Pathogenesis and Treatment of Sickle Cell Disease

Abstract

In 1949, the discovery that sickle hemoglobin (α₂ βS₂) has an abnormal electrophoretic mobility prompted Linus Pauling and his colleagues to christen sickle cell anemia “a molecular disease.”¹ The ensuing five decades have produced a wealth of information on the mechanisms by which a single base substitution in the gene encoding the human β-globin subunit, with the resulting replacement of β6 glutamic acid by valine, leads to the protean and devastating clinical manifestations of sickle cell disease. Until recently there was a disappointing lag in the application of this knowledge to the design of safe and effective . . .