NATURE|Vol 443|5 October 2006 BOOKS & ARTS processes and mediate evolutionary diversifi- determine the exact patterns and repertoires some of the most complex biological phenom- cation than the transcription factors themselves. of developmental gene expression. ena: animal development and the evolution of This makes sense because, in most cases, In general, Davidson does an excellent job body forms. sequence-specific transcription factors or the of reducing the complexity of different devel- This book should be read by all biologists signalling proteins that modulate their activity opmental pathways and modes of embryonic who want to understand how development are highly conserved among organisms with development in diverse animal phyla to a set of and evolution take place and what governs very different shapes and forms. Yet the con- simplified and logical concepts and principles. the workings of genomes. I also recommend stellations of cis-regulatory elements, which He provides excellent illustrations and experi- it to computer scientists and engineers who together make up the cis-regulatory control mental examples derived from several model are interested in the budding field of compu- units that dictate the time, place and magni- organisms: nematode worms, fruitflies, sea tational biology, as reading it does not require tude of gene expression, are more diverse and urchins, tunicates and vertebrates of different an extensive background in developmental seem to evolve more rapidly than the transcrip- sorts. What is especially attractive about the biology. ■ tion factors that recognize them. Furthermore, book are the regulatory networks drawn as sim- Michael Karin is in the Department of such control units also dictate the expression ple wiring and computational diagrams. These Pharmacology, University of California, patterns of transcription factors and signal- go a long way towards explaining the basic San Diego School of Medicine, La Jolla, ling proteins in time and space, and thereby regulatory logic and engineering principles of California 92093, USA.

that hereditary units are ordered linearly on Putting DNA on the map the chromosome, and that genetic mutations and crossing-over experiments could be traced back to the underlying linear arrangement of Reconceiving the Gene: Seymour Benzer’s DNA. Holmes says that Benzer isolated, charac-

Adventures in Phage Genetics S. BENZER terized and crossed about a thousand T4 phage by Frederic Lawrence Holmes Yale University Press: 2006. 320 pp. $50 mutants, most of them in the limited rII region. This was possible thanks to the fantastic resolv- Denis Thieffry ing power of Benzer’s experimental system, In the 1950s, Seymour Benzer set out on a which he progressively improved by using dif- daunting research programme aimed at resolv- ferent types of mutants (extended deletions) to ing the fine structure of the gene. Using bac- speed the mapping of novel mutants. teriophages and various strains of bacteria, his Benzer’s results reached a wide audience genetic-mapping enterprise ultimately united through his contributions to two major con- genetics and structural chemistry. How did ferences: the Brookhaven Symposium on Biol- Benzer conceive and achieve this goal? And ogy in 1955 and the McCollum-Pratt Institute what where the critical components and influ- Symposium on the Chemical Basis of Hered- ences that led to the success of his enterprise? ity at Johns Hopkins University in 1956. On In Reconceiving the Gene, Larry Holmes the latter occasion, Benzer proposed three addresses these questions in a scrupulous and new terms — cistron, recon and muton — to captivating historical analysis. Making exten- solve the ambiguities associated with the term sive use of Benzer’s laboratory notebooks, ‘gene’, which is considered altogether as a unit scientific correspondence, reports and grant of function, recombination (crossing-over) proposals, and complementing these with Fine work: Seymour Benzer created a map of the and mutation. Although these terms (perhaps interviews, Holmes carefully retraces Benzer’s gene with a resolution of just a few nucleotides. with the exception of ‘cistron’) did not become sinuous investigative path and offers us a really popular among the emerging molecular- well-documented day-to-day analysis of the his own results, as well as those of others — biology community, these distinctions helped development of his work. Although Benzer notably an experiment by Hershey and Martha to clarify the relationships between the differ- had previously published his own biographi- Chase demonstrating the hereditary role of ent gene definitions. For a broader historical cal recollection of this period as a chapter in phage DNA, and James Watson and Francis analysis, see The Concept of the Gene in Devel- the edited volume Phage and the Origins of Crick’s work to develop the double-helix opment and Evolution, edited by Peter Beurton, Molecular Biology (Cold Spring Harbor Labora- model of DNA. Raphael Falk and Hans-Jörg Rheinberger tory Press, 1966), Holmes’ extensive analysis Holmes ends his book with extensive (Cambridge University Press, 2000). shows how Benzer sometimes condensed accounts of the main public presentations by Although technical in places, Reconceiving events in his relatively sketchy autobiographi- Benzer of his mapping results. About Benzer’s the Gene should nevertheless be accessible to cal reconstruction. landmark publication (Proc. Natl Acad. Sci. a wide scientifically literate audience as it fur- Trained as a solid-state physicist, Benzer USA 41, 344–354; 1955), Holmes states: “Like ther introduces the broader context of classical was well prepared for quantitative analyses most modern scientific papers, Benzer’s ‘Fine and phage genetics. Holmes initially planned and genetic abstraction. In two years of train- Structure of a Genetic Region in Bacteriophage’ to go beyond Benzer’s fine rII mapping and ing at the California Institute of Technology is a logical reconstruction of the experiments, also cover his contributions towards solving and a year at the Pasteur Institute in Paris, observations, and arguments supporting his the genetic code. This plan was impeded by Benzer progressively penetrated the informal conclusions. It has little narrative structure illness, however, and Holmes died on 27 March international phage network. Initially, he was and does not purport to follow the investiga- 2003. Hopefully, his captivating book will stim- deeply influenced by key players of the phage tive pathway from which it came.” ulate other historians of biology to complete group, including Max Delbrück, Salvador Holmes patiently reconstructs the investi- his project. ■ Luria, André Lwoff, François Jacob, Alfred gative path that led Benzer to draw the first Denis Thieffry is in the Faculté des Sciences de Hershey and Sidney Brenner. However, he high-resolution genetic map (down to a few Luminy, Université de la Méditerranée, progressively altered his pathway in the light of nucleotides). The map supports the contention 13288 Marseille, France.

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