Thomas Pradeu’s The Limits of the Self: Immunology and Biological Identity aims to reset the traditional boundaries of the organism and biological individuality. Pradeu, an accomplished researcher, brings to bare his knowledge of evolutionary and cancer biology, microbiology, philosophy of biology and especially immunology to propose a novel theory of biological individuality motivated by the rejection of the traditional self-nonself distinction in immunology which fails, among other things, to account for the ubiquity of autoreactivity, continuous self-monitoring and symbiotic relations with nonself.

The philosophy of biology and theories of biological individuation are dominated by evolutionary biology essentially claiming that anything acted on by natural selection is a biological individual however that leaves much to be desired. Here the author takes up the challenge of providing a more physiological/mechanistic/molecular theory of biological individuation that views the organism as a functionally integrated whole.

Along the way the book provides an excellent review of both current immunological theories and biological individuation theories with an emphasis on continuous and adaptive immune tolerance including compelling experimental data convincing us that The terms “self” and “nonself,” though situated at the heart of the discipline [of Immunology], are not defined with sufficient precision to constitute scientific terms. That however does not mean that immunology cannot be used to ground a physiological theory of individuation, on the contrary, a major claim of the book is that an improved theory that does account for the ubiquity of auto reactivity and immune tolerance, such as the author’s “Continuity Theory”, is well suited for the task. 

While I find the ‘continuity theory’ to be a bit too general, the ample experimental data provided in the book supports the author’s novel definition of biological individuality. 

Pradeu’s is a naturalist project, in the best sense of the word, using empirical facts to determine the scope and limitations of biological individuality while avoiding uncritical reliance on concepts and questions originating from the unholy alliance of traditional metaphysics and folk psychology. His strict adherence to the principle of continuity –  insisting on a common definition of individuality extending from bacteria to mammals – is reminiscent of other naturalists like Peter Godfrey Smith and the centrality of the principle of continuity (William James) to his work on the relevance of biological proto-selves (including homeostatic ‘Molecular Storms’ and ‘Reafference Compensation based self-modeling’).

I highly recommend this lucid, informative and accessible book to anyone interested in the immune system, ‘self-recognition’ (even if it loses its cognitive halo) and biological identity that enjoy delving into the rich and bewildering world of cellular and molecular biology. While taking great care to be accessible to the layman the book should also  interest researchers in immunology, cancer biology, evolutionary biology, philosophy of biology, system theory but also postmodern philosophers interested in the deconstruction of the self and analytic philosophers interested in deflationary approaches to the ‘subject’.

This lucid and well written book is divided into six chapters an introduction and a conclusion including useful summaries of the main points of each chapter.

The first chapter ‘Immunology, Self and Nonself’ attempts to answer the question “What is immunology?” It begins with an excellent historic review of immunity and our understanding of it including most of the major actors who contributed to this field including ‘immunization techniques’ from 10th century China and an extensive bibliography. After a useful review of the workings and components of immune systems the chapter contrasts the more traditional view of immunology as a discipline that studies how organisms defend themselves from foreign pathogens with the authors definition of immunology as a discipline that studies the specific interactions between immune receptors and antigenic patterns, triggering mechanisms that destroy or prevent the destruction of target antigens.

The second chapter begins with a historical analysis of the notions of self and nonself in immunology (Metchnikoff, Ehrlich) culminating in Burnet’s attempt to elucidate the mechanisms by which an organism learns to not attack the self with his theory of clonal selection and the early deletion of autoreactive antigens.

The third chapter consists of a data driven critique of the sef-nonself theory using results on phagocytosis and regulatory immune cells to show that the triggering of immune reactions by self-antigens in the course of autoreactivity and normal autoimmunity is ubiquitous and essential to the functioning of the immune system,

In the fourth chapter, the author presents his Continuity Theory in which normal autoreactivity and immune tolerance are not just accommodated by the theory (unlike the self-nonself theory) but central to it. The theory is extensive in scope applying to all organisms and also attempting to provide a common explanation to a host of different problems that are explained by different mechanisms, if at all, while at the same time attempting to provide a proper criterion of immunogenicity. The chapter ends with a diagram that lays out seven problems addressed by continuity theory that the self-nonself fails to explain properly.

The fifth chapter lists other major theoretical responses to the failure of the traditional self-nonself theory pointing both at the differences between these theories and the continuity theory and at elements peculiar to these theories that were appropriated by it. Pradeu considers the autopoietic framework (Maturana, Varela), the systemic theory of ‘immune networks’ (Jerne), the self-organization theory (Cohen, Atlan) and the danger theory (Matzinger) suggesting that these are more ‘views’ of immunity than proper scientific frameworks. 

The final chapter consists of a novel attempt to ground biological individuation and the limits of the organism in the authors Continuity Theory.  Thus, contrary to what many philosophers of biology have long said, a field pertaining to physiology, namely immunology, can offer a theoretical framework to understand biological individuality.

Personally, I’m interested in the structural and dynamic similarities between the ways the brain and the immune system process information yet here Pradeu warns against an overly cognitive approach to immunity but the difference between his continuity theory and Cohen and Atlan’s more ‘cognitive’ information theoretic approach may not be that big. Like Pradeu Cohen believes that all biological organisms possess adaptive immunity, that the immune system continuously interacts with auto-antigens monitoring the wellness of the body, and that local differences or surprises to the default expectations of the network can be amplified globally and result in robust immune response. In both cases the pattern differences can manifest at the system, cellular and molecular level and both see adaptive learning as crucial to immune tolerance. One difference between the theories derives from Cohen’s natural biomarkers – a collection of auto-antigens that serves as important network hubs (like heat shock proteins) that represent the state of the body (a bit like a computer user-interface) avoiding unnecessary detail. I imagine that while Preadau claims that any large enough deviations from the default state of the system trigger an immune response Cohen may claim that such a response is only triggered by differences in the biomarker pattern. It seems like that can be determined experimentally. Another important advantage of more cognitive/computational approaches is that they enable us to view different systems like the immune system, the olfactory bulb and a bee’s brain as biological pattern recognizers with common attributes that can help facilitate understanding these different systems. For example, Cohen’s biomarkers based homunculus can be used to draw similarities between the cognitive ‘self we are aware of’ and the contents of self-recognition and help naturalize Dennett’s ‘primitive concept attribution’ arguments (Chalmers) that use  computer icons and ‘user interface’ metaphors to demystify notions of transcendental subjectivity.

While Pradeu does much to tighten up the use of concepts like self and recognition in immunological theories and while his ‘continuity theory’ seems to point immunology in the right direction it is a bit too general, after all differences can always be cashed into information and at least Cohen and the self-organizational theory stresses the importance of computational and information laden approaches to immunology, including big data and  deep-learning, relating supervised machine-learning and training sets to immune tolerance.

The good news is that the Continuity theory and its reliance on multiscale unexpected pattern differences means that it could seamlessly incorporate the methodology of predictive coding and hierarchically nested Bayesian prediction generation which also go well with layered architecture (including hidden layers). I believe that an immune theory that is based on predictive coding combining continuous inhibition-amplification oscillations with a connectionist approach to the formation of generative models that recasts differences as ‘prediction surprises’ may help shed light on a major current problem confronting brain research nowadays in combining the oscillatory picture of the brain (Buzsaki, Lisman) with the predictive coding picture (Friston, Clark).

To sum up, anyone interested in the fantastic and bewildering world of biomolecular recognition will be richly rewarded by this book. 

© 2019 Uziel Awret

 

Uziel Awret