History of Sickle Cell Disease.

The symptoms related to sickle cell crises were known by various names in Africa, long before they were recognized in the western hemisphere . Symptoms of sickle cell anemia could be tracked back to year 1670 in one Ghanian family. It was in 1910 when James Herrick 3 observed, “peculiar elongated sickle shaped RBCs” in the blood of an anemic black medical student, and then the scientific community came to know about it.

It was the discovery of Emmel in 1917 of the sickling phenomenon, in vitro, in the members of a family which first suggested the genetic basis for sickling. So it was discovered to be an inheritable condition. Later on it was explained that the sickling phenomenon, in vitro, was due to deprivation of oxygen . Both Huck and Sydenstricker, who did the detailed analysis of the pedigrees of Huck's patients, concluded that the sickle cell phenomenon was inherited as a Mendelian autosomal recessive characteristic .

In the two separate studies, heterozygous state for sickle gene in sickling positive without significant symptoms and homozygous state for sickle gene in symptomatic individuals were established. In the same year the abnormal slow rate of migration of sickle hemoglobin on electrophoresis was found. The difference in amino acid sequence in one part of polypeptide chain of Hb S was demonstrated in the later years.

Since then there has been a rapid expansion of information about sickle cell disease and it is still unfolding.

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Sickle Cell Timeline

1910 - Herrick provides the first formal description of sickle cell anemia when he reports that the blood smear of a dental student at the Chicago College of Dental Surgery contains "pear-shaped and elongated forms."

1927 - Hahn and Gillespie associate the sickling of red blood cells with low oxygen conditions.

1940 - Sherman reports that the sickling of red blood cells in the absence of oxygen is caused by a change in the hemoglobin molecule structure.

1948 - Watson suggests that the presence of fetal hemoglobin in the red blood cells of sickle cell newborns is the reason they do not show disease symptoms.

1949 - Noted physical chemist Linus Pauling and associates publish "Sickle Cell Anemia, a Molecular Disease" in Science. This paper explains how protein electrophoresis was used to show that sickle cell hemoglobin differed in structure from normal hemoglobin. This was the first time that the cause of a disease was linked to a change in protein structure.

1956 - Vernon Ingram and J.A. Hunt sequence hemoglobin and discover that the change of a single amino acid in the protein sequence is the cause of sickle cell anemia.

1978 - Flavell prepares maps of the human beta and delta globin genes .

1995 - Upon the completion of the Multicenter Study of Hydroxyurea in Sickle Cell Anemia, Charache reports that the anticancer drug hydroxyurea is the first to reduce the frequent, painful complications that characterize sickle cell disease .

Timeline References

Online Mendelian Inheritance in Man, OMIM (TM). Johns Hopkins University, Baltimore, MD. MIM No. 141900 (November 6, 2001) . <http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=OMIM>

A Brief History of Sickle Cell Disease. Joint Center for Sickle Cell and Thalassemic Disorders. (February 25, 2001).