Introduction

In the mid-19th century Augustus Waller found that the distal stump of a severed axon underwent degeneration, while the axon proximal to the site of injury survived (Waller, 1850). Waller's seminal contribution was made in England only 2 years after Schleiden and Schwann articulated the cell theory in 1848. It had previously been recognized that following transection of a nerve, the muscles were paralyzed. Waller brought to such experiments the advent of microscopy. In the frog hypoglossal nerve he observed that distal to the site of section the fibers survived for only a few days, then degenerated so that the “axis cylinders” – the axons – disappeared (Waller, 1850). Proximal to the site of section they survived.

Implicit in the findings of Waller the idea that the nerve cell body is a nutritive source for the axon, without which the axon can only survive for short periods. This observation identified the nerve cell body as the “nourishing mother” of a dependent axon, and suggested that the separation of the severed axon from the cell body resulted in passive starvation of the axon. Waller's inferences have proved largely correct: most macromolecular synthesis occurs largely in the nerve cell body, so that the axon is largely a metabolically dependent structure. Yet the inescapable lesson of the last two decades of research is that Wallerian degeneration is not passive, but an energy-requiring, temperature-sensitive active process of self-destruction, conceptually analogous to apoptotic mechanisms of cell death (see Volume I, Chapter 16).