Animal extrapolation in preclinical studies: An analysis of the tragic case of TGN1412.

According to the received view, the transportation view, animal extrapolation consists in inductive prediction of the outcome of a mechanism in a target, based on an analogical mechanism in a model. Through an analysis of the failure of preclinical studies of TGN1412, an innovative drug, to predict the tragic consequences of its first-in-man trial in 2006, the received view is challenged by a proposed view of animal extrapolation, the chimera view. According to this view, animal extrapolation is based on a hypothesis about how human organisms work, supported by the amalgamation of results drawn from various experimental organisms, and only predicting the 'predictive grid', that is, a global framework of the effects to be expected.