The book presents a new way of understanding Darwinism and evolution by natural selection, combining work in biology, philosophy, and other fields.

Does natural selection act primarily on individual organisms, on groups, on genes, or on whole species? The question of levels of selection - on which biologists and philosophers have long disagreed - is central to evolutionary theory and to the philosophy of biology. Samir Okasha's comprehensive analysis gives a clear account of the philosophical issues at stake in the current debate.

Holobionts are multicellular eukaryotes with multiple species of persistent symbionts. They are not individuals in the genetic sense— composed of and regulated by the same genome—but they are anatomical, physiological, developmental, immunological, and evolutionary units, evolved from a shared relationship between different species. We argue that many of the interactions between human and microbiota symbionts and the reproductive process of a new holobiont are best understood as instances of reciprocal scaffolding of developmental processes and mutual construction of developmental, ecological, and (...) evolutionary niches. Our examples show that mother, fetus, and different symbiotic microbial communities induce or constitute conditions for the development and reproduction of one another. These include the direct induction of maternal or fetus physiological changes, the restructuring of ecological relations between communities, and evolutionary selection against undesirable competitors. The mutual scaffolding and niche constructing processes start early—prior to amniotic rupture. We are evolutionarily, physiologically, and developmentally integrated holobiont systems, strung together through mutual reliance and mutual construction. Bringing the processes of niche construction and developmental scaffolding together to interpret holobiont birth conceptually scaffolds two new directions for research: in niche construction, identifying the evolutionary implications of organisms actively constructing multiple overlapping niches and scaffolds, and in Evolutionary Developmental Biology, characterizing evolutionary and ecological processes as developmental causes. (shrink)

This chapter develops the idea that the germ-soma split and the suppression of individual fitness differences within the corporate entity are not always essential steps in the evolution of corporate individuals. It illustrates some consequences for multilevel selection theory. It presents evidence that genetic heterogeneity may not always be a barrier to successful functioning as a higher-level individual. This chapter shows that levels-of-selection theorists are wrong to assume that the central problem in transitions is always that of minimizing within-group competition. (...) Evidence of intralevel conflict does not qualify as evidence against the existence of a higher level of selection. (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)

Philosophy of immunology is a subfield of philosophy of biology dealing with ontological and epistemological issues related to the studies of the immune system. While speculative investigations and abstract analyses have always been part of immune theorizing, until recently philosophers have largely ignored immunology. Yet the implications for understanding the philosophical basis of organismal functions framed by immunity offer new perspectives on fundamental questions of biology and medicine. Developed in the context of history of medicine, theoretical biology, and medical anthropology, (...) philosophy of immunology differs from these related branches of study in its focus on traditional philosophical questions concerning identity, individuality, ecology, cognition, scientific methodology and theory construction. This broad agenda derives from immunology’s multifaceted research program that has developed from its initial clinical challenges of host defense, transplantation, autoimmunity, tumor immunology, and allergy. In addition to these well-established research areas, immunity is now understood to play a central role in other physiological functions, development, ecology, and evolutionary mechanics. Holding together these diverse domains of inquiry lie philosophical commitments oriented by organismal identity. In this regard, pertinent issues are raised concerning cognition (organization of immune perception and information processing), the character of individuality (framed by the ecological context of immune-mediated assimilation and rejection), and the dynamics of complex systems (understood as holistic systems biology). Indeed, immunology, in the context of cognitive science, evolutionary biology, environmental sciences, and development provides multi-focal perspectives for philosophy of science. (shrink)

In Immunity, Alfred Tauber sets forth a new theory of immunology that rejects the common principle of self and non-self, and the immune system's role as a protector of the self from external threats. Rather than serving to defend an independent entity, he argues, immunity participates in a large, complex eco-system of porous and flexible boundaries. Tauber's new approach to immunology necessitates a new biology in which symbiosis is the rule, not the exception.

One of the major developments in cancer research in recent years has been the construction of models that treat cancer as a cellular population subject to natural selection. We expand on this idea, drawing upon multilevel selection theory. Cancer is best understood in our view from a multilevel perspective, as both a by-product of selection at other levels of organization, and as subject to selection at several levels of organization. Cancer is a by-product in two senses. First, cancer cells co-opt (...) signaling pathways that are otherwise adaptive at the organismic level. Second, cancer is also a by-product of features distinctive to the metazoan lineage: cellular plasticity and modularity. Applying the multilevel perspective in this way permits one to explain transitions in complexity and individuality in cancer progression. Our argument is a reply to Germain’s scepticism towards the explanatory relevance of natural selection for cancer. The extent to which cancer fulfills the conditions for being a paradigmatic Darwinian population depends on the scale of analysis, and the details of the purported selective scenario. Taking a multilevel perspective clarifies some of the complexities surrounding how to best understand the relevance of evolutionary thinking in cancer progression. (shrink)

Somatic diversification of antigen receptor genes depends on the activity of enzymes whose homologs participate in a mutagenic DNA repair in unicellular species. Indeed, by engaging error-prone polymerases, gap filling molecules and altered mismatch repair pathways, lymphocytes utilize conserved components of genomic stress response systems, which can already be found in bacteria and archaea. These ancient systems of mutagenesis and repair act to increase phenotypic diversity of microbial cell populations and operate to enhance their ability to produce fit variants during (...) stress. Coopted by lymphocytes, the ancient mutagenic processing systems retained their diversification functions instilling the adaptive immune cells with enhanced evolvability and defensive capacity to resist infection and damage. As reviewed here, the ubiquity and conserved character of specialized variation-generating mechanisms from bacteria to lymphocytes highlight the importance of these mechanisms for evolution of life in general. (shrink)

It has long been taken for granted that the immune system’s capacity to protect an individual from infection and disease depends on the power of the system to distinguish between self and nonself. However, accumulating data have undermined this fundamental concept. Evidence against the self/nonself discrimination model left researchers in need of a new overarching framework able to capture the immune system’s reactivity. Here, I highlight that along with the self/nonself model, another powerful representation of the immune system’s reactivity has (...) been developed in the twentieth century immunology. According to this alternative view, the immune system is not a killer of nonself strangers but a peace-maker helping to establish harmony with the environment. The balance view of the system has never become part of the dominant paradigm. However, it is gaining more and more currency as new research develops. Advances in mucosal immunology confirm that instead of distinguishing between self and foreign the immune system reacts to microbial, chemical and self-induced alterations to produce responses that counterbalance effects of these changes. (shrink)

Tending Adam's Garden describes and explains the way in which our immune system works from a novel perspective. The book uses metaphors and examples to bring the immune system to life and explores the fundamental miracle of nature. Written in plain language for a broad audience, this book encompasses much more than just immunology, exploring more fundamental matters such as causality, information, energy, evolution, cognition and individuality, as well as the strategy of the immune system and its role in health (...) and disease. (shrink)

To enable microbial colonisation of the gut mucosa, the intestinal immune system must not only react to danger signals but also recognize cues that indicate safety. Safety recognition, paradoxically, is mediated by the same environmental sensors that are involved in signalling danger. Indeed, in addition to their well established role in inducing inflammation in response to stress signals, pattern recognition receptors (PRRs) and a variety of metabolic sensors also promote gut-microbiota symbiosis by responding to "microbial symbiosis factors", "resolution-associated molecular patterns", (...) markers of energy extraction and other signals indicating the absence of pathogenic infection and tissue damage. Here we focus on how the paradoxical role of immune receptors and other environmental sensors define the microbiota signature of the individual. (shrink)

The role of the microenvironment in cancer development is being increasingly appreciated. This paper will review data that highlight an emerging distinction between two different entities: the microenvironment that altered/preneoplastic/neoplastic cells find in the tissue where they reside, and the peculiar microenvironment inside the focal lesion (tumor) that these cells contribute to create. While alteration in the tissue environment can contribute to the selective clonal expansion of altered cells to form focal proliferative lesions, the atypical, non‐integrated growth pattern that defines (...) such focal lesions leads to the appearance of what is correctly referred to as the tumor microenvironment. The latter represents a new and unique biological milieu, characterized by hypoxia, acidosis and other biochemical and metabolic alterations, including genetic instability, that can set the stage for tumor progression to occur. Thus, the two microenvironments act in sequence and play complementary roles in the development of overt neoplasia. This distinction has important implications for the understanding of disease pathogenesis and for the management of preneoplastic/neoplastic lesions at various stages of cancer development. BioEssays 29:738–744, 2007. © 2007 Wiley Periodicals, Inc. (shrink)