Generation of Diversity

In recent decades immunology has been one of the most exciting--and successful--fields of biomedical research. Over the past thirty years immunologists have acquired a detailed understanding of the immune system's unique recognition mechanism and of the cellular and chemical means used to destroy or neutralize invading organisms. This understanding has been formulated in terms of the clonal selection theory, the dominant explanation of immune behavior. That story is the subject of The Generation of Diversity.A major problem for immunologists had long been to determine how cells of the immune system could produce millions of distinct antibodies--and produce them on demand. The clonal selection theory explains that cells with genetic instructions to produce each antibody exist in the body in small numbers until exposure to the right molecule--the antigen--triggers the selective cloning that will reproduce exactly the cell needed. But how can so many different antibody-producing cells be generated from such limited genetic material? The solution to this question came from new applications of molecular biology, and, as the authors argue, the impact of the new techniques changed both the methods and the concepts of immunology.The Generation of Diversity is an intellectual history of the major theoretical problem in immunology and its resolution in the post-World War II period. It will provide for immunologists essential background for understanding the conceptual conflicts occurring in the field today.

Scott Podolsky and Alfred Tauber have written a dense and exhaustive scholarly treatise about the history of [the generation of diversity]. They explore the intellectual setting in which the Tonegawa experiment was performed by reviewing original literature and interviewing the major actors in the drama...Everyone interested in the history of immunology and genetics should read this book., The Generation of Diversity is a remarkable mixture of formal history, literature review, and 'immunophilosophy.' It traces the origins of Burnet's clonal selection theory as a central paradigm of contemporary immunology, then reconciles that theory with the discoveries of the molecular era, and concludes with consideration of 'the immune self'...The authors' meticulously detailed background to the experimental work is a tour de force, which one would never expect to be attempted again, and it stands as a vibrant testament to an extraordinary era for immunology., This book is thoroughly researched, well written, and obviously intended to be definitive with respect to clonal selection and the generation of antibody diversity… Despite, or perhaps because of, the great amount of detail in this book, I enjoyed reading it… For an immunologist, it is satisfying to have the history of two major areas of research recapitulated. This book includes many details I missed earlier or had forgotten, and it is of interest to compare the authors’ assignment of priorities for correct conclusions with those of the principals, as expresses in their own reviews of the topic. This book will be an essential part of the collection of anyone with an interest in the history of immunology., This scholarly historiography is a must for those with more than a passing interest in immunology. Nine well-structured chapters cover the issues that have led to a general acceptance of the clonal selection theory and the establishment of molecular immunology as the arbiter of current thinking… Scott Podolsky and Alfred Tauber’s conceptual grasp of the ideas is anchored by a thorough explanation of critical experiments. They bring an almost extravagant degree of research, and attention to every argument, rendering the finished product as readable as a good novel., Several recent studies have shown the central role of techniques, instruments, reagents and experimental systems in the ‘molecularization of biology and medicine’, first by focusing on the structure of proteins, then on the structure of nucleic acids (DNA and RNA). The Generation of Diversity is a fascinating account of how exactly this change took place in immunology. The book’s main strength [is] telling a very detailed story of a transformation of a single domain of scientific inquiry.

Alfred I. Tauber is Professor of Medicine and Philosophy and Director at the Center for Philosophy and History of Science, Boston University. He is the author of The Immune Self: Theory or Metaphor? and coauthor of Metchnikoff and the Origins of Immunology. Scott H. Podolsky is a First-Year Resident in Medicine at Brigham and Women's Hospital in Boston.