Abstract
70 years ago, Linus Pauling, the legendary genius of 20(th) century chemistry, published his famous work on the molecular cause of sickle cell disease, a paper that gave birth to what is now called molecular medicine. In this paper, Pauling left important questions unanswered that have motivated an enormous amount of scientific and clinical research since then. This retrospective discusses the basic science studies that have answered those questions directly related to the kinetics and thermodynamics of hemoglobin S polymerization.