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BOOK REVIEW

Limits of the Genetic Lexicon

Hans-Jörg Rheinberger

The Century of the Gene. Evelyn Fox Keller. 186 pp. Harvard University Press, 2000. $22.95.

In 1900, three botanists, the Dutch Hugo De Vries, the German Carl Correns and the Austrian Erich von Tschermak, reported, independently of one another, on the regularities of character distribution in hybrid crosses of plants and brought about what soon came to be called the "rediscovery" of the laws that Gregor Mendel had already described in 1865. Where do we stand, a century later, with respect to the science of heredity (termed genetics by William Bateson in 1906) and its elements (termed genes by Wilhelm Johannsen in 1909)? With Century of the Gene, Evelyn Fox Keller attempts to assess the situation at the turn of the new millennium. She does so with a peculiar, elegant blend of linguistic skill, historical reflection, conceptual analysis and synthetic outlook, and with the generously encompassing gesture of someone who participated in and followed the developments of molecular biology and genetics over several decades.

The book's first chapter deals with the remarkable phenomenon of genetic stability. Whereas Darwin's century, in its preoccupation with evolution, could be considered the century of organic change, genetics—with the germ-plasm legacy of August Weismann spilling over into the 20th century—is at least as much about conservation. Genomes, especially those of higher organisms, appear to be reproduced with marvelous accuracy, and so are the organisms that carry such genetic memory. Today, genetic stasis turns out to be dynamically modulated by evolution. It is, as Keller argues, at least as much a consequence of biological organization as it is the prerequisite of organization and evolvability.

Chapter 2 traces the development of geneticists' vision of what genes do and what scientists have learned about how genes are regulated. The story is aptly summarized by Keller as a transition from the early codification of the famed hypothesis of "one gene—one enzyme" to its later replacement by slogans such as "one gene—many proteins" and "one protein—many functions." Gene function, as much as gene structure, needs to be understood in dynamic terms.

Marriage of computers and organisms, by Gloria SharpClick to Enlarge Image

The third chapter is about the making of an organism. It describes the historical path from the concept of gene action to that of gene activation, from the notion of a "genetic program" (propagated by François Jacob and others at the early culmination point of molecular biology around 1960) to what Keller likes to call the "developmental program" of today, with its multiple entrenchments in the organism as a whole. Following Sydney Brenner, Keller sees the secret of making an organism as lying in the details, and she goes so far as to question the very possibility of compressing development into a meaningful algorithm.

Chapter 4 starts with Max Delbrück's famous statement that there are no "absolute phenomena" in biology. It is devoted to what molecular biologists have learned about the details, with all their intricacies and puzzles, of organismic development. Not the least of the more recent puzzles is the fact that organisms with presumably essential genes knocked out have been found to live happily without them. The chapter revolves around the notions of redundancy, robustness and reliability and concludes with an exposition of today's traffic of concepts and models between biology and the computer sciences and engineering.

One of the main messages to which Keller returns throughout the book is that on the one hand, with the recent announcement of the imminent completion of the human genome sequence, the "gene," at times referred to as the "atom of the biologist," has reached the peak of its popularity. On the other hand, and at the very same time, it is on the verge of foundering and even dissolving as a centrally meaningful and operational concept at the very locus where scientists enact their categories and do their work: the laboratory. The therapeutic gap, says Keller, that lies between the potential of genetic screening and the actual scarcity of substantial medical benefit, testifies to the "complexity of the regulatory dynamics" that mediate between genetic constitution and bodily performance. The term gene, she muses, may even have become, as William Gelbart has suggested, a "hindrance to the understanding of biologists," and perhaps "even more of a hindrance to the understanding of lay readers, misleading as often as it informs." Nevertheless, Keller concludes, there are many, mostly pragmatic, reasons for "gene talk" to persist. And she adds the important philosophical observation that it is in the very essence of the construction of scientific meaning that notions can take on different meanings in different empirical contexts. However, whereas Keller assumes that such linguistic imprecision and malleability mediate between the precision of different experimental setups, I would contend that a certain amount of flux and sometimes even undecidability are built into the operational dynamics of the scientific objects themselves. Research experiments can and usually do have as much plasticity as words.

Keller sees her book as a plea for scientific and political realism. Indeed it is. But it is more than just that. It engages historians, philosophers, scientists and the educated lay public alike in a discussion that self-consciously resists the temptation of polemics. The book is partial, but its partiality comes with a well-measured increment of historical judgment about the conceptual and experimental developments in the life sciences during the course of the 20th century. Keller insists that scientists, philosophers and historians have things to communicate among themselves with mutual benefit and can even learn from each other, and that such communication can take place as a well-reasoned exchange of arguments rather than as reciprocal imposition, or even accusation of imposture.

Keller leaves us with a sense of excitement about and a feeling of responsibility for a coming age of biological research in which the dynamics of development and evolution will call for an integrated understanding of the organism as a whole and will not be crudely reduced to genetic mechanism. Nonetheless, she is well aware of the historical irony that the overtly reductionist strategies of classical molecular biology and of gene technology may well be, indeed must be, regarded as an obligatory passage point on the way to a more systemic future view of how organisms work, develop and evolve. It is her contention that the human genome projects have done less than was expected of them to provide simple solutions to all kinds of genetic maladies. Rather, they have transformed these presumed solutions and have thereby radically undermined the classical concept of the gene. Keller regards this as one of those wonderful and rare moments in history "when success teaches us humility." Let us hope that humility will be the guide for all those who are addressed throughout this book as a big community, that familiar "we" whose voice she appears to adopt as a simple matter of course and without further reservation: "we" research scientists, genetic engineers, scientific entrepreneurs and all those accompanying us with their good advice.


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