Determination of the DNA Double Helix (1953)
Summary
The structure of deoxyribonucleic acid (DNA) was determined in the early months of 1953 by James Watson and Francis Crick, working at the Cavendish Laboratory in Cambridge, on the basis of X-ray diffraction data produced by Rosalind Franklin and Raymond Gosling at King’s College London. The result was published in three papers in Nature on 25 April 1953. The double helix made the molecular basis of inheritance physically intelligible and inaugurated molecular biology as a discipline. It was also a complicated and partly disputed event: data collected at one institution were used, without formal authorisation, by researchers at another; the woman whose photograph supplied the decisive evidence was not informed and did not share fully in the credit; and the central paper claimed not to be aware of details that the authors did in fact possess. The discovery is therefore studied not only as a milestone in biochemistry but as a case study in the workings of priority, institutional culture, gender, and analytical technique in twentieth-century science.
Background: The Race and the Question
By 1950 it was widely accepted that DNA, rather than protein, was the carrier of genetic information. What DNA actually looked like at the molecular level remained obscure. Several laboratories were converging on the problem from different directions: Linus Pauling and Robert Corey at Caltech, working from chemical principles and X-ray data on proteins; Maurice Wilkins, Rosalind Franklin and Raymond Gosling at King’s College London, with the best fibre-diffraction patterns then available; and James Watson and Francis Crick at the Cavendish Laboratory in Cambridge, who had no DNA samples of their own and whose mode of work was model-building rather than data collection.
The competitive atmosphere was not hidden. Pauling had shown in spring 1951 that he could solve a protein structure (the alpha helix) by combining chemical knowledge with X-ray data, and the news, when it reached the Cavendish, was felt by Lawrence Bragg as a serious blow. Crick, who was working on protein at the time, observed simply that “helices were in the air.”(Maddox, 2003) If DNA could be solved by the same method, the prize would be larger.
1951: Naples and the First Failed Model
Wilkins announced the King’s group’s preliminary results at a conference in Naples in May 1951. He projected a slide of an X-ray diffraction photograph of DNA (“a sharp discrete set of reflections from the DNA molecule”) that had no precedent in the literature. James Watson was in the audience. The clarity of the pattern persuaded him that DNA had a regular, mappable structure, and from that moment Watson committed himself to the problem.(Maddox, 2003)
Later that year, the King’s group’s internal arrangements were unsettled by the arrival of Rosalind Franklin, a Cambridge-trained physical chemist who had spent the post-war years in Paris perfecting fibre-diffraction technique on coal and graphite. The director of the King’s biophysics unit, J. T. Randall, had recruited Franklin specifically to take over the DNA work; Wilkins, who had previously led that work, had not been told. The misunderstanding hardened. Randall ultimately divided the project formally: Franklin would concentrate on the dry, crystalline “A” form of DNA using the high-grade Signer sample and the new Phillips micro-camera; Wilkins would tackle the wet “B” form using a less suitable sample of pig thymus DNA from Erwin Chargaff. The “treaty” left Wilkins with worse material and a worse instrument, and it left him without access to the A–B transition that Franklin and Gosling had recently demonstrated by controlled humidity inside the X-ray camera.(Maddox, 2003) (Maddox, 2003)
In November 1951, Franklin gave a colloquium at King’s setting out her preliminary results. Watson attended at Wilkins’s invitation. He took no notes (Maddox observes, with feeling, that he “never did”) and he misunderstood her presentation, in particular what she had said about the water content of the molecule. A week later, he and Crick built a three-chain model of DNA with the phosphate groups on the inside. Franklin and Wilkins were invited to Cambridge to inspect it. Franklin saw the error immediately:
Where was the water? She pointed out that DNA is a thirsty molecule — soaking up water more than ten times what they had allowed. The phosphates had to be on the outside, encased in a shell of water.(Maddox, 2003)
Crick later took the blame. “The model was completely wrong because in fact there was a lot of water there. I did not know enough chemistry to know that things like sodium are highly likely to be hydrated anyway.” Bragg ordered the pair to stop DNA work. They obeyed for nearly a year.(Maddox, 2003) (Maddox, 2003)
1952: A Form, B Form, Photo 51
Through 1952, Franklin and Gosling did the painstaking crystallographic work that would later make the model possible. They mastered the cylindrical-section variant of the Patterson function, a method developed by A. Lindo Patterson in the 1920s for circumventing the phase problem of X-ray crystallography by relying only on the intensities, rather than the phases, of the diffraction spots. The standard Patterson method was difficult; the cylindrical-section variant, applied to a fibrous biological sample, was, in Maddox’s phrase, “an order of magnitude more difficult, like trying to do a three-dimensional jigsaw puzzle.”(Maddox, 2003)
By February 1952, Franklin’s Turner and Newall Fellowship report identified DNA’s unit cell as “face-centred monoclinic,” placed the phosphate groups on the outside of the molecule, and described “a helical structure (which must be very closely packed) containing probably 2, 3 or 4 co-axial nucleic acid chains per helical unit, with the phosphate groups near the outside.”(Maddox, 2003) These are the structural conclusions that would, a year later, become the Watson–Crick model.
In May 1952, during an exposure in which the fibre had drifted from A to B form, Franklin and Gosling captured the photograph that became Photograph 51, “the clearest picture ever taken of the B form of DNA, unquestionably a helix.” Franklin set it aside to return to the A-form Patterson analysis she had agreed to complete first.(Maddox, 2003)
Theoretical groundwork for interpreting such pictures was being laid in parallel. A paper by W. Cochran, F. H. C. Crick, and V. Vand received by Acta Crystallographica on 16 February 1952 gave the mathematical prediction of the diffraction pattern that atoms arranged in a helix would produce. The authors noted that the same theory had been “derived independently and simultaneously by Dr. A. R. Stokes” (at King’s) though Stokes preferred not to be cited more directly.(Maddox, 2003) Crick’s later admission, however, was less measured. He said of his and Watson’s response to Franklin’s data:
I’m afraid we always used to adopt — let’s say a patronising attitude towards her. When she told us DNA couldn’t be a helix, we said, Nonsense. And when she said but her measurements showed that it couldn’t, we said, “Well, they’re wrong.” You see, that was our sort of attitude.(Maddox, 2003)
In December 1952, the Medical Research Council’s biophysics committee paid a routine visit to King’s. Franklin’s unpublished results (including the unit-cell measurements she had established “with certainty” earlier in the year) were given to the committee in a printed report. The report was not marked confidential, but, as Maddox notes, “in the customary British manner in which everything official is considered secret until deliberately made public, the report was not expected to reach outside eyes.”(Maddox, 2003) At the close of 1952, Linus Pauling wrote to his son Peter at Cambridge that he and Corey had worked out a structure for DNA. Peter brought the letter to the Cavendish. Watson “was devastated.” The formal phase of the race began.(Maddox, 2003)
January–February 1953: The Pauling Error and Wilkins’s Slip
When Pauling’s manuscript reached Cambridge in early 1953, Watson saw at once that Pauling had made the same mistake he and Crick had made in November 1951:
Pauling had made a fatal chemical error. The phosphates were not ionised — that is, Pauling had not built in the electrical charges phosphates acquire when in water. What he was proposing as a structure for nucleic acid was not an acid at all.(Maddox, 2003)
The Caltech threat dissolved overnight. The remaining problem was to solve the structure before Pauling realised his error. In late January, Watson visited King’s. In the course of the visit, Wilkins (who had a copy of Photo 51 in his desk and who was unaware that Watson was about to resume model-building) showed it to him.
Unguardedly, Wilkins showed Watson Photo 51. There were many diffraction photographs of DNA around the lab; this one was simply the best. As the information in it was not new to Wilkins — Rosalind had related many of the details in her symposium in 1951 — he had no idea it would strike Watson with the force of revelation.(Maddox, 2003)
Within the following week, Max Perutz (a Cavendish colleague and a member of the MRC biophysics committee) gave Watson and Crick the December 1952 MRC report. Crick recognised the unit-cell description as indicating the C2 monoclinic space group, and from that read off the implication that the chains in DNA must run in opposite directions. Maddox is direct about what the report meant to the Cavendish team:
The MRC report was all Watson and Crick could hope for — as valuable as an enemy’s code book.(Maddox, 2003)
The remaining problem was chemistry. Watson was working with the standard textbook tautomers of the bases and the model would not close. The American crystallographer Jerry Donohue, who shared their office at the Cavendish, told him the textbooks were wrong: bases existed in the keto, not the enol, form. With the keto correction, base pairing (adenine with thymine, guanine with cytosine) fell out, and with it the whole structure.(Maddox, 2003)
On 28 February 1953, Watson recalls Crick “winging into the Eagle [pub] and telling everybody we had found the secret of life.” Maddox treats this announcement as Watson’s “myth-making narrative,” which is almost certainly what it is, but the model itself was completed in the days that followed, on 7 March 1953.(Maddox, 2003)
What Franklin Knew and What Followed
Aaron Klug’s later analysis of Franklin’s notebooks shows that by 23 February 1953 she had recognised the base-interchangeability that explained the Chargaff ratios (that A could be exchanged for G and C for T) and had begun to grasp the implications. As Klug acknowledged, “base interchangeability is, of course, a long way from the final truth of base pairing.” But Crick, after the fact, judged that Franklin had been “two steps from the solution” and would have taken those steps within three months.(Maddox, 2003) Maddox attributes the gap not to ability but to scientific temperament: Franklin had been trained “never to overstate the case, never to go beyond hard evidence.” The inductive leap that Watson and Crick made was, in her formation, exactly the kind of move one did not make.
Franklin left King’s for Birkbeck College in March 1953, unaware that the Cavendish team had been working from her data. Wilkins’s letter to Crick on 7 March, written from his perspective as the King’s group’s senior figure, supplied the phrase that would later furnish the title of Maddox’s biography:
I think you will be interested to know that our dark lady leaves us next week … At last the decks are clear and we can put all hands to the pumps! It won’t be long now.(Maddox, 2003)
April 1953: The Three Nature Papers
On 25 April 1953, Nature published three back-to-back papers. The first, by Watson and Crick, proposed the double-helical structure. The second, by Wilkins, Stokes, and Wilson, presented X-ray data from King’s; the third, by Franklin and Gosling, presented Franklin’s own A-form and B-form analyses. Watson and Crick’s paper contained a now-famous sentence:
We were not aware of the details of the results presented there when we devised our structure …
That claim was, Maddox argues, “the truth, narrowly speaking. Even though they had not seen the King’s papers when they sent their own first draft to Wilkins, Watson and Crick did know many of the details of the King’s work. They knew these from Maurice’s conversation, from Rosalind’s photograph and from the MRC report.”(Maddox, 2003)
Franklin’s own paper accompanied the Watson–Crick model, but a single hand-inserted phrase changed its meaning. Onto her typescript, before publication, Franklin wrote:
Thus our general ideas are consistent with the model proposed by Crick and Watson.
Maddox marks the irony of those words: “The alteration transformed her own fundamental findings into a ‘me-too’ effort. So indeed they should have been consistent, considering that the Watson-Crick model was in large part derived from her work.”(Maddox, 2003)
The negotiation over wording was active. Wilkins asked Crick to delete the word “beautiful” from the Watson–Crick acknowledgement of the King’s photographs and to remove the sentence “It is known that there is much unpublished experimental material.”(Maddox, 2003) Some of this complicated history will never be reconstructed in full: the Nature archive that might have shown editorial decisions was thrown out during a 1963 office move.
The Nobel Prize for Physiology or Medicine was awarded to Watson, Crick, and Wilkins in 1962. Franklin had died of ovarian cancer in 1958. Nobel rules at the time excluded posthumous awards.
Wider Implications
The Discovery as a Bioethics Inflection
The publication of the structure had an immediate ripple beyond molecular biology. Albert Jonsen, in his history of bioethics, dates the engagement of bioethicists with genetics from the day the Nature paper appeared:
On April 25, 1953, Nature published a one-page paper entitled “The Molecular Structure of Nucleic Acids” by James D. Watson and Francis H. Crick. … Almost from the day Watson and Crick’s paper was published, the ethics of the new genetics became a matter of concern to geneticists and to many others who were cognizant of the new science. The new genetics became the second topic on the agenda of the new bioethics.(Jonsen, 2000)
What the paper opened was not only a research programme but a long argument about heritability, eugenic risk, genetic engineering, and the responsibilities of biologists to publics that had no language for the new science.
The Discovery as Analytical Mobilisation
The historian John Pickstone, writing in 2001, treats the double-helix discovery as a case study not in experimental science but in the newer “age of analysis.” The double helix, he writes,
was revealed, not by experiment as such, but by the systematic mobilisation of a range of analytical techniques — notably organic analysis of the bases and X-ray crystallography of suitable crystals. Watson and Crick were successful because they realised the importance of the problem, and because they were well placed to collect the relevant analytical results and to see how they could be fitted together; they did few, if any, “experiments.”(Pickstone, John V., 2001)
Pickstone’s framing situates the discovery inside a longer transformation in the way the life sciences came to know their objects.
The Discovery as Epistemological Object
Georges Canguilhem reads the discovery as an example of how a scientific object emerges. Living matter, he argues, is not encountered ready-made. The DNA crystal is
a “superreal,” nonnatural object, the product of considerable technical and theoretical labor. It is the latest in a long series of new scientific objects invented since the end of the nineteenth century: the cellular extract, the intermediate metabolite, the Drosophila gene, the culture of mutant bacteria, and so on. … Thus the creation of a new science by attaching the prefix “bio-” to the word physics or chemistry indicates more than a new domain of research; it indicates conversion to a new view of the world.[cang-ir88-ch05-006]
The double helix is in this respect not a thing that was found but a thing that was constructed, by a particular conjunction of disciplines none of which could have produced it alone:
Our present knowledge of the structure and functions of living matter stems from a systematic combination of results from several biological disciplines (such as cytology, microbiology, and biochemistry) with those of formal genetics. … without technologies that would have been inconceivable fifty years ago, such as X-ray diffraction crystallography, electron microscopy, and radioisotope tracing, it would have been impossible to carry out the work that ultimately enabled researchers to show that the conservative and innovative functions of heredity are embodied in the macromolecules of the cell.[cang-ir88-ch05-009]
Scholarly Assessment
The reception history of the discovery has been shaped by three large interventions: Watson’s 1968 memoir The Double Helix, which gave the early Cambridge story its narrative form and which Maddox treats as substantially myth-making; Anne Sayre’s 1975 corrective biography of Franklin; and Maddox’s 2003 biography, which combined access to family papers, Klug’s analysis of Franklin’s laboratory notebooks, and a calmer view of the institutional structure at King’s. The historiography is now stable enough to support the following claims with reasonable confidence: the data on which the Watson–Crick model rested were Franklin’s; she did not know they had been used; the model could not have been built without them; and the published acknowledgement of that dependence was, by design, less than full.
The historiography is also reasonably clear that Franklin’s own approach was rigorous and very nearly successful. Dorothy Hodgkin defended it in retrospect as scientifically sound. Crick, by his own later admission, treated her work with a “patronising attitude” that was characteristic of the Cambridge group’s general posture. The result is a history in which institutional culture, the gendered structure of British academic science, and the technical division between data collection and model building all bear directly on what the public came to know about the discovery and when.
For the wider history of medicine and biology, the structure determination is treated as the inflection point at which classical genetics (chromosomes as bearers of factors) gave way to molecular biology. It is also the canonical illustration of an analytical, rather than experimental, mid-century life science: the result of mobilising several techniques (X-ray crystallography, organic chemistry, base-pair analysis, helical-diffraction theory) that none of the protagonists could have used alone.
Human Notes
The Watson myth was unusually durable. The Double Helix (1968) was assigned for decades in undergraduate biology courses, and its narrative cadence (the brilliant young men, the hostile woman scientist, the eureka in the pub) survived even after Sayre and Klug had documented its distortions. Maddox’s 2003 biography did not undo the cultural memory of the discovery so much as install a quieter, fairer version alongside it. The case is now a standard one in courses on women in science, on scientific priority, and on research ethics. It is taught not because the protagonists were unusually venal (they were not) but because the structures within which they worked made the outcome difficult to avoid.
See Also
Footnotes
Editorial Notes
Gaps the encyclopaedia compiler flagged for future evidence work, collected from inline markers in the body and frontmatter.
Human Notes
- [GAP: specialist source needed — Franklin & Gosling 1953 Nature paper is a journal article not in Library; direct quotation of Franklin’s crystallographic findings requires journal access]
- [GAP: specialist source needed — Nobel Committee deliberations on posthumous awards are internal institutional records; exact policy-change dates unattested by published secondary source]