The outbreak of World War II transformed Caltech's research priorities. Almost overnight
armed guards appeared, and a flood of federal funding became available for a range
of new projects investigating weapons and defense. Old projects were dropped. New
ones, from building guided missiles to making better gas masks, were started.
Pauling, an ardent anti-fascist, was fingerprinted, given a security check, and invited
to war-research planning meetings in Washington, D.C. He quickly shifted his laboratory's
work toward the development of rocket propellants and explosives, and he personally
worked on better instrumentation for submarines and weapons sighting, and designed
(and patented) an armor-piercing shell. Eventually he was invited to participate in
the Manhattan Project to build the atomic bomb (an invitation from Robert Oppenheimer
himself, which Pauling turned down because, he said, he did not want to relocate his
All of Pauling's prewar protein projects were pushed into the background, with one
exception: antibodies. Funding agencies were interested in wartime medical breakthroughs
as well as military advances. Pauling capitalized on that interest, garnering a government
grant to develop an artificial, gelatin-based substitute for blood plasma, and getting
other funding to expand his research into the workings of the immune system.
Before Pearl Harbor he had already been at work proving, as his theory of antibody
formation proposed, that each antibody molecule had two and only two binding sites.
To do that, he and his coworkers developed ingenious methods using precisely defined
synthetic antigens with one, two, or three binding sites. By reacting these antigens
with antibodies and carefully measuring the resulting complexes, Pauling's work provided
strong evidence that antibody molecules are indeed bivalent, an important step forward
in the field.
He also claimed to have found evidence that a single antibody molecule could bind
to two different antigens, a result also predicted by his theory of antibody formation. Later it was
found that this observation was wrong; in fact, while individual antibody molecules
are indeed bivalent, both "arms" bind to a single type of antigen.
This was not the only time that Pauling's meticulous, often important work with antibodies
was tarnished by his enchantment with his own theories. He seemed always to find results
that matched his preconceived ideas. For instance, Pauling's basic idea about antibody
formation, in which the two ends of a "vanilla" long-chain protein molecule molded
themselves to an antigen's molecular shape, also predicted something that might turn
out to be a gold mine: according to the theory, it should be possible to manufacture
antibodies in the laboratory. If a more or less generic protein, say something common
like beef globulin, was carefully denatured, then allowed to renature in the presence
of antigen, it should mold itself to the antigen to create a specific antibody, a
molecule specifically built to bind that antigen. The result would be artificial antibodies,
made to order.
The possibilities were breathtaking. Antibodies were among the most powerful medicines
known; they were the end result of a million years of evolution that allowed the body
to fight off infections and invaders. If they could be made by the quart in a laboratory,
they would represent a breakthrough in medical care. The rights could mean millions
to the discoverer. Pauling's theory predicted that they were possible. Early experiments
in his lab started to indicate that they were. His excitement grew.
In late 1941, Pauling applied for a patent for a method of making artificial antibodies.