ABSTRACT

This chapter addresses the idea that diseases are caused by abnormal proteins. While this may be taken for granted today, in the 1940s when no one yet understood the genetic basis of heredity, or how DNA dictates the sequence of proteins, Linus Pauling’s linking of a defective hemoglobin protein to sickle cell anemia was a major breakthrough that heralded the new term of molecular disease. This chapter details the experimental basis by which Pauling and his colleagues definitively demonstrated that the hemoglobin protein from erythrocytes of patients with sickle cell anemia had a different isoelectric point (essentially it had charge differences)—resulting from a modified protein sequence. This great discovery eventually led to an understanding that almost all (non-infectious) disease results from abnormal proteins.