ALS 2000: the past points to the future

In this introductory review a number of issues concerning the direction of future research in ALS are addressed in relation to current understanding o f this disorder and its treatment. The importance of understanding the path ways leading to motor neuron dysfunction and death is emphasized. Contempor ary epidemiology, understandably focussed on genetic markers for familiar A Ls, needs to be widened to include as yet undocumented susceptibility- rela ted genetic traits. Potential avenues for therapy are considered, and the f undamental contemporary issue of clinical measurement is discussed, Neglect ed aspects of contemporary research, including disturbed axoplasmic flow, a re brought to attention. The role of experiment derived from clinical obser vation, and vice versa, is described by reference to a number of past and r ecent contributions to the understanding of ALs.