|The Master Molecule
It should be understood first that prior to 1953 very few researchers cared much about DNA. Many were eagerly searching for
the chemical nature of the gene, the master molecule of heredity. It was clear by the 1920s that genes were located in chromosomes,
dense tangles of nucleic acid and protein in the nucleus of cells. But of the two major components of chromosomes, protein
and nucleic acid, most leading researchers favored protein. Only proteins were thought to have the complexity and variety
necessary for determining the growth of an organism. Proteins, after all, were made of 20 or more amino acids. They could
exist in myriad forms, from hair and horn to enzymes and egg whites. The nucleic acids, made of just four building blocks
in monotonously regular proportions, seemed stupid by comparison.
Linus Pauling, the world's leading structural chemist in 1950, believed that genes were made of protein. He and Robert Corey,
his chief assistant at Caltech, had spent decades pinpointing the molecular structure of amino acids and protein subunits.
Their greatest triumph, in the spring of 1951, was the simultaneous publication of seven papers detailing protein structures
at the molecular level. Chief among them was the alpha helix, a basic structure present in many proteins. Pauling was the
first person in history to outline basic protein structures at a very detailed molecular level. He did it through hard work
and daring, publishing the alpha helix structure only after deciding to ignore one important bit of conflicting experimental
evidence. As it turned out, he was right to do so - further analysis showed that the data that appeared to run counter to
his structure could be explained in other ways.
Click images to enlarge
Space-filling model of the alpha-helix. 1951.
Pastel depiction of the DNA base pairs. October 1, 1963.
"A good example...is the case of the alpha helix. Pauling had set up a group to do X-ray crystallography of the subunits of
the proteins, and they got very precise data that enabled him to build up the whole molecule from the parameters of the subunits.
As you know, he did this successfully in 1948 in London, but did nothing about it because his final picture of the alpha helix
in 1948 did not agree with the X-ray diagram of the whole molecule....He then waited two years, until 1950, when the group
at I.C.I. in London published the first X-ray pictures of synthetic polypeptides. These synthetic polypeptides did not have
the anonymous reflection that Astbury's fixtures had had, and could be accommodated to the alpha helix; and he then published
the paper. I think he was hoping to do the same thing with nucleic acids, because enough had been published on the subunits
for him to do it, but he was misled by the erroneous pictures of the whole molecule."