In biology, the ‘ecological orientation' rests on a commitment to examining systems, and the conceptual challenge of defining that system now employs techniques and concepts adapted from diverse disciplines (i.e., systems philosophy, cybernetics, information theory, computer science) that are applied to biological simulations and model building. Immunology has joined these efforts, and the question posed here is whether the discipline will remain committed to its theoretical concerns framed by the notions of protecting an insular self, an entity demarcated from its (...) environment, or will shift its focus of interest to a wider context. An ecological perspective emphasizes the interchange between the organism and its environment, the processing of information, and the regulation arising from responses to this larger context. Moving from the first attempts at modeling the immune system as a closed network, immunologists have joined the general interest in systems analysis, and that move might portend a significant shift to an open, more holistic consideration of immune regulation. *Received December 2006; revised August 2007. †To contact the author, please write to: Center for Philosophy and History of Science, Boston University, 745 Commonwealth Ave., Boston, MA 02215; e-mail: [email protected]. (shrink)

An autobiographical account is offered of how the medical study of self (immunology) became a chapter in the philosophical study of human agency (from Nietzsche and Thoreau to Freud by way of Wittgenstein). Whether viewed scientifically or philosophically, several themes converge on the intractable instability of any notion of selfhood—epistemological or moral. How this problematic motivated an extended analysis of selfhood refracts the psychology of the author and his pursuit of philosophy as self‐knowledge.

Friedrich Nietzsche''s will to power, and the philosophical ediface built on this foundation, is formulated on a biologicism that is indebted to a particular post-Darwinian vision of the organism. Of the various models that attempt to formulate a comprehensive organismal biology, Nietzsche unknowingly grasped that of Elie Metchnikoff, who authored the theoretical foundation of modern immunology. Metchnikoff regarded the organism as a disharmonious entity, in constant inner strife between competing cellular activities. Immune functions were responsible for mediating harmonization, which however (...) remains an elusive ideal. This view of the organism posited an ever-changing, self-defining entity striving for self-actualization while in ceaseless inner struggle as well as in competition with the environment. The theory is no less than an epistemological response of how to establish the subject-object relation in a construct where the subject''s boundaries are dialectical and evolving. The similarity of the philosophical positions of Nietzsche and Metchnikoff regarding the Self offers rich resonance in current attempts to formulate a biomedical language appropriate to address the issues raised by these problems. (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)

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)

Originating in the work of Ernst Haeckel and Wilhelm Preyer, and advanced by a Prussian embryologist, Wilhelm Roux, the idea of struggle for existence between body parts helped to establish a framework, in which population cell dynamics rather than a predefined harmony guides adaptive changes in an organism. Intended to provide a causal-mechanical view of functional adjustments in body parts, this framework was also embraced later by early pioneers of immunology to address the question of vaccine effectiveness and pathogen resistance. (...) As an extension of these early efforts, Elie Metchnikoff established an evolutionary vision of immunity, development, pathology, and senescence, in which phagocyte-driven selection and struggle promote adaptive changes in an organism. Despite its promising start, the idea of somatic evolution lost its appeal at the turn of the twentieth century giving way to a vision, in which an organism operates as a genetically uniform, harmonious entity. (shrink)

Both concepts of the holobiont and the immune system are at the heart of an ongoing scientific and philosophical examination concerning questions of the organism’s individuality and identity as well as the relations between organisms and their environment. Examining the holobiont, the question of boundaries and individuality is challenging because it is both an assemblage of organisms with physiological cohesive aspects. I discuss the concept of immunity and the immune system function from the holobiont perspective. Because of the host-microbial close (...) relations of codependence and interdependence, the holobiont is more often than not confused with the host, as the host is the domain in which this entity exists. I discuss the holobiont unique ecological characteristics of microbial assemblages connected to a host in a network of interactions in which the host is one of the organisms in the community but also its landscape. Therefore, I suggest viewing the holobiont as a host-ecosystem and discuss the implication of such a view on the concept of immunity and the meaning of protection. Furthermore, I show that viewing the holobiont as a host ecosystem opens the possibility of using the same ecological definition of boundaries and immunity dealing with an ecological system. Thus, the holobiont’s boundaries and immunity are defined by the persistence of its complex system of interactions integrating existing and new interactions. This way of thinking presents a notion of immunity that materializes as the result of the complex interdependence relations between the different organisms composing the holobiont similar to that of an ecosystem. Taking this view further, I discuss the notion of immunogenicity that is ontologically heterogeneous with various causal explanations of the processes of tolerance and targeted immune response. Finally, I discuss the possible conceptualization of already existing and new biomedical practices. (shrink)

This essay examines the role of social interactions in the search for blood stem cells, in a recent episode of biomedical research. Linked to mid-20th century cell biology, genetics and radiation research, the search for blood stem cells coalesced in the 1960s and took a developmental turn in the late 1980s, with significant ramifications for immunology, stem cell and cancer biology. Like much contemporary biomedical research, this line of inquiry exhibits a complex social structure and includes several prominent scientific successes, (...) recognized as such by participating researchers. I use personal interviews and the published record to trace the social interactions crucial for scientific success in this episode. All recognized successes in this episode have two aspects: improved models of blood cell development, and new interfaces with other lines of research. The narrative of the search for blood stem cells thus yields a robust account of scientific success in practice, which generalizes to other scientific episodes and lends itself to expansion to include wider social contexts. (shrink)

The language of self and nonself has had a prominent place inimmunology. This paper examines Frank Macfarlane Burnet's introductionof the language of selfhood into the science. The distinction betweenself and nonself was an integral part of Burnet's biological outlook– of his interest in the living organism in its totality, itsactivities, and interactions. We show the empirical and conceptualwork of the language of selfhood in the science. The relation betweenself and nonself tied into Burnet's ecological vision of host-parasiteinteraction. The idiom of (...) selfhood also enabled Burnet to organizeand unify a diversity of immune phenomena. Rather than approach thelanguage of self and nonself as a bluntly imposed metaphor, we focuson its endogenous origins and immanent uses in immunology. (shrink)

[Przekład] Tekst niniejszy jest wprowadzeniem do książki Eda Cohena A Body Worth Defending: Immunity, Biopolitics and the Apotheosis of the Modern Body. Autor bada, w jaki sposób immunologia wpływa na postrzeganie tak ciała ludzkiego, jak i bytów politycznych, ukazując współczesne konceptualizacje tych zjawisk jako wzajemnie od siebie zależne. Zastosowane ujęcie historyczne pozwala na prześledzenie historii metafory odporności w polityce i medycynie.

Zadaniem niniejszego wprowadzenia jest nakreślenie pewnych ram historycznych i teoretycznych współczesnej immunologii. Dyscyplina ta stosunkowo niedawno ukształtowana stara się wyjaśnić wszelkiego rodzaju zjawiska stojące na straży integralności organizmu. Organizmu rozumianego jako złożona struktura, wielosystemowa, ukształtowana w toku ewolucji. W wypadku tak szeroko rozumianego pojęcia odporności ewidentnie wymagana jest wnikliwa dyskusja, dlatego filozofowie biologii i naukowcy immunolodzy od pół wieku analizują podstawowe definicje i dochodzą do interesujących konkluzji.