Monday, 11 August 2014

Chargaff rules, ok

The dogs in the street know the story of the discovery of the structure of DNA.  Daring and iconoclastic model-makers Francis Crick and Jim Watson finally cracked the problem in 1953; signing off their classic Nature paper with a laconic understatement "It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material." The dogs also know that the boys had pulled a fast one on Rosalind Franklin whose key and revealing X-ray crystallographic data was shown to them by her boss (or not her boss, they couldn't agree on the matter and were too British to talk it out) Maurice Wilkins. Wilkins was a personal old-boy-network friend of  Crick who is claimed by scientific chauvinists in New Zealand (where he was born) and Ireland (where his people were buried). Franklin did not get a share of the Nobel Prize because she was dead by the time the Nobel committee got round to recognising that the DNA coup was indeed a) correct and b) ground-breaking. Crick, Watson and Wilkins split the loot three ways.  The youngest of them and the only survivor was in Dublin a couple of weeks ago.  So far, so grossly simplified in the telling.

But Crick and Watson's insight depended on another crucial piece of evidence that had been carefully worked out earlier by Erwin Chargaff. In 1950 he had noted that the ratios of the four bases A, T, C, G in DNA varied according to source: Mycobacterium tuberculosis has a %G+C of about 65% while Bacillus subtilis has a %G+C = 40%.  That was interesting and unexpected under then current theories of DNA structure and function. Chargaff's other (and more revealing) Rule says that the ratio of pyrimidine bases (C & T) to purine bases (A & G) is always 1:1 regardless of source.  In particular he noted that %A = %T and %G = %C.  But it does seem to have escaped his notice that this information offered the crucial insight that A paired with T and C paired with G on opposite strands of the double helix.  Some more detail of who ripped what from whom is found in a Nature Education piece by Leslie Pray.

Chargaff must have been kicking himself when the true meaning of his finding was revealed by Crick and Watson just three years later. Not least because he had a very poor opinion of Crick and Watson as knowledgeable scientists "The [first] impression, one 35 years old, the looks of a fading racing tout, something out of Hogarth's The Rake's Progress, Cruickshank, Daumier; an incessant falsetto with occasional nuggets glittering in the turbid stream of prattle. The other, quite undeveloped at twenty-three, a grin more sly than sheepish; saving little, nothing of consequence." And his description of what they actually knew was even less flattering: "So far as I could make out, they wanted, unencumbered by any knowledge of the chemistry involved, to fit DNA into a helix. The main reason seemed to be Pauling's alpha-helix model of a protein....I told them all I knew. If they had heard before about the pairing rules, they concealed it. But as they did not seem to know much about anything, I was not unduly surprised." After the hullabaloo of the Nobel Prize his opinion was more polished / poetic: "That...such giant shadows are cast by such pygmies only shows how late in the day it has become".  Ouch! But Chargaff had a bit of  a reputation for not holding back to spare someone's feelings: "Erwin Chargaff, had written "an exceedingly sarcastic letter" in assessing his findings" . . . about Arthur Kornberg's Nobel prize winning work on the enzyme that makes copies of DNA.

It's Chargaff's birthday (11th August 1905) today, I think a bitter lemon cake and a glass of vinegar might be appropriate. But I can't help thinking that, of all the DNA principals, Erwin Chargaff would have been the most interesting to have dinner with.

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