Moss - What genes cant do - 2003 (522929), страница 32
Текст из файла (страница 32)
Virchow (1858) placed all tissues intothree groups: those with cells adjacent to one another (epithelial), thosewith cells separated by intercellular substance (connective), and thosewhich have undergone a further transformation: muscle fibers, nervefibers, blood vessels, and so forth (Rather 1978). Where the former cytoblastema theory had posited a unique germinal layer from which allcancers as well as new growths emerged, the move to the doctrine of cellular continuity meant that the origins of cancer could and must be localized to a specific tissue and cell type. At this point Remak and VirchowDialectics of Disorder: Normalization and Pathology as Process127diverged. Virchow, who had been the first to identify the cellular basisof stromal (connective) tissue, postulated stromal tissue to be the principal source of undifferentiated cells that could then be transformed intoepithelioid tumors. Remak, by contrast, held to the epithelial origin ofcancers (Triolo 1965).The Bonn anatomist Franz Boll (1876) made an attempt to mediatethe conflicting claims of stromal versus epithelial priority in cancer causation.
He put forward a theory of cancer based on tissue interaction.Retracing Remak’s studies on lung differentiation in the embryonalchick, Boll suggested that normal development entailed a history ofappositional “conflict” between germinal connective and germinal epithelial tissue (Triolo 1965). In this model the formation of a normal lungwas not the result of a unilateral growth principle but rather a compromise between two dissimilar though reciprocally determined principles.Bonn added a new dimension to the vision of epigenesis, that of inductive interactions. Yet one can see that this possibility was already implicitin the move to a cellular histology in which the Keime und Anlagen ofthe whole had become disseminated into monadic parts. For Boll, thecause of abnormal growth was the untimely resumption of interfaceantagonisms prompted by exposure to external irritants.
Boll thus madethe first move toward explaining, in dynamic epigenetic terms, the effectsof environmental carcinogens. His views bear some resemblance to theepigenetic model of carcinogesis put forward by Farber and Rubin (tobe discussed in detail below) a century later.Within the same logical space as Müller’s anomalous germ cell,Virchow’s idea of a plastic embryonal-like connective tissue stratum andBoll’s formative tissue interactions was Julius Cohnheim’s 1875 notionthat cancer was derived from an embryonic residue that retained its fullpotential.
Cohnheim conceived of an overproduction of cells occurringduring organ morphogenesis. Some of these cells, he hypothesized, detached prior to completion of differentiation, thus retaining the abilityto re-emerge with an active capacity for proliferation at some later date(Triolo 1965).While this model proved to constitute an anticipation of the embolustheory of cancer metastasis, it suffered on several counts as a basic theoryof cancer origination. Specifically, it failed to locate the presence of128Chapter 4residual embryonic cells.
It also failed to account for why such cells, ifpresent, would begin rapid growth at one time versus another (Rather1978). A similar yet independent model had been put forward by theItalian surgeon Durante (1874), who identified “embryonic rests” withnevi (birthmarks). He envisioned the effects of some kind of irritantin triggering a renewed proliferative capacity of “elements which haveretained their anatomic embryonic characters in the adult organism”(Triolo 1965). Beginning in 1894 the histopathologist Hugo Ribberthoped to answer criticisms of Cohnheim’s model by presenting a morecircumspect theory in its place. Ribbert suggested that normal growthwas due to the “coordinated and balanced” development of its cellularcomponents.
If this tissue “tension” were lost, and in direct proportionto the extent to which it was lost, deviation from normal processes wouldthen ensue (Triolo 1965).Oncology after the Phylogenetic TurnThe legacy of the nineteenth century for twentieth-century oncology wasa framework for investigating cancer in terms of a dynamic relationshipof monadic cellular parts to the organismic whole of which they are constitutive. From Virchow through Boll, Durante, Cohnheim, and Ribbertone can see different attempts at modeling carcinogensis within a common framework.
There is of course no single moment at which pointtwentieth-century oncology takes its gene-centered, phylogenetic turn,and certainly no research finding in oncology that leads it in this direction, and yet the shift in interpretive orientation is very clear. Perhapsowing to the lack of a research exemplar that compellingly illustratesthe productivity of the phylogenetic perspective in cancer biology, themonadic-part-to-whole-composed-of-monads perspective is never fullylost; rather it is maintained as an ongoing undercurrent which is periodically rediscovered and rearticulated.
What does occur is a bifurcationsuch that the perspectives of Müller, Virchow, Cohnheim, et al. lead totwo fundamentally different ways of interpreting the nature of the cellthat becomes aberrant.Along with other areas of biology (see Allen, Harwood), cancerresearch in the twentieth century became oriented toward experimentDialectics of Disorder: Normalization and Pathology as Process129and the establishment of good experimental models. Experience withexposure to industrial soots, tars, and dyestuffs during the last twodecades of the nineteenth century provided empirical support with publichealth motivation for an “irritation hypothesis” of cancer causation.The theories of Virchow, Thiersch, Cohnheim, and Ribbert were used byexperimentalists seeking to establish explanatory models for irritantinduced carcinogenesis (Triolo 1965).
One of the first model systems ofcancer causation was established by Katsusaburo Yamagiwa, a studentof Virchow, who had returned to Japan. He had succeeded in his effortsto experimentally produce skin cancer through painting tar onto the earsof rabbits. It was exactly at the point of interpreting the process of experimentally induced carcinogenesis that a bifurcation of explanatory perspectives took place.In the holistic framework of Virchow et al., the monad-like cell isinvested with the potential to develop in any number of ways.
Whatemerges from this legacy as the common focal point for twentiethcentury thinking about cancer is the notion of the “autonomous cell”(Triolo 1964). But company parts with repect to the meaning of anautonomous cell. To heirs of nineteenth-century holism, autonomy wasunderstood in terms of “totipotency,” the possession by the cell of thepotential of the whole. The autonomy of the cell understood this way isthen the precondition for either normal or aberrant growth and a priorguarantee of neither. What determines which way it will go, normal oraberrant, is not its internal features but the subsequent history of itsinteractions. Thus the potential danger of the autonomous cell becoming cancerous is the flip side of its adaptive potential. This is a point thatwill be amplified later.
From a certain viewpoint consistent with thedevelopmental-holistic perspective, cancer is an adaptation, albeit one inwhich the “transformed” cell has become uncoupled from the developmental matrix of the organism. It is adaptive behavior at the level of thecell and its progeny but not at the level of the organism for which it isanything but adaptive.The second interpretation of the meaning of the autonomous cell isthat which first arises in the early twentieth century.
Here cellular autonomy is no longer perceived as the normal state of affairs that is theprecondition of either normal or abnormal growth but rather as a130Chapter 4distinctively aberrant condition, that which is synonymous with cancer.Cancer is no longer conceived as the product of the contingent interaction between cells and other cells and between cells and their extracellular environment but rather as determined from within a cell.
![](https://s.studizba.com/z.php?f=/templates/si/i/noavatar.png&w=100&h=100&t=1"){kind=avatar}
