Cancer is typically spoken of as a “complex” disease. But, in what sense are cancers “complex”? Is there one sense, or several? What implications does this complexity have – both for how we study, and how we intervene upon cancers? The aim of this paper is first, to clarify the variety of senses in which cancer is spoken of as "complex" in the scientific literature, and second, to discover what explanatory and predictive roles such features play.

Applied Evolutionary Epistemology is a scientific-philosophical theory that defines evolution as the set of phenomena whereby units evolve at levels of ontological hierarchies by mechanisms and processes. This theory also provides a methodology to study evolution, namely, studying evolution involves identifying the units that evolve, the levels at which they evolve, and the mechanisms and processes whereby they evolve. Identifying units and levels of evolution in turn requires the development of ontological hierarchy theories, and examining mechanisms and processes necessitates theorizing (...) about causality. Together, hierarchy and causality theories explain how biorealities form and diversify with time. This paper analyzes how Applied EE redefines both hierarchy and causality theories in the light of the recent explosion of network approaches to causal reasoning associated with studies on reticulate and macroevolution. Causality theories have often been framed from within a rigid, ladder-like hierarchy theory where the rungs of the ladder represent the different levels, and the elements on the rungs represent the evolving units. Causality then is either defined reductionistically as an upward movement along the strands of a singular hierarchy, or holistically as a downward movement along that same hierarchy. Upward causation theories thereby analyze causal processes in time, i.e. over the course of natural history or phylogenetically, as Darwin and the founders of the Modern Synthesis intended. Downward causation theories analyze causal processes in space, ontogenetically or ecologically, as the current eco-evo-devo schools are evidencing. This work demonstrates how macroevolution and reticulate evolution theories add to the complexity by examining reticulate causal processes in space–time, and the interactional hierarchies that such studies bring forth introduce a new form of causation that is here called reticulate causation. Reticulate causation occurs between units and levels belonging to different as well as to the same ontological hierarchies. This article concludes that beyond recognizing the existence of multiple units, levels, and mechanisms or processes of evolution, also the existence of multiple kinds of evolutionary causation as well as the existence of multiple evolutionary hierarchies needs to be acknowledged. This furthermore implies that evolution is a pluralistic process divisible into different kinds. (shrink)

The mechanistic framework traditionally comes bundled with a multi-level view. Some ascribe ontological weight to these levels, whereas others claim that characterising a higher-level entity and the corresponding lower-level mechanism are only different descriptions of the same thing. The goal of this paper is to develop a consistent metaphysical picture that can underly the latter position. According to this flat view, wholes and their parts are embedded in the same network of interacting units. The flat view preserves the original virtues (...) of the mechanistic approach and is able to avoid the problems associated with the multi-level view. (shrink)

Despite the importance of network analysis in biological practice, dominant models of scientific explanation do not account satisfactorily for how this family of explanations gain their explanatory power in every specific application. This insufficiency is particularly salient in the study of the ecology of the microbiome. Drawing on Coyte et al. (2015) study of the ecology of the microbiome, Deulofeu et al. (2021) argue that these explanations are neither mechanistic, nor purely mathematical, yet they are substantially empirical. Building on their (...) criticisms, in the present work we make a step further elucidating this kind of explanations with a general analytical framework according to which scientific explanations are ampliative, specialized embeddings (ASE), which has recently been successfully applied to other biological subfields. We use ASE to reconstruct in detail the Coyte et al.’s case study and on its basis, we claim that network explanations of the ecology of the microbiome, and other similar explanations in ecology, gain their epistemological force in virtue of their capacity to embed biological phenomena in non-accidental generalizations that are simultaneously ampliative and specialized. (shrink)

Functional decomposition is an important goal in the life sciences, and is central to mechanistic explanation and explanatory reduction. A growing literature in philosophy of science, however, has challenged decomposition-based notions of explanation. ‘Holists’ posit that complex systems exhibit context-sensitivity, dynamic interaction, and network dependence, and that these properties undermine decomposition. They then infer from the failure of decomposition to the failure of mechanistic explanation and reduction. I argue that complexity, so construed, is only incompatible with one notion of decomposition, (...) which I call ‘atomism’, and not with decomposition writ large. Atomism posits that function ascriptions must be made to parts with minimal reference to the surrounding system. Complexity does indeed falsify atomism, but I contend that there is a weaker, ‘contextualist’ notion of decomposition that is fully compatible with the properties that holists cite. Contextualism suggests that the function of parts can shift with external context, and that interactions with other parts might help determine their context-appropriate functions. This still admits of functional decomposition within a given context. I will give examples based on the notion of oscillatory multiplexing in systems neuroscience. If contextualism is feasible, then holist inferences are faulty—one cannot infer from the presence of complexity to the failure of decomposition, mechanism, and reductionism. (shrink)

Marcello Barbieri has presented code biology as an alternative to the Peircean approach to biosemiotics. Some critics questioned the viability of code biology on grounds that Barbieri’s conception of science is limited. It has been argued that code biology’s mechanistic tendency is the cause of the allegedly limited conception of science. In this paper, I evaluate the scientific viability of the code model from the perspective of scientific realism in the philosophy of science. To be more precise, I draw on (...) resources of the mechanistic view in philosophy to argue that far from harbouring a limited conception of science, code biology could indeed improve the scientific prospects of biosemiotics. I show that the mechanistic and model-based tendency of the code model enhances its vigour as a full-blooded scientific approach to the study of meaning in living systems. To consolidate my claim, I draw on some recent debates in the mechanistic philosophy to argue that even relational approaches to understanding the meaning in living systems—such as an approach that is defended by Vega in a recent paper—could be underpinned by mechanistic processes at a foundational level. (shrink)

Research on diseases such as cancer reveals that primary mechanisms, which have been the focus of study by the new mechanists in philosophy of science, are often subject to control by other mechanisms. Cancer cells employ the same primary mechanisms as healthy cells but control them differently. I use cancer research to highlight just how widespread control is in individual cells. To provide a framework for understanding control, I reconceptualize mechanisms as imposing constraints on flows of free energy, with control (...) mechanisms operating on flexible constraints in primary mechanisms. I argue that control mechanisms themselves often form complex, integrated networks. (shrink)

A major approach to cancer research in the late twentieth century was to search for genes that, when altered, initiated the development of a cell into a cancerous state or failed to stop this development. But as researchers acquired the capacity to sequence tumors and incorporated the resulting data into databases, it became apparent that for many tumors no genes were frequently altered and that the genes altered in different tumors in the same tissue type were often distinct. To address (...) this heterogeneity problem, many researchers looked to a higher level of organization—to mechanisms in which gene products participated. They proposed to reduce heterogeneity by recognizing that multiple gene alterations affect the same mechanism and that it is the altered mechanism that is responsible for the cell developing one or more hallmarks of cancer. I examine how mechanisms figure in this research and focus on two heuristics researchers use to integrate proteins into mechanisms, one focusing on pathways and one focusing on clusters in networks. (shrink)

A theoretical framework is provided to explore teleonomy as a problem of self-causation, distinct from upward, downward and reticulate causation. Causality theories in biology are often formulated within hierarchy theories, where causation is conceptualized as running up or down the rungs of a ladder-like hierarchy or, more recently, as moving between multiple hierarchies. Research on the genealogy of cosmologies demonstrates that in addition to hierarchy theories, causality theories also depend upon ideas of time. This paper explores the roots and impact (...) of both time and hierarchy thinking on causal reasoning in the evolutionary sciences. Within evolutionary biology, the Neodarwinian synthesis adheres to a linear notion of time associated with linear hierarchies that portray upward causation. Eco-evo-devo schools recognize the importance of downward causation and consequently receive resistance from the standard view because downward causation is sometimes understood as backward causation, considered impossible by adherents of a linear time model. In contrast, downward causation works with a spatial or presential time notion. Hybridization, lateral gene transfer, infective heredity, symbiosis and symbiogenesis require recognition of reticulate causation occurring in both space and time, or spacetime, between distinct and interacting ontological hierarchies. Teleonomy is distinct from these types of causation because it invokes the problem of self-causation. By asking how the focal level in a hierarchy can persist through time, self-causation raises philosophical concerns on the nature of duration, identity and individuality. (shrink)

Living organisms act as integrated wholes to maintain themselves. Individual actions can each be explained by characterizing the mechanisms that perform the activity. But these alone do not explain how various activities are coordinated and performed versatilely. We argue that this depends on a specific type of mechanism, a control mechanism. We develop an account of control by examining several extensively studied control mechanisms operative in the bacterium E. coli. On our analysis, what distinguishes a control mechanism from other mechanisms (...) is that it relies on measuring one or more variables, which results in setting constraints in the control mechanism that determine its action on flexible constraints in other mechanisms. In the most basic arrangement, the measurement process directly determines the action of the control mechanism, but in more complex arrangements signals mediate between measurements and effectors. This opens the possibility of multiple responses to the same measurement and responses based on multiple measurements. It also allows crosstalk, resulting in networks of control mechanisms. Such networks integrate the behaviors of the organism but also present a challenge in tailoring responses to particular measurements. We discuss how integrated activity can still result in differential, versatile, responses. (shrink)

When radiocarbon dating techniques were applied to archaeological material in the 1950s they were hailed as a revolution. At last archaeologists could construct absolute chronologies anchored in temporal data backed by immutable laws of physics. This would make it possible to mobilize archaeological data across regions and time-periods on a global scale, rendering obsolete the local and relative chronologies on which archaeologists had long relied. As profound as the impact of 14C dating has been, it has had a long and (...) tortuous history now described as proceeding through three revolutions, each of which addresses distinct challenges of capturing, processing and packaging radiogenic data for use in resolving chronological puzzles with which archaeologists has long wrestled. In practice, mobilizing radiogenic data for archaeological use is a hard-won achievement; it involves multiple transformations that, at each step of the way, depend upon a diverse array of technical expertise and background knowledge. I focus on strategies of triangulation and traceability that establish the integrity of these data and their relevance as anchors for evidential reasoning in archaeology. (shrink)