Tuesday 4 January 2011

The Double Helix

A very interesting book I just read is James Watson's "The Double Helix", his account of the discovery of the structure of DNA. It is a very fun to read story, showing how they finally came up with the double helix structure and the famous Watson-Crick base pairing. It also gives a lot of examples of how science should or should not be done. It is intersting to see how inefficiencies in the system and personal hostilities had to be overcome before the discovery was possible. He has a very interesting personal and funny writing style but is in some cases a little bit harsh, especially against co-researcher Rosalind Franklin (for which he apologizes in the epilogue, though).

I think the key to Watson's success was interdiscplinarity.[1] Only by bringing together x-ray data, experiments from organic chemists, and his own model building was it possible to solve such a complex structure with the intstruments available in the 1950s. Francis Crick is described as a genius, but as a character who most people could not deal with easily. Rosalind Franklin appears as an excellent cristallographer but threatened by a male dominated world. Sir Lawrence Bragg was the head of the institute who could see how his famous equation lead through this breakthrough discovery.

The race starts with Linus Pauling's discovery of the protein α-helix. After that, Watson and Crick as well as Pauling come up with a triple helix for DNA, with the backbone inside. Franklin has some clear evidence that the backbone should be outside but does not open up her data for display. Eventually Watson tries out models with the bases inside and the backbone outside. It is stimulating to hear of his excitement as he develops the concept of base pairing. For his success he had to collect information from quite a number of people. Franklin and her boss Maurice Wilkins provided the x-ray data. Crick was able to derive and solve the diffraction equations for helices. The work of Erwin Chargaff provided the vital clue that the amounts of adenine and thymine, as well as, cytosine and guanine, were equal. A direct connection to structural chemists was important to get the correct tautomers of the bases (which were wrong in many textbooks at the time). Watson's final discovery was that he could form AT and GC base pairs which had about the same shape - therefore yielding a regular helix. To compare the results to the x-ray data they had to create a molecular model. At that time that meant putting it all together into a large metal model after asking the workshop to make the pieces. Finally everything worked out and they could publish their paper with the nicely understated final sentence:
It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material.
A point worth mentioning is the secrecy. It seems that the structure could have been found much quicker, had Wilkins and Franklin released their data earlier. I don't know if this is different in today's "publish or perish" situation, that many results are released as soon as they come. And that they are not kept in secret for so long. But maybe for the big things it is still the same.

Finally it was interesting to read how Watson seemed to be living a very easy going life while he made the most crucial discovery of base pairing. Maybe I should tell that to my boss more often: "When Watson invented base pairing, he played tennis every afternoon. Bye!" At least as far as creative break through work is concerned, flexibility seems to be very important. That is what Lee Smolin points out in his book "The trouble with physics". But I guess a large part of my work is just related to more or less standard data production. That could mean it would be better if I go to work at /:30 and wear a tie...

[1] Interdisciplinarity is a little bit overly popularized these days but I think it is still an important feature to be able to look beyond the narrow horizon of one specific field.

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