On 'reactivity' versus 'tolerance'

In Burnet's review on 'The impact of ideas on immunology' he considers himself an observer of nature using biochemical and molecular analysis for more detailed understanding, a description that applies also to me. I use three examples--repertoire selection of T cells, rules of immune reactivity versus non-reactivity and immunological memory--to illustrate the difficulties we all have in probing nature's immunological secrets and in critically testing immunologists' ideas. At one end of the spectrum of biological research one may argue everything is possible and therefore all results are correct, if correctly measured. But perhaps it is more important to always ask again and again what is frequent and enhances survival versus what is rare and an exception. At the same time one must keep in mind that special situations and special tricks may well be applied for medical benefits, although they may have little impact on physiology and species survival. I will attempt to use disease in virus-infected mice to obtain some answers to what I consider to be important immunological questions with the hope of improving the ratio of answers that are right for the right experimental reasons versus those that are right for the wrong reasons. Some of these experiments falsify hypotheses, previous experiments and interpretations and therefore are particularly important in correcting misleading concepts. They should help to find out which half of immunological ideas and truths in immunological text books written today are likely to be wrong. Ideas are important in immunology, but are often rather demagogically handled and therefore may cost us very dearly indeed. Evaluating immunity to infections and tumours in vivo should help prevent us from getting lost in immunology.