When he resumed life at Caltech in the late summer of 1948, Pauling found himself
diverted from protein spirals by much more exciting work being done in his laboratory.
It had started at the end of the war, when Pauling served on a select committee charged
with designing postwar funding for medical research. At one of their dinner meetings,
the conversation turned to a little-studied blood disease called sickle-cell anemia.
Another committee member, Harvard medical professor William B. Castle, described how the disease deformed the shape of red blood cells from flattened discs
to distorted crescents, which then clogged small blood vessels, leading to the painful
symptoms suffered by its victims. One odd thing, Castle added, was that the misshapen
blood cells were more common in venous blood than in the more highly oxygenated blood
When he heard that, Pauling had an insight. He had studied hemoglobin, the oxygen-carrying
protein inside red blood cells, and had published a paper on how oxygen bound to the
molecule. What if, he thought, hemoglobin was at the heart of the disease? Perhaps
the red blood cells were deformed because something happened to the hemoglobin when
oxygen was released from it. In the fall of 1946 he had hired a young physician-turned-chemist, Harvey Itano, to explore the differences between normal and sickle-cell hemoglobins. Sickle-cell
anemia is more common among blacks than any other American racial group, so Itano
and Pauling had tried to get samples from physicians in the Los Angeles black community.
When that failed to turn up enough, they had sickle-cell blood shipped from Tulane
University in Louisiana.
But all their attempts to find some difference between normal and sickle-cell hemoglobin
had failed. Just before leaving for England Pauling had hired a postdoctoral fellow,
John Singer, to help. Singer was more experienced than Itano in the chemistry of large molecules,
and he knew something about a new piece of protein-separation equipment that might
By carefully comparing the behavior of the two hemoglobins in the new apparatus, Itano
and Singer were able to show that, as Pauling had guessed, there was a measurable
difference in the electrical behavior of molecules of normal hemoglobin versus the
same substance from sickle-cell patients.
This was an astounding finding. A slight change in the electrical charge of a single
type of protein out of the thousands in the body meant the difference between sickness
and health. In some patients it meant the difference between life and death.
"Sickle Cell Anemia, a Molecular Disease," published in the fall of 1949 (with Pauling's
name ahead of Itano's and Singer's), was a landmark paper. It not only traced human
disease definitively and for the first time to a single molecule in the body, but
went on to link this finding firmly to a genetic pattern.
People began talking about a second Nobel Prize for Pauling, this time in Physiology
or Medicine, to reward this important insight. It was no wonder he paid little attention
to the keratin bedspring he had sketched in London.