The wisdom of hindsight.

This essay is a highly personalized account of some of the important conceptual contributions to immunology. I have asked myself, "What were the ideas that caught my attention and how and by whom were they presented?" I have learned that most of what immunologists have called concepts deal with too small a slice of the subject. They are essentially inductive extrapolations from one experiment to a possible next step. Historically, these extrapolations extended over too narrow a chasm to account for the information available at the time. The result was that an extrapolation from one misleading observation could dominate and distort, for a significant time, the course of the field. It is also why there has been an inverse relationship between the clarity of a theory and its ease of acceptance by immunologists. Looking to the past, I have used two areas to illustrate the role of conceptualization: the self-nonself discrimination and the origin of the humoral repertoire. To illustrate all of this I have chosen as a cast of characters the founding fathers of immunology as we know it today. I hope that by taking this look into the rear view mirror our efforts will be guided in more productive ways. The take-home lesson is that we need to widen our horizon constantly to make more general concepts that then render the manipulation of the immune system more useful.