Between Language and Science: The Question of Directed Mutation in Molecular Genetics

BETWEEN LANGUAGE AND SCIENCE: THE QUESTION OF DIRECTED MUTATION IN MOLECULAR GENETICS EVELYN FOX KELLER* Francis Crick first articulated the "central dogma" of molecular biology in 1957. This principle, Crick explained, states that once "information" has passed into the protein it cannot get out again. [Italics in original.] In more detail, the transfer of information from nucleic acid to nucleic acid, or from nucleic acid to protein may be possible, but transfer from protein to protein, or from protein to nucleic acid is impossible. [1] A few years later, Jacques Monod elaborated further: [W]hat molecular biology has done ... is to prove beyond any doubt but in a totally new way the complete independence of the genetic information from events occurring outside or even inside the cell—to prove by the very structure of the genetic code and the way it is transcribed that no information from outside, of any kind, can ever penetrate the inheritable genetic message. [2] But the credit Monod attributed to molecular biology must be seen in retrospect as clearly hyperbolic. The unidirectionality of the flow of genetic information was not in fact proved by the structure of the genetic code, and even the relatively simple process of transcription then envisioned did not entirely preclude penetration of all "information from outside." Today, as the complexities of the transcription process have become vastly elaborated and theoretical possibilities for reverse translation correspondingly easier to imagine, it should be evident that confidence in the central dogma now requires, as it indeed required then, grounds well beyond the mere logic of genetic structure. In retrospect, it rather appears that the basis for this claim lay in a consensus that had earlier emerged in the biological community, and especially among geneticists, that biological variation among individual The author thanks Maurice S. Fox, Helen Longino, John Cairns, Andy Wedel, and Sahotra Sarkar for their helpful comments and discussion. *Department of Rhetoric, University of California, Berkeley, California 94720.© 1992 by The University of Chicago. AU rights reserved. 003 1-5982/92/3502-076 1$01 .00 292 Evelyn Fox Keller ¦ Question ofDirected Mutation organisms always arose spontaneously and never adaptively. Much of this consensus had been forged by the neo-Darwinian synthesis of the 1920s and 1930s. To many biologists, however, bacteria continued to provide an outstanding example of biological adaptation directly induced by environmental stress. Thus, full consensus around the spontaneous origin of biological variation—at least, in the standard account appearing in virtually all genetics textbooks of the last several decades —was cemented neither by the neo-Darwinian synthesis nor by molecular biology, but by a pivotal analysis of bacterial mutation published 10 years before Watson and Crick. In their 1943 paper [3], Salvador Luria and Max Delbrück examined the origin of mutations rendering E. coli resistant to infection by the bacterial virus that is now called Tl and concluded that the presence of the selective agent (in this case, the virus itself) had no influence on the emergence of these particular bacterial mutants. (Their exact wording is as follows: "We consider the above results as proof that in our case the resistance to virus is due to a heritable change of the bacterial cell which occurs independently of the action of the virus" [3].) In most textbook accounts, their proviso ("in our case") is dropped, and the work is taken as conclusive demonstration that even bacteria (which Luria himself described as "the last stronghold of Lamarckism") were organized by genes subject to spontaneous mutation and hence to the conventional process of natural selection . With this, biology appeared, finally, to be cleansed of the last traces of Lamarckian thought. But the ghost of Lamarck has proved curiously difficult to lay to final rest. Its resurrection has been periodically attempted ever since, and perhaps most dramatically in a recent article in Nature by the highly respected and widely known molecular biologist, John Cairns, and his colleagues. In 1988, Cairns et al. published a critical review of the principal source of our belief in the "spontaneous" generation of genetic variation (namely, the Luria-Delbruck experiment), followed by a description of their own experiments suggesting that bacteria may in fact be able to...