Science for Health
Katrin Rittinger and Annalisa Pastore
Deoxyribonucleic acid, in short DNA, is the basis for heredity and contains a blueprint for the synthesis of proteins that, in turn, carry out nearly every chemical process in our body. The description of the three-dimensional structure of DNA in 1953, the famous double helix, is a milestone in science that heralded the era of modern ‘molecular’ biology. This achievement was rewarded with the Nobel Prize, the highest distinction in science, and the names of the joint Nobel laureates James Watson, Francis Crick and Maurice Wilkins will forever be connected with the double helix. However, one name is missing from this list, that of Rosalind Franklin. Her X-ray photographs of DNA were described as “the most beautiful X-ray photographs of any substance ever taken” and they provided the key evidence for Watson and Crick’s model of the double helix. Rosalind Franklin died prematurely of ovarian cancer in 1958, four years before the Nobel Prize was awarded. Because this prize cannot be given posthumously, nor to more than three people, she was excluded. The question remains whether had she lived longer she would have been included.
Her story is one of the most controversial of any female scientist that has ever lived. She was stereotyped and described as a frump by James Watson in his famous, and to some infamous, account of the discovery of the structure of DNA, “The Double Helix”; defended by her friend Anne Sayre in the book “Rosalind Franklin and DNA”; and occasionally hailed as a feminist icon – it is difficult to unearth the real Rosalind Franklin behind the myth. Recently several voices have been raised to give Rosalind credit for her contribution to science and to allow her personality “to emerge from the accretion of myth and caricature”. Among these stands Brenda Maddox’s recent biography, which constitutes a well balanced account of Franklin’s life and the circumstances surrounding the determination of the structure of DNA. Without taking sides Maddox allows readers to make their own judgement based on the facts.
Franklin was born in 1920 into a wealthy family for whom charitable community work played an important role in every day life. Her parents strongly believed in the importance of education for women but assumed that Rosalind would use her education to carry on the tradition of social work rather than to pursue her own professional career. Nevertheless, at the tender age of twelve, Rosalind became determined to ‘do’ science. She later obtained a degree in chemistry at Newnham College, Cambridge. At the time, this was an environment in which women were not regarded as peers in the scientific community, a situation that was not unique to Cambridge and was to resurface, much to her disappointment and frustration, at various times in her life. During the second world war she continued her scientific work at the British Coal Utilisation Research Association studying the structure of coal and how it could be exploited more efficiently. This research resulted in several scientific publications and she was eventually awarded her Ph.D. from Cambridge in 1945. During these formative years Franklin appears as a serious young woman with a strong character. Like many talented people in any walk of life, she was sometimes plagued by self-doubts but nevertheless was possessed of a strong determination to succeed. Her friend Ann Piper said “…she was one of those very able people of great sensitivity who tend to mask their shyness with a brusque, abrupt manner. She never suffered fools gladly!”.
During the war Franklin met Adrienne Weill, a fellow woman scientist and French refugee, who was to become a close friend and who helped her in 1947 to find a position as “chercheur”, literally ‘investigator’, at the Laboratoire Central des Services Chimique de L’Etat in Paris. Franklin spent four years in Paris, possibly the happiest years of her life. She enjoyed life and work in surroundings where she was accepted as equal and felt that her work was appreciated. She interacted well with her colleagues, made many good friends and enjoyed being part of a social circle within which discussions of science, politics and philosophy were a part of daily life. Photographs of her from that period show that she took to Christian Dior’s ‘New Look’ and dressed stylishly, far from the frump described by Watson. She loved to travel and mountaineering was among her greatest passions. She enjoyed life as an intelligent, open young woman who was truly independent for the first time. Nevertheless after four years she decided to return to England due to the difficulties in obtaining a permanent research position in France. She had by now gained a lot of experience in X-ray crystallography which was the primary experimental method for determination of molecular structures. She accepted an independent fellowship to carry out X-ray work on biological material, a subject of emerging importance, at King’s College, London.
She joined the MRC Biophysics Research Unit, headed by Sir John Randall, and was appointed to lead a research team “investigating the structure of certain biological fibres”, which turned out to be DNA. At this point, Franklin’s life took a turn for the worse. After her happy years in Paris, in an environment without gender discrimination, she found herself excluded from joining her colleagues at King’s in the Senior Common Room where women were still not allowed. She reacted rather angrily, a response that most likely did not help in starting a good working relationship with her colleagues, many of whom were ex-military and not used to regarding women as equals. To make matters worse Maurice Wilkins, a colleague who had already started to work on the structure of DNA, was on holiday when she arrived and the nature of their working relationship was not clearly established at the outset. While Rosalind understood that she herself would be responsible to lead the research on X-ray crystallographic studies on DNA, Wilkins assumed that she would work under him as a member of his team. Given these circumstances she never enjoyed working at King’s but felt excluded and not taken seriously as a female scientist, a feeling she tried to hide and which made her seem unapproachable and withdrawn. However, with the help of her graduate student Raymond Gosling she quickly succeeded in obtaining remarkably good X-ray photographs of DNA. Due to her exceptional skills as an experimentalist she discovered that DNA exists in two forms, which she called the A-form and B-form, a nomenclature that has persisted to the present day. This knowledge proved essential for any further interpretation of the data. On the other hand, Maurice Wilkins felt that the DNA work had been taken away from him. He became increasingly frustrated that Franklin was, apparently, unwilling to share her data or to cooperate in the way he expected of her. Because of this frustration he spent time with his friend Francis Crick, who at the time was preparing his Ph.D. thesis in Cambridge at the Cavendish Laboratory. Although supposedly working on the structure of hemoglobin, the oxygen-carrying protein in red blood cells, Crick was much more interested in DNA. The arrival of a brash young American scientist, James Watson, who shared his interest in DNA, initiated their collaborative work on the elucidation of its structure. They embarked on the problem of building a model of the molecule, an approach that was inspired by the chemist and Nobel Laureate Linus Pauling. Pauling had previously used molecular models to show the helical structure of proteins, an approach that differed fundamentally from Franklin’s efforts which were based on doing experiments. Molecular modelling is a well-accepted method nowadays and implies a degree of guesswork in order to predict the shape of a molecule. The final model must be able to accommodate known experimental data but should also make predictions that are testable by experiment. Franklin did not like speculation. She correctly believed that it was possible to determine the structure directly by using her X-ray diffraction data, stating that “once we know, we do not need to guess”. Somewhat naively, Watson saw her rigorous experimental approach as a weakness and did not seem to believe that Franklin would be able to solve the structure of DNA based on her X-ray photographs alone. Even after attending a seminar in which she proposed that certain repeated chemical groups in the structure, the phosphates, were on the outside of the helix, he ignored her ideas. Instead he and Crick built a model in which they placed the phosphates on the inside. It was only after Franklin had seen this model and pointed out their mistake that they started building models with the phosphates on the outside.
DNA is composed of two chains, twisted around each other. Each chain is formed from four building blocks, the nucleotides. Each of these is made up of three parts: a phosphate group, a sugar molecule and one of four organic bases. The bases are called adenine, cytosine, guanine and thymine, and are commonly abbreviated to A, C, G and T. An identical sugar is linked to each base and phosphate groups link the sugars together in chains that form the backbones of DNA. The bases of each strand are on the inside of the chains and interact with the opposite base, thereby holding the two chains together much like the rungs in a ladder. The sequence in which the four bases are repeated is the blueprint for the synthesis of proteins and is generally referred to as the genetic code.
Much of Franklin’s data, which was crucial for building the correct model of DNA, reached Watson and Crick by indirect means, often without her knowledge. Some data was given to them by Maurice Wilkins, during his many visits to Cambridge, and some came from a confidential report which Franklin had written as part of the evaluation of the King’s College unit by the Medical Research Council. The “race” for the structure of DNA, as it was called by Watson, was hotting up in 1952, when it became clear that Linus Pauling was also working on DNA and was close to a solution. This prompted Watson to travel to London and consult with Wilkins, a visit that resulted in Wilkins showing Franklin’s famous photo 51 of B-form DNA to Watson. This photo provided the final information that Watson and Crick needed to build their model of a double-stranded helix with the two strands running in opposite directions.
Much controversy has surrounded these events. Indeed, it has been unfairly suggested that Franklin did not believe in the helical nature of DNA and was sitting on data she did not understand. However, it is clear from her notes that by the time Watson and Crick had built their model, she had come largely to the same conclusions and thought that DNA was helical and formed by two chains running antiparallel to each other. These findings were published in separate, back-to-back papers in the scientific magazine Nature in 1953.
By this time, Franklin had become so unhappy with her work at King’s that she had found herself a new position at Birkbeck College London in the department of J.D.Bernal, an extremely bright scientist. At Birkbeck she started to work on viruses, in particular the tobacco mosaic virus. She built up a successful group of young scientists and soon became a world leader in the study of virus structure by X-ray crystallography. While her former colleagues, who saw her as an unreasonable and difficult person, celebrated her departure from King’s, she was well liked at Birkbeck and many of her colleagues from that time are still dearly fond of her. She remained at Birkbeck until her death in 1958 after four and a half extremely successful years there. The number of papers she published at that time is impressive, even by modern standards. She had retained her passion for travelling and in 1954 went for the first time to America, which she increasingly liked and where she was to return many times.
During her time at Birkbeck her dedication and care for the people who worked with her clearly emerged and she worked hard to maintain sufficient funding to support her group. This is illustrated by the fact that she remembered one of her junior colleagues in her will. Aaron Klug, who won the Nobel prize for chemistry in 1982, was a foreigner and was considering going back to his home country for financial reasons. Franklin left him money to help him to stay in England. She interacted well with her colleagues at Birkbeck and she regarded her environment as one in which she could work in a stimulating atmosphere. Nevertheless, she still had to fight for status. She had an important grant rejected and complained bitterly: “…the Agricultural Research Council refuses to support any project that has a woman directing it”. Thankfully her research programme was rescued through a grant from the U.S. Public Health Service and later by the MRC.
In spite of all the difficulties and unfortunate circumstances that surrounded the discovery of the structure of DNA, Franklin did not bear any grudge against Watson and Crick. In fact she became good friends with Crick and his wife Odile to the point that they later went on holiday together. During her time at Birkbeck she often visited Crick in Cambridge, who had also become interested in RNA and virus structures, and she valued his opinion highly.
During a visit to America, Franklin began to experience severe pains in her lower abdomen and was diagnosed with ovarian cancer upon her return to England. She was uncomplaining, maintained great hopes in every treatment she underwent and was never willing to give up hope of recovery. Indeed, until about three weeks before her death she went to the laboratory almost every day.
While Rosalind Franklin is increasingly remembered for her role in the discovery of the structure of DNA, it is often forgotten that her scientific career extended much further. In her impressive but tragically short career, she managed to make essential contributions to science that went much beyond the ability to take ‘beautiful’ X-ray photographs of DNA.
People who have met her describe her sometimes as a woman with extreme determination, who was serious and could at times be rather abrupt. In this respect, Maddox’s biography is probably the most balanced account of Franklin’s personality yet written. It allows us to see another side of Rosalind Franklin, that of a woman who enjoyed life, who was passionate about travelling and mountaineering, adored children and flourished when she was surrounded by friends who shared her love of discussion. This leads one to wonder what went wrong at King’s, to have engendered such strong antipathy to her, as immortalised in Watson’s remark in ‘The Double Helix’: “The real problem, then, was Rosie. The thought could not be avoided that the best home for a feminist is in another person’s lab”. Reading Maddox’s account of Franklin’s life one never gets the feeling that Franklin was a feminist nor a bluestocking. She only expected to be accepted as a scientist and to be appreciated for her work, something every male scientist takes for granted. Even Watson wrote in the epilogue to “The Double Helix”: “…we both came to appreciate greatly her personal honesty and generosity, realising years too late the struggles that the intelligent woman faces to be accepted by a scientific world which often regards women as a mere diversion from serious thinking.”
Brenda Maddox’s biography gives one the feeling of having witnessed a remarkable woman’s life. A woman who was not afraid to break out of tradition to follow her vocation to become a scientist; a woman who, despite loving children, never married and had children of her own, something which seemed irreconcilable with being a scientist at that time. She was a woman who all the same was a loving person with a social conscience.
Would Franklin have received the Nobel Prize had she lived longer? Brenda Maddox suggests “Franklin did not have her eyes on the prize. Nor did she worry about having been outrun in the race that no one but Watson and Crick knew was a race.” – “She was cheated of the only thing she really wanted: the chance to complete her work. The lost prize was life.”
This essay was published in the Mill Hill Essays 2002
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