Reasons to suggest that the genetic research on cancer is a degenerative research program.

Adelaida Ambrogi
Universidad de las Islas Baleares, Dpt. Filosofía

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     Last modified: June 15, 2005
     Presentation date: 07/15/2005 9:00 AM in ROZH 108
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Abstract
Reasons to suggest that the genetic research on cancer is a degenerative research programme

Adelaida Ambrogi (PhD, UIB University, Spain); Ana M. Soto (MD,Tufts University, USA, ana.soto@tufts.edu); and Carlos Sonnneschein (MD,Tufts University, USA, carlos.Sonnenschein@tufts.edu)

PART I. Adelaida Ambrogi (20m.)
A Lakatosian look at the present status of the genetic research: the case of Breast Cancer.

Introduction.
While philosophers were mired on controversies about the rationality of scientific change Lakatos suggested an evaluation model claimed to ensure the rationality of the choice between scientific programs. The conceptual tools he proposed overrode the traditional theories and expanded the “elbow-room” for manuvering. The objective of this double-presentation is to propose the use of Lakatos’ conceptual tool kit for the evaluation of the success (or lack thereof) of the cancer research genetic program. In Part I we will use as an example the research program ob breast cancer genetics. Our intent is to suggests that this program is either degenerative or is at standstill. In Part II we will present an alternative program, a required step for performing an evaluation according to Lakatos’ method. Once the alternative program is re-constructed according to Lakatos’ categories we will conclude that the alternative program is promising and progressive
The genetic research on BC.
We will organize our presentation following the main Lakatosian categories: we will begin by presenting the core of the genetic research program: the somatic mutation theory (SMT). We will then point to the empirical predictions this theory (plus initial conditions); as well as the new and/or unprecedented data with which it is compatible, including results not predicted from this theory. Our next step will be to study how this theory has been confronting anomalies by proposing new ad hoc hypothesis, new entities, new genetic events… Finally we will have a systematic look at the several failures of the program.
As a way of conclusions of this first part we will try to answer the question: May we conclude from that that the genetic research on BC is a degenerative program?


PART II: Ana Soto and Carlos Sonneschein (20m.)
SMT or TOFT: may we evaluate and decide according to Lakatos’ Model?

Core hypothesis: The somatic mutation theory has been the prevailing paradigm in cancer research for the last 50 years. Its premises are: (1) cancer is derived from a single somatic cell that has accumulated multiple DNA mutations, (2) the default state of cell proliferation in metazoa is quiescence, and (3) cancer is a disease of cell proliferation caused by mutations in genes that control proliferation and the cell cycle. The premises of the Tissue Organization Field Theory (TOFT) are: (1) that carcinogenesis represents a problem of tissue organization, comparable to organogenesis, and (2) that proliferation is the default state of all cells.
Predictions: The predictions of the TOFT are: (1) carcinogenesis arises from alterations of tissue organization, for example, when the reciprocal interactions between an epithelium and its subjacent stroma are modified; i.e., alterations of the stroma may result in the development of carcinomas (tumors of epithelial origin) (2) cells from a neoplasm are normalized when placed in a normal tissue environment; i.e., the neoplastic phenotype is reversible.
Supporting data: Prediction #1: Using a model of induction of mammary carcinogenesis by the chemical nitroso-methyl urea, we found that exposure of the stroma and subsequent recombination with epithelial cells not exposed to carcinogen resulted in the development of neoplasms, while the reverse recombination (non-exposed stroma plus exposed epithelial cells) did not. This result is consistent with the TOFT and inconsistent with the SMT, which predicts that cancer should arise when the epithelial cells are exposed. Prediction #2: Teratocarcinoma cells introduced into blastocysts get integrated into the normal tissues in the embryo, transplantation of the nuclei of cancer cells into enucleated zygotes result in normal development, hepatocarcinoma cells injected into a normal liver behave as normal cells, mammary carcinoma cells injected into normal mammary gland stroma of adult animals form normal mammary ducts.

Conclusion.
We will conclude by defending our evaluation of the first as a regressive program; and the second as a progressive, and promising one.
It is not our intention to take Lakatos’ proposal as a definitive model; as it is well known the premature death of the philosopher left his proposal un-ended. Nevertheless we will defend in our conclusion the fruitfulness of our use of it.