On physicalism and Downward Causation in Developmental and Cancer Biology

The dominant position in Philosophy of Science contends that downward causation is an illusion. Instead, we argue that downward causation doesn't introduce vicious circles either in physics or in biology. We also question the metaphysical claim that "physical facts fix all the facts." Downward causation does not imply any contradiction if we reject the assumption of the completeness and the causal closure of the physical world that this assertion contains. We provide an argument for rejecting this assumption. Furthermore, this allows us to reconsider the concept of diachronic emergence.     

Making sense of downward causation in manipulationism: illustrations from cancer research

Many researchers consider cancer to have molecular causes, namely mutated genes that result in abnormal cell proliferation (e.g. Weinberg 1998). For others, the causes of cancer are to be found not at the molecular level but at the tissue level where carcinogenesis consists of disrupted tissue organization with downward causation effects on cells and cellular components (e.g. Sonnenschein and Soto 2008). In this contribution, I ponder how to make sense of such downward causation claims. Adopting a manipulationist account of causation (Woodward 2003), I propose a formal definition of downward causation and discuss further requirements (in light of Baumgartner 2009). I then show that such an account cannot be mobilized in support of non-reductive physicalism (contrary to Raatikainen 2010). However, I also argue that such downward causation claims might point at particularly interesting dynamic properties of causal relationships that might prove salient in characterizing causal relationships (following Woodward 2010).     

Zooming in on Downward Causation

An attempt is made to identify a concept of ‘downward causation’ that will fit the claims of some recent writers and apply to interesting cases in biology and cognitive theory, but not to trivial cases. After noting some difficulties in achieving this task, it is proposed that in interesting cases commonly used to illustrate ‘downward causation’, (a) regularities hold between multiply realizable properties and (b) the explanation of the parallel regularity at the level of the realizing properties is non-trivial. It is argued that the relation between a realizable property and the property that realizes its effect in a particular case is not usefully regarded as a species of causation and that use of the concept of downward causation deflects our attention from our central explanatory tasks.     

A biological relativity view of the relationships between genomes and phenotypes

This article explores the relativistic principle that there is no privileged scale of causality in biology to clarify the relationships between genomes and phenotypes. The idea that genetic causes are primary views the genome as a program. Initially, that view was vindicated by the discovery of mutations and knockouts that have large and specific effects on the phenotype. But we now know that these form the minority of cases. Many changes at the genome level are buffered by robust networks of interactions in cells, tissues and organs. The ‘differential’ view of genetics therefore fails because it is too restrictive. An ‘integral’ view, using reverse engineering from systems biological models to quantify contributions to function, can solve this problem. The article concludes by showing that far from breaking the supervenience principle, downward causation requires that it should be obeyed.     

Rethinking Causation for Data-intensive Biology: Constraints,Cancellations, and Quantized Organisms

Complex organisms thwart the simple rectilinear causality paradigm of “necessary and sufficient,” with its experimental strategy of “knock down and overexpress.” This Essay organizes the eccentricities of biology into four categories that call for new mathematical approaches; recaps for the biologist the philosopher's recent refinements to the causation concept and the mathematician's computational tools that handle some but not all of the biological eccentricities; and describes overlooked insights that make causal properties of physical hierarchies such as emergence and downward causation straightforward. Reviewing and extrapolating from similar situations in physics, it is suggested that new mathematical tools for causation analysis incorporating feedback, signal cancellation, nonlinear dependencies, physical hierarchies, and fixed constraints rather than instigative changes will reveal unconventional biological behaviors. These include “eigenisms,” organisms that are limited to quantized states; trajectories that steer a system such as an evolving species toward optimal states; and medical control via distributed “sheets” rather than single control points.     

Emergence,therefore antireductionism? A critique of emergent antireductionism

Emergent antireductionism in biological sciences states that even though all living cells and organisms are composed of molecules, molecular wholes are characterized by emergent properties that can only be understood from the perspective of cellular and organismal levels of composition. Thus, an emergence claim (molecular wholes are characterized by emergent properties) is thought to support a form of antireductionism (properties of higher-level molecular wholes can only be understood by taking into account concepts, theories and explanations dealing with higher-level entities). I argue that this argument is flawed: even if molecular wholes are characterized by emergent properties and even if many successful explanations in biology are not molecular, there is no entailment between the two claims.     

The theory of organism and the culturalist foundation of biology

Summary After the disappearance of organism was diagnosed, the discussion about the role of a theory of organism in biology is characterised by a significant contradiction. On the one hand, the importance of a theory of organism is stated. Particularly developmental biology demands organism-centred approaches as a basis for conceptual integration. On the other hand, several modern biological disciplines such as genetics and molecular biology simply don’t need a theory of organism for their work. Consequently, the determination of the status of the organism and its relevance for biology at all is an unsolved problem. In order to clarify the methodological status of the organism in biology we start with the reconstruction of three important propositions. A life oriented approach and a hierarchy concept - which both are from a neo-Darwinian origin - are confronted with a structuralist approach of organism, that can be characterised as a non-Darwinist approach. Our own attempt for the solution of the organism problem applies the tools of culturalist methodology. In accordance to this pragmatic approach, the term organism is introduced as a concept of notion. A constructional morphological case study exemplifies the applicability of this concept. From the culturalist point of view a methodological foundation of biology can be achieved, that provides a consistent basis for a comprehensive integration of biological knowledge.     

IS MACROEVOLUTION MORE THAN SUCCESSIVE ROUNDS OF MICROEVOLUTION?

Abstract:  Whether macrovolution is reducible to microevolution is one of the persistent debates in evolutionary biology. Although the concept of emergence is important to answering this question, it has not been extensively discussed within palaeobiology. A taxonomy of emergence concepts is presented to clarify the ways in which emergence relates to this debate. Weak emergence is a particularly helpful way to understand the hierarchical nature of biology: it captures the ways in which higher-level traits depend on lower-level processes, while recognizing that emergent traits can nonetheless provide the basis for autonomous higher-level theories. A brief review of the biological literature suggests that geographical range size is weakly emergent. While some concepts of emergence do not block the attempt to reduce macroevolution (i.e. the attempt to explain all macroevolutionary phenomena in terms of microevolutionary processes), weak emergence does. Thus, if geographical range is weakly emergent, it provides a basis for arguing that macroevolutionary phenomena cannot be fully explained by microevolutionary processes.     

Origins and evolution of biological novelty

Understanding the origins and impacts of novel traits has been a perennial interest in many realms of ecology and evolutionary biology. Here, we build on previous evolutionary and philosophical treatments of this subject to encompass novelties across biological scales and eco-evolutionary perspectives. By defining novelties as new features at one biological scale that have emergent effects at other biological scales, we incorporate many forms of novelty that have previously been treated in isolation (such as novelty from genetic mutations, new developmental pathways, new morphological features, and new species). Our perspective is based on the fundamental idea that the emergence of a novelty, at any biological scale, depends on its environmental and genetic context. Through this lens, we outline a broad array of generative mechanisms underlying novelty and highlight how genomic tools are transforming our understanding of the origins of novelty. Lastly, we present several case studies to illustrate how novelties across biological scales and systems can be understood based on common mechanisms of change and their environmental and genetic contexts. Specifically, we highlight how gene duplication contributes to the evolution of new complex structures in visual systems; how genetic exchange in symbiosis alters functions of both host and symbiont, resulting in a novel organism; and how hybridisation between species can generate new species with new niches.     

Individual essentialism in biology

A few philosophers of biology have recently explicitly rejected Essential Membership, the doctrine that if an individual organism belongs to a taxon, particularly a species, it does so essentially. But philosophers of biology have not addressed the broader issue, much discussed by metaphysicians on the basis of modal intuitions, of what is essential to the organism. In this paper, I address that issue from a biological basis, arguing for the Kripkean view that an organism has a partly intrinsic, partly historical, essence. The arguments appeal to the demands of biological explanation and are analogous to arguments that I have given elsewhere that a taxon has a partly intrinsic, partly historical, essence. These conclusions about the essences of individuals and taxa yield an argument for Essential Membership. Finally, I cast doubt on LaPorte’s objection to that doctrine arising from the view that a species cannot survive having a daughter.     

The expansion of information in ecological systems: Emergence as a quantifiable state

Although the term ‘emergence’ has received wide attention in the literature, most of this attention has been focused on epistemological discussions about the nature of what might be considered emergent behavior in self-organizing systems. For the concept of emergence to have any great utility for biologists, it must (1) be perceptible as a physical, quantitative property rather than just a philosophical one; (2) have a quantitative definition applicable to all levels of biological organization; and (3) be an essential component of biological system performance or evolution. Using an independent, cellular population model (running in the StarLogo system), we have developed a mutual information calculation to measure the information expansion when considering the interactions between a population of herbivores and an environment in comparison to the interactions between the individual herbivores and that environment. In self-organizing biological systems, the collective action of massively parallel units generates a greater potential complexity in the information processing capacity of the ‘whole’ system relative to the ‘individual’ parts, and as such, there is a demonstrable increase in mutual information content. From this perspective, we consider emergence to exist as a simple information expansion that is a default behavior of any system with multiple, component parts governed by a simple, probabilistic rule set. It is not a first principle of self-organizing biological systems, but rather a collective behavior that can be quantitatively described in practical terms for experimental biologists. With a quantitative formulation, the concept of emergence may become a useful information statistic in assessing the structure of biological systems.     

Synthetic biology in biofilms: Tools,challenges, and opportunities

The field of synthetic biology seeks to program living cells to perform novel functions with applications ranging from environmental biosensing to smart cell-based therapeutics. Bacteria are an especially attractive chassis organism due to their rapid growth, ease of genetic manipulation, and ability to persist across many environmental niches. Despite significant progress in bacterial synthetic biology, programming bacteria to perform novel functions outside the well-controlled laboratory context remains challenging. In contrast to planktonic laboratory growth, bacteria in nature predominately reside in the context of densely packed communities known as biofilms. While biofilms have historically been considered environmental and biomedical hazards, their physiology and emergent behaviors could be leveraged for synthetic biology to engineer more capable and robust bacteria. Specifically, bacteria within biofilms participate in complex emergent behaviors such as collective organization, cell-to-cell signaling, and division of labor. Understanding and utilizing these properties can enable the effective deployment of engineered bacteria into natural target environments. Toward this goal, this review summarizes the current state of synthetic biology in biofilms by highlighting new molecular tools and remaining biological challenges. Looking to future opportunities, advancing synthetic biology in biofilms will enable the next generation of smart cell-based technologies for use in medicine, biomanufacturing, and environmental remediation.     

Cancer as an emergent phenomenon in systems radiation biology

Radiation-induced DNA damage elicits dramatic cell signaling transitions, some of which are directed towards deciding the fate of that particular cell, while others lead to signaling to other cells. Each irradiated cell type and tissue has a characteristic pattern of radiation-induced gene expression, distinct from that of the unirradiated tissue and different from that of other irradiated tissues. It is the sum of such events, highly modulated by genotype that sometimes leads to cancer. The challenge is to determine as to which of these phenomena have persistent effect that should be incorporated into models of how radiation increases the risk of developing cancer. The application of systems biology to radiation effects may help to identify which biological responses are significant players in radiation carcinogenesis. In contrast to the radiation biology paradigm that focuses on genomic changes, systems biology seeks to integrate responses at multiple scales (e.g. molecular, cellular, organ, and organism). A key property of a system is that some phenomenon emerges as a property of the system rather than of the parts. Here, the idea that cancer in an organism can be considered as an emergent phenomenon of a perturbed system is discussed. Given the current research goal to determine the consequences of high and low radiation exposures, broadening the scope of radiation studies to include systems biology concepts should benefit risk modeling of radiation carcinogenesis. Presented at the First International Workshop on Systems Radiation Biology, February 14–16 2007, GSF-Research Centre, Neuherberg, Germany.     

Organisms as natural purposes: the contemporary evolutionary perspective

Kant's conception of organisms as natural purposes raises a challenge to the adequacy of mechanistic explanation in biology. Certain features of organisms appear to be inexplicable by appeal to mechanical law alone. Some biological phenomena, it seems, can only be accounted for teleologically. Contemporary evolutionary biology has by and large ignored this challenge. It is widely held that Darwin's theory of natural selection gives us an adequate, wholly mechanical account of the nature of organisms. In contemporary biology, the category of the organism plays virtually no explanatory role. Contemporary evolutionary biology is a science of sub-organismal entities-replicators. I argue that recent advances in developmental biology demonstrate the inadequacy of sub-organismal mechanism. The category of the organism, construed as a 'natural purpose' should play an ineliminable role in explaining ontogenetic development and adaptive evolution. According to Kant the natural purposiveness of organisms cannot be demonstrated to be an objective principle in nature, nor can purposiveness figure in genuine explain. I attempt to argue, by appeal to recent work on self-organization, that the purposiveness of organisms is a natural phenomenon, and, by appeal to the apparatus of invariance explanation, that biological purposiveness provides genuine, ineliminable biological explanations.     

Reconciling emergences: An information-theoretic approach to identify causal emergence in multivariate data

The broad concept of emergence is instrumental in various of the most challenging open scientific questions—yet, few quantitative theories of what constitutes emergent phenomena have been proposed. This article introduces a formal theory of causal emergence in multivariate systems, which studies the relationship between the dynamics of parts of a system and macroscopic features of interest. Our theory provides a quantitative definition of downward causation, and introduces a complementary modality of emergent behaviour—which we refer to as causal decoupling. Moreover, the theory allows practical criteria that can be efficiently calculated in large systems, making our framework applicable in a range of scenarios of practical interest. We illustrate our findings in a number of case studies, including Conway’s Game of Life, Reynolds’ flocking model, and neural activity as measured by electrocorticography.     

Emergent properties and the context objection to reduction

Reductionism is a central issue in the philosophy of biology. One common objection to reduction is that molecular explanation requires reference to higher-level properties, which I refer to as the context objection. I respond to this objection by arguing that a well-articulated notion of a mechanism and what I term mechanism extension enables one to accommodate the context-dependence of biological processes within a reductive explanation. The existence of emergent features in the context could be raised as an objection to the possibility of reduction via this strategy. I argue that this objection can be overcome by showing that there is no tenable argument for the existence of emergent properties that are not susceptible to a reductive explanation.     

Organisational closure in biological organisms

The central aim of this paper consists in arguing that biological organisms realize a specific kind of causal regime that we call "organisational closure"; i.e., a distinct level of causation, operating in addition to physical laws, generated by the action of material structures acting as constraints. We argue that organisational closure constitutes a fundamental property of biological systems since even its minimal instances are likely to possess at least some of the typical features of biological organisation as exhibited by more complex organisms. Yet, while being a necessary condition for biological organization, organisational closure underdetermines, as such, the whole set of requirements that a system has to satisfy in order to be taken as a paradigmatic example of organism. As we suggest, additional properties, as modular templates and control mechanisms via dynamical decoupling between constraints, are required to get the complexity typical of full-fledged biological organisms.     

The Mastodon in the room: how Darwinian is neo-Darwinism?

Failing to acknowledge substantial differences between Darwinism and neo-Darwinism impedes evolutionary biology. Darwin described evolution as the outcome of interactions between the nature of the organism and the nature of the conditions, each relatively autonomous but both historically and spatially intertwined. Furthermore, he postulated that the nature of the organism was more important than the nature of the conditions, leading to natural selection as an inevitable emergent product of biological systems. The neo-Darwinian tradition assumed a creative rather than selective view of natural selection, with the nature of the organism determined by the nature of the conditions, rendering the nature of the organism and temporal contingency unnecessary. Contemporary advances in biology, specifically the phylogenetics revolution and evo-devo, underscore the significance of history and the nature of the organism in biology. Darwinism explains more biology better, and better resolves apparent anomalies between living systems and more general natural laws, than does neo-Darwinism. The "extended" or "expanded" synthesis currently called for by neo-Darwinians is Darwinism.     

Ins and Outs of Systems Biology vis-à-vis Molecular Biology: Continuation or Clear Cut?

The comprehension of living organisms in all their complexity poses a major challenge to the biological sciences. Recently, systems biology has been proposed as a new candidate in the development of such a comprehension. The main objective of this paper is to address what systems biology is and how it is practised. To this end, the basic tools of a systems biological approach are explored and illustrated. In addition, it is questioned whether systems biology ‘revolutionizes’ molecular biology and ‘transcends’ its assumed reductionism. The strength of this claim appears to depend on how molecular and systems biology are characterised and on how reductionism is interpreted. Doing credit to molecular biology and to methodological reductionism, it is argued that the distinction between molecular and systems biology is gradual rather than sharp. As such, the classical challenge in biology to manage, interpret and integrate biological data into functional wholes is further intensified by systems biology’s use of modelling and bioinformatics, and by its scale enlargement.