The extent to which normal (nonmalignant) cells of the body can evolve through mutation and selection during the lifetime of the organism has been a major unresolved issue in evolutionary and developmental studies. On the one hand, stable multicellular individuality seems to depend on genetic homogeneity and suppression of evolutionary conflicts at the cellular level. On the other hand, the example of clonal selection of lymphocytes indicates that certain forms of somatic mutation and selection are concordant with the organism-level fitness. (...) Recent DNA sequencing and tissue physiology studies suggest that in addition to adaptive immune cells also neurons, epithelial cells, epidermal cells, hematopoietic stem cells and functional cells in solid bodily organs are subject to evolutionary forces during the lifetime of an organism. Here we refer to these recent studies and suggest that the expanding list of somatically evolving cells modifies idealized views of biological individuals as radically different from collectives. (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)

part, whole, ideal quality, foundation, unity, space, topoontology, topophilosophy, formal ontology, topology, mathematical philosophy, topology, topology of the person, topology of mind, mathematics in philosophy, mereology, mereotopology, phenomenology, Benedict Bornstein, Edmund Husserl, Roman Ingarden, Kurt Lewin, René Thom.

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)

This paper argues that the well-established fact of political irrationality imposes substantial constraints on how governments may combat the threat of political misinformation. Though attempts at regulating misinformation are becoming increasingly popular, both among policymakers and theorists, I intend to show that, for a wide range of anti-misinformation interventions (collectively termed “debunking” and “source labeling”), these attempts ought to be abandoned. My argument relies primarily on the fact that most people process politically-relevant information in biased and motivated ways. Since debunking (...) or factual correction of politically relevant misinformation (as well as source labeling) themselves consist of providing politically-relevant information, they are also very likely to be processed in irrational ways. This makes it extremely difficult to effectively correct people’s political beliefs and political information processing. Since governments should not pursue policies likely to be futile, they should refrain from mandating such interventions. My conclusion is of relevance to considerable literature in digital ethics of misinformation. It shows that many celebrated works in the field ignore political irrationality and fail to consider its implications. (shrink)

At the dawn of the computational era, immunology is at a crossroads: Its efforts to frame microbial-host interactions in combative, war-related terms no longer fit the larger picture of immune protection, and its focus on antimicrobial responses barely captures the diverse functions of the immune system, from tissue maintenance to cancer surveillance to development. As the classical view of immune processes becomes increasingly complex, the problem of self, individuality, mind-body interactions, and disease causation have stimulated extensive philosophical comment. Relating these (...) disparate research topics to changing avenues of theoretical studies, philosophy of immunology helps to reframe basic conceptions of the organism from an atomistic, insular entity to one characterized by fluidity, hybridity, and porosity. In addition, highlighting the role of the observer in experimental research, this interdisciplinary field has redefined classical demarcations between science and culture while advancing our understanding of biology as a fundamentally human endeavor. (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)

Central to vaccination-induced responses, antibodies are suggested by Vaz to operate as observer-dependent entities that owe their status to categorization schemes of immunologists. Inspired by color research by Maturana, he argues that antibodies should be distinguished from immunoglobulins, which unlike the former can be considered as constituents of structural dynamics of an organism, products of millions of years of evolution. However, a deeper understanding of the historical roots of the concept of immunoglobulin and associated “languaging” and naming processes reveals that (...) immunoglobulins, as much as antibodies, are contingent on conceptual schemes of immunology. (shrink)

Commensal and pathogenic organisms employ camouflage and mimicry to mediate mutualistic interactions and predator escape. However, the immune mechanisms accounting for the establishment and maintenance of symbiotic bacterial populations are poorly understood. A promising hypothesis suggests that molecular mimicry, a condition in which different organisms share common antigens, is a mechanism of establishing tolerance between commensals and their hosts. On this view, certain bacteria may mimic the structural features of some of their host’s T-cell receptors (TCRs), namely those that survive (...) thymic selection due to their lack of complementarity to self-antigens. With such “holoimmunity” the mimicking micro-organisms avoid immune recognition as the copied TCRs become mirror images of an extended super-organismal self, consisting of symbiotic and host antigens. Accordingly, analysis of genomic and metagenomic data suggests a tripartite mimicry between TCRs, self-antigens, and commensal antigens that would serve as the basis for immune tolerance between these populations. And conversely, in an autoimmune scenario, both symbiotic microbes and the mimicked host tissue would be targeted for immune destruction. (shrink)

Dominant views of personal identity in philosophy take some kind of psychological continuity or connectedness over time to be criterial for the identity of a person over time. Such views assign psychological states, particularly those necessary for narrative memory of some kind, special importance in thinking about the nature of persons. The extended mind thesis, which has generated much recent discussion in the philosophy of mind and cognitive science, holds that a person’s psychological states can physically extend beyond that person’s (...) body. Since “person” is a term of both metaphysical and moral significance, and discussions of both extended minds and personal identity have often focused on memory, this article explores the relevance of extended cognition for the identity of persons with special attention to neuroethics and memory. (shrink)

There is a deep-seated neopositivist view which regards the language of science as a neutral medium of communication, radically different from indirect symbolic forms of discourse characteristic of arts and humanities. But naturalists, like poets and social scientists, also draw on the dominant images in their culture to organize their thoughts and simplify complex concepts. By conceptualizing one thing in terms of another, metaphors in science not only aid mutual communication between researchers but also structure their understanding of experience and (...) reality. Too transparent to be noticed and critically analyzed within the framework of science itself, metaphors act as lenses, making selected aspects of complex phenomena visible to study and investigation (Reynolds 2018). By linking two seemingly unrelated ideas, for example, those of a machine and DNA replication, metaphors establish new interactions of meaning evoking shared associated connotations between these interacting concepts (Black 1962). This, in turn, may not only transform the perception of a target domain but also open up new prospects for experimental and interpretative avenues. Understanding Metaphors by Andrew Reynolds draws on this vision of metaphors as indispensable tools of scientific thinking to elucidate their role in the life sciences. (shrink)

The fight to find effective, long-lasting treatments for cancer has led many researchers to consider protein degrading entities. Recent developments in PROteolysis TArgeting Chimeras (PROTACs) have signified their potential as possible cancer therapies. PROTACs are small molecule, protein degraders that function by hijacking the built-in Ubiquitin-Proteasome pathway. This review mainly focuses on the general design and functioning of PROTACs as well as current advancements in the development of PROTACs as anticancer therapies. Particular emphasis is given to PROTACs designed against various (...) types of Leukemia/Blood malignancies. (shrink)