Marta Bertolaso

Why network approach can promote a new way of thinking in biology

This work deals with the particular nature of network-based approach in biology. We will comment about the shift from the consideration of the molecular layer as the definitive place where causative process start to the elucidation of the among elements (at any level of biological organization they are located) interaction network as the main goal of scientific explanation. This shift comes from the intrinsic nature of networks where the properties of a specific node are determined by its position in the entire network (top-down explanation) while the global network characteristics emerge from the nodes wiring pattern (bottom-up explanation). This promotes a “middle-out” paradigm formally identical to the time honored chemical thought holding big promises in the study of biological regulation.

On the coherent behavior of pancreatic beta cell clusters

Abstract Beta cells in pancreas represent an example of coupled biological oscillators which via communication pathways, are able to synchronize their electrical activity, giving rise to pulsatile insulin release. In this work we numerically analyze scale free self-similarity features of membrane voltage signal power density spectrum, through a stochastic dynamical model for beta cells in the islets of Langerhans fine tuned on mouse experimental data. Adopting the algebraic approach of coherent state formalism, we show how coherent molecular domains can arise from proper functional conditions leading to a parallelism with “phase transition” phenomena of field theory.

On the structure of biological explanations: beyond functional ascriptions in cancer research

Al di la delle attribuzioni funzionali nella ricerca sul cancro. Questo studio si propone di valutare la rilevanza delle attribuzioni funzionali nella spiegazione del cancro. Nella prima parte del lavoro, si analizzano brevemente diverse teorie filosofiche sulle funzioni biologiche e si indaga fino a che punto i modelli cellulari del cancro soddisfano le caratteristiche che definiscono le teorie piu tradizionali. Cio che ne emerge e che questi modelli richiedono un’integrazione delle spiegazioni funzionali adottate che, purtuttavia, non sono soddisfacenti per i presupposti riduzionistici di questi modelli. Nella seconda parte del lavoro sono quindi presentati alcuni modelli non-riduzionisti del cancro e si spiega come il loro contributo nella comprensione del cancro sia legato a una nozione organizzazionale delle funzioni biologiche. Alcune conclusioni finali riguardano, infine, la dimensione normativa delle funzioni biologiche e la rilevanza del contesto in riferimento ad essa.

Evidence amalgamation, plausibility, and cancer research

Cancer research is experiencing ‘paradigm instability’, since there are two rival theories of carcinogenesis which confront themselves, namely the somatic mutation theory and the tissue organization field theory. Despite this theoretical uncertainty, a huge quantity of data is available thanks to the improvement of genome sequencing techniques. Some authors think that the development of new statistical tools will be able to overcome the lack of a shared theoretical perspective on cancer by amalgamating as many data as possible. We think instead that a deeper understanding of cancer can be achieved by means of more theoretical work, rather than by merely accumulating more data. To support our thesis, we introduce the analytic view of theory development, which rests on the concept of plausibility, and make clear in what sense plausibility and probability are distinct concepts. Then, the concept of plausibility is used to point out the ineliminable role played by the epistemic subject in the development of statistical tools and in the process of theory assessment. We then move to address a central issue in cancer research, namely the relevance of computational tools developed by bioinformaticists to detect driver mutations in the debate between the two main rival theories of carcinogenesis. Finally, we briefly extend our considerations on the role that plausibility plays in evidence amalgamation from cancer research to the more general issue of the divergences between frequentists and Bayesians in the philosophy of medicine and statistics. We argue that taking into account plausibility-based considerations can lead to clarify some epistemological shortcomings that afflict both these perspectives.

The role of coherence in emergent behavior of biological systems.

Abstract In his research activity, Emilio Del Giudice explored the possibility to move towards a unified view of some long-range dynamics in nature, ranging from quantum field theory in physics up to biology. Such a view is adopted in this contribution by discussing a mathematical model for synchronized electrical behavior of pancreatic beta cells. The stochasticity is a fundamental component of the physiological synchronized behavior of this system. On the contrary, in a pathological type I diabetes scenario, the cells are destroyed by the autoimmune system and their coherent behavior is lost. This phenomenology conceptually links to ideas of coherent dynamics in quantum physics. Possible implications both for physical sciences and for the epistemology of life sciences are outlined.

Cancer and intercellular cooperation

The major transitions approach in evolutionary biology has shown that the intercellular cooperation that characterizes multicellular organisms would never have emerged without some kind of multilevel selection. Relying on this view, the Evolutionary Somatic view of cancer considers cancer as a breakdown of intercellular cooperation and as a loss of the balance between selection processes that take place at different levels of organization (particularly single cell and individual organism). This seems an elegant unifying framework for healthy organism, carcinogenesis, tumour proliferation, metastasis and other phenomena such as ageing. However, the gene-centric version of Darwinian evolution, which is often adopted in cancer research, runs into empirical problems: proto-tumoural and tumoural features in precancerous cells that would undergo ‘natural selection’ have proved hard to demonstrate; cells are radically context-dependent, and some stages of cancer are poorly related to genetic change. Recent perspectives propose that breakdown of intercellular cooperation could depend on ‘fields’ and other higher-level phenomena, and could be even mutations independent. Indeed, the field would be the context, allowing (or preventing) genetic mutations to undergo an intra-organism process analogous to natural selection. The complexities surrounding somatic evolution call for integration between multiple incomplete frameworks for interpreting intercellular cooperation and its pathologies.

A System Approach to Cancer. From Things to Relations

“I think that SB will still play an important role in appreciating, first of all, the explanatory relevance of systemic perspectives that hopefully will allow us to avoid reductionist and relativist perspectives or excessive simplifications driven by mere pluralistic accounts of human understanding and scientific knowledge. Therefore the irreducibility of understanding typical of different disciplines is no obstacle but a condition of an integration process of different kinds of human understanding. Moving from physics and chemistry to biological or life sciences more generally, we aim to make explicit the explanatory categories that structure explanations in these fields and to clarify the systemic and relational features of any epistemology and their specificity in the different fields.”

Understanding Musical Consonance and Dissonance: Epistemological Considerations from a Systemic Perspective

Different accounts have been given in order to face the problem of the emergence of musical consonance and dissonance. Getting a more adequate comprehension of such phenomenology may require a systemic view to integrate such multidimensionality into a unitary picture in which every partial solution enlightens a particular aspect of the very same problem. Such a systemic viewpoint shifts the focus from different explanations to analytic dimensions that seem to be embedded in music perception. Taking into consideration these dimensions means understanding consonance and dissonance in an embodied context, in which arithmetic, physics, psychology and physiology are part of a complex and dynamic process of understanding, which is not reducible to any privileged explanatory level.

Changing Framework in Explaining Complex Dynamics: Convergences on Systemic Accounts from Two Different Case Studies

Starting from two different case studies—cancer explanatory theories and musical consonance and dissonance perception theories—we aim to show how different analytical aspects of complex phenomena can be grasped by apparently divergent accounts. Reaching a more adequate understanding of these phenomena thus needs an integrated systemic view in which every partial solution enlightens a particular aspect of the very same phenomenon. Such systemic viewpoint shifts the focus from different explanations to analytic dimensions that integrate the multidimensional phenomenology of our case studies: cancer pathology and music perception. Taking into consideration these dimensions means understanding the relationship between the systems and the environment in a discrete, continuous and embodied, i.e. context-dependent, way. To this purpose, we need to integrate the understanding activity through an authentic transdisciplinary approach.