It's in the Blood! A Documentary History of Linus Pauling, Hemoglobin and Sickle Cell Anemia Narrative  
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Alpha and Beta Chains
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In 1958 and afterwards, Pauling liked to discuss the small difference between normal and sickle cell hemoglobin in order to mention work completed at Caltech. In 1957 Pauling and two of Caltech's research associates, Herbert S. Rhinesmith and W. A. Schroeder, announced that normal adult hemoglobin has four polypeptide chains of two different types, which they called alpha and beta.

After Ingram announced that one amino acid differs in normal and sickle cell hemoglobins and after Rhinesmith, Schroeder, and Pauling determined that hemoglobin has two types of polypeptide chains, many researchers tried to ascertain where the amino acid substitution occurred on the polypeptide. In 1958 Itano and Singer were unable to state the exact location of the replacement, but narrowed down the possibilities. They concluded that the replacement had to occur within five Angstroms from where the hemes are bound together in order to support the explanation of how sickle cell hemoglobin contorts into a crescent shape as described in "Sickle Cell Anemia, a Molecular Disease." In addition, they stated that if only one amino acid replacement occurs, then only one of the two types of polypeptide chains (either the alpha or the beta) differs between normal and sickle cell hemoglobin.

In 1959 two experiments showed that the replacement of glutamic acid with valine occurs on the beta-chains. Jerome R. Vinograd, W. D. Hutchinson, and Schroeder of Caltech showed that the beta-chains of sickle cell and normal hemoglobin differ, whereas their alpha-chains are identical. Ingram also demonstrated that the difference occurs in the beta-chains and, in addition, stated that the substitution occurs at the sixth position from the N-terminus.

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See Also: Memorandum from Walt Schroeder to Linus Pauling. July 11, 1957. 

Click images to enlarge 

Members of the Caltech Chemistry faculty. 1950.

Amino acid sequence of hemoglobin. 1950s.

"Life is too complicated to permit a complete understanding through the study of whole organisms. Only by simplifying a biological problem -- breaking it down into a multitude of individual problems -- can you get the answers. In 1935, for example, Charles Coryell and I made our discovery about how oxygen molecules are attached to the iron atoms of hemoglobin, not by getting a cow and putting it into our magnetic apparatus, but by getting some blood from the cow and studying this blood."

Linus Pauling
December 1986
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