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book reviews (which degrade critical ecosystem services) deserves more attention. On the positive side, I think that the development of countryside biogeography as a framework for enhancing the preser- vation of biodiversity in human-dominated ANUP SHAH/NATUREPL landscapes deserves attention alongside pros- pects for establishing large-scale reserves, which Wilson discusses very thoroughly. On a separate issue, I’m more sceptical about heritability estimates churned out by behavioural geneticists (often based on badly analysed twin studies) for such attri- butes as proneness to agoraphobia and fear of snakes. But these are trivial matters compared to the magisterial sweep of The Future of Life, and I find myself in total agreement with its major points. Wilson was recently attacked viciously in the pages of The Economist. He was critical of Bjørn Lomborg’s anti-environmental book The Skeptical Environmentalist, which the magazine and Cambridge University Press The same, only more so: gene regulation is similar for organisms have been heavily promoting. In my view, ranging from the elephant to the bacterium Escherichia coli. Wilson had accurately pointed out that busy scientists were having to waste a huge pioneered by François Jacob and Jacques confor- amount of time replying to the book’s dis- Monod in the early 1950s. By the mid-1960s, mational tortions. The Future of Life, by coincidence, three basic types of specific DNA sequence change in an inactive polymerase already is Wilson’s perfect response. It clearly lays that determine the level of expression under bound at the promoter, thereby stimulating out the reasons for his deep concern for the particular physiological conditions were transcription. And in a third mechanism, the human future (shared by the vast majority defined in the bacterium Escherichia coli. activator induces a conformational change of his colleagues) and why he thinks that Such regulatory DNA sequences turn out to in the promoter, effectively changing it from scientists and society have no time to waste. be specific binding sites for RNA polymer- an inactive to an active form. This section of KIM/SPL KWANGSHIN It also reveals him to be a thoughtful, caring, ase, repressor proteins and activator pro- the book presents the key experiments and life-loving human being. ■ teins. Regulation of an individual gene is arguments for these mechanisms in a manner Paul R. Ehrlich is in the Department of Biological determined by the quality of its polymerase that is exceptionally lucid and beautifully Sciences, Stanford University, Stanford, California binding site, the particular activator and/or illustrated. It is understandable to the non- 94305, USA. repressor proteins that bind in the vicinity expert, for whom it was intended, and is a of RNA polymerase, and the physiological ‘must read’ for anyone interested in gene conditions that modulate the function of regulation. the activators and/or repressors. Armed with these lessons from bacteria, From E. coli Monod once wrote that “anything that Ptashne and Gann consider yeast, a single- is true of E. coli must be true of elephants, celled eukaryote, and conclude that acti- to elephants except more so”. In a lucid and provocative vation occurs by regulated recruitment of Genes and Signals book, Mark Ptashne, a leading figure in the the transcription machinery (which contains by Mark Ptashne and Alexander Gann field for nearly 40 years, and Alexander more than 50 proteins and so is much Cold Spring Harbor Laboratory Press: 2002. Gann argue for a unifying principle of gene more complex than bacterial polymerases). 208 pp. $59, £43 (hbk); $39, £28 (pbk) regulation that centres on the concept of Again, the authors use the device of a Kevin Struhl regulated recruitment by means of adhesive well-chosen example for clarity, the brief interactions between proteins. They go on is convincingly argued, and the end result The regulation of gene expression is a funda- to argue that such regulated recruitment is illuminating to both the expert and the mental aspect of biological phenomena such is a general strategy used by many other novice. The emphasis on regulated recruit- as the response to environmental conditions, biological mechanisms involving enzyme ment is important for the overall theme of the development of multicellular organisms, specificity, regulatory precision and evolu- the book, and it is certainly true that this morphology and disease. Gene regulatory tionary flexibility. mechanism predominates in yeast cells. patterns are extraordinarily diverse and Using a few well-chosen examples, However, in emphasizing the funda- complex, yet the regulation of each gene is Ptashne and Gann first describe three distinct mental similarities between bacteria and precise with respect to when and how much mechanisms of transcriptional activation in eukaryotes, Ptashne and Gann have made expression occurs. Gene regulation is also bacteria. In one mechanism, DNA-binding an unconventional choice in classifying remarkably flexible, both to rapidly alter the activator proteins stimulate gene expression chromatin-modifying activities as part of constellation of genes expressed in response by recruiting RNA polymerase to the pro- the transcription machinery. Chromatin to new conditions, and to accommodate moter sequences that lie just upstream of and chromatin-modifying enzymes affect evolutionary demands. At most, a few thou- the gene. Recruitment is mediated by short all eukaryotic processes involving DNA, sand proteins account for the complexity ‘adhesive’ surfaces between the activator and are typically considered as part of the and precision of gene regulation in humans. and polymerase, and the adhesive proper- DNA template, rather than the transcrip- How is this accomplished? ties per se are sufficient for activation. In a tion machinery. So although activators and Molecular studies of gene regulation were second mechanism, the activator induces a repressors use adhesive surfaces for regu- 22 © 2002 Macmillan Magazines Ltd NATURE | VOL 417 | 2 MAY 2002 | www.nature.com book reviews lated recruitment of chromatin-modifying activities, such recruitment does not directly Science in culture affect transcription and indeed is analogous to (although mechanistically distinct from) Seeing stains the bacterial mechanism in which activators Mary Osborn’s immunofluorescence images modify promoter structure. In eukaryotes, of cellular structures. the basic chromatin structure renders core Martin Kemp promoters inherently inactive in the absence Stains (and those who have pioneered their use) of an activator, whereas bacterial promoters are the unsung heroes of microscopy — well are generally accessible to the polymerase. known to microbiologists, certainly, but not In my view, chromatin fundamentally affects generally enjoying a high public profile. New the logic of gene regulation in eukaryotes, instruments for seeing ever smaller details but fundamentalism is in the belief of the seem to present more eye-catching examples of beholder. scientific advance. The only disappointing part of the book The story began with the progress from the is the brief section on higher eukaryotes. primitive microscopes of the seventeenth century, Unlike the rest of this book, and unlike in the hands of such pioneers of discriminating Colour coding: an immunofluorescence Ptashne’s previous influential monograph seeing as Anthony von Leeuwenhoek and Robert micrograph of epithelial and fibroblastic cells. A Genetic Switch, this section covers many Hooke, and the gradual refining of optical different phenomena (all very interesting resolution to its theoretical limits. Then came the disclose microtubules and intermediate filaments and important) in a rather sketchy fashion. non-optical revelations of electron microscopes, as functional components in cells. This subject calls for another book, although as developed by Vladimir Zworykhin and others, The story of the microtubules vividly shows it is probably premature to write one at the and the molecular marvels disclosed by the how optical and electron microscopy need to level to which we have become, and wish to scanning tunnelling microscope devised by work hand in hand, and how the greater remain, accustomed. Gerd Binning and Heinrich Rohrer. Yet without magnification of the latter does not necessarily In the grand scheme, the principles of selective staining and other marking techniques deliver fully coherent results when visualizing regulated recruitment through weak, adhe- we would not be able adequately to differentiate the structural continuities of forms that extend sive interactions between proteins are applied key components in the tiny structures. across the cell. In the late 1970s there was an to other examples of enzyme specificity One of the most elegant and widely acrimonious debate about the length and and regulation (such as splicing, proteolysis applicable techniques, immunofluorescence, number of microtubules. Weber and Osborn and signal transduction), where diversity, has, as its name suggests, ingeniously adopted were even accused of “painting white lines” on precision, and evolutionary flexibility are techniques from immunology. Albert Coons their images. Only when the same cell was paramount. Some may consider this section used it to reveal pneumococci in infected mouse visualized by the Göttingen group, both with to be a statement of the obvious, namely that tissues in 1942. But its power in visualizing immunofluorescence staining