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In 1957-8 I was already deeply interested in what was coming to be called auto-immune disease and it became immediately obvious that if a clonal selection theory of immunity was to be accepted it must be applicable, with appropriate modifications, to pathological manifestations of immunity as well. The concept of the ‘forbidden clone’ emerged almost at once and I have seen no reason to withdraw the phrase or the idea since. It is a concept which can accept infinite elaboration to fit specific instances but yet remain basically very simple. In essence, a forbidden clone arises from a stem cell line in which two types of genetic individuality develop in the course of differentiation and somatic mutation. One is concerned with the nature of the ‘immune receptor’. It must allow the immunologically reactive cell (immunocyte) to react specifically with some accessible component of the body acting as an antigenic determinant. The second is a genetic anomaly that makes the cell more resistant than normal to the processes which should result in the elimination of such autoreactive cells from the body. Instead, when conditions are appropriate, it is stimulated to proliferate to form a forbidden clone with potentially pathogenic effect.

With the rapidly expanding population of old people in every affluent country, important new social problems are emerging. It is natural, therefore, that gerontology is attracting many of the academically minded, and within the medical profession a fully fledged speciality of geriatrics is growing up. With age every bodily system becomes less efficient and more vulnerable, though in some the effect is more striking than in others. Anyone interested in almost any aspect of human biology will find that some facet of ageing is relevant to his field of study. Immunologists are no exception and in any recent discussion on theories of ageing the auto-immune or immunological approach will be found mentioned. It is characteristic of theorizing in any difficult biological area not susceptible to effective experimental study that the three formulations of immunological approaches to ageing, by Walford, Burch, and myself, have not very much in common. There is a great deal more to ageing than the development of low-grade auto-immune disease, but this is part of the story and it would be inappropriate to omit the topic in a book on general aspects of auto-immunity.