Reversing the hemoglobin switch.

Natural observations can often provide important clues for how therapies can be developed to ameliorate disease. Disorders of β-hemoglobin, including sickle cell disease and β-thalassemia, are good examples of this maxim, since a variety of clinical observations have shown that increased levels of fetal hemoglobin can ameliorate the severity of these diseases. This observation has led to the decades-long hunt for strategies to increase the expression of fetal hemoglobin in a targeted manner. There has been some success in developing drugs to achieve such increased expression of fetal hemoglobin for therapeutic benefit, as exemplified by the use of hydroxyurea. However, . . .