[DNA]

One of approximately 6 known examples, this example presented to either Linus Pauling or Robert B. Corey by James Watson, Francis Crick and Sir Lawrence Bragg; Offered by the Estate of American Biochemist Richard E. Dickerson (1931-2025), Distinguished Professor, Director of the Molecular Biology Institute at UCLA from 1983-1994, elected to the National Academy of Sciences and American Academy of Arts and Sciences in 1985. Dickerson later helped to determine the complete structure of crystalline DNAs, which largely confirmed Watson and Crick’s model.

The April 25, 1953 issue of Nature (pp 737-738) printed Jim Watson’s and Francis Crick’s first article on what would turn out to be a watershed discovery. “A Structure for Deoxyribose Nucleic Acid” described two phosphate-sugar chains, each coiled around the same fiber axis, held together by perpendicular purine and pyrimidine bases (adenine with thymine or guanine with cytoside), creating a double helix form – DNA or Deoxyribose Nucleic Acid. They ended their article with the “coy” statement: “It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material.” They followed with “Genetical Implications of the Structure of Deoxyribonucleic Acid” (Nature, May 30, 1953), in which they explained how the molecule “could exist in forms various enough to encode the messages of heredity” (Medawar, “Lucky Jim,” New York Review of Books, March 28, 1968, pp 3-5).

“The discovery of the DNA double helix opened up enormous vistas to the imagination. It was to provide the highroad to understanding how genetic material functions” (Stent. “The Double Helix and the Rise of Molecular Biology,” p xviii, in Watson, The Double Helix). They are vistas still open to this day and the discovery ranks as one of the most important and profound of the entire 20^th century. The work led to a Nobel Prize in Physiology or Medicine for Watson, Crick and Maurice Wilkins.

Watson and Crick weren’t the only scientists that had been working to discover the key to life. By the early 1950s a race had developed between some of the world’s most brilliant scientists. CalTech’s Linus Pauling, one of the greatest scientific minds of his day, had, with the assistance of Robert B. Corey, determined the α-helix structure of protein in 1951. It was the first great triumph in the young field of structural molecular biology. He had hoped, due to their complexity, that proteins would be the hereditary material but he soon found this not to be the case. Pauling, along with other groups including Maurice Wilkins and Rosalind Franklin at King’s College, London and, surreptitiously, Jim Watson and Francis Crick of Cavendish Laboratory at Cambridge turned their focus to DNA.

Model building was at the center of Linus Pauling’s stochastic approach to problem solving whereby he used also his deep chemical knowledge to make what was essentially an educated guess. This method allowed him to discover the alpha helix structure of protein – a problem on which Nobel laureate Sir Lawrence Bragg and his team at Cambridge had also been working. In fact, when Bragg had learned that Pauling’s model was being accepted by the scientific community, “he rushed into the Cambridge chemistry office of Alexander Todd, the eminent organic chemist and an old friend of Pauling’s. Todd had never before seen Sir Lawrence in that part of the university and immediately took note of the physicist’s red face and the papers – Pauling’s – that he clutched in one hand.” The agitated Bragg “demanded to know how anyone could make a decision between Pauling’s spirals and the ones he had proposed earlier. Todd, who had already seen Pauling’s manuscript, said he would certainly pick Pauling’s because of the planar peptide bond. When Bragg said the bond could not be planar, Todd explained to him about resonance structures and double-bond character. ‘If you had checked with me before, I’d certainly have told you so,’ he said. Nonplussed, Bragg returned to the physics department” (Hager p378).

Pauling and Corey had eventually shifted their focus to DNA’s structure. Never one to be accused of modesty, Pauling had considered the problem “his to solve.” While he realized that DNA had a helical structure, he made an error when he decided that the phosphate groups were at the structure’s center, just as Watson and Crick had done a year prior, and arrived at a triple helix structure. He was also at a disadvantage as he was using William Astbury’s 1938 x-ray diffraction images of DNA – greatly inferior to those of Rosalind Franklin. Pauling and Corey toiled at the model but the structure was too tightly packed and no matter how he adjusted he was unable to perfect it.

Pauling was in the middle of his DNA work when he was named as a concealed communist by professional (and often questionable) FBI informer Louis Budnez before a special congressional committee. It was a major distraction and combined with the urgency of the race to discover the DNA structure, Pauling and Corey published a paper describing a triple helix structure well before they were ready. They were quickly proven wrong: a terrible embarrassment to the greatest living chemist. Later, when reporters kept asking Pauling why he hadn’t discovered the structure before Watson and Crick, Pauling’s wife Ava asked him: “If that was such an important problem, why didn’t you work harder on it?” (Hager p 431).

Earlier in Watson’s and Crick’s journey, when Sir Lawrence Bragg had discovered that they were working on the DNA problem and had presented an erroneous triple helix structure, he ordered a DNA moratorium at Cambridge since he considered that problem the province of King’s College. It wasn’t lifted until Pauling’s paper announcing his triple helix model made it clear that the field was wide open. “Still smarting from the defeat over Pauling’s α-helix protein structure and impatient with the ‘internal squabbling’ at King’s, Bragg could not, would not allow Linus to get the thrill of discovering the structure of another important molecule” (Markel p 310).

Fortunes would change after Watson made a visit to King’s College where, after a heated encounter with King’s College chemist and X-ray crystallographer Rosalind Franklin, Maurice Wilkins allowed Watson a peak at Franklin’s Photograph No. 51, which gave a clear view of the B-form of DNA. “The instant I saw the picture my mouth fell open and my pulse began to race.... With the B form, however, mere inspection of its X-ray picture gave several of the vital helical parameters. Conceivably, after only a few minutes’ calculations, the number of chains in the molecule could be fixed” (Watson p98). Watson and Crick, both great admirers of Pauling, had earlier borrowed his stochastic approach to problem solving, closely studied his classic book The Nature of the Chemical Bond, but now had the advantage of Franklin’s superior X-ray diffraction image to guide them.

Watson returned from King’s College and he and Crick immersed themselves in model building based upon the new data. They ordered new pieces from the Cambridge machine shop and began to work with them as soon as each batch was delivered. Several dead-ends later, they began to see a solution. The final key was determining the arrangement of the base pairs – with the help of American crystallographer and office mate Jerry Donohue, there on a Guggenheim Fellowship endorsed by Pauling. “Let’s face it, if the fates hadn’t ordained that I share an office with Watson and Crick in the Cavendish in 1952-1953, they’d still be puttering around trying to pair ‘like-with-like’ enol form on the bases” (Donahue pp285-289). Everything fell into place and before long Crick was crowing in their crowded local pub that they had just found the secret of life – as the supposedly-apocryphal Watson anecdote goes. They, along with Maurice Wilkins, were awarded the 1962 Nobel Prize in Physiology or Medicine "for their discoveries concerning the molecular structure of nucleic acids and its significance for information transfer in living material.”

The present model, identical to the example that James D. Watson brought to the June 1953 Cold Springs Harbor Conference and which was pictured in the 7 April, 1954 issue of Proceedings of the Royal Society (A, 223, p.90), was almost certainly made by Cavendish Laboratory technician Tony Broad who is on record as the maker of Watson’s model. A January 12, 1955 letter from Francis Crick to Leonard D. Hamilton, who had supplied DNA samples to Maurice Watkins at King’s College, mentions that “I had a letter from Rhoads, asking about the little DNA model. I have replied that Tony Broad could make one for him for around 50 (pounds), but that I was not keen to lend ours, as we find it useful.” Crick would confirm this again in an April 6, 2004 letter to Dick Dickerson: “The DNA models were almost certainly made by Tony Broad, probably in the middle of 1953, though I can’t be certain of this. He made ‘several’ – probably three or four, but the exact number I don’t know. I had one, but I don’t remember to whom I gave it.”

Dickerson had visited Nobel Prize-winning molecular biologist and doctoral advisor to Francis Crick Max Perutz at Cambridge in 1985 and was shown a model identical to the present example. Perutz had also mentioned that laboratory technician Tony Broad had made about 4-5 models and had probably sent one to Pauling.

Watson, Crick and the head of Cavendish Laboratory, Sir Lawrence Bragg attended Pauling’s 1953 Pasadena Conference on the Structure of Proteins that September. This meeting of the founding fathers of molecular biology was the likeliest time that this model was presented.

The model was still at CalTech when Richard E. Dickerson joined in 1963. Pauling left the institute the following year but his colleague Robert Corey remained there for several years before he retired. Neither Pauling nor Corey had prominently displayed the models – they don’t appear in any contemporary lab photos. Of course, the models would have been a constant reminder of the missteps that they had taken in late 1952 with their proposed triple helix model of DNA. While Pauling was gracious in his praise for Watson and Crick’s accomplishments – and had invited both along with Sir Lawrence Bragg to his 1953 conference - as a “gift” from Sir Lawrence and company, it seemed more boastful than benevolent. It was likely easier to bear the following year when Pauling was awarded the Nobel Prize in Chemistry “for his research into the nature of the chemical bond and its application to the elucidation of the structure of complex substances” – such as the alpha helix structure of protein.

Dickerson left CalTech for UCLA in 1981, thereby shutting down the protein crystallography lab. He transferred the equipment and models from Caltech to UCLA, including the present model. Dickerson, in a 2004 message, described “when I had moved into single-crystal DNA structure analysis in 1977, the model took on extra significance. Watson and Crick had based their 1953 helix structure on fiber diffraction x-ray patterns, and could not observe the effects of particular base pair sequences. Graduate student Horace Drew and I solved the first structure analysis of single-crystals of DNA of defined base sequence in 1979. The 1953 Cambridge model became a kind of talisman or good luck charm in my office.”

Donahue, “Honest Jim?” In: Quarterly Review of Biology 51, June 1951, pp. 285-89; Hager, Thomas. Force of Nature: The Life of Linus Pauling. New York: Simon & Schuster, [1995]; Markel, Howard. The Secret of Life. [New York]: W.W.Norton, [2021]; Watson, J.D. and F.C. Crick. “A Structure for Deoxyribose Nucleic Acid,” In: Nature, April 25, 1953, pp. 737-738; ___ & ___. “Genetical Implications of the Stucture of Deoxyribonucleic Acid.” In: Nature, May 30, pp. 964-967; Watson, James D. The Double Helix. New York: W.W. Norton, [1980]. Edited by Gunther S. Stent.