Organization Field Theory Research Articles

The tissue organization field theory of cancer: A testable replacement for the somatic mutation theory

The somatic mutation theory (SMT) of cancer has been and remains the prevalent theory attempting to explain how neoplasms arise and progress. This theory proposes that cancer is a clonal, cell-based disease, and implicitly assumes that quiescence is the default state of cells in multicellular organisms. The SMT has not been rigorously tested, and several lines of evidence raise questions that are not addressed by this theory. Herein, we propose experimental strategies that may validate the SMT. We also call attention to an alternative theory of carcinogenesis, the tissue organization field theory (TOFT), which posits that cancer is a tissue-based disease and that proliferation is the default state of all cells. Based on epistemological and experimental evidence, we argue that the TOFT compellingly explains carcinogenesis, while placing it within an evolutionarily relevant context.

Cancer as development gone awry: the case for bisphenol-A as a carcinogen

The discovery of a rare clear cell carcinoma of the vagina in young women gestationally exposed to the estrogen diethylstilbestrol (DES) lent empirical support to the hypothesis that prenatal exposure to xenoestrogens might cause cancer. This fact contradicted two well-accepted notions: (i) mammalian development was merely the unfolding of a genetic program and (ii) only mutagenic agents could cause cancer. The ecological developmental biology (eco–devo) movement revitalized the concept of developmental plasticity through the occurrence of polyphenisms whereby a single genotype produces diverse phenotypes which are determined by environmental cues. Based on the principles of eco–devo and the tissue organization field theory of carcinogenesis, we hypothesized that developmental exposure to xenoestrogens increased the propensity to develop mammary cancer during adulthood. Bisphenol-A (BPA), a ubiquitous xenoestrogen, was chosen as a model for environmental estrogen exposure. In mice, perinatal exposure to environmentally relevant BPA levels induced alterations of the mammary gland architecture which manifested during fetal morphogenesis and throughout life, including the development of pre-neoplastic lesions. In rats, gestational exposure to BPA induced pre-neoplastic lesions and carcinomain situthat manifested in adulthood in the absence of any additional treatment. Emerging epidemiological data reveal an increased incidence of breast cancer in women exposed to DES during gestation. Hence, both animal experiments and epidemiological data strengthen the hypothesis that fetal exposure to xenoestrogens may be an underlying cause of the increased incidence of breast cancer observed over the past 50 years.

Neoplasia as development gone awry: the role of endocrine disruptors

The hypothesis that prenatal exposure to endocrine disruptors might cause cancer arose from challenging two well-accepted notions: (i) mammalian development is merely the unfolding of a genetic programme and (ii) only mutagenic agents can cause cancer. This hypothesis required challenging genetic determinism. The ecological developmental biology (eco-devo) movement revitalized the concept of developmental plasticity through the occurrence of polyphenisms (a single genotype produces diverse phenotypes which are determined by environmental cues). Based on the principles of eco-devo and the tissue organization field theory of carcinogenesis and neoplasia, we tested the hypothesis that exposure to xenoestrogens during foetal development in rats increased the propensity to develop mammary cancer during adulthood. We chose exposure to bisphenol A (BPA) as a model for environmental oestrogen exposure. This endocrine disruptor induced the development of ductal hyperplasias and carcinoma in situ. These highly proliferative lesions contained an increased number of oestrogen receptor alpha-positive cells. Thus, foetal BPA exposure was sufficient to induce the development of oestrogen-sensitive pre-neoplastic and neoplastic lesions in the mammary gland in the absence of any additional treatment aimed at increasing tumour incidence.

Defining and exploring the terrorism field: Toward an intertheoretic, agent-based approach

Drawing upon organizational design, contingency, and field theory, we outline a conceptual model for studying terrorism at the field level and argue that existing computational organizational theory could be extended to enable such inquiry. We introduce the terrorism field as the system of dynamic interaction between the terrorism, counterterrorism and political governance industries, defining the overarching functions of each. We then argue that intertheoretic, field-level inquiry could lead to explicit conceptual and computational models with significant benefits for researchers and policy makers, to include enhancing understanding of the proximate environmental conditions that are deleterious to the use of terrorism by political challengers. Using POW-ER, an illustrative field-level case of a basic terrorist attack is then modeled based on two archetypes of terrorist organizational forms emerging from the new terrorism debate: 1) hierarchy and 2) network, and two treatments: 1) applying counterterrorism techniques and 2) reducing knowledge within the terrorist organization. Preliminary findings compared to the baseline case are discussed, as well as implications for future research.

The Institutional and Technical Structuring of Nonprofit Ventures: Case Study of a U.S. Hybrid Organization Caught Between Two Fields

This paper engages the concept of the organizational field to explore the status of a growing set of organizations referred to as social enterprises, nonprofit ventures, and social purpose businesses. The argument is developed through an ethnographic case study of a nonprofit hybrid organization (in the United States) that is training welfare recipients in their own in-house businesses. First, this paper provides an overview of the commercial trends in the nonprofit sector and the rise of social purpose enterprises. Then, employing key concepts from neo-institutional theory, the author proposes framing nonprofit-business hybrids as organizations positioned in two different organizational fields—each necessitating different internal organizational technologies—to elucidate the structural tensions that can emerge inside these new hybrid models. Internal organizational tensions identified in the case study are highlighted. Finally, the proposed use of organizational field theory developed from the case analysis is discussed in terms of social enterprise more generally.

Emergentism as a default: Cancer as a problem of tissue organization

During the last fifty years the dominant stance in experimental biology has been reductionism. For the most part, research programs were based on the notion that genes were in 'the driver's seat' controlling the developmental program and determining normalcy and disease (genetic reductionism and genetic determinism). Philosophers were the first to realize that the belief that the Mendelian genes were reduced to DNA molecules was questionable. Soon after these pronouncements, experimental data confirmed their misgivings. The optimism of molecular biologists, fueled by early success in tackling relatively simple problems, has now been tempered by the difficulties found when attempting to understand complex biological problems. Here, we analyse experimental data that illustrate the shortcomings of this sort of reductionism. We also examine the prevailing paradigm in cancer research, the somatic mutation theory (SMT), the premises of which are: (i) cancer is derived from a single somatic cell that has accumulated multiple DNA mutations; (ii) the default state of cell proliferation in metazoa is quiescence; and (iii) cancer is a disease of cell proliferation caused by mutations in genes that control proliferation and the cell cycle. We challenge the notion that cancer is a cellular problem caused by mutated genes by assessing data gathered both from within the reductionist paradigm and from an alternative view that regards carcinogenesis as a developmental process gone awry. This alternative view, explored under the name of the tissue organization field theory (TOFT), is based on premises that place cancer in a different hierarchical level of complexity from that proposed by the SMT, namely: (i) carcinogenesis represents a problem of tissue organization comparable to organogenesis, and (ii) proliferation is the default state of all cells. We propose that the organicist view, in which the TOFT is based, is a good starting point from which to explore emergent phenomena. However, new theoretical concepts are needed in order to grapple with the apparent circular causality of complex biological phenomena in development and carcinogenesis.

The somatic mutation theory of cancer: growing problems with the paradigm?

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. From this compelling simplicity, an increasingly complicated picture has emerged as more than 100 oncogenes and 30 tumor suppressor genes have been identified. To accommodate this complexity, additional ad hoc explanations have been postulated. After a critical review of the data gathered from this perspective, an alternative research program has been proposed. It is based on the tissue organization field theory, the premises of which are that carcinogenesis represents a problem of tissue organization, comparable to organogenesis, and that proliferation is the default state of all cells. The merits of these competing theories are evaluated herein.

Somatic mutation theory of carcinogenesis: why it should be dropped and replaced.

The somatic mutation theory of carcinogenesis has been the dominant force driving cancer research during the 20th century. In brief, it proposes that successive DNA mutations in a single cell cause cancer (monoclonality). This theory places carcinogenesis at the cellular and subcellular hierarchical levels of biological complexity. Its basic premises are that (1) cancer is a defect of the control of cell proliferation and (2) the default state of metazoan cells is quiescence. These two premises have recently been contradicted by evidence. Supporters of the theory have dealt with these lacks of fit by incorporating ad hoc explanations similar to the use of epicycles in pre-Copernican astronomy. We propose the adoption of an alternative theory, the tissue organization field theory of carcinogenesis and neoplasia. Its basic premises are that (1) proliferation is the default state of all cells and (2) carcinogenesis and neoplasia are defects of tissue architecture. Carcinogens would act initially by disrupting the normal interactions that take place among cells in the parenchyma and stroma of an organ (the equivalent of the "morphogenetic fields" of developing organisms). Stroma appears as the primary target of carcinogens. Carcinogenesis and neoplasia occur entirely through emergent (supracellular) phenomena. Neoplastic cells may be reprogrammed to behave like "normal" cells within normal tissues. We argue that it is necessary to abandon the somatic mutation theory. Researchers will then become free to adopt alternative reliable premises to build a theory that explains carcinogenesis as another outcome, aberrant as it may be, of biological organization.