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A memoir about “how the structure of DNA was discovered” (ix)

“science seldom proceeds in a straightforward manner . . . . personalities and cultural traditions play major roles.”

“the way I saw things then, in 1951-1953: the ideas, the people & myself.” [1967]

“the tale was not simple . . . . it was a matter of five people: Maurice Wilkins, Rosalind Franklin, Linus Pauling, Francis Crick . . . .” (14)

2 older approaches to science: {knowledge of the natural world
(physical, chemical, & biological)

Bragg the theorist - Perutz the experimentalist

heuristics - crystallography through x-ray diffraction revealing geometric forms of proteins, which are chains of amino acids { that are made into chains by DNA. }

inspired by physicist, Erwin Schrodinger, who wrote: What is Life? (1944)

18) DNA was known to occur in the chromosomes of all cells . . . . all genes were composed of DNA.

23) “one half the mass of the bacterial virus was DNA.”

27) “Though I knew nothing about the X-ray diffraction techniques that dominated structural analysis, I was optimistic that the spoken arguments would be more comprehensible than the journal articles, which passed over my head.”

28) “In contrast, Maurice’s X-ray diffraction picture of DNA was to the point. . . . Before Maurice’s talk I had worried about the possibility that the gene might be fantastically irregular.”
“...genes could crystallize; hence they must have a regular structure that could be solved in a straightforward fashion.”

30) “The fact that I was unable to interpret it did not bother me.”
“Linus {Pauling} explained the specific characteristics that made his model -- the alpha helix [a protein] -- uniquely beautiful.”

At the Cavendish Laboratory, Cambridge University, England:
33) “I did not follow Max [Delbrück] at all. I was even ignorant of Bragg’s Law, the most basic of all crystallographic techniques.”

38) “Particularly important were the exact arguments needed to understand how Linus Pauling had discovered the a-helix.”
“simple laws of structural chemistry.” “ask which atoms like to sit next to each other.”
“a set of molecular models superficially resembling the toys of preschool children.”
“we assumed that the DNA molecule contained a very large number of nucleotides linearly linked together in a regular way.”

39) “DNA molecules packed together to for the crystalline aggregates”

“DNA diameter was thicker than would be the case for” a - helix
“A further complication arose from the fact that four types of nucleotides were found in DNA.”
“Their uniqueness lay in their nitrogenous bases, which were either a purine (A&G) or a pyrimidine (C&T). . . . The sugar-phosphate backbone was very regular, and the order of bases of necessity very irregular.”

James Watson on the discovery of DNA’s structure.

39) “If the base sequences were always the same, all DNA molecules would be identical and there would not exist the variability that must distinguish one gene from another.”

40) diagram

irregular regular “backbone”

BASE -------> Sugar
phosphate
BASE -------> Sugar
phosphate
BASE --------> Sugar
phosphate

BASE --------> Sugar
phosphate

41) “he [Wilkins] had shown X-ray diffraction pictures of DNA which revealed a marked absence of reflections on the median. This was a feature that his colleague, the theoretician Alex Stokes, had told him was compatible with a helix.”

51) “the crux of the matter was whether Rosy’s new X-ray pictures would lend any support for the DNA helical structure.”
experimental crystallography through x-ray diffraction vs model building

52) “her x-ray photographs were somewhat sharper.”

52) “True, she had done some more detailed measurements of the water content of her DNA samples
“all most of them wanted out of life was to set their students on to impenetrable details of chromosome behavior or to give elegantly phrases, fuzzy minded speculations over the wireless on topics like the role of the geneticist in this transitional age of changing values.”

53) she emerges as an impediment to speedy research.
“Particularly [important] unfortunate was my failure to babble to exactly report the water content of the DNA samples upon which Rosy had done her measurements.”

54) “there seemed no indication that he thought the answer would come from playing with models.”

55) “Though the mathematics eluded me, the crux of the matter was not difficult to follow. Decisions had to be made about the number of polynucleotide chains within the DNA molecule.”
“It was all a question of the angle and the radii at which the DNA strands twisted about the central axis”
Molecular basis of life DNA & RNA

57) Carbon & Oxygen covalent bonds of the sugar phosphate “backbone” of DNA
nitrogen, carbon, phosphorus, hydrogen, oxygen are the atomic elements used in the structural parts of the double helix.
“Frank saw that the paradox vanished if crystals were not as regular as suspected, but contained dislocations resulting in the perpetual presence of cozy corners into which new molecules could fit.”

77) “Most important, the simplest way to generate cozy corners was to have the subunits helically arranged.”
every helical staircase

83) steps of the staircase: nitrogen bases

adenine = A
thymine = T
guanine = G
cytosine = C

2 types of DNA groups based on excess of AT or excess of GC

84) Max Delbruck: “quantum mechanics favored a gene duplicating mechanism involving the synthesis of complementary replicas.”

95) John Griffiths role: “Francis learned that a semirigorous argument hinted that adenine and thymine should stick to each other by their flat surfaces.”

92) “Chargarf’s rules were a real key.”

95) “she [Rosalind Franklin] thought there was evidence that the sugar phosphate backbone was on the outside of the molecule.” {98}

98) Virtually all the evidence then available made me believe that DNA was the template upon which RNA chains were made. In turn, RNA chains were the likely candidates for the templates for protein synthesis.”

“expressed the transfer of genetic information from the sequences of nucleotides in DNA molecules to the sequence of amino acids in proteins.”

99) “my inability to think in three dimensions became all too apparent.”

107) B & A structures of DNA with the black cross revealed the print of helical structure

109) “DNA was a helix that repeated its pattern every 34 A¾ along the helical axis.”

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