Somatic Mutation and Chronic Disease

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Abstract
In this review somatic mutation is depicted as an important factor in the genesis of a wide variety of chronic diseases and in the process of ageing itself. The nature of somatic mutation (a) in expendable acitvely replicating cells and (b) in non-replicating tissue cells is discussed and the consequences considered. Malignant disease is included only en passant but autoimmune disease is discussed extensively from the standpoint of the forbidden-clone hypothesis, which makes it virtually equivalent to conditioned malignancy. Various possibilities are discussed by which somatic mutation in one or very small numbers of cells may be "magnified" sufficiently to produce demostrable effects. There is much to suggest that somatic mutation, particularly as expressed through autoimmune disease, may be of special importance in the process of ageing. The requirements for an autoimmune theory of ageing are: that forbidden clones capable of minor attack on a variety of tissues may arise with greater frequency with advanicing age; that forbidden clones are themselves subject to partial or complete control and that this control may diminish in effec -tiveness with advancing age.