It's in the Blood! A Documentary History of Linus Pauling, Hemoglobin and Sickle Cell Anemia Narrative  
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The Genetics of Disease
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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.

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Audio Clip  Audio: The Definition of Molecular Disease. February 26, 1962. (1:10) Transcript and More Information

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Video Clip  Video: The Genetics of Disease -- a New Field. 1960. (4:53) Transcript and More Information

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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.'"

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