the double helix -- 8/16/23
Today's selection -- from Brilliant Blunders by Mario Livio. A blunder by the world’s greatest chemist, Linus Pauling, left an opening for young upstarts James Watson and Francis Crick to race to be the first to discover the double-helix structure of DNA:
“Contrary to the somewhat tentative spirit of the scientific paper, in his personal communications about the proposed model, Pauling expressed more confidence and was extremely upbeat. In a letter to the Scottish biochemist (and eventual Nobel laureate) Alexander Todd, dated December 19, 1952, Pauling wrote: ‘We have, we believe, discovered the structure of the nucleic acids. I think that it will be about a month before we send off a manuscript describing the structure, but I have practically no doubt about the correctness of the structure that we have discovered ... The structure is really a beautiful one.’ In a letter sent on the same day to Henry Allen Moe, president of the Guggenheim Foundation, Pauling repeated the same sentiment: ‘I have now discovered, I believe, the structure of the nucleic acids themselves.’
“Another person with whom Pauling was corresponding regularly was his son Peter, who, as luck would have it, had arrived at Cambridge just a few months earlier to work as a research student with John Kendrew. Peter's desk was in an office with four other colleagues. In Peter's words: ‘To my left, near the window, was a rather noisy fellow named Francis Crick. On my right was a desk occasionally occupied by Jim Watson. Also in the room was a visiting scientist, Jerry Donohue, whom I knew well from his long association with Caltech, and Michael Bluhm, John Kendrew's research assistant.’ In a pre-email era, Peter, through his frequent exchange of letters with his father, became the main line of communication between Caltech and Cambridge. Consequently, as soon as Linus informed Peter of his paper on the structure of DNA, the latter asked for a copy. This was on January 13, 1953. Peter added in his letter a brief comment that spoke volumes about the pressure the British scientists were feeling: ‘I was told a story today. You know how children are threatened “You had better be good or the bad ogre will come get you.” Well, for more than a year, Francis [Crick] and others have been saying to the nucleic acid people at King's “You had better work hard or Pauling will get interested in nucleic acids.’’’
|The structure of the DNA double helix (type B-DNA).|
“Under these conditions, it was only natural that the news from Peter that Pauling had discovered the structure of DNA hit Watson and Crick like a thunderbolt. With the memory of Pauling's previous victory with the alpha-helix still fresh in the minds of everybody at Cambridge, the two young men were wondering if this was a catastrophic case of deja vu. On January 23 Peter sent Linus another letter, this time complaining only that ‘I wish Jim Watson were here [Watson was on a quick visit to Milan, Italy]. It is rather dull now. Nothing to do. No interesting girls, just young affected little things only interested in sex, in an indirect manner.’
“The weeks between Peter's request for a copy of Pauling's paper, and the manuscript's arrival on January 28, felt like an eternity to Watson and Crick. When Peter finally brought the paper, Watson quickly pulled it out of Peter's outside coat pocket, and instantly devoured the summary and the introduction. Then, after staring at the illustrations for a few minutes, he couldn't believe his eyes. Pauling's structure, with the phosphates in the center and the bases on the outside, was strikingly similar to his and Crick's abortive model. The model was preposterously wrong!
“Watson did not conclude that Pauling's DNA model was wrong just because it had three strands. Pauling's nucleic acid molecule was simply not an acid at all. That is, it could not release positively charged hydrogen atoms when dissolved in water, the very definition of an acid. Instead, the hydrogen atoms were bound firmly to the phosphate groups, rendering those electrically neutral, while every elementary chemistry book (including Pauling's own book!) stated that the phosphates had to be charged negatively (the acid is highly ionized in aqueous solution). There was no way to extract those hydrogen atoms, either, since they were actually the key links holding together the three strands through hydrogen bonds.
“This blunder was just too much for Watson and Crick to swallow. The world's greatest chemist constructed a completely defective model, and the model was wrong not because of some subtle biological feature but because of a major blooper in the most basic chemistry. Still incredulous, Watson rushed to Cambridge chemist Roy Markham and to the organic chemistry laboratory to check with them whether there was any doubt that DNA, as it occurs in nature, was indeed the salt of an acid. To Watson's satisfaction, they all confirmed the unthinkable: Pauling had utterly botched the chemistry.
“There were only two things left to do that day. First, Crick hurried to Perutz and Kendrew to convince them that urgency was of the utmost importance. Unless he and Watson got busy with modeling immediately, he argued, it wouldn't be long before Pauling discovered his mistake and revised his model. Crick estimated that they had no more than about six weeks to come up with a correct model. Watson and Crick's second action was equally obvious to the two young men: They went to celebrate at the Eagle Pub on Bene't Street. Watson later recalled, ‘As the stimulation of the last several hours had made further work that day impossible, Francis and I went over to the Eagle. The moment its doors opened for the evening we were there to drink a toast to the Pauling failure.’
“How could this blunder have happened? Why was Pauling's model-building approach so spectacularly successful with the alpha-helix and so disastrously ineffective with the triple helix?”