The Generation of Diversity: Clonal Selection Theory and the Rise of Molecular Immunology - Hardcover

Podolsky, Scott H.; Tauber, Alfred I.

Hardcover

ISBN 10: 0674771818 ISBN 13: 9780674771819

Publisher: Harvard University Press, 1998

Synopsis

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.

About this title

About the Authors

Scott H. Podolsky is a First-Year Resident in Medicine at Brigham and Women's Hospital in Boston.

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.

Reviews

This book reviews the history of the clonal-selection theory and the debate about the generation of antibody diversity. The theory of clonal selection that was advanced independently by Burnet and Talmage in 1957 is now a generally accepted concept among immunologists. According to this theory, each B lymphocyte has a set of antibody receptors of a single specificity; when activated by the antigen, its descendants (the clone) produce antibodies with the same specificity as the receptors of the original B cell. Contrary to earlier, "instructive" theories, the antigen plays no part in determining the specificity of the receptors.

From about 1900 to 1980, the basis of antibody diversity was one of the most interesting unresolved problems in biology. The central question was the mechanism by which antibodies that are closely related in structure can exhibit an enormous variety of distinct specificities. This problem attracted the attention not only of immunologists but also of many other scientists. One of them was Susumo Tonegawa, a molecular biologist whose work at the level of DNA and RNA virtually resolved the issue and won him a Nobel prize.

This book is thoroughly researched, well written, and obviously intended to be definitive with respect to clonal selection and the generation of antibody diversity. Three major topics are covered in detail. First is a review of the relevant experiments (supported by about 900 references), with attention to the correct assignment of priorities for discoveries. Second is a thorough analysis of the viewpoints, often conflicting, expressed by scientists before consensus was achieved. Third is the evolution of scientific thinking and the roles of theory and methodology in the design and interpretation of experiments. These discussions inform the entire book; in addition, chapter 7 applies a threefold analysis to the contents of the first six chapters. The last chapter applies philosophical analysis to recent theories on the fundamental nature of the immune system, some of which are controversial. "We wish to explore the issue by mobilizing philosophical debates concerning how meaning is generated in language," state the authors. They also "believe that the dominant conceptual innovations in contemporary immunology are less concerned with the direct application of molecular biological techniques to problems in immune function than with significant turns in the underlying theory of the field." Personally, I put my money on molecular biology.

This book contains numerous references to related data from disciplines other than immunology. Biographical sketches illustrate how scientists' backgrounds often determine their viewpoint and experimental approach. Most of these sketches are rather brief; an exception is that of Sir Frank Macfarlane Burnet, whose career is discussed in considerable detail, together with the evolution of his thinking on clonal selection, antibody diversity, and immunologic self-recognition and tolerance. Far less space is assigned to the work of David Talmage, who proposed the current version of the clonal-selection theory at the same time as Burnet, if not slightly earlier.

Despite, or perhaps because of, the great amount of detail in this book, I enjoyed reading it. I believe, however, that it may prove difficult for someone not familiar with the terminology of immunology or molecular biology. In addition, one chapter deals with the numerous hypotheses that were proposed between 1965 and 1976 about possible mechanisms of the generation of diversity. It is interesting to compare these hypotheses with current dogma, but a nonspecialist who does not know the outcome might find this material less enjoyable (especially because the answers do not appear until a later chapter).

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 expressed 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. Together with earlier books by Tauber, Arthur Silverstein, and others, it provides a comprehensive view of immunology as it has evolved in this century.

Reviewed by Alfred Nisonoff, Ph.D.

Edition details

• Publisher: Harvard University Press
• Publication date: 1998
• Language: English
• ISBN 10: 0674771818
• ISBN 13: 9780674771819
• Binding: Hardcover
• Edition number: 1
• Number of pages: 508