The Discovery of DNA - a photo finish.

James Watson Francis Crick
died 7/28/2004
Maurice Wilkins
died 10/05/04
Rosalind Franklin
died in 1958
Linus Pauling
died in 1994
Erwin Chargaff
died 6/20/02

    James Watson, a biologist from Indiana University and Francis Crick, a physicist, were working at the Cavendish Lab in Cambridge, England on the structure of DNA. Maurice Wilkins, a New Zealand physicist who had worked on the Manhattan Project, was the deputy director of the King's College biophysics lab. Linus Pauling was a Caltech chemist, who in 1951 had discovered the alpha helical nature of protein structure. Rosalind Franklin was a 30 year old English chemist and native of London, who was working in an X-ray crystallography lab in Paris, France in 1951. Erwin Chargaff was a professor of biochemistry at Columbia University, who discovered that the molar base ratios of A equal T and G equal C, which helped solidify our understanding of the structure of DNA.

    A primary technique for structural analysis of biological molecule is X-ray crystallography. The wavelength of X-rays is about the same as the space between the atoms in crystalline matter. Deflected X-rays can give an image pattern on a photographic plate, whose angles, when analyzed mathematically can lead to the details of each atoms arrangement with respect to the other atoms.

    Rosalind Elise Franklin was born in 1920 in London and attended St. Paul's Girls School where she excelled in science, mathematics, and athletics. In 1938, she was awarded a scholarship in physics and chemistry to attended Cambridge University, where she undertook studies in X-ray crystallography. After earning her PhD and publishing seminal papers on coal she took a job offer in one of the best labs in Paris. She was a good experimenter, perfected her X-ray techniques, and published, spoke at conferences, and was well liked by her peers. It has been reported that she was a fashion-minded lady of Paris wearing Dior and socializing as a chef for her friends. After 4 years in Paris she decided at age 30 year to return to London. She was hired by John.T. Randall, Director of King's College  Medical Research Council's Biophysics Unit, for the express purpose of working on DNA, a project that was currently headed by Maurice Wilkins and his student Raymond Gosling. Randall did not inform Wilkins of Franklin's appointment, who was on vacation when she arrived, nor did Randall tell Franklin that the DNA project would be hers and she would be Gosling advisor. Franklin arrived at the King's College lab in 1951.

   Maurice Wilkins, the assumed overseer of the King's College lab, had in 1951 taken the first X-ray pictures of DNA that lead him to suggest the DNA structure might be a helix (similar to just announced Linus Pauling alpha helical structure of proteins). The atmosphere at King's was akin to an old boy's club (the lunch room was from men only) which lead to conflict. In addition, Randall had not clearly delineated a chain of command, and though he had hired Franklin as director of the X-ray lab, Wilkins, who was away when Franklin was hired believed himself to be in charge. Wilkins and Franklin did not get along. Wilkins called Franklin Rosy, which she perceived as 'bad' nick name. She was never called Rosy to her face.

   Rudolf Signer, a Swiss chemist had isolated some quality calf thymus DNA, which he gave in a "jelly jar" to Maurice Wilkins at a scientific meeting sometime in 1951. At the time this was the... "best sample of DNA in the world". Franklin was given Signer's DNA by the King's College biophysics lab director, J.T. Randall.

   J.D. Watson arrived in England and having seen Wilkins pictures of DNA wanted a post-doc at King's, but instead goes to the Cavendish lab at Cambridge where he meets Francis Crick. Crick had joined the Cavendish lab to pursue a PhD on the structure of hemoglobin using X-ray diffraction. Watson and Crick "connected" wanting to learn the structure of the gene.

   Franklin discovered that Signer's DNA X-ray patterns indicated 2 forms... alpha "a wet form" and beta "a drier form". Franklin's effort photo 51often included X-ray pictures that took over 100 hours of exposure and in November of  1952 she obtained a pattern from the wet form... a stark X-array of black stripes radiating from the center Franklin presents the data at an in houses colloquium at King's on the "X" pattern at a colloquium, which Watson attended. Crick was keen on the "idea" that DNA was helical. Watson and Crick begin to build a model upon the "X" pattern. Franklin was asked to review the model, which she belittles and criticizes.The Director of Cavendish Lab, Sir Lawrence Bragg, suggests Watson and Crick do no further model building. The now famous photograph 51, [Anatomy of Photo 51] was set aside and Franklin spends all her efforts on the dry form pictures, that did not point as strongly toward a helix. In fact Franklin never formally published or reported on any of her X-ray photos. Conditions at King's had gotten very unsociable. In January of 1953 Franklin told Raymond Gosling to give photo 51 to Maurice Wilkins. Wilkins was struck by the generous offer of Franklin and could instantly see that the X-pattern of photo 51 was demonstrative of a helix

    Watson and Crick pursued model building, using balls and sticks. Their first model was a triple helixWatson & Crick with the bases pointed outward. However, chemically it wouldn't hold itself together, thus they knew it was incorrect.

    In May of 1952 Linus Pauling was to go the Royal Society meetings in London, but he was denied a passport by the U.S. State Department because of McCarthyism suspicions for his anti-nuclear weapons proclamations. It was suggested he might be a communist sympathizer. A State Department telegram demanded that Linus Pauling swear he was never a Communist Party member.  Peter Pauling, Linus' son, did go to Cambridge and discussed his father's January 28, 1953 published model of DNA, not unlike the first Watson/Crick earlier incorrect version that was criticized by Franklin. It proposed a 3 stranded helix with the bases on the outside.

   Franklin became fed up with the scientific atmosphere at King's College and accepted a position at Brikbeck College, London, with crystallographer J.D. Bernal to work on the structure of viruses. In her final seminar at King's College, she never showed photo 51. Watson came to King's College to show Franklin the Pauling model, but the story goes that she confronted Watson, and so he retreated and quickly walked out of her lab. Watson and Crick realized they had about a 2 month lead, before Pauling realized that chemically his model wouldn't hold itself together.

   The key to Watson and Crick's model building came from the MRC Report. J.T. Randall had requested a report of the work in biophysics done by several Medical Research Council's Biophysics Unit funded projects, which included Franklin's work in December of 1952. Max Perutz of the Cavendish Lab showed the report to Crick in February of 1953.  The MRC Report included space groupings, which give geometric depictions of atoms, immediately suggested to Crick that the structure would be antiparallel and added momentum to the view that the phosphates lie on the outside, not inside. This was the breakthrough that Watson and Crick needed. All that remained was fro Watson to get the base-pairing right (A:T and G:C).

   Together, Watson and Crick, build a model of the structure of DNA as 2 helical chains, with antiparallel properties, and the bases facing inward and paired to hold the molecule together. Watson and Crick published their model. On Saturday, February 28, 1953 it is reported that Crick came into the Eagle, a Cambridge pub, and announced to everyone there that they had "found the secret of life". Franklin, in fact, came to Cambridge to see their model, and readily accepts it. Save for an acknowledgement at the end of their paper, Rosy Franklin is not recognized for her contribution to the discovery of the structure of DNA.

    With the discovery of the structure of DNA solved, the question of who gets the credit arises. The Director's of the Cavendish and King's College labs approach Nature and suggest that 3 papers be published in sequence: one by Watson and Crick, one by Wilkins, Stokes & Wilson, and a third by Franklin and Gosling. In April of 1953 the Watson and Crick paper appeared in the journal  Nature 171: 737-738  along with ones by Wilkins, Stokes, and Wilson Nature 171: 738-740   and by Franklin and Gosling Nature 171: 740-741 (April 25, 1953).

   While Rosalind Franklin's photo-51 was a pivotal moment in the discovery of the double helix, it is the MRC report that provides the detailed clue to the structure of DNA.  At 38 (1958) Rosalind Franklin died of ovarian cancer, probably due to constant exposure to X-rays. In 1962 Francis Crick, James Watson, and Maurice Wilkins shared the Nobel Prize.

     The discord surrounding who deserved credit for each component of the discovery of the structure of DNA is thought by some to have slowed the progress of how DNA works for at least a decade by limiting collaborations and the open sharing of ideas.