Whatever tied Astbury's long-chain molecular yarn to Bernal's globular jellyfish remained
a mystery. Were these two radically different structures? Or were long chains somehow
folded into globular proteins? If all proteins were, at heart, long-chain molecules,
how did they become arranged into the compact, highly specific forms taken by enzymes,
hemoglobin, and the other globular proteins?
Pauling took on the problem using antibodies as his tools. In July 1939, Landsteiner
published a note in Science linking Pauling's and Mirsky's theory of protein structure – with its emphasis on
long chains held in specific shapes by hydrogen bonds – with his own ideas about antibody
formation. Perhaps, he wrote, antibodies were all the same basic molecule, simply
folded in different ways to make them specific for certain targets.
Pauling had been thinking along the same lines. The chemical evidence still pointed,
ever more strongly, toward the central importance of long chains. The physical evidence
pointed toward a relatively dense, tight-knit structure for globular proteins, including
antibodies. What if, Pauling reasoned, antibodies were secreted from antibody-producing
cells as long filaments, chains of amino acids, that came into contact with a target
substance, a virus or the wall of a bacterium or some other unwanted invader in the
body. What if the loose end of the antibody formed itself in some complementary way
to the structure of some part of the invader, like wet clay pushed against a coin?
The two complementary structures might then stick to one another, held by a variety
of weak forces that could come into play when atoms got very close to one another.
Once that happened, the middle part of the antibody molecule might then fold on itself,
like a stack of pancakes, creating the characteristic density of a globular protein.
The back end of the antibody molecule, in this model, would be free to shape itself
to another invader, making antibodies two-armed, and explaining how they were able
to attack and clump target substances into a mass.
The model fit a great deal of data. It was simple and clean. Pauling wrote it up and
sent what he hoped would be a landmark paper on antibody formation to the Journal of the American Chemical Society in the summer of 1940. "What is the simplest structure which can be suggested . .
. for a molecule with the properties observed for antibodies, and what is the simplest
reasonable process of formation for such a molecule?" he asked at the beginning. Then
he elegantly and persuasively put forward his ideas.
His paper made a great stir. It was another demonstration of the power of applying
chemical ideas to biology. It was a new vindication of Weaver's approach, which he
was now calling "molecular biology."
It was only later that it was proven completely wrong.