Sickle cell anemia — basic research reaches the clinic

Fifty years ago this spring, a conversation between an eminent clinical investigator and an extraordinarily imaginative physical chemist led to the insight that introduced the era of molecular medicine. Although their recollections of the encounter differed slightly, this meeting of Drs. William B. Castle and Linus Pauling soon led to the identification, by Pauling’s laboratory, of an abnormal hemoglobin molecule in the erythrocytes of patients with sickle cell anemia. In the subsequent decades, the techniques of genetics, biochemistry, and cell biology have all contributed to the detailed elucidation of the molecular and cellular pathophysiology of this inherited disease. Nevertheless, a.