A dozen years had passed since Pauling's first, failed attempt to solve the keratin
structure. Now, in 1948, he was ready to try again. The intervening decade-plus of
protein work (Pauling's portion of which was conducted around his wartime research,
continued work on other molecular structures, the writing of a textbook, the search
for grants, and the duties of chairman of the chemistry division) was beginning to
yield important insights into the relationship between protein structure and function.
On the practical side, Corey's work with amino acids was providing more precise information
on sizes and bond angles of protein's subunits. From a theoretical standpoint, Pauling
remained focused on the lessons he had learned from antibody research: Proteins recognized
and bound to each other through precise complementary shapes. He now saw this basic
idea of molecular complementarity working in other biological systems.
He included enzymes, for instance, biomolecules that acted as catalysts by speeding
reactions in the body without themselves being changed. Enzymes were necessary for
life itself. But how did they work? Here again there was great specificity involved
in the reaction, with each enzyme highly targeted in its action, binding to a single
starting molecule (called a substrate) and transforming it into a new molecule (product).
Pauling thought that complementarity was responsible. In his view, the protein enzyme
would have a shape that loosely fit a molecule of substrate. This fit would tighten,
grow more precise, if the substrate was twisted or bent a bit into a form called an
activated complex. This strain would make it more likely that the starting substance
might participate in a chemical reaction to form the product. The product, once formed,
would again be only loosely held to the enzyme, ready to let go and free space for
another reaction. Enzymes, according to this theory, acted like molecular pliers,
bending the substrate and making it easier to break into pieces that could be reformed
into new products.
Pauling's ideas about enzymes were proven to be essentially correct. But there was
more to come. The senses of taste and smell, Pauling thought, might operate through
a complementary fit between sensed molecule and specific binding sites in the body
(a theory still in favor among odor researchers). New drugs might be devised that
would act by mimicking the complementary structure of natural substances. Complementarity,
he thought, might help explain how viruses worked.
Then there was the biggest question in biology: how genes operated. As Pauling and
Delbrück had hinted in 1940, complementarity might also play a part in the replication
of genes. In a number of lectures and presentations Pauling gave on complementarity
in 1948, he fleshed out the idea: "In general the use of a gene or virus as a template
would lead to the formation of a molecule not with an identical structure, but with
a complementary structure. It might happen, of course, that a molecule could be at
the same time identical with and complementary to the template upon which it is molded,"
he said. "If the structure that serves as a template (the gene or virus molecule)
consists of, say, two parts, which are themselves complementary in structure, then
each of these parts can serve as the mold for the production of a replica of the other
part, and the complex of two complementary parts thus can serve as the mold for the
production of duplicates of itself."
This was a description of the basic duplex nature of the double helix – four years
before it was discovered.