A New Theory of Mutation and the Origin of Cancer *

At present there is much discussion on the relation of carcinogenesis to mutation. There are several puzzling problems to be considered, differing somewhat between cancers of spontaneous origin and those induced by some sort of treatment. The hereditary influence in the origin of spontaneous neoplasms has been repeatedly demonstrated, though there are many cases lacking such evidence. Here is a primary indication that cancerous changes, whatever they may be, have a close relationship to the genes. However, this relationship may be of an indirect sort, some argue; perhaps the inherited trait is rather a specific or local debility predisposing to cancerous development induced by other agents. At any rate there seems to be little evidence for the inheritance of a "general tendency" to cancer. The significance of pre-cancerous conditions, whether hereditary (e.g., moles?) or induced by irritation or other treatment, is of great interest. If cancer is to be considered analogous to somatic mutation, it would seem to be at least a two-stage affair, one mutation acting to complete the work of another. But why consider a neoplasm the effect of somatic mutation? The arguments again are varied. There may be difficulty in precise definition of mutation; some sort of "permanent" alteration of the cell, probably of the nucleus, may suffice. Neoplasms maintain their cell-specific features even after long transplanting; statistical study of their induction (Dunning and Curtis5) indicates a close relation to dosage of carcinogen, as mutations follow dosage of mutagen; and various cytological peculiarities have been noted in cancer cells, notably polyteny (Biesele). Arguments bearing upon the somatic mutation (alteration) idea both pro and con are also given by many investigators (Bauer,2 Dahlberg,4 Jones6' 7, 8, 9). Against the somatic mutation hypothesis are arrayed arguments whose weight derives mainly from the technical difliculty of proving a concept. The virus-agent hypothesis again has technical handicaps. When the virus is considered a permanent, usually latent parasite, rather than a