Clinical and translational research makes the biggest leaps in human disease when effective biomarkers are developed and put into play. Effective biomarkers are often convenient surrogate markers of clinical outcomes that dramatically speed up the development of clinically useful interventions. They also often point to new mechanistic pathways that open up opportunities for new intervention strategies. The biomarkers may be biochemical, physiological, imaging, or any other reproducible indicator. Familiar examples of effective biomarkers that guide clinical management resulting in improved clinical outcomes include blood pressure, serum cholesterol, or tumor size from radiographic imaging.

In sickle cell disease (SCD), the first truly successful biomarker was fetal hemoglobin [1]. Natural history epidemiological investigation demonstrated that patients with higher levels suffer fewer clinical complications of SCD. Bench investigations showed that fetal hemoglobin inhibited polymerization of sickle hemoglobin. Intervention with hydroxyurea raises fetal hemoglobin levels, and improves clinical outcomes. Hydroxyurea is now an approved, standard of care drug in sickle cell disease, and indications for its prescription continue to expand.