Apoptosis, necrosis, or whatever: how to find out what really happens?

There is no doubt that thorough knowledge of apoptotic cell death is of paramount importance for many areas of current research. Despite many available ways of detecting apoptotic cell death, the analysis of apoptosis reveals considerable conceptual and technological problems. In this issue of The Journal of Pathology, Grogan and colleagues offer an interesting study, in which they present a promising model system for investigating the spatio-temporal events of initiation and progression of apoptosis (and other forms of cell death). The confusing complexity of results based on parallel experiments in this paper might be partly due to technical variability or insufficiency; more likely, however, this provides evidence that most if not all approaches thought to be 'specific' for apoptotic cell death address different aspects of cell death, have different sensitivities and specificities, and are rather complementary than redundant. Grogan and colleagues provide an excellent demonstration of the uncertainties and ambiguities which result from basically all currently available technologies, yielding, even in one system, results which are partly confusing, because they are partly contradictory. This situation is typical for cell death analysis at present-not only in the cartilage field.