|The Genetics of Disease
The final section of the 1949 paper discussed genetics. The Caltech authors stated that people suffering from sickle cell
anemia were homozygous, whereas people with sickle cell trait were heterozygous. The Longsworth scanning diagrams that they
reproduced with their article, definitively show that those with sickle cell trait hemoglobin have two distinct peaks – one
that resembles the peak of sickle cell anemia hemoglobin and one that resembles the peak of normal hemoglobin. Thus, they
found that sicklemics had one normal allele producing normal hemoglobin and one sickle cell allele producing sickled hemoglobin.
In their discussion on genetics, the authors mentioned that geneticist James V. Neel of the Heredity Clinic at University of Michigan had published a paper earlier that year and proposed the same genetic conclusion.
Neel had analyzed the blood of parents and their children and concluded that sickle cell trait is a heterozygous trait, and
sickle cell anemia is homozygous recessive. Science published Neel's paper in July 1949, four months before the Caltech paper. Pauling and his collaborators wanted it to be
on the record that they reached the same conclusion independently of Neel.
The men at Caltech provided more information about sickle cell anemia than Neel. Their chemical analysis of blood using electrophoresis
demonstrated the difference between normal and sickle cell hemoglobin as well as showed sickle cell trait hemoglobin to be
a mixture of normal and sickle cell hemoglobins.
Click images to enlarge
Linus Pauling lecturing on sickle cell anemia, Kyoto, Japan. 1955.
Mead-Swing Lectures, October 16 - 18, 1956.
"The demonstration that sickle cell hemoglobin differs in electrophoretic mobility from normal hemoglobin led to the entitled
inference: 'Sickle cell anemia, a molecular disease.' This astonishingly simple concept is of fundamental importance to medicine
for the ultimate understanding of the origins of sickness, and to biology for the insight into what genes do. In the author's
words, 'This investigation...reveals a clear case of a change produced in a protein molecule by an allelic change in a single
gene involved in synthesis.'"
Samuel H. Boyer IV