Understanding translational research: a play in four acts.

Translational research (TR) bridges discovery to clinical delivery. All TR also requires the development of an intervention. Classical 'bench to bedside' TR is responsible for many important advances, but cannot account for many others, which begin with clinical observations. My personal involvement in TR has ranged from exploration of long-term mechanical circulatory support devices to amelioration of the progression of Alzheimer's disease to the pharmacologic cure of smallpox. This experience suggests that most TR is opportunistic and inefficient. A strategic approach to TR based on a better understanding of the processes it entails could enhance progress in TR despite its increasing complexity.