Linus Pauling's copy of Photo 51, click for larger image

Linus Pauling's copy of Photo 51, 2 May 1953. Oregon State University Library

Rosalind Franklin and the Structure of DNA

Sometime in May 1952 Raymond Gosling, a doctoral candidate under Rosalind Franklin at the Wheatstone Physics Labratory, King’s College, took some 35 strands of sodium thymonucleate obtained from a calf thymus, stretched them taut across a paperclip mounted to a cork with rubber cement and sealed the makeshift assembly in a camera fitted to an X-ray tube. Gosling then bubbled water and hydrogen through the camera and exposed the film for nearly 90 hours. Later he recalled “looking at the developer, and up through the tank swam this beautiful spotted photograph.”

Franklin and Gosling’s “spotted photograph” – now known as simply Photo 51 – was to anyone who could interpret it the first clear evidence of the structure of DNA. It would become the most iconic photograph in the history of biology.

In 1869 the Swiss physician Johannes Miescher first isolated and identified a molecule which he called “nuclein” in the pus of left over surgical bandages. Later researchers including the Lithuanian-American biochemist Phoebus Levene and the Austrian-American biochemist Erwin Chargroff determined the basic chemical composition of the molecule, which was now known as nucleic acid. In 1944 Oswald Avery at Rockfeller University conclusively determined that this molecule, now known as desoxyribonucleic acid (or deoxyribonucleic acid, or just DNA), was responsable for the transmission of genetic material.1

By this time researchers had figured out the composition and role of DNA, but its physical structure – and therefore how it worked – remained elusive so scientists began to apply the relatively new method of X-ray diffraction to the problem. The first X-ray photos were from the lab of William Astbury at the University of Leeds:

Astbury, 1947, click for larger image

Sodium thymonucleate and clupein thymonucleate. From ref. 2

The physicist Maurice Wilkins at King’s college, who had spent the war on the Manhattan Project, produced this image using a Unicam camera and Raymax tube in 1950:

wilkins, 1950, click for larger image

Wilkins and Gosling. Multifiber specimen, 1950. King's College Archive

Aside from the rather obvious fact that DNA was somehow symmetrical, these early photos did little to explain the structure. This is where Rosalind Franklin comes in.

Rosalind Franklin, click for larger image

Rosalind at Birkbeck, 1955. National Library of Medicine

Franklin spent her childhood enjoying memory games and doing arithmetic for pleasure. As her aunt said “she was alarmingly clever.” It was clear that she was destined for a career in science and, against her parents wishes, received an M.S. degree in chemistry from Newham College, Cambridge in 1941 (the highest degree Cambridge awarded to a women at the time). After work on coal for the war effort and a stint in Paris she accepted a position with John Randall at the Biophysics Unit at King’s College with the express purpose of applying X-ray crystallography to DNA. The problem was that Wilkins was already on faculty studying the same subject and he had no use for a female scientist, derisively referring to her as “Rosy” or later “The Dark Lady.” She was not even welcome in the faculty dining room.3

Nevertheless Franklin began her research and soon determined that DNA exists in two forms, a low humidity A form and a “wet” B form (the one found in situ). It turned out that every previous X-ray image was a confusing mixture of the two. She obtained clear images of both forms using a much better Phillips micro-camera:

Franklin, A form, click for larger image

The A form, early 1952. From ref. 4

Franklin, B form, click for larger image

Photo 51, the B form, May 1952. From ref. 4

According to her notes she was close to solving the B structure by the end of 1952, but fed up with the mysoginistic culture in the lab, she accepted a new position studying viruses with John Bernal at Birkbeck College and was busy writing up her findings on the A form.

Of course, Franklin and Wilkins were not the only ones working on the structure of DNA at the time. The Nobel laureate Linus Pauling at Caltech and the grad students James Watson and Francis Crick at Cambridge were also in the race to publish the correct structure. Watson and Crick published a disasterous, chemically impossable model in the fall of 1951 and Pauling published an equally incorrect model by the end of the year.5 The problem was they didn’t have Franklin’s photo, but that was about to change.

In early 1953, with Franklin’s departure from King’s imminent, Wilkins, without her knowledge or consent, showed Watson and Crick her image of the B form – photo 51. It was, as Watson later wrote, a revelation:

“I was shown Rosalind's X ray photograph and ‘Whooo! That was a helix!’... I knew roughly what it meant and it was that the Franklin photograph was the key event psychologically, it mobilized us back into action.”

Using her photo and measurements the pair went back to model-building, literally moving cardboard cutouts around on their desks. They soon determined that DNA was an antiparallel double helix with a 34 Å repeat. Within a month – on 28 February 1953 – they had figured out the structure and built their famous aluminum model:

Watson and Crick, 1953,, click for larger image

Antony Barrington Brown. James Watson and Francis Crick, 1953

In what has to be one of the most important issues of a scientific journal ever, short papers from Watson and Crick, Wilkins, et. al. and Franklin and Gosling all appeared together in the 25 April 1953 issue of Nature.6 Of course it would be the one-page Watson and Crick paper that would be remembered.

Ironically, a lifetime of X-ray exposure and perhaps a mutated BRCA gene led to ovarian cancer for Franklin.7 She died in 1958 at the age of 37. Four years later Watson, Crick and Wilkins were awarded the Nobel Prize in Medicine for their work on DNA. That same year Pauling won his second Nobel, this time the Peace Prize.

Would Franklin have shared in the Prize were she still alive? That’s impossable to know, but according to the unsealed Nobel records Rosalind was never even considered for a nomination.

1. Avery, O.T., et. al. Studies on the Chemical Nature of the Substance Inducing Transformation of Pneumococcal Types. Journal of Experimental Medicine. 1944 Jan; 79: 137–158 (online).

2. Astbury W.T. X-Ray Studies of Nucleic Acids. Symposia of the Society of Experimental Biology. 1947; 1: 66–76 (online).

3. For a complete biography see: Maddox, Brenda. Rosalind Franklin: The Dark Lady of DNA. New York: HarperCollins, 2003 (WorldCat).

4. Attar, N. Raymond Gosling: the Man who Crystallized Genes. Genome Biology. 2013; 14: 402 (online).

5. Pauling. L., Corey, R. A Proposed Structure for the Nucleic Acids. Proceedings of the National Academy of Sciences. 1953 Feb: 39: 84-97 (online).

6. Watson J.D., Crick, F.C. A Structure for Deoxyribose Nucleic Acid. Nature. 25 Apr 1953; 171: 737-738 (online, annotated). Wilkins M.F., Stokes A.R., Wilson H.R. Molecular Structure of Deoxypentose Nucleic Acids. Nature. 25 Apr 1953; 171: 738-740 (online). Franklin R., Gosling R.G. Molecular Configuration in Sodium Thymonucleate. Nature. 25 Apr 1953; 171: 740-741 (online).

7. AKA the early-onset breast cancer/ovarian cancer gene. This was the mutated gene Angelina Jolie discovered she had. For more details see the Gene Card for BRCA1 and BRCA2.

1 Jan 2014 ‧ Photography

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