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One could not be a successful scientist without realizing that, in contrast to the popular conception supported by newspapers and mothers of scientists, a goodly number of scientists are not only narrow-minded and dull, but also just stupid.
One would not expect someone at Berkeley to ignore a first-rate problem merely because someone at Caltech had started first. In England, however, it simply would not look right.
Later, in graduate school at Indiana University, it was my hope that the gene might be solved without my learning any chemistry. This wish partially arose from laziness since, as an undergraduate at the University of Chicago, I was principally interested in birds and managed to avoid taking any chemistry or physics courses which looked of even medium difficulty.
One article started with the sentence, ‘Collagen is a very interesting protein’. It inspired me to compose opening lines of the paper I would write about DNA, if I solved its structure. A sentence like ‘Genes are interesting to geneticists’ would distinguish my way of thought from Pauling’s.
Worrying about complications before ruling out the possibility that the answer was simple would have been damned foolishness.
over our gooseberry pie we looked at the pros and cons of one, two, three, and four chains, quickly dismissing one-chain helices as incompatible with the evidence in our hands. As to the forces that held the chains together, the best guess seemed to be salt bridges in which divalent cations like Mg++ held together two or more phosphate groups. Admittedly there was no evidence that Rosy’s samples contained any divalent ions, and so we might be sticking our necks out. On the other hand, there was absolutely no evidence against our hunch. If only the King’s groups had thought about models, they
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To our annoyance, there seemed every reason to believe that the phosphodiester bonds which bound together the successive nucleotides in DNA might exist in a variety of shapes.
Three chains twisted about each other in a way that gave rise to a crystallographic repeat every 28 Å along the helical axis. This was a feature demanded by Maurice’s and Rosy’s pictures,
Ever since she had told him that gravity went only three miles into the sky, this aspect of their relationship was set. Not only did she not know any science, but any attempt to put some in her head would be a losing fight against the years of her convent upbringing.
She became positively aggressive when we got on the topic of Mg++ ions that held together the phosphate groups of our three-chain model. This feature had no appeal at all to Rosy, who curtly pointed out that the Mg++ ions would be surrounded by tight shells of water molecules and so were unlikely to be the kingpins of a tight structure.
Most annoyingly, her objections were not mere perversity: at this stage the embarrassing fact came out that my recollection of the water content of Rosy’s DNA samples could not be right.
By now I had decided to mark time by working on tobacco mosaic virus (TMV). A vital component of TMV was nucleic acid, and so it was the perfect front to mask my continued interest in DNA.
he and Martha Chase established that a key feature of the infection of a bacterium by a phage was the injection of the viral DNA into the host bacterium. Most important, very little protein entered the bacterium. Their experiment was thus a powerful new proof that DNA is the primary genetic material.
Rutherford had believed in discouraging students from night work,
In all their DNA preparations the number of adenine (A) molecules was very similar to the number of thymine (T) molecules, while the number of guanine (G) molecules was very close to the number of cytosine (C) molecules.
She gave no sign, however, of liking helices any better.
In addition, she thought there was evidence that the sugar-phosphate backbone was on the outside of the molecule.
DNA→RNA→protein.
Much more important was the news that Rosy’s days at King’s were numbered.
he quickly told us that the model was a three-chain helix with the sugar-phosphate backbone in the centre.
At once I felt something was not right. I could not pinpoint the mistake, however, until I looked at the illustrations for several minutes. Then I realized that the phosphate groups in Linus’s model were not ionized, but that each group contained a bound hydrogen atom and so had no net charge. Pauling’s nucleic acid in a sense was not an acid at all. Moreover, the uncharged phosphate groups were not incidental features. The hydrogens were part of the hydrogen bonds that held together the three intertwined chains. Without the hydrogen atoms, the chains would immediately fly apart and the
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Markham predictably expressed pleasure that a giant had forgotten elementary college chemistry. He then could not refrain from revealing how one of Cambridge’s great men had on occasion also forgotten his chemistry. Next I hopped over to the organic chemists’, where again I heard the soothing words that DNA was an acid.
The moment its doors opened for the evening we were there to drink a toast to the Pauling failure.
I asserted that the simplest form for any regular polymeric molecule was a helix. Knowing that she might counter with the fact that the sequence of bases was unlikely to be regular, I went on with the argument that, since DNA molecules form crystals, the nucleotide order must not affect the general structure. Rosy by then was hardly able to control her temper, and her voice rose as she told me that the stupidity of my remarks would be obvious if I would stop blubbering and look at her X-ray evidence.
To my surprise, he revealed that with the help of his assistant Wilson he had quietly been duplicating some of Rosy’s and Gosling’s X-ray work.
Of course this presumed that Rosy had hit it right in wanting the bases in the centre and the backbone outside.
As far as I could tell, the reason the King’s group did not like two chains was not foolproof. It depended upon the water content of the DNA samples, a value they admitted might be in great error. Thus by the time I had cycled back to college and climbed over the back gate, I had decided to build two-chain models. Francis would have to agree. Even though he was a physicist, he knew that important biological objects come in pairs.
Finally over coffee I admitted that my reluctance to place the bases inside partially arose from the suspicion that it would be possible to build an almost infinite number of models of this type. Then we would have the impossible task of deciding whether one was right. But the real stumbling block was the bases. As long as they were outside, we did not have to consider them. If they were pushed inside, the frightful problem existed of how to pack together two or more chains with irregular sequences of bases.
Chargaff’s rules then suddenly stood out as a consequence of a double-helical structure for DNA.
This had the important consequence that a given chain could contain both purines and pyrimidines.
At the same time, it strongly suggested that the backbones of the two chains must run in opposite directions.
But with the sugar-phosphate backbone on the outside, it did not matter which salt was present.
Her past uncompromising statements on this matter thus reflected first-rate science, not the outpourings of a misguided feminist.
It also became apparent to us that Rosy’s difficulties with Maurice and Randall were connected with her understandable need for being equal to the people she worked with.
‘It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material.’
That the result came out of the Cavendish and not Pasadena was obviously a factor. More important was the unexpectedly marvellous nature of the answer, and the fact that the X-ray method he had developed forty years before was at the heart of a profound insight into the nature of life itself.
