Many biological investigations are organized around a small group of species, often referred to as ‘model organisms’, such as the fruit fly Drosophila melanogaster. The terms ‘model’ and ‘modelling’ also occur in biology in association with mathematical and mechanistic theorizing, as in the Lotka–Volterra model of predator-prey dynamics. What is the relation between theoretical models and model organisms? Are these models in the same sense? We offer an account on which the two practices are shown to have different epistemic characters. (...) Theoretical modelling is grounded in explicit and known analogies between model and target. By contrast, inferences from model organisms are empirical extrapolations. Often such extrapolation is based on shared ancestry, sometimes in conjunction with other empirical information. One implication is that such inferences are unique to biology, whereas theoretical models are common across many disciplines. We close by discussing the diversity of uses to which model organisms are put, suggesting how these relate to our overall account. 1 Introduction2 Volterra and Theoretical Modelling3 Drosophila as a Model Organism4 Generalizing from Work on Model Organisms5 Phylogenetic Inference and Model Organisms6 Further Roles of Model Organisms6.1 Preparative experimentation6.2 Model organisms as paradigms6.3 Model organisms as theoretical models6.4 Inspiration for engineers6.5 Anchoring a research community7 Conclusion. (shrink)

Many scientific models are representations. Building on Goodman and Elgin’s notion of representation-as we analyse what this claim involves by providing a general definition of what makes something a scientific model, and formulating a novel account of how they represent. We call the result the DEKI account of representation, which offers a complex kind of representation involving an interplay of, denotation, exemplification, keying up of properties, and imputation. Throughout we focus on material models, and we illustrate our claims with the (...) Phillips-Newlyn machine. In the conclusion we suggest that, mutatis mutandis, the DEKI account can be carried over to other kinds of models, notably fictional and mathematical models. (shrink)

The new mechanists and the autonomy approach both aim to account for how biological phenomena are explained. One identifies appeals to how components of a mechanism are organized so that their activities produce a phenomenon. The other directs attention towards the whole organism and focuses on how it achieves self-maintenance. This paper discusses challenges each confronts and how each could benefit from collaboration with the other: the new mechanistic framework can gain by taking into account what happens outside individual mechanisms, (...) while the autonomy approach can ground itself in biological research into how the actual components constituting an autonomous system interact and contribute in different ways to realize and maintain the system. To press the case that these two traditions should be constructively integrated we describe how three recent developments in the autonomy tradition together provide a bridge between the two traditions: (1) a framework of work and constraints, (2) a conception of function grounded in the organization of an autonomous system, and (3) a focus on control. (shrink)

ABSTRACTExperimentation is traditionally considered a privileged means of confirmation. However, why and how experiments form a better confirmatory source relative to other strategies is unclear, and recent discussions have identified experiments with various modeling strategies on the one hand, and with ‘natural’ experiments on the other hand. We argue that experiments aiming to test theories are best understood as controlled investigations of specimens. ‘Control’ involves repeated, fine-grained causal manipulation of focal properties. This capacity generates rich knowledge of the object investigated. (...) ‘Specimenhood’ involves possessing relevant properties given the investigative target and the hypothesis in question. Specimens are thus representative members of a class of systems, to which a hypothesis refers. It is in virtue of both control and specimenhood that experiments provide powerful confirmatory evidence. This explains the distinctive power of experiments: although modelers exert extensive control, they do not exert this control over specimens; although natural experiments utilize specimens, control is diminished. (shrink)

Scientists use models to understand the natural world, and it is important not to conflate model and nature. As an illustration, we distinguish three different kinds of populations in studies of ecology and evolution: theoretical, laboratory, and natural populations, exemplified by the work of R.A. Fisher, Thomas Park, and David Lack, respectively. Biologists are rightly concerned with all three types of populations. We examine the interplay between these different kinds of populations, and their pertinent models, in three examples: the notion (...) of “effective” population size, the work of Thomas Park on /Tribolium/ populations, and model-based clustering algorithms such as /Structure/. Finally, we discuss ways to move safely between three distinct population types while avoiding confusing models and reality. (shrink)

This paper discusses what it means and what it takes to integrate data in order to acquire new knowledge about biological entities and processes. Maureen O’Malley and Orkun Soyer have pointed to the scientific work involved in data integration as important and distinct from the work required by other forms of integration, such as methodological and explanatory integration, which have been more successful in captivating the attention of philosophers of science. Here I explore what data integration involves in more detail (...) and with a focus on the role of data-sharing tools, like online databases, in facilitating this process; and I point to the philosophical implications of focusing on data as a unit of analysis. I then analyse three cases of data integration in the field of plant science, each of which highlights a different mode of integration: inter-level integration, which involves data documenting different features of the same species, aims to acquire an interdisciplinary understanding of organisms as complex wholes and is exemplified by research on Arabidopsis thaliana; cross-species integration, which involves data acquired on different species, aims to understand plant biology in all its different manifestations and is exemplified by research on Miscanthus giganteus; and translational integration, which involves data acquired from sources within as well as outside academia, aims at the provision of interventions to improve human health and is exemplified by research on Phytophtora ramorum. Recognising the differences between these efforts sheds light on the dynamics and diverse outcomes of data dissemination and integrative research; and the relations between the social and institutional roles of science, the development of data-sharing infrastructures and the production of scientific knowledge. (shrink)

Community databases have become crucial to the collection, ordering and retrieval of data gathered on model organisms, as well as to the ways in which these data are interpreted and used across a range of research contexts. This paper analyses the impact of community databases on research practices in model organism biology by focusing on the history and current use of four community databases: FlyBase, Mouse Genome Informatics, WormBase and The Arabidopsis Information Resource. We discuss the standards used by the (...) curators of these databases for what counts as reliable evidence, acceptable terminology, appropriate experimental set-ups and adequate materials (e.g., specimens). On the one hand, these choices are informed by the collaborative research ethos characterising most model organism communities. On the other hand, the deployment of these standards in databases reinforces this ethos and gives it concrete and precise instantiations by shaping the skills, practices, values and background knowledge required of the database users. We conclude that the increasing reliance on community databases as vehicles to circulate data is having a major impact on how researchers conduct and communicate their research, which affects how they understand the biology of model organisms and its relation to the biology of other species. (shrink)

Microbiome research shows that human health is foundationally intertwined with the ecology of microbial communities living on and in our bodies. This challenges the categorical separation of organisms from environments that has been central to biomedicine, and questions the boundaries between them. Biomedicine is left with an empirical problem: how to understand causal pathways between host health, microbiota and environment? We propose a conceptual tool – environmentality – to think through this problem. Environmentality is the state or quality of being (...) an environment for something else in a particular context: a fully perspectival proposition. Its power lies partly in what Isabelle Stengers has called the efficacy of the word itself, contrasting the dominant sense of the word environment as something both external and fixed. Through three case studies, we argue that environmentality can help think about the causality of microbiota vis-a-vis host health in a processual, relational and situated manner, across scales and temporalities. We situate this intervention within historical trajectories of thought in biomedicine, focusing on the challenge microbiome research poses to an aperspectival body. We argue that addressing entanglements between microbial and human lives requires that the environment is brought into the clinic, thus shortening the conceptual gap between medicine and public health. (shrink)

Stanford’s argument against scientific realism focuses on theories, just as many earlier arguments from inconceivability have. However, there are possible arguments against scientific realism involving unconceived (or inconceivable) entities of different types: observations, models, predictions, explanations, methods, instruments, experiments, and values. This paper charts such arguments. In combination, they present the strongest challenge yet to scientific realism.

Waters’s (2007) actual difference making and Weber’s (2013, 2017) biological normality approaches to causal selection have received many criticisms, some of which miss their target. Disagreement about whether Waters’s and Weber’s views succeed in providing criteria that uniquely singles out the gene as explanatorily significant in biology has led philosophers to overlook a prior problem. Before one can address whether Waters’s and Weber’s views successfully account for the explanatory significance of genes, one must ask whether either view satisfactorily meets the (...) necessary conditions for causal selection in the first place. An adequate defense of causal selection must meet two desiderata. First, there must be an explanatory property that sets some causes apart from others. Second, the property identified must be one that is recognized by biologists as relevant to their domain(s) of inquiry. I argue that both fall short of meeting the second condition. I demonstrate this by showing how many of the biological technologies crucial to experimentation do not fit either view very well. I offer a more adequate proposal that accommodates non-actual and artificial causal variables. A consequence of my view is the following: When analyzing the causal selection practices of biologists, philosophers should consider the explanatory targets relevant to a research program – including ones whose explanans must appeal to biological technologies. I then explain how this proposal can inform the existing debate between Weber (2017) and Griffiths et al. (2015). (shrink)

Experimental modeling in biology involves the use of living organisms (not necessarily so-called "model organisms") in order to model or simulate biological processes. I argue here that experimental modeling is a bona fide form of scientific modeling that plays an epistemic role that is distinct from that of ordinary biological experiments. What distinguishes them from ordinary experiments is that they use what I call "in vivo representations" where one kind of causal process is used to stand in for a physically (...) different kind of process. I discuss the advantages of this approach in the context of evolutionary biology. (shrink)

Criticism is a staple of the scientific enterprise and of the social epistemology of science. Philosophical discussions of criticism have traditionally focused on its roles in relation to objectivity, confirmation, and theory choice. However, attention to criticism and to criticizability should also inform our thinking about scientific pursuits: the allocation of resources with the aim of developing scientific tools and ideas. In this paper, we offer an account of scientific pursuitworthiness which takes criticizability as its starting point. We call this (...) the apokritic model of pursuit. Its core ideas are that pursuits are practices governed by norms for asking and answering questions, and that criticism arises from the breach of these norms. We illustrate and advertise our approach using examples from institutional grant review, neuroscience, and sociology. We show that the apokritic model can unify several indices of criticizability, that it can account for the importance of criticizing pursuits in scientific practice, and that it can offer ameliorative advice to erstwhile pursuers. (shrink)

Philosophers of science have paid close attention to climate simulations as means of projecting the severity and effects of climate change, but have neglected the full diversity of methods in climate science. This paper shows the philosophical richness of another method in climate science: the practice of using paleoclimate analogues to inform our climate projections. First, I argue that the use of paleoclimate analogues can offer important insights to philosophers of the historical sciences. Rather than using the present as a (...) guide to the past, as is common in the historical sciences, paleoclimate analogues involve using the past as a guide to the future. I thereby distinguish different methods in the historical sciences and argue that these distinctions bear on debates over whether the historical sciences can produce generalizations or predictions. Second, I suggest that paleoclimate analogues might actually be considered a type of climate model, and, as such, their use expands on common characterizations of models to include those that are full-scale, naturally occurring, and non-manipulable. (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)

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)

In recent years, the philosophical focus of the modeling literature has shifted from descriptions of general properties of models to an interest in different model functions. It has been argued that the diversity of models and their correspondingly different epistemic goals are important for developing intelligible scientific theories. However, more knowledge is needed on how a combination of different epistemic means can generate and stabilize new entities in science. This paper will draw on Rheinberger’s practice-oriented account of knowledge production. The (...) conceptual repertoire of Rheinberger’s historical epistemology offers important insights for an analysis of the modelling practice. I illustrate this with a case study on network modeling in systems biology where engineering approaches are applied to the study of biological systems. I shall argue that the use of multiple means of representations is an essential part of the dynamic of knowledge generation. It is because of – rather than in spite of – the diversity of constraints of different models that the interlocking use of different epistemic means creates a potential for knowledge production. (shrink)

The discovery of RNA interference in 1998 has made a lasting impact on biological research. Identifying the regulatory role of small RNAs changed the modes of molecular biological inquiry as well as biologists' understanding of genetic regulation. This article examines the early years of small RNA biology's success story. I query which factors had to come together so that small RNA research came into life in the blink of an eye. I primarily look at scientific repertoires as facilitators of rapid (...) scientific change. I show that for a short period of time, between the years 1998 and 2002, different model organism communities, investigative strategies, technological innovations, and research interests could be successfully aligned to take small RNA research off the ground. I discuss how the keystone discoveries were situated in specific experimental traditions and what strategies were employed to establish these discoveries as more general phenomena. Providing thus a practice-based approach of rapid scientific change, I ask how to relate the change in propositional bits of scientific knowledge with changes in scientific practice. (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)

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)

Model organisms are central to contemporary biology and studies of embryogenesis in particular. Biologists utilize only a small number of species to experimentally elucidate the phenomena and mechanisms of development. Critics have questioned whether these experimental models are good representatives of their targets because of the inherent biases involved in their selection (e.g., rapid development and short generation time). A standard response is that the manipulative molecular techniques available for experimental analysis mitigate, if not counterbalance, this concern. But the most (...) powerful investigative techniques and molecular methods are applicable to single-celled organisms (‘microbes’). Why not use unicellular rather than multicellular model organisms, which are the standard for developmental biology? To claim that microbes are not good representatives takes us back to the original criticism leveled against model organisms. Using empirical case studies of microbes modeling ontogeny, we break out of this circle of reasoning by showing: (a) that the criterion of representation is more complex than earlier discussions have emphasized; and, (b) that different aspects of manipulability are comparable in importance to representation when deciding if a model organism is a good model. These aspects of manipulability harbor the prospect of enhancing representation. The result is a better understanding of how developmental biologists conceptualize research using experimental models and suggestions for underappreciated avenues of inquiry using microbes. More generally, it demonstrates how the practical aspects of experimental biology must be scrutinized in order to understand the associated scientific reasoning. (shrink)

Evo-Devo exhibits a plurality of scientific “cultures” of practice and theory. When are the cultures acting—individually or collectively—in ways that actually move research forward, empirically, theoretically, and ethically? When do they become imperialistic, in the sense of excluding and subordinating other cultures? This chapter identifies six cultures – three /styles/ (mathematical modeling, mechanism, and history) and three /paradigms/ (adaptationism, structuralism, and cladism). The key assumptions standing behind, under, or within each of these cultures are explored. Characterizing the internal structure of (...) the cultures is necessary for understanding how they collaborate or compete, and how they are fragmented or integrated, in the rich interdisciplinary /trading zone/ (Galison 1997) of Evo-Devo. Evo-Devo is an important example of how science can progress through a radical plurality of perspectives and cultures. (shrink)

Collections of living organisms are reservoirs of biological knowledge that operate across times and places. From the mid-20th century, scientific institutions dedicated to the cultivation of such collections have routinized and professionalized their care. But “care,” for these collections, is focused not just on individual organisms—instead, a principal aim of a curator is to maintain the integrity of a reproducing “strain,” “variety,” “line,” or “stock,” and the composition of a collection as a whole. This paper explores the forms, the material (...) dimensions, the temporalities, and the values of that care, to recover the conditions under which scientist-custodians maintain continuity of research over many decades. This paper does so by focusing on two rather different kinds of scientific collection: that of Drosophila fruit flies on the one hand, and plant seeds on the other. Their comparison is valuable because their vastly different needs and life cycles engender very different practices of care. Comparing the materialities, life cycles, needs, and values of these divergent collections helps to draw attention to the routine and the apparently mundane. First, the paper asks: what kinds of work go into managing such collections—that is, the day-to-day management and cultivation, surveillance, and administration of information? Second, it asks: how do these practices maintain the integrity of the strains and stocks, and the collections themselves? What kinds of value does this work create? Third, what are the future imaginaries that are rhetorically drawn into the funding strategies of these collections, and how do they envision future use, ownership, and control? (shrink)

This paper argues that research on normative issues in the life sciences will benefit from a tighter integration of philosophy of science. We examine research on ethical, legal and social issues in the life sciences (“ELSI”) and discuss three illustrative examples of normative issues that arise in different areas of the life sciences. These examples show that important normative questions are highly dependent on epistemic issues which so far have not been addressed sufficiently in ELSI, RRI and related areas of (...) research. Accordingly, we argue for the integration of research on the epistemic aspects of the relevant areas of science into ELSI research to provide a better basis for addressing normative questions. (shrink)

ArgumentWe examine the criteria used to validate the use of nonhuman organisms in North-American alcohol addiction research from the 1950s to the present day. We argue that this field, where the similarities between behaviors in humans and non-humans are particularly difficult to assess, has addressed questions of model validity by transforming the situatedness of non-human organisms into an experimental tool. We demonstrate that model validity does not hinge on the standardization of one type of organism in isolation, as often the (...) case with genetic model organisms. Rather, organisms are viewed as necessarily situated: they cannot be understood as a model for human behavior in isolation from their environmental conditions. Hence the environment itself is standardized as part of the modeling process; and model validity is assessed with reference to the environmental conditions under which organisms are studied. (shrink)

Many biologists appeal to the so-called Krogh principle when justifying their choice of experimental organisms. The principle states that “for a large number of problems there will be some animal of choice, or a few such animals, on which it can be most conveniently studied”. Despite its popularity, the principle is often critiqued for implying unwarranted generalizations from optimal models. We argue that the Krogh principle should be interpreted in relation to the historical and scientific contexts in which it has (...) been developed and used. We interpret the Krogh Principle as a heuristic, i.e., as a recommendation to approach biological problems through organisms where a specific trait or physiological mechanism is expected to be most distinctively displayed or most experimentally accessible. We designate these organisms “Krogh organisms.” We clarify the differences between uses of model organisms and non-standard Krogh organisms. Among these is the use of Krogh organisms as “negative models” in biomedical research, where organisms are chosen for their dissimilarity to human physiology. Importantly, the representational scope of Krogh organisms and the generalizability of their characteristics are not fixed or assumed but explored through experimental studies. Research on Krogh organisms is steeped in the comparative method characteristic of zoology and comparative physiology, in which studies of biological variation produce insights into general physiological constraints. Accordingly, we conclude that the Krogh principle exemplifies the advantages of studying biological variation as a strategy to produce generalizable insights. (shrink)

A powerful idea put forward in the recent philosophy of science literature is that scientific models are best understood as instruments, tools or, more generally, artifacts. This idea has thus far been developed in combination with the more traditional representational approach: accordingly, current artifactualist accounts treat models as representational tools. But artifactualism and representationalism are independent views, and adopting one does not require acceptance of the other. This paper argues that a leaner version of artifactualism, free of representationalist assumptions, is (...) both desirable and viable. Taking seriously the idea that models are artifacts can help us philosophically to make sense of how and why scientific modeling works even without reference to representation. (shrink)

ZusammenfassungTrotz seiner großen Verbreitung in den Lebenswissenschaften wurde dem Aquarium bisher wenig wissenschafts- und technikhistorische Aufmerksamkeit zuteil. Dies ist nicht zuletzt durch den Umstand begründet, dass das Aquarium und seine Geschichte bisher größtenteils als außerwissenschaftlich aufgefasst wurden. Dabei spielen so unterschiedliche Kontexte wie Akklimatisierung, Amateurnaturkunde und bürgerliche Populärkultur eine wichtige Rolle. Gleichzeitig ist die Entwicklung des Aquariums aber auch eng mit der Geschichte der Lebenswissenschaften verbunden. Mit Blick auf die zweite Hälfte des 19. Jahrhunderts verstehe ich das Aquarium als techno-natural (...) assemblage, in der Technologie, Kultur und Natur zu einem künstlichen Naturraum verbunden sind. Seine Geschichte beginnt in der britischen Amateurnaturkunde und der französischen Akklimatisierungsbewegung. Im Deutschland des späten 19. Jahrhunderts entwickelte sich das Aquarium zu einem Massenphänomen. Gleichzeitig hielt es Einzug in die Lebenswissenschaften, wo es als Einfallstor, Instrument und Umwelt Verwendung fand. Wie sich zeigt, ist das Aquarium eine hochgradig konstruierte Technologie, die sich aus einer Verbindung unterschiedlicher Traditionen herausgebildet und das Leben in die Lebenswissenschaften gebracht hat. (shrink)

I am grateful for Joshua Alexander and Jonathan Weinberg’s, Avner Baz’s and Max Deutsch’s insightful comments on Philosophy Within Its Proper Bounds. I have lea.

Building computational models of engineered exemplars, or prototypes, is a common practice in the bioengineering sciences. Computational models in this domain are often built in a patchwork fashion, drawing on data and bits of theory from many different domains, and in tandem with actual physical models, as the key objective is to engineer these prototypes of natural phenomena. Interestingly, such patchy model building, often combined with visualizations, whose format is open to a wide range of choice, leads to the discovery (...) of new concepts and control structures. Two key questions are raised by this practice: how could discoveries arise from building external representations for which there is wide latitude in choice of the components from which they are built, and thus can be considered significantly arbitrary, and how could such discoveries allow engineering a real-world prototype system. To examine these questions, we present two case studies of discoveries that emerged from the building of such computational models in the bioengineering sciences. We then develop a process model that accounts for the discovery and transfer problems raised by both these cases, focusing on the process of building the model. Specifically, to account for the discovery problem, we propose that the process of building such models gradually leads to a close coupling between the modeler’s internal processes and the external dynamic model. To account for the transfer problem, we propose that the process of building the model leads to the creation of an enactive model that is generic, which closely enacts, and thus reveals, the way the system-level behavior of the engineered prototype emerges in time through the interaction of its parts. This enactive replication process leads to the model and the prototype forming a new class, which allows concepts and control structures developed for the computational model to be transfered to the real-world prototype. We argue that this account requires rethinking correspondence in engineering sciences as a plastic and enactive relation. A closer focus on the process of building models is required to develop a general account of this emerging approach to discovery. (shrink)

Patient-derived xenografts are currently promoted as new translational models in precision oncology. PDXs are immunodeficient mice with human tumors that are used as surrogate models to represent specific types of cancer. By accounting for the genetic heterogeneity of cancer tumors, PDXs are hoped to provide more clinically relevant results in preclinical research. Further, in the function of so-called “mouse avatars”, PDXs are hoped to allow for patient-specific drug testing in real-time. This paper examines the circulation of knowledge and bodily material (...) across the species boundary of human and personalized mouse model, historically as well as in contemporary practices. PDXs raise interesting questions about the relation between animal model and human patient, and about the capacity of hybrid or interspecies models to close existing translational gaps. We highlight that the translational potential of PDXs not only depends on representational matching of model and target, but also on temporal alignment between model development and practical uses. Aside from the importance of ensuring temporal stability of human tumors in a murine body, the mouse avatar concept rests on the possibility of aligning the temporal horizons of the clinic and the lab. We examine strategies to address temporal challenges, including cryopreservation and biobanking, as well as attempts to speed up translation through modification and use of faster developing organisms. We discuss how featured model virtues change with precision oncology, and contend that temporality is a model feature that deserves more philosophical attention. (shrink)

Historians and philosophers of twentieth-century life sciences have demonstrated that the choice of experimental organism can profoundly influence research fields, in ways that sometimes undermined the scientists’ original intentions. The present paper aims to enrich and broaden the scope of this literature by analysing the career of unicellular green algae of the genus Chlorella. They were introduced for the study of photosynthesis in 1919 by the German cell physiologist Otto H. Warburg, and they became the favourite research objects in this (...) field up to the 1960s. The paper argues that dealing with Chlorella’s high metabolic flexibility was crucial for the emergence of a new conception of photosynthesis, as a plastic, integrated system of pathways. At the same time, it led to new collaborations between physiologists and phycologists, both of whom started to re-orient their studies in ecologically informed directions. Following Chlorella’s trail, hence, not only elucidates how experimental organisms forced scientists to change their conceptual approaches and techniques, but also provides insight into the interaction of different lines of research of mid-twentieth century plant sciences. (shrink)

Contemporary action theory is generally concerned with giving theories of action ontology. In this paper, we make the novel proposal that the standard view in action theory—the Causal Theory of Action—should be recast as a “model”, akin to the models constructed and investigated by scientists. Such models often consist in fictional, hypothetical, or idealized structures, which are used to represent a target system indirectly via some resemblance relation. We argue that recasting the Causal Theory as a model can not only (...) accomplish the goals of causal theorists, but also give the theory greater flexibility in responding to common objections. (shrink)

I propose an approach that expands philosophical views of scientific change, on the basis of an analysis of contemporary biomedical research and recent developments in the philosophy of scientific change. Focusing on the establishment of the exposome in epidemiology as a case study and the role of data as a context for contrasting views on change, I discuss change at conceptual, methodological, material, and social levels of biomedical epistemology. Available models of change provide key resources to discuss this type of (...) change, but I present the need for an approach that models transfer, alignment, and influence as key processes of change. I develop this as a pragmatic approach to scientific change, where processes might change substantially depending on specific circumstances, thus contributing to and complementing the debate on a crucial epistemological issue. (shrink)

A general view in philosophy of science says that the appropriateness of an object to act as a surrogate depends on the user’s decision to utilize it as such. This paper challenges this claim by examining the role of surrogative reasoning in high-throughput sequencing technologies as they are used in contemporary microbiome science. Drawing on this, we argue that, in technology-driven surrogates, knowledge about the type of inference practically permitted and epistemically justified by the surrogate constrains their use and thus (...) puts a limit to the user’s intentions to use any object as a surrogate for what they please. Ignoring this leads to a serious epistemic misalignment, which ultimately prevents surrogative reasoning. Thus, we conclude that knowledge about the type of surrogate reasoning that the technologies being used allow is fundamental to avoid misinterpreting the consequences of the data obtained with them, the hypothesis this data supports, and what these technologies are surrogates of. (shrink)

Philosophers use historical case studies to support wide-ranging claims about science. This practice is often criticized as problematic. In this paper we suggest that the function of case studies can be understood and justified by analogy to a well-established practice in biology: the investigation of model organisms. We argue that inferences based on case studies are no more problematic than inferences from model organisms to larger classes of organisms in biology. We demonstrate our view in detail by reference to a (...) case study with a long history: Semmelweis’s discovery of the cause of childbed fever. (shrink)

The 1981 Dahlem conference was a catalyst for contemporary evolutionary developmental biology (Evo-devo). This introductory chapter rehearses some of the details of the history surrounding the original conference and its associated edited volume, explicates the philosophical problem of conceptual change that provided the rationale for a workshop devoted to evaluating the epistemic revisions and transformations that occurred in the interim, explores conceptual change with respect to the concept of evolutionary novelty, and highlights some of the themes and patterns in the (...) different contributions to the present volume, Conceptual Change in Biology: Scientific and Philosophical Perspectives on Evolution and Development. (shrink)

Synthetic biology presents a challenge to traditional accounts of biology: Whereas traditional biology emphasizes the evolvability, variability, and heterogeneity of living organisms, synthetic biology envisions a future of homogeneous, humanly engineered biological systems that may be combined in modular fashion. The present paper approaches this challenge from the perspective of the epistemology of technoscience. In particular, it is argued that synthetic-biological artifacts lend themselves to an analysis in terms of what has been called ‘thing knowledge’. As such, they should neither (...) be regarded as the simple outcome of applying theoretical knowledge and engineering principles to specific technological problems, nor should they be treated as mere sources of new evidence in the general pursuit of scientific understanding. Instead, synthetic-biological artifacts should be viewed as partly autonomous research objects which, qua their material-biological constitution, embody knowledge about the natural world—knowledge that, in turn, can be accessed via continuous experimental interrogation. (shrink)

This paper responds to a recent challenge for the validity of extrapolation of neurobiological knowledge from laboratory animals to humans. According to this challenge, experimental neurobiology, and thus neuroscience, is in a state of crisis because the knowledge produced in different laboratories hardly generalizes from one laboratory to another. Presumably, this is so because neurobiological laboratories use simplified animal models of human conditions that differ across laboratories. By contrast, I argue that maintaining a multiplicity of experimental protocols and simple models (...) is well justified. It fosters rather than precludes the validity of extrapolation of neurobiological knowledge. The discipline is thriving. (shrink)

Model organisms became an indispensable part of experimental systems in molecular developmental and cell biology, constructed to investigate physiological and pathological processes. They are thought to play a crucial role for the elucidation of gene function, complementing the sequencing of the genomes of humans and other organisms. Accordingly, historians and philosophers paid considerable attention to various issues concerning this aspect of experimental biology. With respect to the representational features of model organisms, that is, their status as models, the main focus (...) was on generalization of phenomena investigated in such experimental systems. Model organisms have been said to be models for other organisms or a higher taxon. This, however, presupposes a representation of the phenomenon in question. I will argue that prior to generalization, model organisms allow researchers to built generative material models of phenomena – structures, processes or the mechanisms that explain them – through their integration in experimental set-ups that carve out the phenomena from the whole organism and thus represent them. I will use the history of zebrafish biology to show how model organism systems, from around 1970 on, were developed to construct material models of molecular mechanisms explaining developmental or physiological processes. (shrink)

Ankeny and Leonelli propose “repertoires” as a new way to understand the stability of certain research programs as well as scientific change in general. By bringing a more complete range of social, material, and epistemic elements into one framework, they position their work as a correction for the Kuhnian impulse in philosophy of science and other areas of science studies. I argue that this “post-Kuhnian” move is not complete, and that repertoires maintain an internalist perspective, caused partly by an asymmetrical (...) emphasis on the scientists’ side of practice. If we compare “repertoires” to alternative frameworks, like “sociotechnical imaginaries” of Jasanoff and Kim, it is evident that repertoires are missing two specific things. First, I argue that the framework needs to include the role of audience, without whom the repertoires of science are unintelligible. Second, I suggest that the framework also lacks an explicit place for ethical and political imagination, which provide meaning for otherwise mechanical promotion of particular research programs. With these modifications, Ankeny and Leonelli’s framework might fulfill its post-Kuhnian potential. (shrink)

This paper attempts to reconcile the conceptual conflict between typological and population thinking to provide a philosophical foundation for extended evolutionary synthesis. Typological thinking has been considered a pre-Darwinian, essentialist dogma incompatible with population thinking, which is the core notion of Darwinism. More recent philosophical and historical studies suggest that a non-essentialist form of typology has some advantages in the study of evolutionary biology. However, even if we adopt such an epistemological interpretation of typological thinking, there still remains an epistemological (...) and methodological conflict between these two styles of thinking. How can we relate typological thinking with population thinking in pursuit of more integrated or interconnected research into evolutionary biology? I propose that homology thinking, which is another style of thinking that recognizes homologous characters, provides a common basis for typological representations of character states and for character dynamics in an evolving population. Good examples of this bridging role are found in teratology and breeding, where variation and novelty are recognized in developmental and morphological traits, gene expression patterns, and so on. Essentialism-free, dynamic views of homology have great potential to reconcile typological and population thinking and to set the stage for the EES. (shrink)

in a nervous system of a given species. This chapter provides a critical perspective on the role of connectomes in neuroscientific practice and asks how the connectomic approach fits into a larger context in which network thinking permeates technology, infrastructure, social life, and the economy. In the first part of this chapter, we argue that, seen from the perspective of ongoing research, the notion of connectomes as “complete descriptions” is misguided. Our argument combines Rachel Ankeny’s analysis of neuroanatomical wiring diagrams (...) as “descriptive models” with Hans-Joerg Rheinberger’s notion of “epistemic objects,” i.e., targets of research that are still partially unknown. Combining these aspects we conclude that connectomes are constitutively epistemic objects: there just is no way to turn them into permanent and complete technical standards because the possibilities to map connection properties under different modeling assumptions are potentially inexhaustible. In the second part of the chapter, we use this understanding of connectomes as constitutively epistemic objects in order to critically assess the historical and political dimensions of current neuroscientific research. We argue that connectomics shows how the notion of the “brain as a network” has become the dominant metaphor of contemporary brain research. We further point out that this metaphor shares (potentially problematic) affinities to the form of contemporary “network societies.” We close by pointing out how the relation between connectomes and networks in society could be used in a more fruitful manner. (shrink)

Microbial model systems have a long history of fruitful use in fields that include evolution and ecology. In order to develop further insight into modelling practice, we examine how the competitive exclusion and coexistence of competing species have been modelled mathematically and materially over the course of a long research history. In particular, we investigate how microbial models of these dynamics interact with mathematical or computational models of the same phenomena. Our cases illuminate the ways in which microbial systems and (...) equations work as models, and what happens when they generate inconsistent findings about shared targets. We reveal an iterative strategy of comparative modelling in different media, and suggest reasons why microbial models have a special degree of epistemic tractability in multimodel inquiry. (shrink)