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

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Harvard University Press, 2000 - Science - 508 pages

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.


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A Conceptual Orientation
The Burnet Legacy
CST and Molecular ImmunologyA Dogmatic Alliance
The Conventional History
Germline Somatic Mutation and Recombinatorial
Immunobiological Theories of Antibody Diversity
From Protein to DNA
The Recombinant Revolution
A Historiographic Reappraisal
Heavy Chain Diversity and the Molecular Finale
An Accounting
The Fate of the Immune Self

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Page 442 - EL Sheldon, and O. Smithies (1977). Charon Phages: Safer Derivatives of Bacteriophage Lambda for DNA Cloning.
Page 485 - Crystal structure of the human class II MHC protein HLA-DR1 complexed with an influenza virus peptide. Nature 368, 215-221.
Page 451 - Desiderio SV, Yancopoulos GD, Paskind M., Thomas E., Boss MA, Landau N., Alt FW and Baltimore D. (1984) Insertion of N regions into heavy-chain genes is correlated with expression of terminal deoxytransferase in B cells. Nature 311, 752-755. Durandy A., Thuillier L., Forveille M. and Fischer A. (1990) Phenotypic and functional characteristics of human newborns
Page 480 - Wall, R. 1980. Two mRNAs with different 3' ends encode membrane-bound and secreted forms of immunoglobulin u chain.
Page 442 - WILEY, DC (1987): Structure of the human class I histocompatibility antigen, HLA-A2.
Page 464 - Jr. 1983. Both a monoclonal antibody and antisera specific for determinants unique to individual cloned helper T cell lines can substitute for antigen and antigen-presenting cells in the activation of T cells.

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About the author (2000)

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.

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