Landmark Papers, Part 1

Over the next two weeks, I’m going to read a series of landmark scientific papers from various fields. I’ll be writing down my notes here.

Part 1, Molecular Structure of Nucleic Acids by James Watson & Francis Crick

This landmark paper correctly describes the structure of the DNA for the first time as a double helix of two chains running in opposite directions joined by purine-pyramidine bonding, ending the race for the structure of the genetic molecule and triumphing over the more established scientists such as Linus Pauling (interested readers can check out the movie The Race for the Double Helix).

The most impressive thing about this paper is its conciseness, at exactly one page long, it outlines the structural characteristics of DNA. The paper starts with an understated

“We wish to suggest a structure for the salt of deoxyribose nucleic acid (D.N.A). This structure has novel features which are of considerable biological interest.”

Yet through a brilliant process of elimination and logical deduction, the paper has established the suggested structure as the genetic molecule through the following steps.

  1. Pauline and Corey’s triple helix structure was rejected based on the X-ray diffraction pattern, that the phosphates in the middle would repel each other, and that “some of the van der Walls distances appear too small”.
  2. Fraser’s triple helix structure was rejected because it was “ill-defined” (I sense a bit of derision…lol)
  3. The suggested structure contains the same structural materials, but is in a configuration that simply makes more sense in the following ways:
    • The structure has a high water content, “at lower water contents we should expect the bases to tilt so that the structure could become more compact”. This hints at how so much genetic materials could be packed into a nucleus.
    • The two-chains of the double helix are held together through base-pair bonding (adenine to thymine, and guanine to cytosine), which means knowing one strand is sufficient to determine the other. This led to probably the greatest understatement in science:

      It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material

    • The base-pairing bonding mechanism was shown to make sense based on the experimental ratio of adenine to thymine, and guanine to cytosine in the molecule.
    • This structure has to be made of deoxyribose sugar based on van der Waals contact argument.
    • The suggested structure fits well with the X-ray diffraction data of the structure.

The derivation of the DNA structure is exemplary of deduction of structure from function that is now so widespread in science.


About collapsedwavefn

I have a lot of thoughts. Some of them I'd like to share.
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