The goal of this essay is to assess the Selected-Effects Etiological Theory of biological function, according to which a trait has a function F if and only if it has been selected for F. First, I argue that this approach should be understood as describing the paradigm case of functions, rather than as establishing necessary and sufficient conditions for function possession. I contend that, interpreted in this way, the selected-effects approach can explain two central properties of functions and can satisfactorily (...) address some recent counterexamples. This reading, however, shows that there is only a partial overlap between biological functions and selected effects, so the former cannot be reduced to the latter. Finally, I maintain that this result is still compatible with a naturalistic theory of function that appeals to some evolutionary process. (shrink)

Cancer biology features the ascription of normal functions to parts of cancers. At least some ascriptions of function in cancer biology track local normality of parts within the global abnormality of the aberration to which those parts belong. That is, cancer biologists identify as functions activities that, in some sense, parts of cancers are supposed to perform, despite cancers themselves having no purpose. The present paper provides a theory to accommodate these normal function ascriptions—I call it the Modeling Account of (...) Normal Function (MA). MA comprises two claims. First, normal functions are activities whose performance by the function-bearing part contributes to the self-maintenance of the whole system and, thereby, results in the continued presence of that part. Second, MA holds that models of system-level activities that are (partly) constitutive of self-maintenance are improved by including a representation of the relevant function-bearing part and by making reference to the activity/activities that part performs which contribute(s) to those system-level activities. I contrast MA with two other accounts that seek to explicate the ascription of normal functions in biology, namely, the organizational account and the selected effects account. Both struggle to extend to cancer biology. However, I offer ecumenical readings which allow them to recover some ascriptions of normal function to parts of cancers. So, though I contend that MA excels in this respect, the purpose of this paper is served if it provides materials for bridging the gap between cancer biology, philosophy of cancer, and the literature on function. (shrink)

Cancer is often seen as a case of multilevel selection, in which selfish cancer cells pursue short-term proliferation to the detriment of the collective. Thus cancer cells are described as ‘cheats’, and an analogy is often drawn between the mechanisms by which organisms fight cancer and the mechanisms by which social groups enforce cooperation. Recently, Andy Gardner and Max Shpak and Jie Lu have argued that cancer is not a true case of multilevel selection, that cancer cells should be not (...) regarded as cheats, and that the analogy between anti-cancer adaptations and suppression mechanisms in social groups is misleading. Their arguments are powerful. However, by drawing on the (presumed) link between cancer and the evolution of multicellularity, the notion that cancer represents a form of selective conflict between cells and organisms can be salvaged. (shrink)

Design thinking in general, and optimality modeling in particular, have traditionally been associated with adaptationism—a research agenda that gives pride of place to natural selection in shaping biological characters. Our goal is to evaluate the role of design thinking in non-evolutionary analyses. Specifically, we focus on research into abstract design principles that underpin the functional organization of extant organisms. Drawing on case studies from engineering-inspired approaches in biology we show how optimality analysis, and other design-related methods, play a specific methodological (...) role that is tangential to the study of adaptation. To account for the role of these reasoning strategies in contemporary biology, we therefore suggest a reevaluation of the connection between design thinking and adaptationism. (shrink)

One of the major developments in cancer research in recent years has been the construction of models that treat cancer as a cellular population subject to natural selection. We expand on this idea, drawing upon multilevel selection theory. Cancer is best understood in our view from a multilevel perspective, as both a by-product of selection at other levels of organization, and as subject to selection at several levels of organization. Cancer is a by-product in two senses. First, cancer cells co-opt (...) signaling pathways that are otherwise adaptive at the organismic level. Second, cancer is also a by-product of features distinctive to the metazoan lineage: cellular plasticity and modularity. Applying the multilevel perspective in this way permits one to explain transitions in complexity and individuality in cancer progression. Our argument is a reply to Germain’s scepticism towards the explanatory relevance of natural selection for cancer. The extent to which cancer fulfills the conditions for being a paradigmatic Darwinian population depends on the scale of analysis, and the details of the purported selective scenario. Taking a multilevel perspective clarifies some of the complexities surrounding how to best understand the relevance of evolutionary thinking in cancer progression. (shrink)

The notion of biological function is fraught with difficulties—intrinsically and irremediably so, we argue. The physiological practice of functional ascription originates from a time when organisms were thought to be designed and remained largely unchanged since. In a secularized worldview, this creates a paradox which accounts of functions as selected effect attempt to resolve. This attempt, we argue, misses its target in physiology and it brings problems of its own. Instead, we propose that a better solution to the conundrum of (...) biological functions is to abandon the notion altogether, a prospect not only less daunting than it appears, but arguably the natural continuation of the naturalisation of biology. (shrink)

Cancer biologists ascribe normal functions to parts of cancer. Normal functions are activities that parts of systems are in some minimal sense supposed to perform. Cancer biologists’ finding normality within the abnormality of cancer pose difficulties for two main approaches to normal function. One approach claims that normal functions are activities that parts are selected for. However, some parts of cancers that have normal functions aren’t selected to perform them. The other approach claims that normal functions are part-activities typical for (...) the system and that contribute to survival/reproduction. However, cancers are too heterogeneous to establish what’s typical across a type. (shrink)

It has long been recognized that cancer onset and progression represent a type of reversion to an ancestral quasi‐unicellular phenotype. This general concept has been refined into the atavistic model of cancer that attempts to provide a quantitative analysis and testable predictions based on genomic data. Over the past decade, support for the multicellular‐to‐unicellular reversion predicted by the atavism model has come from phylostratigraphy. Here, we propose that cancer onset and progression involve more than a one‐off multicellular‐to‐unicellular reversion, and are (...) better described as a series of reversionary transitions. We make new predictions based on the chronology of the unicellular‐eukaryote‐to‐multicellular‐eukaryote transition. We also make new predictions based on three other evolutionary transitions that occurred in our lineage: eukaryogenesis, oxidative phosphorylation and the transition to adaptive immunity. We propose several modifications to current phylostratigraphy to improve age resolution to test these predictions. Also see the video abstract here: https://youtu.be/3unEu5JYJrQ. (shrink)

In response to Germain argument that evolution by natural selection has a limited explanatory power in cancer, Lean and Plutynski have recently argued that many adaptations in cancer only make sense at the tumor level, and that cancer progression mirrors the major evolutionary transitions. While we agree that selection could potentially act at various levels of organization in cancers, we argue that tumor-level selection is unlikely to actually play a relevant role in our understanding of the somatic evolution of human (...) cancers. (shrink)

What has been called the new mechanistic philosophy conceives of mechanisms as the main providers of biological explanation. We draw on the characterization of the p53 gene in molecular oncology, to show that explaining a biological phenomenon implies instead a dynamic interaction between the mechanistic level—rendered at the appropriate degree of ontological resolution—and far more general explanatory tools that perform a fundamental epistemic role in the provision of biological explanations. We call such tools “explanatory frameworks”. They are called frameworks to (...) stress their higher level of generality with respect to bare mechanisms; on the other hand, they are called explanatory because, as we show in this paper, their importance in explaining biological phenomena is not secondary with respect to mechanisms. We illustrate how explanatory frameworks establish selective and local criteria of causal relevance that drive the search for, characterisation and usage of biological mechanisms. Furthermore, we show that explanatory frameworks allow for changes of scientific perspective on the causal relevance of mechanisms going beyond the account provided by the new mechanistic philosophy. (shrink)

The clonal evolution model and the cancer stem cell model are two independent models of cancers, yet recent data shows intersections between the two models. This article explores the impacts of the CSC model on the CE model. I show that CSC restriction, which depends on CSC frequency in cancer cell populations and on the probability of dedifferentiation of cancer non-stem cells into CSCs, can favor or impede some patterns of evolution and some processes of evolution. Taking CSC restriction into (...) account for the CE model thus has implications for the way in which we understand the patterns and processes of evolution, and can also provide new leads for therapeutic interventions. (shrink)

This paper builds on previous work that investigated anticancer drugs as ‘informed materials’, i.e., substances that undergo an informational enrichment that situates them in a dense relational web of qualifications and measurements generated by clinical experiments and clinical trials. The paper analyzes the recent transformation of anticancer drugs from ‘informed’ to ‘informing material’. Briefly put: in the post-genomic era, anti-cancer drugs have become instruments for the production of new biological, pathological, and therapeutic insights into the underlying etiology and evolution of (...) cancer. Genomic platforms characterize individual patients’ tumors based on their mutational landscapes. As part of this new approach, drugs targeting specific mutations transcend informational enrichment to become tools for informing their targets, while also problematizing the very notion of a ‘target’. In other words, they have become tools for the exploration of cancer pathways and mechanisms. While several studies in the philosophy and history of biomedicine have called attention to the heuristic relevance and experimental use of drugs, few have investigated concrete instances of this role of drugs in clinical research. (shrink)

There is an active research program currently underway, which treats cancer progression as an evolutionary process. This contribution investigates the ways that cancer progression is like and unlike evolution in other contexts. The aim is to take a multi-level perspective on cancer, investigating the levels at which selection may be acting, the unit or target of selection, the relative roles of selection and drift, and the idea that cancer progression may be a by-product of selection at other levels of organization.