Moss - What genes cant do - 2003, страница 2

My claim would be that one simply cannotappreciate the twists and turns and the tensions and bifurcations of twentieth century biology without recognizing the stakes that were set up bythat transition. I have referred to this transition as the “phylogeneticturn” to mark the movement away from ontogeny and toward phylogenyas the new center of gravity for the explanation of biological form.The conceptual chunk-of-anlagen that Mendel dubbed the unitcharacter did indeed become the prototype for a new genetic preformationism, but, as Raphael Falk has argued, for Mendel it was only meantto serve as an instrumental function for breeders and not as a universaltheory for all of biology.

The path from an instrumental to a constitutive attribution of status to the chunk-of-anlagen is recounted, as is thesuppression-marginalization of the hereditary role of the cytoplasm (withthanks to Jan Sapp).Special emphasis is placed on the insightful and critical reflections ofWilhelm Johannsen. It was after all Johannsen who introduced the terms“gene,” “genotype,” and “phenotype” and who did so precisely as a critique of preformationist fallacies and on behalf of a return to a holismdefined in terms of the full range of developmental phenotypic potentialsassociated with any genotype. Several pages are devoted to consideringthe real contemporary relevance of Johannsen’s stunning reflections of1926.

Using Johannsen as a point of departure, I introduce my distinction between the preformationist Gene-P and the epigenesis Gene-D,and from this follows a consideration of what it would mean for agene to satisfy the conditions for being both a Gene-P and a Gene-Dsimultaneously.IntroductionxviiThe empirical fruits of several decades of research in molecular, cell,and developmental biology have revealed that what distinguishes onebiological form from another is seldom, if ever, the presence or absenceof a certain genetic template but rather when and where genes areexpressed, how they are modified, and into what structural and dynamicrelationships their “products” become embedded. If genes are to beboth molecules which function as physical templates for the synthesis ofother molecules and determinants of organismic traits and phenotypes,then somehow genes would have to, in effect, provide their own instructions for use.

They would have to be able to specify when and wheretheir templates would be put to use, how such products would bemodified and targeted, as well as in what structural and dynamic relationship they would reside. Indeed, it is just this sense of genes beingable to do this which appears to be conveyed with references to genes asinformation, as programs, as blueprints, as encyclopedias of life, and thelike.Following the strategy of chapter 1, chapter 2 examines the historical genesis of the genes-as-text metaphor, but in so doing a new set ofissues arises.

The growth of the gene-as-text discussion appears to veeroff from empirical reality (or perhaps becomes central to determiningwhat would count as empirical reality). The idiom of the language-ofthe-gene became written not by those whose hypotheses were successfulbut rather by those whose metaphors were successful. The intuitions ofpostmodernist critics who see a runaway rhetoric of life that simply constructs itself cannot be responsibly ignored.

Chapter 2 embarks onseveral lines of inquiry. In locating the foundation of the textual genetalk in Schrödinger’s notion of the hereditary code-script, I show thatwhat becomes a rhetorical tradition begins with an interesting, empirically accountable, argument which has since been forgotten or ignored,and I go to some length to explicate that argument. The subsequentdivergence of empirical and rhetorical achievements is adumbrated bythe benefit of the recent work of Lily Kay.I then explore the cognitive consequences of this new rhetoric of lifein the course of examining the perceptive insights of rhetoric-of-sciencecritic Richard Doyle.

Ultimately, however, I take issue with Doyle overwhat appears to be his own tacit methodological complicity with thatxviiiIntroductionautonomization of rhetoric that he ostensibly means to be criticizing.With the interpretive sensitivity of a good literary critic, Doyle exposesthe semantic stakes in a manner that far outreaches any narrowlyanalytical talk about intertheoretic reductionism or the like.

However,when it comes to the practical-normative dimension of social-intellectualcritique, Doyle simply drops the ball.Chapter 3 is principally concerned with clarifying the cellular andmolecular basis of biological order using Schrödinger as a point of departure. It is precisely in light of the semantic consequences of the conflatedgene-rhetoric (and all the ramifications of this suggested above) that thebasis of such rhetoric—to the extent that there is one—cannot be leftunexamined.

Schrödinger argued that only the thermodynamics of thesolid state (and thus the “aperiodic crystal”), newly (for him) revealedby quantum mechanics, could account for the existence and continuityof biological order. Whether the subsequent history of empirical investigations have ruled in his favor or not must be made relevant to the forceof his rhetorical legacy. Ongoing claims on behalf of what I refer to asthe “conflated gene” must be held empirically accountable.The principal intention of chapter 3 is to demonstrate that biologicalorder is distributed over several parallel and mutually dependent systemssuch that no one system, and certainly no one molecule, could reasonably be accorded the status of being a program, blueprint, set of instructions, and so forth, for the remainder.

The idea of characterizing threesubcellular epigenetic systems is derived from Jablonka and Lamb,although I signficantly depart from them in my treatment of the first twoof these systems (organizational structure and steady-state dynamics).With respect to the former, I offer a fairly detailed account of the differentiated, membrane-based, structural, and functional compartmentalization of the cell. Biochemically distinct membranous bodies constitutethe necessary and irreplaceable templates of their own production andreproduction, are passed along from one generation to the next, andprovide the unavoidable context in which DNA can be adequately interpreted, that is, in which genes can be genes.Under the heading of steady-state dynamics, I offer an extended discussion of the theoretical work of Stuart Kauffman.

Kauffman’s workis most relevant here because he too presents an explicit response toIntroductionxixSchrödinger, relying, in his case, on the implications of computersimulated models of complex nonlinear systems. Kauffman finds thatgiven certain internal parameters a complex system will gain “order forfree” by converging on some comparatively small number of attractorstates. Kauffman’s model, while complex as a formal system, is still farsimpler than any actual biological system.

While his work provides apowerful window into the nonintuitive, self-ordering consequences of thedynamics of nonequilibrium complex systems and an important rejoinder to Schrödinger and his descendents, it is shown to pose reductionistic dangers of its own.The final category of parallel epigenetic systems that I consider isthat of chromatin marking. My discussion here is comparatively briefand pertains to the ability of cells to chemically modify genomic DNAin developmentally and environmentally sensitive ways, including thegender-specific chromosome marking found in all mammals and referredto as imprinting. The larger significance of such mechanisms may onlycome to be fully appreciated when the extent of the plasticity of DNAitself is more fully disclosed.

Chapter 3 concludes with a brief consideration of the implications of this understanding of biological order (forwhich Gene-D would provide the proper gene concept) for rethinkingevolutionary theory.Chapter 4 begins with an historical analysis that parallels that ofchapter 1 but this time with an emphasis on how conceptions of cancerfollow from different conceptions of the basis of biological order. Bythe end of the nineteenth century the Keime und Anlagen of the neoKantians had become localized to within cells in general and to the ovumin particular.

As repositories of the developmental potential of the whole,cells took on a certain monadic status, being both constituent parts andyet also self-contained reflections of the whole. So conceived, cancer isnot determined from within, as any cell could potentially veer off in anovel direction, but rather in terms of those supracellular pathways ofinteraction and organization that must be the basis on which developmental destinations are realized. The monadic view of cells leads to acellular-organizational field theory that would understand carcinogenesis to be the result of disruptions of an organizational field. A disruptionmight result from an environmental “irritant,” leading to the misplacedxxIntroductionexpression of cellular developmental potential.

However, with thephylogentic turn that takes place early in the twentieth century, a clearbifurcation in lines of thought takes place. Boveri’s somatic mutationhypothesis localized the cause of cancer to within the cell. Cellular autonomy becomes understood not as the norm but as a kind of aberration,a malignant determination from within, as contrasted with the earlierview whereby it simply followed from the monadic nature of the cell.The fate of the monadic cell was not determined from within but ratherhistorically and contingently according to its interactive place in successive developmental fields.

With these two divergent perspectives in place,Chapter 4 reconstructs the lessons of twentieth century oncology in theform of a de facto dialectic, historically enacted. From the earliest oncogene hypothesis through the most recent work on colorectal cancer asthe very paradigm of the step-wise mutation model, it will be argued thatthe somatic mutation hypothesis, fueled by a conflationary conceptionof the gene, has unexpectedly provided some of the strongest evidenceon behalf of the anticonflationary, epigenesist critique.Finally, chapter 5 will look beyond the Human Genome Projectand the “century of the gene” (Keller 2001) into what appears to be thelineaments of a new rebirth of biology and its philosophy in thetwenty-first century.What Genes Can’t Do1Genesis of the GeneBut however far we may proceed in analysing the genotypes into separable genesor factors, it must always be borne in mind, that the characters of the organism—their phenotypical features—are the reaction of the genotype in toto.