The value of failure: the discovery of TNF and its natural inhibitor erythropoietin.

The hurtful feelings associated with failing can be devastating especially if the failure occurs after the investment of a considerable effort. The reflection of a lifetime of work in translational medicine has revealed that the study of failures can give birth to new insights that can be explored with important consequences. This article discusses the analysis of two failures that have led to remarkable discoveries. The first led to the discovery of TNF as an important mediator of inflammation that can, if unchecked, cause severe damage in mammals. The second is the identification of erythropoietin as the natural inhibitor of the production and biological activity of TNF. I hope that this paper will help give students the courage to persist in looking for the insights that are the by-products of failure, and to understand the long time lines in the path of discoveries.