Since Wilkins was not in his office, Watson went to Franklin’s lab with his urgent message that they should all collaborate before Pauling discovered his error. Rosalind was unimpressed and became angry when Watson suggested she did not know how to interpret her own data. Watson hastily retreated, backing into Wilkins who had been attracted by the commotion. Wilkins commiserated with his harried friend and then, but accounts differ, changed the course of DNA history with the following disclosure. Wilkins imprudently showed Watson Franklin’s DNA X-ray image without her permission. Watson, in turn, showed Wilkins a prepublication manuscript by Pauling and Corey. Franklin and Gosling’s photo 51 gave the Cambridge pair critical insights into the DNA structure, whereas Pauling and Corey’s paper described a molecule remarkably like their first incorrect model.
Watson, who with Crick was already significantly on the track of a helical structure but not a double helix, later wrote “The instant I saw the photograph, my mouth fell open and my pulse began to race”. According to some sources, Wilkins shared all Rosalind’s data with Watson and Crick without her knowledge, allowing them to publish the proposed double helix structure of DNA in the April 1953 issue of Nature. However, the same issue contained a paper by Rosalind and her research student, R Gosling, supporting their views.
In February 1953, Francis Crick and James D. Watson of the Cavendish Laboratory in Cambridge University had started to build a model of the B form of DNA using data similar to that available to both teams at King’s. Much of their data were derived directly from research done at King’s by Wilkins and Rosalind. Rosalind’s research was completed by February 1953, ahead of her move to Birkbeck, and her data were critical. Model building had been applied successfully in the elucidation of the structure of the alpha helix by Linus Pauling in 1951, but Rosalind was opposed to prematurely building theoretical models, until sufficient data were obtained to properly guide the model building. She took the view that building a model was to be undertaken only after enough of the structure was known.
Ever cautious, she wanted to eliminate misleading possibilities. Photographs of her Birkbeck work table show that she routinely used small molecular models, although certainly not ones on the grand scale successfully used at Cambridge for DNA. In the middle of February 1953, Crick’s thesis advisor, Max Perutz, gave Crick a copy of a report written for a Medical Research Council biophysics committee visit to King’s in December 1952, containing many of Rosalind’s crystallographic calculations.
By mid-March 1953, Rosalind had joined J D Bernal, who was well known for encouraging women students in their careers, at Birkbeck College where she continued to use X-ray techniques to study viruses, laying the foundations for modern structural virology. Unfortunately Randall had insisted that all DNA work must stay at King’s, Wilkins was given copies of Rosalind’s diffraction photographs by Gosling. By 28 February 1953, Watson and Crick felt they had solved the problem enough for Crick to proclaim (in the local pub) that they had “found the secret of life”. However, they knew they must complete their model before they could be certain.
Watson and Crick finished building their model on 7 March 1953, one day before they received a letter from Wilkins stating that Rosalind had left Kings and they could put “all hands to the pump”. This was also one day after Franklin’s two A form papers had reached Acta Crystallographica. Wilkins came to see the model the following week, according to Franklin’s biographer Brenda Maddox on 12 March, and allegedly informed Gosling on his return to King’s.
Crick and Watson then published their model in Nature on 25 April 1953 in an article describing the double-helical structure of DNA with only a footnote acknowledging “having been stimulated by a general knowledge of” Franklin and Wilkins’ “unpublished” contribution. Actually, although it was the bare minimum, they had just enough specific knowledge of Franklin and Gosling’s data upon which to base their model. As a result of a deal struck by the two laboratory directors, articles by Wilkins and Franklin, which included their X-ray diffraction data, were modified and then published second and third in the same issue of Nature, seemingly only in support of the Crick and Watson theoretical paper which proposed a model for the B form of DNA.
On 10th April, Rosalind wrote to Crick for permission to see their model. She is reported to have commented, “It’s very pretty, but how are they going to prove it?” As an experimental scientist, Franklin seems to have been interested in producing far greater evidence before publishing-as-proven a proposed model. As such, her response to the Watson – Crick Model was in keeping with her cautious approach to science. Most of the scientific community hesitated several years before accepting the double helix proposal. At first mainly geneticists embraced the model because of its obvious genetic implications.
Rosalind’s move to Birkbeck Franklin had been planned for some time. She worked as a senior scientist with her own research group, funded by the Agricultural Research Council (ARC). Despite Bernall telling her to stop her interest in nucleic acids, she helped Gosling to finish his thesis, although she was no longer his official supervisor. Together they published the first evidence of double helix in the A form of DNA in 25 July issue of Nature. Moreover, she continued to explore another major nucleic acid, RNA, a molecule equally central to life as DNA. She again used X-ray crystallography to study the structure of the tobacco mosaic virus (TMV), an RNA virus.
An electronmicrograph of tobacco mosaic virus
Rosalind’s meeting with Aaron Klug in the early 1954 led to a longstanding and successful collaboration. Klug had just earned his PhD from Trinity College, Cambridge, and joined Birkbeck in the late 1953. In 1955 Franklin published her first major works on TMV in Nature, in which she described that all TMV virus particles were of the same length. This was in direct contradiction to the ideas of the eminent virologist Norman Pirie, though her observation ultimately proved correct.
Rosalind assigned the study of the complete structure of TMV to her PhD student Kenneth Holmes. They soon discovered (published in 1956) that the covering of TMV was protein molecules arranged in helices. Her colleague Klug worked on spherical viruses with his student John Finch, with Franklin coordinating and overseeing the work. As a team, from 1956 they started publishing seminal works on TMV, cucumber virus 4 and turnip yellow mosaic virus.
Rosalind also had a research assistant, James Watt, who was subsidised by the National Coal Board. She was now the leader of the ARC group at Birkbeck. The Birkbeck team members continued working on RNA viruses affecting several plants, including potato, turnip, tomato and pea. In 1955 the team was joined by an American post-doctoral student Donald Caspar. He worked on the precise location of RNA molecules in TMV. In 1956 he and Franklin published individual but complimentary papers in 10 March issue of Nature, in which they showed that the RNA in TMV is wound along the inner surface of the hollow virus. Casper was not an enthusiastic writer such that Franklin had to write the entire manuscript for him.
In 1957 Rosalind’s research grant from ARC had expired, and she was given a one-year extension ending in March 1958. She applied for a new grant from the US National Institute of Health, which approved ₤10,000 for three years, the largest fund ever received at Birkbeck.
In mid-1956, while on a work-related trip to the United States, Franklin first began to suspect a health problem. While in New York she found difficulty in zipping her skirt, her stomach had bulged. An operation on 4 September of the same year revealed two tumours in her abdomen.
Rosalind decided not to convalesce with her parents because her mother’s uncontrollable grief and crying upset her too much. Even while undergoing cancer treatment, Franklin continued to work, and her group continued to produce results – seven papers in 1956 and six more in 1957. In 1957, the group was also working on the polio virus and had obtained funding from the Public Health Service of the National Institutes of Health in the United States for this.
At the end of 1957, Franklin again fell ill and she was admitted to the Royal Marsden Hospital. She returned to work in January 1958, and she was given a promotion to Research Associate in Biophysics on 25 February. She fell ill again on 30 March, and she died on 16 April 1958, in Chelsea, London, of bronchopneumonia, secondary carcinomatosis, and ovarian cancer. Exposure to X-ray radiation is sometimes considered to be a possible factor in her illness.
Rosalind was never nominated for a Nobel Prize as before her death the DNA structure was not considered as fully proven. It took Wilkins and his colleagues about seven years to collect enough data to prove and refine the proposed DNA structure. Moreover, its biological significance, as proposed by Watson and Crick, was not established. General acceptance for the DNA double helix and its function did not start until late in the 1950s, leading to Nobel nominations in 1960, 1961, and 1962 for Nobel Prize in Physiology or Medicine, and in 1962 for Nobel Prize in Chemistry. Crick felt that Wilkins should be included in the DNA Nobel prize having initiated the DNA diffraction work.
It is not clear whether Rosalind would have been included in the Nobel Prize nomination, had she lived. The award was for Watson and Crick’s body of work on nucleic acids and not exclusively for the discovery of the structure of DNA. By the time of the award Wilkins had been working on the structure of DNA for more than 10 years, and had done much to confirm the Watson–Crick model. Crick had been working on the genetic code at Cambridge and Watson had worked on RNA for some years. Watson has suggested that ideally Wilkins and Franklin would have been awarded the Nobel Prize in Chemistry.
Blue plaque on SW10, Drayton Gardens, Donovan Court
Rosalind may not have won a Nobel Prize but there have been many other honours. The Royal Society has just awarded for the first time the annual Rosalind Franklin Award for an outstanding scientist or engineer who is committed to encouraging women and girls to participate more fully in science, engineering and technology.
Louise was born on the 26th September 1940 in Worcester and attended Wimbledon High School for Girls from 1952 to 1959 where girls were encouraged to study science and to pursue useful careers.
She went to University College London in 1959 to read Physics and coming from an all-girls school, she was surprised to find herself one of only 4 girls, in a class of 40. She took theoretical physics as her third year option and graduated with a 2.1 degree.
Whilst working at the Atomic Energy Authority, Harwell, on neutron diffraction Louis met Dr. Uli Arndt, an instrument scientist, who worked at the Royal Institution, London. She was impressed by the work taking place there and in 1962 she moved to the Royal Institution to do a PhD in Biophysics.
She gained her PhD in 1965 as part of the team who found the crystal structure of lysozyme. This was the third protein structure ever solved by x-ray crystallography, and the first enzyme.
Lysozyme crystals stained blue with Izit dye
In 1966 Louise had a postdoctoral year in Yale University working in the laboratory of Professor F.M. Richards. At Yale she worked as part of a team with Fred Richards and Hal Wyckoff on the crystal structure of another enzyme, ribonuclease, which was solved shortly after she left: the fourth protein structure solved.
Louise returned to University of Oxford in 1967 and took up the post of Departmental Demonstrator in the Department of Zoology, University of Oxford. She married theoretical physicist Abdus Salam in 1968
At Oxford Louise was able to combine teaching with independent research and continued her work on lysozyme and new crystal studies on other enzymes. In 1972 she received some crystals of glycogen phosphorylase and this was the beginning of a major chapter in her research career. She began a detailed x-ray crystallographic analysis of the protein, which was eight times larger than lysozyme and much larger than any of the other proteins whose structures had been solved at that time.
In 1973 she was appointed University Lecturer, a post which was associated with Somerville College.
Louise became an Additional Fellow of the college and the Janet Vaughan Lecturer. She was now able to expand her team of graduate students and post-doctoral researchers.
In 1976 Louise wrote an influential textbook with Tom Blundell on protein crystallography (academic Press ISBN 0121083500)
The phosphorylase work developed by the team in 1978 had discovered its structure and were able to work on its biological control properties.
Louise was David Phillips Professor in Molecular Biophysics, University of Oxford, 1990-2007 and in 1990 she became a Fellow of the Royal Society
Louise’s lab at Oxford solved and studied many other protein structures, and she was a depositor on 100 PDB entries including many forms of glycogen phosphorylase and of cell cycle CDK/cyclin complexes. As well as carrying out cutting-edge research, she nurtured numerous careers, training a generation of crystallographers in Oxford who themselves now train future leaders across the world.
Between 1991 and 2012 Louise became an Honorary Fellow of Somerville College, Oxford
In 2003 Louise was awarded a Dame of the British Empire
Between 2003 and 2008 Louise became Director of Life Sciences at Diamond Light Source, the UK’s national synchrotron facility at Harwell, Oxfordshire.
Between 2008 and 2012 Louise was Emeritus Fellow Corpus Christi College, Oxford
She died on the 25th of September 2012 in Cambridge, England
Obituaries were published in ‘The Telegraph’ 8 Oct 2012, The Guardian by Tom Blundell 10 October 2012, and The Times