CLONAL EVOLUTION, IMMUNE RESPONSE AND CANCER
E. M. NICHOLLS *
Department of Safety Science, University of New South Wales, Australia, 2033
*Author to whom correspondence should be addressed.
Beginning in 1964, observations of sunlight related phenomena in the skin of approximately 2000 subjects, mainly of European ancestry, were made in Sydney, Austalia (34° S. Lat.). Pigmented lesions were counted and many new relationships were indentified. The theory proposed to explain these relationships was of spontaneous or UVLinduced somatic mutation, with evidence of immune rejection responses to the benign or malignant tumours observed. A theory of initiation of tumour formation by somatic mutation of normal tissue differentiation genes was proposed: cells blocked from final differentiation might in many cases fail to recognize normal homoeostatic growth controls. It was further proposed that all cell types have such differentiation genes and that the specific tumours of the phacomatoses are grouped according to their relationship to such genes. This paper reviews some aspects of the author's original theory and emphasizes features of that theory which have beenlargely neglected in the last 25 years or so. It is his view that some current dogmas are misleading when applied in detail.