The survival of the fittest theory of immunology

The Generation of Diversity
October 29, 1999

This scholarly historiography is a must for all 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.

Molecular biology at its simplest is a technological tool, but it has achieved a hegemonic domination of the life sciences. But how does this relate to something so compellingly cellular as clonal selection, and what is clonal selection theory anyway? Jan Klein notes in his authoritative textbook, Immunology , that clonal selection theory is no longer a theory but is one of the foundations on which immunology stands. Diversity, the hallmark of the immune response, resides in individual cells by way of clonally distributed receptors. Each cell carries only one receptor specificity and for any given antigen, only a few cells carry receptors with sufficient affinity to bind that antigen and become activated. As with natural selection, the immune response selects the "fittest" cells to survive and multiply.

A number of theories have competed over the past 50 years to explain how the immune system responds to an antigenic universe that might consist of over ten billion determinants. It was thought that antigen receptors might be largely homogeneous and able to provide the instructions for their own recognition. Although it sounds bizarre with hindsight, this theory was held by some of the intellectual giants of that time. "Instructionists" were confident that the genome could not encode so much diversity. But, as the one-way traffic of information from DNA to RNA to protein became clear,they gave way and the new era of molecular science dawned.

At the core of the book is a profile of Susumu Tonegawa. For many, his Nobel prize was the public consummation of the association between molecular biology and immunology. Tonegawa showed how the immune system was able to flout the "one gene, one polypeptide chain" rule by a process of recombination from a limited set of genetic elements. As Tonegawa related: "the straightforward interpretation of these results is that genes which are some distance away from each other in the embryo genome are brought together during differentiation to form a continuous stretch". Translocation of genetic elements had been proven as the "two genes one polypeptide" hypothesis.

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.

Richard Lake is research fellow in immunology, Queen Elizabeth II Medical Centre, Perth, Australia.

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

Author - Scott H. Podolsky and Alfred I. Tauber
ISBN - 0 674 77181 8
Publisher - Harvard University Press
Price - £49.95
Pages - 508

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