Biologists often study particular biological systems as models of a phenomenon of interest even if they already know that the phenomenon is produced by diverse mechanisms and hence none of those systems alone can sufficiently represent it. To understand this modeling practice, the present paper provides an account of how multiple model systems can be used to study a phenomenon that is produced by diverse mechanisms. Even if generalizability of results from a single model system is significantly limited, generalizations concerning (...) specific aspects of mechanisms often hold across certain ranges of biological systems, which enables multiple model systems to jointly represent such a phenomenon. Comparing mechanisms that operate in different biological systems as examples of the same phenomenon also facilitates characterization and investigation of individual mechanisms. I also compare my account with two existing accounts of the use of multiple model systems and argue that my account is distinct from and complementary to them. (shrink)

While the importance of mechanisms in determining causality in medicine is currently the subject of active debate, the role of mechanistic reasoning in clinical practice has received far less attention. In this paper we look at this question in the context of the treatment of a particular individual, and argue that evidence of mechanisms is indeed key to various aspects of clinical practice, including assessing population-level research reports, diagnostic as well as therapeutic decision making, and the assessment of treatment effects. (...) We use the pulmonary condition bronchiectasis as a source of examples of the importance of mechanistic reasoning to clinical practice. (shrink)

ArgumentThis article uses four historical case studies to address epistemological issues related to the animal model of human diseases and its use in medical research on human diseases. The knowledge derived from animal models is widely assumed to be highly valid and predictive of reactions by human organisms. In this contribution, I use three significant historical cases of failure (ca. 1890, 1960, 2006), and a closer look at the emergence of the concept around 1860/70, to elucidate core assumptions related to (...) the specific practices of animal-human knowledge transfer, and to analyze the explanations provided by historical actors after each of the failures. Based on these examples, I argue that the epistemological status of the animal model changed from that of a helpful methodological tool for addressing specific questions, but with precarious validity, to an obligatory method for the production of strong knowledge on human diseases. As a result, there now exists a culture of biomedical research in human disease that, for more than a century, has taken the value of this methodological tool as self-evident, and more or less beyond question. (shrink)

Philosophical discussions on causal inference in medicine are stuck in dyadic camps, each defending one kind of evidence or method rather than another as best support for causal hypotheses. Whereas Evidence Based Medicine advocates the use of Randomised Controlled Trials and systematic reviews of RCTs as gold standard, philosophers of science emphasise the importance of mechanisms and their distinctive informational contribution to causal inference and assessment. Some have suggested the adoption of a pluralistic approach to causal inference, and an inductive (...) rather than hypothetico-deductive inferential paradigm. However, these proposals deliver no clear guidelines about how such plurality of evidence sources should jointly justify hypotheses of causal associations. We here develop such guidelines by first giving a philosophical analysis of the underpinnings of Hill’s viewpoints on causality. We then put forward an evidence-amalgamation framework adopting a Bayesian net approach to model causal inference in pharmacology for the assessment of harms. Our framework accommodates a number of intuitions already expressed in the literature concerning the EBM vs. pluralist debate on causal inference, evidence hierarchies, causal holism, relevance, and reliability. (shrink)

A recent series of experiments have demonstrated that a classical fluid mechanical system, constituted by an oil droplet bouncing on a vibrating fluid surface, can be induced to display a number of behaviours previously considered to be distinctly quantum. To explain this correspondence it has been suggested that the fluid mechanical system provides a single-particle classical model of de Broglie’s idiosyncratic ‘double solution’ pilot wave theory of quantum mechanics. In this paper we assess the epistemic function of the bouncing oil (...) droplet experiments in relation to quantum mechanics. We find that the bouncing oil droplets are best conceived as an analogue illustration of quantum phenomena, rather than an analogue simulation, and, furthermore, that their epistemic value should be understood in terms of how-possibly explanation, rather than confirmation. Analogue illustration, unlike analogue simulation, is not a form of ‘material surrogacy’, in which source empirical phenomena in a system of one kind can be understood as ‘standing in for’ target phenomena in a system of another kind. Rather, analogue illustration leverages a correspondence between certain empirical phenomena displayed by a source system and aspects of the ontology of a target system. On the one hand, this limits the potential inferential power of analogue illustrations, but, on the other, it widens their potential inferential scope. In particular, through analogue illustration we can learn, in the sense of gaining how-possibly understanding, about the putative ontology of a target system via an experiment. As such, the potential scientific value of these extraordinary experiments is undoubtedly a significant one. (shrink)

Analogue experiments have attracted interest for their potential to shed light on inaccessible domains. For instance, ‘dumb holes’ in fluids and Bose–Einstein condensates, as analogues of black holes, have been promoted as means of confirming the existence of Hawking radiation in real black holes. We compare analogue experiments with other cases of experiment and simulation in physics. We argue—contra recent claims in the philosophical literature—that analogue experiments are not capable of confirming the existence of particular phenomena in inaccessible target systems. (...) As they must assume the physical adequacy of the modelling framework used to describe the inaccessible target system, arguments to the conclusion that analogue experiments can yield confirmation for phenomena in those target systems, such as Hawking radiation in black holes, beg the question. (shrink)

Leading animal models are powerful tools for translational research, but they also present obstacles. Poorly conducted preclinical research in animals is a common cause of translational failure, but even when such research is well-designed and carefully executed, challenges remain. In particular, dominant models may bias research directions, elide essential aspects of human disease, omit important context, or subtly shift research targets. Recognizing these stumbling blocks can help us find ways to avoid them: employing a wider range of models, incorporating more (...) realistic environmental conditions, better aligning studies between animals and patients, and focusing on human biology and therapeutic goals. Such changes are costly; but insisting it would be impractical or unrealistic to change strategies offers no way out of the current impasse. Rather, we must acknowledge the obstacles as well as the advantages presented by core models, and direct some of our investments in translational research toward getting around them. The dominance of biomedical research by a handful of animal models introduces subtle but significant obstacles to translation. Recognizing these obstacles is a critical first step toward finding ways around them; this paper describes how dominant models can create roadblocks, and suggests strategies to improve the efficiency of translation from animal models to humans. (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)

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)

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)

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...

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)