Abstract
Students of medical history observe a familiar sequence in the growth of knowledge about many diseases. The initial description is often a pathologic one, involving patients with the most advanced, usually fatal, form of the disease. Clinical–pathological correlations are then carried out in living patients in whom the condition is recognized and in whom the pathologic findings are confirmed during operation or at autopsy. Detailed explorations of the clinical and laboratory manifestations then provide clues to the underlying pathophysiology and help in establishing diagnostic criteria. Often much later, the fundamental cellular defects are identified, and ultimately the molecular or even . . .