Cancer is a singular cellular state, the emergence of which destabilises the homeostasis reached through the evolution to multicellularity. We present the idea that the onset of the cellular disobedience to the metazoan functional and structural architecture, known as the cancer phenotype, is triggered by changes in the cell's external environment that occur with ageing: what ensues is a breach of the social contract of multicellular life characteristic of metazoans. By integrating old ideas with new evidence, we propose that with (...) ageing the environmental information that maintains a multicellular organisation is eroded, rewiring internal processes of the cell, and resulting in an internal shift towards an ancestral condition resulting in the pseudo‐multicellular cancer phenotype. Once that phenotype emerges, a new local social contract is built, different from the homeostatic one, leading to tumour formation and the foundation of a novel local ecosystem. (shrink)

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.magnified imagemagnified imageAna Soto and Carlos Sonnenschein are at Tufts University School of Medicine, Boston, MA, USA. (shrink)

Generelle Morphologie der Organismen - Allgemeine Grundzuge der organischen Formen-Wissenschaft mechanisch begrundet durch die von Charles Darwin reformierte Deskendenz-Theorie ist ein unveranderter, hochwertiger Nachdruck der Originalausgabe aus dem Jahr 1866. Hansebooks ist Herausgeber von Literatur zu unterschiedlichen Themengebieten wie Forschung und Wissenschaft, Reisen und Expeditionen, Kochen und Ernahrung, Medizin und weiteren Genres.Der Schwerpunkt des Verlages liegt auf dem Erhalt historischer Literatur.Viele Werke historischer Schriftsteller und Wissenschaftler sind heute nur noch als Antiquitaten erhaltlich. Hansebooks verlegt diese Bucher neu und tragt damit (...) zum Erhalt selten gewordener Literatur und historischem Wissen auch fur die Zukunft bei. (shrink)

In the atavistic model of cancer progression, tumor cell dedifferentiation is interpreted as a reversion to phylogenetically earlier capabilities. The more recently evolved capabilities are compromised first during cancer progression. This suggests a therapeutic strategy for targeting cancer: design challenges to cancer that can only be met by the recently evolved capabilities no longer functional in cancer cells. We describe several examples of this target‐the‐weakness strategy. Our most detailed example involves the immune system. The absence of adaptive immunity in immunosuppressed (...) tumor environments is an irreversible weakness of cancer that can be exploited by creating a challenge that only the presence of adaptive immunity can meet. This leaves tumor cells more vulnerable than healthy tissue to pathogenic attack. Such a target‐the‐weakness therapeutic strategy has broad applications, and contrasts with current therapies that target the main strength of cancer: cell proliferation. (shrink)

“That a being should be born resembling in certain characters an ancestor removed by two or three, and in some cases by hundreds or even thousands of generations, is assuredly a wonderful fact. . . . If . . . we suppose . . . that many characters lie dormant in both parents during a long succession of generations, the foregoing facts are intelligible.” In October 2006, a group of fishermen working off the west coast of Japan, in the whaling (...) town of Taiji, found a bottlenose dolphin with an extra pair of flippers protruding at the back in the proximity of the tail. They might have guessed that it would become an immediate headline snatcher (Tabuchi 2006). What was less obvious at that moment was that their .. (shrink)

According to the somatic mutation theory (SMT), cancer begins with a genetic change in a single cell that passes it on to its progeny, thereby generating a clone of malignant cells. It is strongly supported by observations of leukemias that bear specific chromosome translocations, such as Burkitt's lymphoma, in which a translocation activates the c‐myc gene, and chronic myeloid leukemia (CML), in which the Philadelphia chromosome causes production of the BCR‐ABL oncoprotein. Although the SMT has been modified and extended to (...) encompass tumor suppressor genes, epigenetic inheritance, and tumor progression through accumulation of further mutations, perhaps the strongest validation comes from the successful treatment of certain malignancies with drugs that directly target the product of the mutant gene.magnified imageDavid Vaux is at the Walter and Eliza Hall Institute and La Trobe Institute for Molecular Science, Melbourne, Australia. (shrink)

Many biologists assume, as Darwin did, that natural selection acts mainly on late embryonic or postnatal development. This view is consistent with von Baer's observations of morphological divergence at late stages. It is also suggested by the conserved morphology and common molecular genetic mechanisms of pattern formation seen in embryos. I argue here, however, that differences in adult morphology may be generated at a variety of stages. Natural selection may have a major action on developmental mechanisms during the organogenetic period, (...) because this is when many adult traits are specified. Evolutionary changes in these early developmental mechanisms probably include subtle shifts in the timing of gene expression. Changes of this kind have little or no gross effect on the anatomy of the embryo; they are only phenotypically expressed, or readily detected, when amplified at later stages. The phylotypic stage, the developmental hourglass, modularity, and von Baerian divergence are reassessed in terms of these arguments. BioEssays 21:604–613, 1999. © 1999 John Wiley & Sons, Inc. (shrink)