Rosalind Franklin – forgotten scientist

Rosalind Franklin was instrumental in discovering the structure of DNA, but until recently, many knew nothing of the contribution the x-ray crystallographer made – Laboratory News investigates.

A British x-ray crystallographer played an important role in determining the structure of DNA, but her contribution often gets overlooked and for many years went unrecognised. Faced with sexism, patronising colleagues and a battle against cancer, Rosalind Franklin achieved much in her short life.

Franklin was born in July 1920 to a British-Jewish family. She was educated at St Paul’s Girls’ School and North London Collegiate School where at the age of 15 decided she wanted to be a scientist. Her father was against higher education for women and wanted the young Rosalind to become a social worker but she fought hard and won her first major battle: her father backed down and she enrolled to study for a degree at Newnham College, Cambridge¹. Women were not entitled to full degrees at the time and upon passing her finals in 1941, Franklin received a titular degree. She remained at Cambridge where she worked towards a PhD in physical chemistry, which she received in 1945².

In January 1951, Franklin became a research associate at Kings College London in the Medical Research Council’s biophysics unit. She was a highly skilled x-ray crystallographer and was originally employed to work on x-ray diffraction of proteins. However, before she even reached Kings College, unit director John Randall reassigned Franklin to work on x-ray diffraction of DNA.

Franklin was the only experienced experimental diffraction researcher at the college, and Randall ordered her to take over the DNA project on which Maurice Wilkins – a molecular biologist – and his PhD student Raymond Gosling had been working. Wilkins and Gosling were not informed of this which caused friction between Franklin and Wilkins. This was only exacerbated by Franklin’s air of cool superiority and it didn’t help that on their first meeting Wilkins assumed – perhaps because she was a woman – that Franklin was simply a technician.

After refining and adjusting the equipment Wilkins had purchased, Franklin discovered that there were two forms of DNA: type A DNA was dry, short and fat, while type B DNA was a wet, long, thin fibre. The work on DNA was split: Franklin chose to work on type A DNA with Gosling – who she was now guiding through his thesis – because she felt it would yield more results, and Wilkins was left to work on type B DNA.

Towards the end of 1951, Franklin presented the type A and B DNA at a conference, and highlighted how the phosphate units were located on the external part of the backbone. James Watson – an American molecular biologist who was also working on DNA with his colleague Francis Crick – attended this seminar.

Franklin was convinced type B DNA was a helix, but was not so sure about type A, but she set about painstakingly applying the Patterson function to the x-ray pictures she and Gosling had produced. By January 1953, Franklin had reconciled her research and began drafting three manuscripts – two of which included the double helix backbone. They reached Acta Crystallographica in Copenhagen on 6 March 1953 – both were written before she knew of Watson and Crick’s work on DNA, and one day before Crick and Watson had completed their model.

Franklin was approached in January 1953 by Watson who wanted to collaborate on research and publish the structure of DNA before rival Linus Pauling. Many scientists were working to solve the mystery of how genetic instructions were held inside organisms and how they were passed from generation to generation, and Watson and Crick felt like they were in a race against time to unlock the secrets of DNA

Originally Wilkins was their target, but upon finding his office empty, Watson turned to Franklin. Watson showed Franklin a pre-print of Linus Pauling’s incorrect structure. She was unimpressed, even more so when Watson accused her of being unable to interpret her own data, so they never shared each other’s knowledge.

Watson did also meet with Wilkins who shared some of Franklin’s work without her knowledge. This included the infamous photo 51 – an x-ray diffraction image of DNA which was critical in identifying its structure. This photograph ultimately proved what Watson and Crick were thinking – DNA was a helical structure – and they set about building their now famous model. Unlike Watson and Crick, Franklin was not a firm believer of theoretical model building, thinking they should only be constructed when enough of the structure was known and any uncertainties and misleading possibilities eliminated.

By February 1953, Franklin had stopped working on DNA – she was preparing to move to Birkbeck College where she was to become a senior researcher with her own research group – and her work on DNA was to remain property of Kings College. Randall ordered her not to even think about DNA.

When Franklin’s paper –including photo 51 – was published on 25th April 1953 in Nature, it appeared third in a series of three, seemingly in support of and Watson and Crick’s piece Molecular Structure of Nucleic Acids; A Structure for Deoxyribo Nucleic Acid. Franklin had been usurped and patronised.

“The x-ray work she did at King’s is increasingly regarded as superb. The sorting out of the A and B forms, by itself, would have made her reputation”

Watson and Crick did acknowledge– by way of a footnote in their Nature article – that their work was ‘stimulated by experimental results from Kings College researchers’. Scientists were sceptical of Watson and Crick’s structure, but they continued to work on DNA, as did Wilkins. Over a period of seven years, Wilkins and his colleagues collected data to refine the proposed structure of DNA. By 1961 the work was more widely accepted and in 1962 Wilkins was awarded the Nobel Prize in Physiology or Medicine along with Watson and Crick. Rules state that the prize can only be awarded to a maximum of three people, and cannot be awarded posthumously; Franklin remained unacknowledged.

It wasn’t until 1968 when James Watson published his personal account of the discovery of DNA – The Double Helix – that Franklin’s work was truly acknowledged although he did try to bury this under claims that she couldn’t read her own data, and constantly referred to her as Rosy – a patronising name she never used.

Wilkins and Watson objected to the memoirs, and the book has been criticised for being excessively sexist towards Franklin. In the preface, Watson acknowledges that his initial perception of Franklin was wrong:

“Since my early impressions of her, both scientific and personal (as recorded in the early pages of this book) were often wrong, I want to say something here about her achievements. The x-ray work she did at King’s is increasingly regarded as superb,” Watson wrote, “The sorting out of the A and B forms, by itself, would have made her reputation, even better was her 1952 demonstrations, using Patterson superposition methods, that the phosphate groups must be on the outside of the DNA molecule.”³

Watson also acknowledged the struggles that Franklin faced as a woman in the male-dominated scientific world, and praised her courage and integrity when “knowing she was mortally ill, she did not complain but continued working on a high level until a few weeks before her death.”

After her move to Birkbeck, Franklin and her research team began working on the tobacco mosaic virus, focussing in particular on RNA. She became ill in 1956 but continued to work while being treated for ovarian cancer. In 1956 her research team published seven papers, and a further six in 1957.

Rosalind Franklin died on 16 April 1958 of bronchopneumonia, secondary carcinomatosis and carcinoma of the ovary – possibly caused by exposure to x-ray radiation – unaware of the legacy she left behind her. Who knows what else she might have achieved if she hadn’t fallen ill and passed away at the age of 37?

Franklin’s legacy Rosalind Franklin’s work was important for so many reasons – not only did it confirm that Watson and Crick’s structure was correct, it helped open the door to a whole new world of genetics, stem cell research and cloning. Without it, we wouldn’t know that DNA contains instruction to make proteins or that linear sequences of nucleotides in DNA correspond to linear sequences of amino acids in proteins. The work of Franklin – and Wilkins, Watson and Crick – has: •    Enabled the sequencing of the entire human genome. Watson played an important role in getting government funding for the Human Genome Project, which determined the sequence of chemical base pairs which make up DNA, and identified and mapped the thousands of genes in the human genome. Among findings during the project was the gene MSH2 (colon cancer), five variants of the FAD gene (Alzheimer’s) and the breast cancer gene BRCA2. •    Enabled scientists to sequence DNA for amplification, or for artificial cloning to give new organisms like Dolly the sheep. •    Enabled stem cell research to create embryos for research and therapeutic purposes. Many years after her death, Franklin’s was work recognised in the form several awards and building being named after her – there is even the Rosalind Franklin University of Medicine and Science in Chicago.

References 1. Women in Science – Rosalind Elsie Franklin http://www.sdsc.edu/ScienceWomen/franklin.html 2. Rosalind Franklin http://en.wikipedia.org/wiki/Rosalind_franklin 3. The Double Helix A personal Account of the Discovery of the Structure of DNA by James D Watson (1968) pg 225-226