The Century of the Gene (review)

Evelyn Fox Keller. The Century of the Gene. Cambridge: Harvard University Press, 2000. 186 pp. Ill. $22.95 (0-674-000372-1).

Evelyn Fox Keller opens her monograph as follows: "In 1900 three papers appeared in the same volume of the Proceedings of the German Botanical Society [title translated by Keller]. . . . [Three botanists] had independently 'rediscovered' the rules of inheritance [of] Gregor Mendel" (p. 1). This rediscovery opened what Keller calls "the century of the gene." Her book suggests that the twenty-first century will be, as others have suggested, the century of the genome. The announcement of the first draft of the complete human sequence at the White House on 26 June 2000 was comparable to the 1900 reports.

The term gene was introduced in 1909 by Wilhelm Ludvig Johanssen of Copenhagen to designate Mendel's unit of inheritance. It has, Keller intimates, outlived its usefulness. She states that "if, as Gelbart suggests, the term gene may in fact have become a hindrance to the understanding of biologists, it has perhaps become even more of a hindrance to the understanding of lay readers, misleading as often as it informs" (p. 148).

The alternative term genome appears to have been first used in 1920 by H. Winkler, who created it by elision of GENes and chromosOMES, and that is what the term means--the set of chromosomes and the genes they contain. Genomics is a term of more recent vintage (as is also the discipline it represents): it was invented in July 1986 by T. H. Roderick of the Jackson Laboratory, Bar Harbor, Maine, as the proposed title of a new scientific journal and the discipline it covers.

Keller confesses her skepticism concerning the human genome project when it was proposed in the 1980s. She writes, however: "What is more impressive to me is not so much the ways in which the genome project has fulfilled our expectations but the ways in which it has transformed them," and she points to "surprising effects . . . on biological thought" (p. 5). Indeed, she ends her monograph "with the prediction of a great deal more to come, perhaps even of another Cambrian period, only this time not in the realm of new forms of biological life but in new forms of biological thought" (p. 132). She ends chapter 4 with a bow to the wisdom accrued by "a billion years of experimentation or, as François Jacob might put it, to the generative creativity of eons of bricolage [pottering]--of chance recombinations of existing parts that, by virtue of such recombinations and with the help of ongoing feedback, both from their neighbors and from their environment, artlessly acquire new function" (p. 131). She also quotes Darwin, speaking in the same vein.

The book includes discussions of the functional redundancy of the genome, indicated by the lack of discernible effects of many knock-out experiments in mice; the mechanisms of genetic and developmental stability and variability; and the significance of alternative splicing in permitting many functions from one gene. In the notes, which are detailed and useful, Keller refers, for example, to the identification of 576 possible splicing variants of a gene active in the hair cells of the inner ear of the chick. Alternative splicing may account, in part at least, for the fact that the total number of genes counted in the now-finished human sequence is only one-half or one-third of the lowest previous estimates. Also, fewer genes may be necessary if their effects acting together are greater than (or different from) the summed effects of the individual genes. This is so-called emergence, a word I did not find in Keller's book.

Discussion of the "genetic program" logically is followed by a discussion of reprogramming--as in the classic experiments of Briggs and King (1952) in the frog, and the popularly famous experiments of Ian Wilmut and his colleagues (1997) in sheep. Keller states...