Photo 51, DNA, and the Wronged Heroine
Rosalind Franklin — confirming the modelling of the DNA, having her research stolen and missing out on the Nobel Prize
The famous 1953 edition of Nature featured three papers that eventually confirmed the structure of the DNA (Deoxyribose Nucleic Acid).
A Structure for Deoxyribose Nucleic Acid (by James Watson and Francis Crick) proposed the model of the molecule. In contrast, the papers, Molecular Structure of Deoxypentose Nucleic Acids (Maurice H F Wilkins, A R Stokes & H R Wilson) and Molecular Configuration in Sodium Thymonucleate (Rosalind Franklin and Raymond G Gosling) described the molecular structure using X-Ray diffraction photography.
Francis Crick, James Watson and Maurice Wilkins were awarded the Nobel Prize in 1962 for their work on DNA.
Deoxyribose Nucleic Acid (DNA)
DNA is a double helix chain of molecule, a large biomolecule, that creates, encodes, and then stores information of the cellular organism. They are responsible for carrying genetic instructions for the reproduction, development and functioning of all living organisms and viruses.
Double helix in molecular biology means double strands. A single strand of the biomolecule consists of nucleotides. Each nucleotide has three subunits: a carbon sugar, a charged phosphate group, and a nitrogenous base(containing a nitrogen atom).
DNA resembles a ladder!
Consider the step of a ladder; the sugar molecule acts as the rail, and the nitrogen base serves as the step. The phosphate group joins these units to form one half of the ladder — a single strand.
Hydrogen bonds link the two strands at the nitrogenous bases to form a double-stranded nucleic acid. The DNA looks like a twisted ladder.
1951
Rosalind Franklin — English chemist and X-ray crystallographer and the heroine of this story, joined King’s College London in January 1951 as a research associate in the Medical Research Council’s (MRC) Biophysics Unit, then directed by John Randall.
He assigned her to lead the work on DNA fibers. She was the only experienced experimental diffraction researcher at King’s at that time.
Before her arrival, Maurice Wilkins and Raymond Gosling had obtained an outstanding diffraction image of DNA which sparked further interest in the molecule. They had been conducting X-ray diffraction analysis of DNA since May 1950.
Randall reassigned Gosling, a graduate student under Wilkins, to be Rosalind’s assistant. He also asked her to take over the DNA diffraction work from Wilkins and also guide Gosling in his thesis.
This knowledge, unbeknownst to Wilkins, subsequently developed the well-documented friction between him and Rosalind. Wilkins later learnt about this decision after Rosalind’s death. He later wrote:
“My opinion is very clear: that Randall was very wrong to have written to Rosalind telling her that Stokes and I wished to stop our work on DNA, without consulting us. After Raymond [Gosling] and I got a clear crystalline X-ray pattern I was very eager to continue that work … Trying to understand ‘what really happened’ when a very admirable scientist [Randall] models himself on Napoleon is not easy … [but the letter] was very damaging to her and to me”
Work on DNA fibers
X-rays were preferred over standard light beams to get the required pattern on the photographic plate, as X-rays had a wavelength that was the same size as that of the average distance between atoms in the molecule(0.1 nanometers).
The target in X-ray diffraction experiments were usually crystals as the molecules within the crystals had the same orientation — a criterion important for clear images. In contrast, Rosalind used purified calf thymus DNA fiber about the thickness of a human hair as the subject/target.
Furthermore, the fibers revealed different alignment under humid conditions. Rosalind and Gosling discovered that there were two forms of DNA: at high humidity, the fiber became long and thin; when dried, it turned short and fat. They named the latter A-Form DNA and the former B-Form DNA.
1952
Franklin improved her method of collecting diffraction images. She pumped hydrogen to minimize the scattering of X-rays, controlled the concentration of the salt solution and humidity surrounding the DNA fiber to keep it in the B-Form.
On 6 May 1952, Franklin and Gosling captured a clear image of the fiber by exposing it to X-rays for a total of sixty-two hours. This image was labelled Photo 51.
The DNA fiber was much less organised than a crystal, rendering difficulty in obtaining a clear image. Thus, the clarity of Photo 51 is a testament to Franklin’s expertise.
1953
Though she had obtained the photograph by May, she would not finish her analysis of Photo 51 until early 1953. Since she was transferring to Birkbeck College, she informed Gosling to hand over all research about DNA to Wilkins.
Wilkins innocently revealed Franklin’s finding, Photo 51, without her knowledge to James Watson — a researcher working at the University of Cambridge’s Cavendish Laboratory. From that image, Watson concluded that the nucleic acid was helical. Watson hurried to his lab at Cambridge to construct the backbone of the successful DNA model.
From Franklin’s work, included in Max Perutz’s copy of MRC’s report, Crick determined that DNA contains two strands with each running in opposite directions. In April 1953, they suggested a three-dimensional structure of DNA partly based on Photo 51.
By the time Watson’s and Crick’s Nature journal paper had come out, Franklin was already working at Birkbeck College. Wilkins verified their research, in the summer of 1953, by building the first accurate model of DNA and checking it against diffraction data such as Photo 51.
Watson and Crick later published another paper that described the duplication of DNA.
For their research, Wilkins, Crick and Watson shared the Nobel Prize in medicine/physiology in 1962. Sadly Franklin passed away on16 April 1958, at the age of 37 from ovarian cancer. She could not share the prize as the committee did not grant the award posthumously.
Why did Franklin move to Birkbeck College?
At King’s, Franklin was singularly unhappy, not so much because of her gender, but because of her class and Anglo-Jewish heritage.
She felt out of place in a Church of England setting at King’s College London. In her correspondence with Sayre, she wrote, “At King’s, there are neither Jews nor foreigners”.
For her moving out as early as possible was more important than completing her work on DNA.
How far she had progressed was reported by Sir Aaron Klug, Franklin’s closest collaborator at Birkbeck, in two articles in Nature research journal. He deduced that she had come very close to discovering the structure of DNA herself.
An irony of the story is that by the time news of the Watson-Crick model had reached King’s College, she had already prepared her manuscript summarising her results. Thus she inserted a hand-written amendment in her paper, published in the 1953 edition of Nature, stating that the general ideas were not inconsistent with the model proposed by Watson and Crick. And they were consistent as the Watson-Crick conclusions were based on her data.
Late credit
Watson and Crick never seem to have confided the fact that their breakthrough was because of her diffraction image and data. It is even astounding to know that the three of them shared a close, cordial working relationship.
Franklin was happy at Birkbeck College and their non-sectarian atmosphere. She had an excellent team assisting her in studying Tabacco Mosaic Virus (TMV). She, Watson and Crick corresponded, commented on each other’s work on TMV.
She even accompanied Crick and his spouse on tours and stayed with them when recuperating from her treatments for ovarian cancer.
She would never have imagined that she would be remembered as the unsung heroine of DNA. Nor could she have envisioned that King’s College London, where she spent the unhappiest two years of her professional life, would dedicate a building — the Franklin–Wilkins building — in honour of her and Maurice Wilkins.
Sources:
- A photo that changed the world
- Behind the picture: Photo 51
- FRANKLIN, R., GOSLING, R. Molecular Configuration in Sodium Thymonucleate. Nature 171, 740–741 (1953). https://doi.org/10.1038/171740a0
- Hernandez, Victoria, “Photograph 51, by Rosalind Franklin (1952)”. Embryo Project Encyclopedia (2019–12–30). ISSN: 1940–5030 http://embryo.asu.edu/handle/10776/13138.
- “James Watson, Francis Crick, Maurice Wilkins, and Rosalind Franklin”. Science History Institute. June 2016. Archived from the original on 21 March 2018. Retrieved 20 March 2018.
- Maddox, B. The double helix and the ‘wronged heroine’. Nature 421, 407–408 (2003). https://doi.org/10.1038/nature01399
- Wikipedia: Maurice Wilkins
- Photo 51 — Fiber diffraction and the DNA double helix
- Rosalind Franklin and the Double Helix, Physics Today 56, 3, 42 (2003); https://doi.org/10.1063/1.1570771
- Watson, James D. The Double Helix: A Personal Account of the Discovery of the Structure of DNA. New York: Athenaeum Press, 1968.
- X marks the spot of the double helix
