There is plenty of evidence to show that a high metabolic rate slowly destabilizes the optimal differentiated state of cells as a result of nonenzymatic processes. Because of the continuing high energy demands of the brain in homeothermic organisms, an evolutionary expansion of this organ has to go with the development of maintenance systems which effectively counteract these degenerative processes. Thus the nerve cells in more encephalized and longer-lived species are probably inherently more stable in maintaining their cellular and molecular integrity in the presence of destabilizing insults than do low encephalized species with short life spans.