Dartmouth College Dartmouth Digital Commons Open Dartmouth: Published works by Dartmouth faculty Faculty Work 1-1-2000 The problem of the gene Michael Dietrich Dartmouth College Follow this and additional works at: https://digitalcommons.dartmouth.edu/facoa Part of the Biology Commons Dartmouth Digital Commons Citation Dietrich, Michael, "The problem of the gene" (2000). Open Dartmouth: Published works by Dartmouth faculty. 27. https://digitalcommons.dartmouth.edu/facoa/27 This Article is brought to you for free and open access by the Faculty Work at Dartmouth Digital Commons. It has been accepted for inclusion in Open Dartmouth: Published works by Dartmouth faculty by an authorized administrator of Dartmouth Digital Commons. For more information, please contact [email protected]. C.R. Acad. Sci. Paris, Sciences de la vie / Life Sciences 323 (2000) 1139–1146 © 2000 Académie des sciences/Éditions scientifiques et médicales Elsevier SAS. Tous droits réservés S0764446900012579/FLA The problem of the gene Michael R. Dietrich* Department of Biological Sciences, Dartmouth College, Hanover, NH 03755, USA Abstract – During the early 20th century the diverse practices of genetics were unified by the concept of the gene. This classical gene was simultaneously a unit of structure, function, mutation, and recombination. Starting in the 1940s, however, the classical gene began to fragment. Today when we speak of a gene for some malady, a regulatory gene, a structural gene, or a gene frequency, it is entirely possible that we are deploying different gene concepts even though we are using the same term. The problem of the gene addresses the fragmentation of the classical gene concept by asking to what extent a comprehensive and unifying gene concept is possible or desirable. Fully comprehen- sive gene concepts seem untenable today, but, within different disciplinary domains, unifying, but non-comprehensive, gene concepts can be epistemically worthwhile. The problem of the gene persists, however, not because of its epistemic value, but because of its political value. Using both the arguments for newly proposed gene concepts and the historical dispute over the classical gene, I argue that the desirability of gene concepts rests in part on the political ramifications of their deployment and contestation. © 2000 Académie des sciences/Éditions scientifiques et médicales Elsevier SAS Résumé – La problématique du gène. Au début du XXe siècle, les diverses pratiques de la génétique furent unifiées grâce au concept de gène. Le gène « classique » était à la fois une unité de structure, de fonction, de mutation et de recombinaison. À partir de 1940, le gène classique a commencé à se fragmenter. Aujourd’hui, lorsque nous parlons d’un gène impliqué dans une maladie, d’un gène régulateur, d’un gène structural ou de fréquences de gènes, il est tout à fait possible que, sous le même terme, nous fassions référence à différents concepts de gène. En quelle mesure un concept global et unificateur du gène est-il possible ou désirable? Il semble impossible aujourd’hui de proposer un concept global, mais la recherche, à l’intérieur des différents domaines disciplinaires, de concepts unificateurs peut être importante. Que la notion de gène reste un problème ne vient pas des ambiguïtés de son usage scientifique, mais des enjeux politiques qui y sont liés. En se basant à la fois sur les arguments qui ont été utilisés pour justifier une nouvelle définition du gène, et sur les controverses qui ont agité la génétique classique, je conclus que la nécessité de proposer de nouvelles définitions du gène vient surtout des conséquences politiques de son utilisation ou de sa critique. © 2000 Académie des sciences/Éditions scientifiques et médicales Elsevier SAS 1. Introduction the classical gene which had once unified structure, func- tion, recombination, and mutation had been fragmented. At the 100th anniversary of the publication of Gregor Perhaps because his own work on mutability had reluc- Mendel’s paper, Milislav Demerec noted that during the tantly contributed to the dissolution of the classical gene first half of the 20th century the gene had been regarded as concept, Demerec’s commemorative essay makes its frag- ‘a unit of a genetic system, an indivisible entity in the mentation an historical inevitability. Beginning with De processes of recombination, self-reproduction and muta- Vries and Correns, Demerec argued that supposedly ’Men- tion’ [1]. Writing as he was in 1965, Demerec knew that delian’ characters in plants were not always so well * Correspondence and reprints. E-mail address: [email protected] (Michael R. Dietrich). 1139 M.R. Dietrich / C.R. Acad. Sci. Paris, Sciences de la vie / Life Sciences 323 (2000) 1139–1146 behaved. Citing later work on variegation in plants, includ- desirability of gene concepts rests in part on the political ing his own research, as well as research on step-allelism, ramifications of their deployment and contestation. Demerec documented the genetics community’s growing doubts about the indivisibility of the gene. Of course, to 2. Unifying the gene Demerec’s list of work undermining the classical gene, we could add H.J. Muller’s work on the position effect and Part of the allure of the classical gene lay in its ability to distribution of scute alleles, Richard Goldschmidt’s attacks unify significant aspects of the theory and practice of on the gene, and E.B. Lewis’s work on pseudo-alleles such genetics in the early 20th century. In Thomas Hunt Mor- as the star, asteroid system [2–5]. In the intervening gan’s The Theory of the Gene, for instance, genes are 35 years since Demerec wrote his essay, the classical gene assumed to be stable, paired elements in the germinal concept has been buried in a proliferation of molecular material which follow Mendel’s laws, exist in a linear genetic structures and processes. Phenomena such as the order on the chromosome, and remain in tact during various kinds of regulatory elements, different forms of crossing over [10]. As such Morgan’s gene becomes a RNA splicing, satellite DNA, and pseudogenes seem to common object for practices of determining patterns of guarantee that we cannot return to a comprehensive gene transmission, inferring linkage, and mapping. Later, concept [6–8]. Nevertheless, gene concepts still prove H.J. Muller and L.J. Stadler would make the gene the irresistible to biologists and philosophers of biology. object of the study of mutation as well [11, 12]. Accepting The problem of the gene is rooted in the fragmentation the classical gene as a common object of research meant of the classical gene concept and asks to what extent a accepting that different aspects of genetics were in fact comprehensive and unifying gene concept is possible or dealing with the same phenomena. In the eyes of philoso- desirable. Hans-Jörg Rheinberger recently posed the prob- phers such as Michael Friedman this is what makes unifi- lem of the gene as this question, ‘Do molecular biologists cation valuable. need a unified and generalized gene concept?’ [6]. Although philosophers of science have typically dis- Molecular biology is understood by Rheinberger as a cussed unification in conjunction with issues of explana- hybrid array of experimental systems ranging from bio- tion, Friedman motivates his theory of explanatory unifi- physics and biochemistry to evolutionary genetics and cation by appealing to phenomena. According to developmental genetics which produce a corresponding Friedman, ‘science increases our understanding of the array of gene concepts. From his perspective, it is not world by reducing the total number of independent phe- ‘necessary or even desirable to have a unified concept of nomena that we have to accept as ultimate or given. A the gene in order to tie all of these disciplinary specializa- world with fewer independent phenomena is, other things tions together and to develop them in a coordinated being equal, more comprehensible than one with more’ fashion’. In fact he argues that ‘an attempt to do so today [13]. The key to Friedman’s claim lies in defining what would produce nothing more than an exercise in rhetoric’ counts as independent phenomena. Being an analytic [6]. From a conceptual perspective, Rheinberger is cor- philosopher, Friedman quickly translates ’independent rect. A single comprehensive gene concept is not needed phenomena’ into ’logically independent lawlike sentences’ by molecular biologists or biologists in general. More and proceeds with his argument. We can resist the urge to specific gene concepts, such as a developmental gene axiomatize, however, and allow that for practical pur- concept or an evolutionary gene concept, are not valued poses whether phenomena are independent or not because they are fully comprehensive. Nevertheless, they depends on whether they are the common objects of provide a means to unify or systematize circumscribed different scientific practices or not. Scientific practices are disciplinary domains. When considering the problem of operations involving theoretical and/or experimental sys- the gene then we must drive a wedge between the scien- tems. They can be individuated by noting differences in tific values of generality and unification. The problem of operations (constructing a model, running a simulation, the gene should be decomposed into two problems: Is it performing an experiment) or in experimental systems necessary or desirable to have a comprehensive or gener- (Drosophila population cages versus bacterial chemostats, alized concept of the gene? and Is it necessary or desirable for instance). Phenomena that form the common object of to have a unifying concept of the gene? Rheinberger and many different scientific practices offer the opportunity to others have convincingly argued that we do not need a find interconnections that will allow scientists to unify or comprehensive gene concept. The case against generality systematize their beliefs more readily than if no such does not extend to unification, however. Within different phenomena existed. disciplinary domains unifying, but non-comprehensive, Consider a molecular gene concept recently proposed gene concepts can be epistemically worthwhile.