The new mechanistic philosophy is divided into two largely disconnected projects. One deals with a metaphysical inquiry into how mechanisms relate to issues such as causation, capacities and levels of organization, while the other deals with epistemic issues related to the discovery of mechanisms and the intelligibility of mechanistic representations. Tudor Baetu explores and explains these projects, and shows how the gap between them can be bridged. His proposed account is compatible both with the assumptions and practices of experimental (...) design in biological research, and with scientifically accepted interpretations of experimental results. (shrink)

Both clinical research and basic science rely on the epistemic practice of extrapolation from surrogate models, to the point that explanatory accounts presented in review papers and biology textbooks are in fact composite pictures reconstituted from data gathered in a variety of distinct experimental setups. This raises two new challenges to previously proposed mechanistic-similarity solutions to the problem of extrapolation: one pertaining to the absence of mechanistic knowledge in the early stages of research and the second to the large number (...) of extrapolations underpinning explanatory accounts. An analysis of the strategies deployed in experimental research supports the conclusion that while results from validated surrogate models are treated as a legitimate line of evidence supporting claims about target systems, the overall structure of research projects also demonstrates that extrapolative inferences are not considered definitive or sufficient evidence, but only partially justified hypotheses subjected to further testing. 1 Introduction2 Surrogate Models2.1 What exactly is a surrogate model?2.2 Why use surrogate models?3 Prior Validation of Surrogate Models3.1 The validation and ranking of surrogate models in the early stages of basic research3.2 The validation of surrogate models in later stages of basic research and in clinical research4 ‘Big Picture’ Accounts and the Extrapolations Underpinning Them4.1 The mosaic nature of mechanistic descriptions in basic science4.2 Challenges for mechanistic-similarity-based validation protocols5 Retrospective Testing of Extrapolated Knowledge5.1 Holistic confirmation5.2 Fallback strategies6 Conclusions. (shrink)

The paper discusses methodological guidelines for evaluating mechanistic explanations. According to current accounts, a satisfactory mechanistic explanation should include all of the relevant features of the mechanism, its component entities and activities, and their properties and organization, as well as exhibit productive continuity. It is not specified, however, how this kind of mechanistic completeness can be demonstrated. I argue that parameter sufficiency inferences based on mathematical model simulations provide a way of determining whether a mechanism capable of producing the phenomenon (...) of interest can be constructed from mechanistic components organized, acting, and having the properties described in the mechanistic explanation. (shrink)

Current debates surrounding the virtues and shortcomings of randomization are symptomatic of a lack of appreciation of the fact that causation can be inferred by two distinct inference methods, each requiring its own, specific experimental design. There is a non-statistical type of inference associated with controlled experiments in basic biomedical research; and a statistical variety associated with randomized controlled trials in clinical research. I argue that the main difference between the two hinges on the satisfaction of the comparability requirement, which (...) is in turn dictated by the nature of the objects of study, namely homogeneous or heterogeneous populations of biological systems. Among other things, this entails that the objection according to which randomized experiments fail to provide better evidence for causation because randomization cannot guarantee comparability is mistaken. (shrink)

A survey of models in immunology is conducted and distinct kinds of models are characterized based on whether models are material or conceptual, the distinctiveness of their epistemic purpose, and the criteria for evaluating the goodness of a model relative to its intended purpose. I argue that the diversity of models in interdisciplinary fields such as immunology reflects the fact that information about the phenomena of interest is gathered from different sources using multiple methods of investigation. To each model is (...) attached a description specifying how information about a phenomenon of interest has been acquired, highlighting points of commonality and difference between the methodological and epistemic histories of the information encapsulated in different models. These points of commonality and difference allow investigators to integrate findings from different models into more comprehensive explanatory accounts, as well as to troubleshoot anomalies and faulty accounts by going back to the original building blocks. (shrink)

Multidisciplinary models aggregating ‘lower-level’ biological and ‘higher-level’ psychological and social determinants of a phenomenon raise a puzzle. How is the interaction between the physical, the psychological and the social conceptualized and explained? Using biopsychosocial models of pain as an illustration, I argue that these models are in fact level-neutral compilations of empirical findings about correlated and causally relevant factors, and as such they neither assume, nor entail a conceptual or ontological stratification into levels of description, explanation or reality. If inter-level (...) causation is deemed problematic or if debates about the superiority of a particular level of description or explanation arise, these issues are fueled by considerations other than empirical findings. (shrink)

The Fukushima nuclear accident from 2011 provided an occasion for the public display of radiation maps generated using decision-support systems for nuclear emergency management. Such systems rely on computer models for simulating the atmospheric dispersion of radioactive materials and estimating potential doses in the event of a radioactive release from a nuclear reactor. In Germany, as in Japan, such systems are part of the national emergency response apparatus and, in case of accidents, they can be used by emergency task forces (...) for planning radioprotection countermeasures. In this context, the paper addresses the epistemology of dose projections by critically analyzing some of the sources of epistemic opacity and non-knowledge affecting them, and the different methods and practices used by German radioprotection experts to improve their trustworthiness and reliability. It will be argued that dose projections are part of an entire radioprotection regime or assemblage built around the belief that the effects of nuclear accidents can be effectively mitigated thanks to the simulation technologies underlying different protocols and practices of nuclear preparedness. And, as the Fukushima experience showed, some of these expectations will not be met in real emergencies due to the inherent uncertainties entailed by the use of dose projections when planning protective countermeasures. (shrink)

This article critically examines the rationales for the well-settled principle in sentencing law that an offender’s remorse is to be treated as a mitigating factor. Four basic types of rationale are examined: remorse makes punishment redundant; offering mitigation can induce remorse; remorse should be rewarded with mitigation; and remorse should be recognised by mitigation. The first three rationales each suffer from certain weaknesses or limitations, and are argued to be not as persuasive as the fourth. The article then considers, and (...) rejects, two arguments against remorse as a mitigating factor in sentencing: that the crime, not the offender, is the focus of punishment; and that the truly remorseful offender would not ask for mitigation. The article concludes with a brief consideration of whether a lack of remorse should be an aggravating factor. (shrink)

The article analyses in detail the Meselson–Stahl experiment, identifying two novel difficulties for the crucial experiment account, namely, the fragility of the experimental results and the fact that the hypotheses under scrutiny were not mutually exclusive. The crucial experiment account is rejected in favour of an experimental-mechanistic account of the historical significance of the experiment, emphasizing that the experiment generated data about the biochemistry of DNA replication that is independent of the testing of the semi-conservative, conservative, and dispersive hypotheses. _1_ (...) Introduction _2_ The Meselson–Stahl Experiment _3_ Some Difficulties for the Crucial Experiment Account _3.1_ Additional experiments were required _3.2_ Simplicity considerations are unconvincing _3.3_ The fragility of the experimental results _3.4_ The problematic interpretation of falsifyng results _3.5_ Not all possible hypotheses considered or tested _3.6_ The tested hypotheses were not mutually exclusive _4_ The Historical and Scientific Significance of the Meselson–Stahl Experiment _4.1_ The challenge for the crucial experiment account _4.2_ A mechanistic perspective on the experiment _4.3_ The experimental design and its independence from theoretical speculations _4.4_ The advantages of a ‘bottom-up’ mechanistic account _5_ Conclusion. (shrink)

An important strategy in the discovery of biological mechanisms involves the piecing together of experimental results from interventions. However, if mechanisms are investigated by means of ideal interventions, as defined by James Woodward and others, then the kind of information revealed is insufficient to discriminate between modular and non-modular causal contributions. Ideal interventions suffice for constructing webs of causal dependencies that can be used to make some predictions about experimental outcomes, but tell us little about how causally relevant factors are (...) organized together and how they interact with each other in order to produce a phenomenon. I argue that lab research relies on more elaborated types of interventions targeting in a controlled fashion multiple variables at the same time in order to probe the temporal organization of causally-relevant factors along distinct causal pathways and to test for non-modular interaction effects, thus providing crucial spatial-temporal constraints guiding the formulation of more detailed mechanistic explanations. (shrink)

Causal pluralism can be defended not only in respect to causal concepts and methodological guidelines, but also at the finer-grained level of causal inference from a particular source of evidence for causation. An argument for this last variety of pluralism is made based on an analysis of causal inference from randomized experiments (RCTs). Here, the causal interpretation of a statistically significant association can be established via multiple paths of reasoning, each relying on different assumptions and providing distinct elements of information (...) in favour of a causal interpretation. (shrink)

This paper is trying to put together two different researches, from theology and from genetics, about a general and undetermined topic, death. It is undetermined because no one can say something demonstrable and unequivocal about it, since no person alive can cross over the edge of life and come back from the domain of death with information about it. But we can discuss nevertheless things that are obvious and possible to be reasonably inferred about death even by livings. In this (...) regard Theology will provide the mainline of what is to be known as death for religion in general, while Genetics will try to come with its research to sustain or contradict the general premise: death is not an ontological behavior of living matter, but an imposed attribute after the sin occurred into the world. (shrink)

Multidisciplinary models aggregating ‘lower-level’ biological and ‘higher-level’ psychological and social determinants of a phenomenon raise a puzzle. How is the interaction between the physical, the psychological and the social conceptualized and explained? Using biopsychosocial models of pain as an illustration, I argue that these models are in fact level-neutral compilations of empirical findings about correlated and causally relevant factors, and as such they neither assume, nor entail a conceptual or ontological stratification into levels of description, explanation or reality. If inter-level (...) causation is deemed problematic or if debates about the superiority of a particular level of description or explanation arise, these issues are fueled by considerations other than empirical findings. (shrink)

Starting with an empirical study of several Jehovah’s Witnesses1 congregations we aim to highlight the social mechanisms of religious conversion and the phases an individual passes through before becoming a Witness. By applying Lewis Rambo’s systemic stage model of conversion we are able to identify a series of elements that characterize the conversion to this religion in Romania, such as: social filtering, delegitimation of the previous religion, and incipient identification with the Witnesses’ group. The article asserts that the Witnesses’ decision (...) to convert implies the deliberate assumption of the others’ disapproval and even social stigmatization. Nevertheless they opt for this religious status because the immediate benefits brought by the religious community and the future benefits of the earthly Heaven offer them sufficient motives for becoming Witnesses. (shrink)

Hierarchical structures are rapidly and flexibly built up in the domains of human language and music. These domains require a tree-building capacity – “dendrophilia” – to dynamically infer hierarchical structures from sensory input, based on subunits stored in a lexicon. This dynamic process involves a crucial class of abstracta overlooked in the target article.

Savage et al. make a compelling case, Mehr et al. less so, for social bonding and credible signalling, respectively, as the main adaptive function of human musicality. We express general advocacy for the former thesis, highlighting: overlap between the two; direct versus derived biological functions, and aspects of music embedded in cultural evolution, for example, departures from tonality.

Examples from the sciences showing that mechanisms do not always succeed in producing the phenomena for which they are responsible have led some authors to conclude that the regularity requirement can be eliminated from characterizations of mechanisms. In this article, I challenge this conclusion and argue that a minimal form of regularity is inextricably embedded in examples of elucidated mechanisms that have been shown to be causally responsible for phenomena. Examples of mechanistic explanations from the sciences involve mechanisms that have (...) been shown to produce phenomena with a reproducible rate of success. By contrast, if phenomena are infrequent to the point that they amount to irreproducible observations and experimental results, they are indistinguishable from the background noise of accidental happenings. The inability to detect or measure the phenomenon of interest against the background noise of accidental correlations makes it impossible to elucidate a mechanism by experimental means, to demonstrate that a proposed mechanism actually produces the phenomenon, and ultimately to justify why a hypothetical scenario involving an irregular mechanism should be preferred over attributing irreproducible happenings to chance. (shrink)

In this article, I argue that genomic programs are not substitutes for multi-causal molecular mechanistic explanations of inheritance, but abstract representations of the same sort as mechanism schemas already described in the philosophical literature. On this account, the program analogy is not reductionistic and does not ignore or underestimate the active contribution of epigenetic elements to phenotypes and development. Rather, genomic program representations specifically highlight the genomic determinants of inheritance and their organizational features at work in the wider context of (...) the mechanisms of genome expression. (shrink)

I argue that informational models of consciousness, including those proposed by the Integrated Information Theory, don’t presuppose or entail any particular view about the physical or metaphysical nature of consciousness. Such models only tell us how certain properties of consciousness can be mathematically described, thus providing a quantitative characterization of the phenomenon of consciousness that may contribute to the development of new methods of assessment and guide the explanatory project by supplying additional constraints on theoretical proposals. While informational models are (...) in principle compatible with multiple physical interpretations, a preliminary argument in favour of the continuity between informational approaches and the mechanistic project in neuroscience can be made based on historical precedents. (shrink)

Kenneth Waters and Marcel Weber argue that the joint use of distinct gene concepts and the transfer of knowledge between classical and molecular analyses in contemporary scientific practice is possible because classical and molecular concepts of the gene refer to overlapping chromosomal segments and the DNA sequences associated with these segments. However, while pointing in the direction of coreference, both authors also agree that there is a considerable divergence between the actual sequences that count as genes in classical genetics and (...) molecular biology. The thesis advanced in this paper is that the referents of classical and molecular gene concepts are coextensive to a higher degree than admitted by Waters and Weber, and therefore coreference can provide a satisfactory account of the high level of integration between classical genetics and molecular biology. In particular, I argue that the functional units/cistrons identified by classical techniques overlap with functional elements entering the composition of molecular transcription units, and that the precision of this overlap can be improved by conducting further experimentation. (shrink)

According to the hypothesis-generator account, valid extrapolations from a source to a target system are circular, since they rely on knowledge of relevant similarities and differences that can onl...

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. (shrink)

This article discusses the key existential stakes of implementing biometrics in human lifeworlds. In this pursuit, we offer a problematization and reinvention of central values often taken for granted within the “ethical turn” of AI development and discourse, such as autonomy, agency, privacy and integrity, as we revisit basic questions about what it means to be human and embodied. Within a framework of existential media studies, we introduce an existential ethics of care—through a conversation between existentialism, virtue ethics, a feminist (...) ethics of care and post-humanist ethics—aiming to deepen and nuance our understanding of the human behind “human-centered” AI directives. The key argument is that biometrics implicates humans through unprecedented forms of objectification, through which the existential body—the relational, intimate and frail human being—is at risk. We interrogate these risks as they become visible at three sites where embodied humans are challenged by biometrics, and thus where the existential body is challenged by the biometric body. This occurs through reductionism (biometric passports nailing bodies to identities, removing human judgment and compromising agency at the AI border), enforced transparency (smart home assistants surveying human intimacies and invading intimate spaces in the bedroom) and the breaching of bodily integrity (chipping bodies to capture sensory data, challenging the very concept of bodily integrity through self-invasive biohacking). Our existential ethics of care is importantly not a solutionist list of principles or suggestions, but a manifesto for a way of thinking about the ethical challenges of living with biometrics in today’s world, by raising the right questions. We argue that a revitalized discussion of the basic existential stakes within human lived experience is needed and should serve as the foundation on which comprehensive frameworks can be built to address the complexities and prospects for ethical machines, responsible biometrics and AI. (shrink)

The pore‐forming BCL‐2 family proteins are effectors of mitochondrial poration in apoptosis initiation. Two atypical effectors—BOK and truncated BID (tBID)—join the canonical effectors BAK and BAX. Gene knockout revealed developmental phenotypes in the absence the effectors, supporting their roles in vivo. During apoptosis effectors are activated and change shape from dormant monomers to dynamic oligomers that associate with and permeabilize mitochondria. BID is activated by proteolysis, BOK accumulates on inhibition of its degradation by the E3 ligase gp78, while BAK and (...) BAX undergo direct activation by BH3‐only initiators, autoactivation, and crossactivation. Except tBID, effector oligomers on the mitochondria appear as arcs and rings in super‐resolution microscopy images. The BH3‐in‐groove dimers of BAK and BAX, the tBID monomers, and uncharacterized BOK species are the putative building blocks of apoptotic pores. Effectors interact with lipids and bilayers but the mechanism of membrane poration remains elusive. I discuss effector‐mediated mitochondrial poration. (shrink)

The Soul is considered, both for religions and philosophy, to be the immaterial aspect or essence of a human being, conferring individuality and humanity, often considered to be synonymous with the mind or the self. For most theologies, the Soul is further defined as that part of the individual, which partakes of divinity and transcends the body in different explanations. But, regardless of the philosophical background in which a specific theology gives the transcendence of the soul as the source of (...) its everlasting essence – often considered to survive the death of the body –, it is always appraised as a higher existence for which all should fight for. In this regard, all religious beliefs assert that there are many unseen battles aiming to take hold of the human soul, either between divinity and evil, or between worlds, or even between the body and the soul itself. These unseen battles over the human soul raging in the whole world made it the central item of the entire universe, both for the visible and the unseen worlds, an item of which whoever takes possession will also become the ruler of the universe. Through this philosophy, the value of the soul became abysmal, incommensurable, and without resemblance. The point for making such a broad overview of the soul in religious beliefs is the question of whether we can build an interfaith discourse based on the religions’ most debated and valuable issue, soul? Regardless of the variety of religious beliefs on what seems to be the soul, there is always a residual consideration in them that makes the soul more important than the body. This universal impression is due to another belief or instead need of believing that above and beyond this seen, palpable, finite life and the world should exist another one, infinite, transcendent, and available all the same after here. This variety stretches from the minimum impact that soul has on the body, as being the superior essence that inhabitants and enlivens the matter, to the highest impact in which soul has nothing to do with matter[1] and is only ephemeral linked to it, but its existence is not at all limited, defined or depended on the matter [2], or even placed to the extreme, as the very life of the matter thus this seen universe is merely a thought in the soul/mind [3]. In this extensive variety of soul overviews, the emphasis of the soul’s importance gives an inverse significance to the body/matter, from being everything that matters to a thin, dwindle item that has no existence at all outside consciousness. (shrink)

The purpose of this article is to update and defend syntax-based gene concepts. I show how syntax-based concepts can and have been extended to accommodate complex cases of processing and gene expression regulation. In response to difficult cases and causal parity objections, I argue that a syntax-based approach fleshes out a deflationary concept defining genes as genomic sequences and organizational features of the genome contributing to a phenotype. These organizational features are an important part of accepted molecular explanations, provide the (...) theoretical basis for a large number of experimental techniques and practical applications, and play a crucial role in in annotating the genome, deriving predictions and constructing bioinformatics models. (shrink)

Different concepts define species at the pattern-level grouping of organisms into discrete clusters, the level of the processes operating within and between populations leading to the formation and maintenance of these clusters, or the level of the inner-organismic genetic and molecular mechanisms that contribute to species cohesion or promote speciation. I argue that, unlike single-level approaches, a multi-level framework takes into account the complex sequences of cause-effect reinforcements leading to the formation and maintenance of various patterns, and allows for revisions (...) and refinements of pattern-based characterizations in light of the gradual elucidation of the causes and mechanisms contributing to pattern formation and maintenance. (shrink)

In this paper, we provide a semantic analysis of the well-known knowability paradox stemming from the Church–Fitch observation that the meaningful knowability principle /all truths are knowable/, when expressed as a bi-modal principle F --> K♢F, yields an unacceptable omniscience property /all truths are known/. We offer an alternative semantic proof of this fact independent of the Church–Fitch argument. This shows that the knowability paradox is not intrinsically related to the Church–Fitch proof, nor to the Moore sentence upon which it (...) relies, but rather to the knowability principle itself. Further, we show that, from a verifiability perspective, the knowability principle fails in the classical logic setting because it is missing the explicit incorporation of a hidden assumption of /stability/: ‘the proposition in question does not change from true to false in the process of discovery.’ Once stability is taken into account, the resulting /stable knowability principle/ and its nuanced versions more accurately represent verification-based knowability and do not yield omniscience. (shrink)

This commentary examines the use of Y-chromosome testing to reconstruct a genetic ancestry for the Lemba, a group in southern Africa.