The Dark Lady of DNA
The Dark Lady of DNA title was given to Rosalind Franklin, a scientist whose work helped discover the structure of DNA. It was given by Brenda Maddox.
In 1951, the race to publish the structure of DNA was heating up with the fanaticism apropos of an athletic contest. That race ended in 1953, when Rosalind Franklin’s unpublished measurements of the crucial distances in the DNA molecule were provided without her knowledge to James Watson and Francis Crick, enabling them to build a model of DNA. Many scientists think Franklin deserved to share the Nobel Prize awarded to Watson, Crick, and Maurice Wilkins in 1962 for determining the structure of DNA. She had died four years earlier at the age of 37, and the prize is never awarded posthumously.
Brenda Maddox’s Rosalind Franklin: The Dark Lady of DNA published by HarperCollins in October 2002, is a meticulous study of a brilliant scientist and a chronology of an epochal scientific adventure. Maddox is a science journalist, an editor for the Economist. No details of Franklin’s personal or scientific life escaped her. Maddox interviewed scientists, talked with Franklin’s relatives, and read her personal and scientific correspondence. Maddox is a prize-winning biographer; Franklin was a perfectionist. The biographer and her subject are well matched.
My introduction to Rosalind Franklin was through reading James Watson’s The Double Helix (Atheneum, 1968). Watson’s now infamous personal descriptions of her are a well-remembered chapter in scientific history. It is difficult to read any biography of Franklin dispassionately. The first biography of Franklin, Rosalind Franklin and DNA (W. W. Norton, 1975), was by her personal friend Anne Sayre. Maddox did not know Franklin, and wrote with a 44-year perspective. The success of Maddox’s biography is that its extensive scholarly detail eases the reader into objectivity. Maddox devotes four chapters to Franklin’s childhood and formal education. From her family life, Franklin learned to trust her judgments, live modestly, and scorn self-indulgence. She understood her capabilities and was forthright about speaking up, an unexpected and perhaps unwelcome trait for a female scientist.
Rosalind Franklin was born in 1920, the second of six children, two of them girls. She attended St. Paul’s, a private day school, where she not only won a Foundation Scholarship but also excelled in sports and sewing. Summers were spent at her grandparents’ country estate. She also joined her family in hiking, and continued to do a great deal of mountain climbing all of her life. At school she received an award that noted her work in physics. She was accepted at both of the women’s colleges at Cambridge, and attended Newnham College. The atmosphere for women at Newnham was mixed. Cambridge had accepted women since 1869, much earlier than Oxford, but they made up less than 10% of the student body and, until the early 1930s, were expected to sit together in the front row.
The female heads of the two women’s colleges could not take part in University ceremonies or wear academic garb. However, women students had men as supervisors and often as research partners, and marriage was no bar to teaching. Franklin heard lectures by J.J. Thomson and J.B.S. Haldane and saw the first appointment of a woman professor. It is interesting that a sketch in an early notebook shows a helical structure for DNA and a note reading “geometric basis for inheritance?” .Apparently, this idea was later forgotten. She was most concerned about the rise of Hitler and her fellow students’ lack of concern. Later, she was distressed because a number of her colleagues were Communists.
Franklin is best known for her work on the X-ray diffraction images of DNA while at King’s College London, particularly Photo 51, taken by her student Raymond Gosling, which led to the discovery of the DNA double helix for which Francis Crick, James Watson, and Maurice Wilkins shared the Nobel Prize in Physiology or Medicine in 1962. Watson suggested that Franklin would have ideally been awarded a Nobel Prize in Chemistry, along with Wilkins but, although there was not yet a rule against posthumous awards, the Nobel Committee generally did not make posthumous nominations.
Working under John Desmond Bernal, Franklin led pioneering work at Birkbeck on the molecular structures of viruses.On the day before she was to unveil the structure of tobacco mosaic virus at an international fair in Brussels, she died of ovarian cancer at the age of 37 in 1958. Her team member Aaron Klug continued her research, winning the Nobel Prize in Chemistry in 1982.
Career and Research:
Introduction to Crystallography:
Franklin’s first position was in a government laboratory where she learned to do x-ray crystallography, expertise that she used to great advantage in her later work on DNA. She studied the permeability of coal to gas or water, and received her PhD Cantab in 1945 in physical chemistry with a thesis entitled, “The Physical Chemistry of Solid Organic Colloids with Special Reference to Coal and Related Materials.”
Soon thereafter, she accepted an offer as a physical chemist to study holes in coal in a Paris government research laboratory. It was there that she learned to do x-ray crystallography on disordered materials, a skill that would serve her so well in the future. Her life was varied and enjoyable; she directed her own work, explored Paris and its surroundings, swam, hiked, bicycled, and took pleasure in clothes, cooking, and her friends.
In 1951, although highly ambivalent about returning to England, Franklin accepted a three-year fellowship at Kings College, a religious but nonsectarian institution. Women were not allowed in the Senior Common Room, although some of the staff lunched there.
However, John Turton Randall, the head of her department, was unusual in that eight of the 31 scientists in his group were women. (The physics deartment at Harvard did not hire women even as instructors until about 1970, and no woman was tenured until 1992; at Princeton, no women were allowed in the physics building!)
Early Work in DNA:
Randall suggested that Franklin work with Raymond Gosling, a graduate student, on fibers of DNA, which of course she did. Ms. Maddox’s book not only gives an account of the sequence of discovery of the genetic code, but illustrates clearly the complicated ways in which science progresses.
Thus, Avery had found in 1943 that transplanting DNA from a dead strain of pneumococcus into a living strain transferred the hereditary attributes of the donor, showing that DNA, not protein, was the genetic messenger.
In 1949, Chargaff had shown that DNA contained equal amounts of purines (adenine and guanine) and pyrimidines (thymine and cytosine). Linus Pauling’s demonstration of the alpha helical structure of proteins was another vital link.
The encounters of scientists with one another at meetings or visits to one another’s laboratory were an important source of exchange. The possible problem with openness is illustrated by the impetus given to James Watson’s ideas by Franklin’s sharp x-ray photograph of a DNA crystal that was shown to him unthinkingly by her senior, Wilkins.
Brenda Maddox’s book suggests the different ways in which scientists work and think: Franklin’s meticulous orderly way and Watson and Crick’s intuitive approach and construction of models.
Birkbeck college
Franklin left King’s College London in mid-March 1953 for Birkbeck College, in a move that had been planned for some time and that she described (in a letter to Adrienne Weill in Paris) as “moving from a palace to the slums … but pleasanter all the same”. She was recruited by physics department chair John Desmond Bernal, a crystallographer who was a communist, known for promoting women crystallographers. Her new laboratories were housed in 21 Torrington Square, one of a pair of dilapidated and cramped Georgian houses containing several different departments; Franklin frequently took Bernal to task over the careless attitudes of some of the other laboratory staff, notably after workers in the pharmacy department flooded her first-floor laboratory with water on one occasion.
Despite the parting words of Bernal 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 the 25 July issue of Nature. At the end of 1954, Bernal secured funding for Franklin from the Agricultural Research Council (ARC), which enabled her to work as a senior scientist supervising her own research group. John Finch, a physics student from King’s College London, subsequently joined Franklin’s group, followed by Kenneth Holmes, a Cambridge graduate, in July 1955. Despite the ARC funding, Franklin wrote to Bernal that the existing facilities remained highly unsuited for conducting research “…my desk and lab are on the fourth floor, my X-ray tube in the basement, and I am responsible for the work of four people distributed over the basement, first and second floors on two different staircases.”
RNA research:
Franklin 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. Her meeting with Aaron Klug in early 1954 led to a longstanding and successful collaboration. Klug had just then earned his PhD from Trinity College, Cambridge, and joined Birkbeck in 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. Franklin also had a research assistant, James Watt, subsidised by the National Coal Board and 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 complementary papers in the 10 March issue of Nature, in which they showed that the RNA in TMV is wound along the inner surface of the hollow virus. Caspar was not an enthusiastic writer, and Franklin had to write the entire manuscript for him.
Her research grant from ARC expired at the end of 1957, and she was never given the full salary proposed by Birkbeck. After Bernal requested ARC chairman Lord Rothschild, she was given a one-year extension ending in March 1958.
Expo 58, the first major international fair after World War II, was to be held in Brussels in 1958. Franklin was invited to make a five-foot high model of TMV, which she started in 1957. Her materials included table tennis balls and plastic bicycle handlebar grips. The Brussels world’s fair, with an exhibit of her virus model at the International Science Pavilion, opened on 17 April, one day after she died.
Polio Virus:
In 1956, Franklin visited the University of California, Berkeley, where colleagues suggested her group research the polio virus. In 1957 she applied for a grant from the United States Public Health Service of the National Institutes of Health, which approved £10,000 (equivalent to £242,871 in 2019) for three years, the largest fund ever received at Birkbeck. In her grant application, Franklin mentioned her new interest in animal virus research. She obtained Bernal’s consent in July 1957, though serious concerns were raised after she disclosed her intentions to research live, instead of killed, polio virus at Birkbeck. Eventually, Bernal arranged for the virus to be safely stored at the London School of Hygiene and Tropical Medicine during the group’s research. With her group, Franklin then commenced deciphering the structure of the polio virus while it was in a crystalline state. She attempted to mount the virus crystals in capillary tubes for X-ray studies, but was forced to end her work due to her rapidly failing health.
After Franklin’s death, Klug succeeded her as group leader, and he, Finch and Holmes continued researching the structure of the polio virus. They eventually succeeded in obtaining extremely detailed X-ray images of the virus.
A Life Cut Short
Franklin never married, as she was always dedicated to her work. She had many women friends; she remained close to them after they married, and was especially fond of their children.
Franklin’s only romantic relationship that the author could document was with Don Caspar, an American biophysicist who worked with her in Cambridge in 1955. After several encounters at scientific meetings, she visited him at his home in Colorado Springs. They met again when he spent the summer in Cambridge with his mother, but Franklin was already ill.
Rosalind Franklin, the unsung hero of DNA!
The end of the story is well known. In 1956, Franklin was diagnosed with metastatic breast cancer, first detected after she noticed that her waist had expanded. She continued to work intensely until close to her death in April 1958.
There is no question that had she lived, Rosalind Franklin would have been awarded a Nobel Prize for her contribution to knowledge of DNA structure. However, Wilkins, her “boss,” received the prize in 1962 along with Watson and Crick, and it is not given posthumously.
It is worth calling attention to the edition of Watson’s The Double Helix published by W.W. Norton and Company in 1980. It contains not only the text of that book, but also facsimiles of some of Watson’s letters; comments by Crick, Pauling, and Klug; and copies of the book’s reviews and of some of the original papers.
Brenda Maddox’s book is highly recommended both for its content and its style.
