This paper is devoted to an examination of the discovery, characterization, and analysis of the functions of microRNAs, which also serves as a vehicle for demonstrating the importance of exploratory experimentation in current (post-genomic) molecular biology. The material on microRNAs is important in its own right: it provides important insight into the extreme complexity of regulatory networks involving components made of DNA, RNA, and protein. These networks play a central role in regulating development of multicellular organisms and illustrate the importance (...) of epigenetic as well as genetic systems in evolution and development. The examination of these matters yields principled arguments for the historicity of the functions of key biological molecules and for the indispensability of exploratory experimentation in contemporary molecular biology as well as some insight into the complex interplay between exploratory experimentation and hypothesis-driven science. This latter result is not only important for philosophy of science, but also of practical importance for the evaluation of grant proposals, although the elaboration of this latter claim must be left for another occasion. (shrink)

Exploratory experiments are widely characterized as experiments that do not test hypotheses. Experiments that do test hypotheses are characterized as confirmatory experiments. Philosophers have pointed out that research programmes can be both confirmatory and exploratory. However, these definitions preclude single experiments being characterized as both exploratory and confirmatory; how can an experiment test and not test a hypothesis? Given the intuition that some experiments are exploratory, some are confirmatory, and some are both, a recharacterization of the relationship between exploratory and (...) confirmatory experimentation is needed. I discuss ‘phase IV’ trials to show what this recharacterization could look like. Phase IV trials can be exploratory and confirmatory insofar as they concurrently test hypotheses and explore for unforeseen phenomena. Even if it is uncontroversial that a single experiment can have multiple aims, the recharacterization of the relationship between exploratory and confirmatory experimentation is still required for these aims to be held together coherently. I offer an alternative characterization of the relationship between exploratory and confirmatory experimentation where the former remains a distinct kind of experimentation but is not characterized as non-hypothesis-testing. (shrink)

Philosophers of science diverge on the question what drives the growth of scientific knowledge. Most of the twentieth century was dominated by the notion that theories propel that growth whereas experiments play secondary roles of operating within the theoretical framework or testing theoretical predictions. New experimentalism, a school of thought pioneered by Ian Hacking in the early 1980s, challenged this view by arguing that theory-free exploratory experimentation may in many cases effectively probe nature and potentially spawn higher evidence-based theories. Because (...) theories are often powerless to envisage workings of complex biological systems, theory-independent experimentation is common in the life sciences. Some such experiments are triggered by compelling observation, others are prompted by innovative techniques or instruments, whereas different investigations query big data to identify regularities and underlying organizing principles. A distinct fourth type of experiments is motivated by a major question. Here I describe two question-guided experimental discoveries in biochemistry: the cyclic adenosine monophosphate mediator of hormone action and the ubiquitin-mediated system of protein degradation. Lacking underlying theories, antecedent data bases, or new techniques, the sole guides of the two discoveries were respective substantial questions. Both research projects were similarly instigated by theory-free exploratory experimentation and continued in alternating phases of results-based interim working hypotheses, their examination by experiment, provisional hypotheses again, and so on. These two cases designate theory-free, question-guided, stepwise biochemical investigations as a distinct subtype of the new experimentalism mode of scientific enquiry. (shrink)

Whether we live in a world of autonomous things, or a world of interconnected processes in constant flux, is an ancient philosophical debate. Modern biology provides decisive reasons for embracing the latter view. How does one understand the practices and outputs of science in such a dynamic, ever-changing world - and particularly in an emergency situation such as the COVID-19 pandemic, where scientific knowledge has been regarded as bedrock for decisive social interventions? We argue that key to answering this question (...) is to consider the role of the activity of reification within the research process. Reification consists in the identification of more or less stable features of the flux, and treating these as constituting stable things. As we illustrate with reference to biological and biomedical research on COVID-19, reification is a necessary component of any process of inquiry and comes in at least two forms: means reification, when researchers create objects meant to capture features of the world, or phenomena, in order to be able to study them; and target reification, when researchers infer an understanding of phenomena from an investigation of the epistemic objects created to study them. We note that both objects and phenomena are dynamic processes and argue that have no reason to assume that changes in objects and phenomena track one another. We conclude that failure to acknowledge these forms of reification and their epistemic role in scientific inquiry can have dire consequences for how the resulting knowledge is interpreted and used. (shrink)

Discussions of reproducibility are casting doubts on the credibility of experimental outcomes in the life sciences. Although experimental evolution is not typically included in these discussions, this field is also subject to low reproducibility, partly because of the inherent contingencies affecting the evolutionary process. A received view in experimental studies more generally is that standardization (i.e., rigorous homogenization of experimental conditions) is a solution to some issues of significance and internal validity. However, this solution hides several difficulties, including a reduction (...) of external validity and reproducibility. After explaining the meaning of these two notions in the context of experimental evolution, we import from the fields of animal research and ecology and suggests that systematic heterogenization of experimental factors could prove a promising alternative. We also incorporate into our analysis some philosophical reflections on the nature and diversity of research objectives in experimental evolution. (shrink)

To explain their role in discovery and contrast them with theory-driven research, philosophers of science have characterized exploratory experiments in terms of what they lack: namely, that they lack direction from what have been called “local theories” of the target system or object under investigation. I argue that this is incorrect: it’s not whether or not there is direction from a local theory that matters, but instead how such a theory is used to direct an experiment that matters. Appealing to (...) contemporary exploratory experiments that involve the use of experimental techniques—specifically, examples where scientists explore the interaction of neural activity and human behavior by magnetically stimulating brains—I argue that local theories of a target system can inform auxiliary hypotheses in exploratory experiments, which direct these experiments. These examples illustrate how local theories can direct the exploration of target systems where researchers do not aim to evaluate these theories. (shrink)

Observation and experiment as categories for analysing scientific practice have a long pedigree in writings on science. There has, however, been little attempt to delineate observation and experiment with respect to analysing scientific practice; in particular, scientific experimentation, in a systematic manner. Someone who has presented a systematic account of observation and experiment as categories for analysing scientific experimentation is Ian Hacking. In this paper, I present a detailed analysis of Hacking’s observation versus experiment account. Using a range of cases (...) from various fields of scientific enquiry, I argue that the observation versus experiment account is not an adequate framework for delineating scientific experimentation in a systematic manner. (shrink)

1. Overview and organizing themes 2. Historical Review: Aristotle to Mill 3. Logic of method and critical responses 3.1 Logical constructionism and Operationalism 3.2. H-D as a logic of confirmation 3.3. Popper and falsificationism 3.4 Meta-methodology and the end of method 4. Statistical methods for hypothesis testing 5. Method in Practice 5.1 Creative and exploratory practices 5.2 Computer methods and the ‘third way’ of doing science 6. Discourse on scientific method 6.1 “The scientific method” in science education and as seen (...) by scientists 6.2 Privileged methods and ‘gold standards’ 6.3 Scientific method in the court room 6.4 Deviating practices 7. Conclusion Bibliography Academic Tools Other Internet Resources Related Entries . (shrink)

Recently, biologists have argued that data - driven biology fosters a new scientific methodology; namely, one that is irreducible to traditional methodologies of molecular biology defined as the discovery strategies elucidated by mechanistic philosophy. Here I show how data - driven studies can be included into the traditional mechanistic approach in two respects. On the one hand, some studies provide eliminative inferential procedures to prioritize and develop mechanistic hypotheses. On the other, different studies play an exploratory role in providing useful (...) generalizations to complement the procedure of prioritization. Overall this paper aims to shed light on the structure of contemporary research in molecular biology. (shrink)

This paper aims to identify the key characteristics of model organisms that make them a specific type of model within the contemporary life sciences: in particular, we argue that the term “model organism” does not apply to all organisms used for the purposes of experimental research. We explore the differences between experimental and model organisms in terms of their material and epistemic features, and argue that it is essential to distinguish between their representational scope and representational target. We also examine (...) the characteristics of the communities who use these two types of models, including their research goals, disciplinary affiliations, and preferred practices to show how these have contributed to the conceptualization of a model organism. We conclude that model organisms are a specific subgroup of organisms that have been standardized to fit an integrative and comparative mode of research, and that it must be clearly distinguished from the broader class of experimental organisms. In addition, we argue that model organisms are the key components of a unique and distinctively biological way of doing research using models.Keywords: Experimental organism; Genetics; Model organism; Modeling; Philosophy of biology; Representation. (shrink)

This chapter offers a review of standard views about the requirements for natural selection to shape evolution and for the sorts of ‘units’ on which selection might operate. It then summarizes traditional arguments for genic selectionism, i.e., the view that selection operates primarily on genes (e.g., those of G. C. Williams, Richard Dawkins, and David Hull) and traditional counterarguments (e.g., those of William Wimsatt, Richard Lewontin, and Elliott Sober, and a diffuse group based on life history strategies). It then offers (...) a series of responses to the arguments, based on more contemporary considerations from molecular genetics, offered by Carmen Sapienza. A key issue raised by Sapienza concerns the degree to which a small number of genes might be able to control much of the variation relevant to selection operating on such selectively critical organs as hearts. The response to these arguments suggests that selection acts on many levels at once and that sporadic selection, acting with strong effects, can act successively on different key traits (and genes) while maintaining a balance among many potentially conflicting demands faced by organisms within an evolving lineage. (shrink)

Farmers all over the world perform experiments, and have done so since long before modern experimental science and its recognized forerunners. There is a rich anthropological literature on these experiments, but the philosophical issues that they give rise to have not received much attention. Based on the anthropological literature, this study investigates methodological and philosophical issues pertaining to farmers’ experiments, including the choice of interventions to be tested, the planning of experiments, and the use of control fields and other means (...) to deal with confounding factors. Farmers’ experiments have some advantages over the field trials of agricultural scientists, but also some comparative disadvantages. The two experimental traditions are complementary, and neither of them can replace the other. Several aspects of farmers’ experiments are shown to have a direct bearing on central topics in the philosophy of science. (shrink)

I propose a framework that explicates and distinguishes the epistemic roles of data and models within empirical inquiry through consideration of their use in scientific practice. After arguing that Suppes’ characterization of data models falls short in this respect, I discuss a case of data processing within exploratory research in plant phenotyping and use it to highlight the difference between practices aimed to make data usable as evidence and practices aimed to use data to represent a specific phenomenon. I then (...) argue that whether a set of objects functions as data or models does not depend on intrinsic differences in their physical properties, level of abstraction or the degree of human intervention involved in generating them, but rather on their distinctive roles towards identifying and characterizing the targets of investigation. The paper thus proposes a characterization of data models that builds on Suppes’ attention to data practices, without however needing to posit a fixed hierarchy of data and models or a highly exclusionary definition of data models as statistical constructs. (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)

“Ancient DNA Research” is the practice of extracting, sequencing, and analyzing degraded DNA from dead organisms that are hundreds to thousands of years old. Today, many researchers are interested in adapting state-of-the-art molecular biological techniques and high-throughput sequencing technologies to optimize the recovery of DNA from fossils, then use it for studying evolutionary history. However, the recovery of DNA from fossils has also fueled the idea of resurrecting extinct species, especially as its emergence corresponded with the book and movie Jurassic (...) Park in the 1990s. In this paper, I use historical material, interviews with scientists, and philosophical literature to argue that the search for DNA from fossils can be characterized as a data-driven and celebrity-driven practice. Philosophers have recently argued the need to seriously consider the role of data-driven inquiry in the sciences, and likewise, this history highlights the need to seriously consider the role of celebrity in shaping the kind of research that gets pursued, funded, and ultimately completed. On this point, this history highlights that the traditional philosophical and scientific distinctions between data-driven and hypothesis-driven research are not always useful for understanding the process and practice of science. Consequently, I argue that the celebrity status of a particular research practice can be considered as a “serious epistemic strategy” that researchers, as well as editors and funders, employ when making choices about their research and publication processes. This interplay between celebrity and methodology matters for the epistemology of science. (shrink)

The life sciences are said to be in the midst of a replication crisis because a majority of published results are irreproducible, and scientists rarely replicate existing data. Here I argue that point 2 of this assessment is flawed because there is a hitherto unidentified form of replication in the experimental life sciences, which I call ‘microreplications’. Using a case study from biochemistry, I illustrate how MRs depend on a key element of experimentation, namely, experimental controls. I end by reflecting (...) on what MRs mean for the broader debate about the replication crisis. (shrink)

. Early microbiome research found numerous associations between microbial community patterns and host physiological states. These findings hinted at community-level explanations. “Top-down” experiments, working with whole communities, strengthened these explanatory expectations. Now, “bottom-up” mechanism-seeking approaches are dissecting communities to focus on specific microbes carrying out particular biochemical activities. To understand the interplay between methodological and explanatory scales, we examine claims of “dysbiosis,” when host illness is proposed as the consequence of a community state. Our analysis concludes with general observations about (...) how methodologies relate to explanations, and the implications for microbiome research. (shrink)

ArgumentIn the theory-dominated view of scientific experimentation, all relations of theory and experiment are taken on a par; namely, that experiments are performed solely to ascertain the conclusions of scientific theories. As a result, different aspects of experimentation and of the relations of theory to experiment remain undifferentiated. This in turn fosters a notion of theory-ladenness of experimentation (TLE) that is toocoarse-grainedto accurately describe the relations of theory and experiment in scientific practice. By contrast, in this article, I suggest that (...) TLE should be understood as anumbrella conceptthat has different senses. To this end, I introduce a three-fold distinction among the theories of high-energy particle physics (HEP) as background theories, model theories, and phenomenological models. Drawing on this categorization, I contrast two types of experimentation, namely, “theory-driven” and “exploratory” experiments, and I distinguish between the “weak” and “strong” senses of TLE in the context of scattering experiments from the history of HEP. This distinction enables identifying the exploratory character of the deep-inelastic electron-proton scattering experiments – performed at the Stanford Linear Accelerator Center (SLAC) between the years 1967 and 1973 – thereby shedding light on a crucial phase of the history of HEP, namely, the discovery of “scaling,” which was the decisive step towards the construction of quantum chromo-dynamics as a gauge theory of strong interactions. (shrink)

Exploratory inquiry has difficulty attracting research funding because funding agencies have little sense of how to detect good science in exploratory contexts. After documenting and explaining the focus on hypothesis testing among a variety of institutions responsible for distinguishing between good and bad science, I analyze the NIH grant review process. I argue that a good explanation for the focus on hypothesis testing—at least at the level of science funding agencies—is the fact that hypothesis-driven research is relatively easy to appraise. (...) I then explore one method by which we might gauge the epistemic merits of different styles of inquiry. (shrink)

My aim in this article is to introduce readers to the topic of exploratory experimentation and briefly explain how the three articles that follow, by Richard Burian, Kevin Elliott, and Maureen O'Malley, advance our understanding of the nature and significance of exploratory research. I suggest that the distinction between exploratory and theory-driven experimentation is multidimensional and that some of the dimensions are continuums. I point out that exploratory experiments are typically theory-informed even if they are not theory-driven. I also distinguish (...) between research programs and experiments. Research programs that are largely exploratory, such as the ones discussed in these case studies, can involve both exploratory and theory-driven experimentation. (shrink)

The experimental practice in contemporary molecular biology oscillates between the creativity of the researcher in tinkering with the experimental system, and the necessity of standardization of methods of inquiry. Experimental procedures, when standardized in lab protocols, might definitely be seen as actual recipes. Considering these protocols as recipes can help us understand some epistemological characteristics of current practice in molecular biology. On the one hand, protocols represent a common ground, i.e. the possibility of reproducibility, which constitutes one of the essential (...) properties for contemporary science to define an actual discovery. At the same time, however, protocols are flexible enough to be adapted by the individual researcher (within a space of maneuver given by the experimental system and by the practices that each individual discipline gives to itself) to his/her specific needs. These variations, just like the recipes, remind us that the legitimacy of an experimental practice, involves both objective and subjective constraints and it is articulated on a fuzzy background rather than a rigid and clear context. Moreover, looking at experiments according to this perspective can provide a key to understanding how different forms of science (which adopt different methodologies but which investigate the same phenomena), such as computational biology, are precisely different in the use of a different “cookbook”.Indeed, given the procedural/operational realism of biologists towards phenomena, the clash of different procedures has opened a discussion also about the nature and the meaning of the obtained results. Thus, according to the recipe-perspective that, the methodological struggle over the nature of biological phenomena (and their ways of discovery) among scientists, might be seen as a not always explicit, epistemological debate, however coming from the practice of science itself. (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)

Along three measurements at the Large Hadron Collider (LHC), a high energy particle accelerator, we analyze procedures and consequences of exploratory experimentation (EE). While all of these measurements fulfill the requirements of EE: probing new parameter spaces, being void of a target theory and applying a broad range of experimental methods, we identify epistemic differences and suggest a classification of EE. We distinguish classes of EE according to their respective goals: the exploration where an established global theory cannot provide the (...) details of a local phenomenon, exploration of an astonishing discovery and exploration to find a new entity. We find that these classes also differ with respect to the existence of an identifiable target and their impact on the background theory. The characteristics distinguish EE from other kinds of experimentation, even though these different kinds have not yet been systematically studied. The formal rigor and precision of LHC physics facilitates to analyze concept formation in its early state. In particular we emphasize the importance for nil–results for conceptualization and argue that conceptualization can also be achieved from nil–results only. (shrink)

Driven by an appreciation of the field’s early stage of development, I apply the concept of exploratory experimentation, originally put forward in the late 90s philosophy of biology, to current research in cognitive neuroscience. I concentrate on functional magnetic resonance imaging and how this wide-spread technique is used, from experimental design to data analysis. I claim that, although subject to certain significant modifications with respect to the concept’s original rendering, the exploratory character of neuroimaging experiments can be appreciated considering their (...) goals, centered on the stabilization of experimental systems for phenomenological description, and the relevance of their methodological facet. Although I do not claim that there is a specific kind of experiment that one can single out as definitely exploratory, exploration can be seen as a general trait imbuing fMRI-based experimentation. (shrink)

The discovery and ongoing investigation of microRNAs suggest important conceptual and methodological lessons for philosophers and historians of biology. This paper provides an account of miRNA research and the shift from viewing these tiny regulatory entities as minor curiosities to seeing them as major players in the post-transcriptional regulation of genes. Conceptually, the study of miRNAs is part of a broader change in understandings of genetic regulation, in which simple switch-like mechanisms were reinterpreted as aspects of complex cellular and genome-wide (...) processes. Among them are the activities of small RNAs, previously regarded as non-functional. Methodologically, the miRNA story suggests new ways of characterizing biological research that should prove helpful to philosophers of science who seek to develop more pluralistic, pragmatic models of scientific inquiry. miRNA research displays iterative movements between multiple modes of investigation that include not only the proposal and testing of hypotheses but also exploratory, technology-oriented and question-driven modes of research. As an exemplary story of scientific discovery and development, the miRNA case illustrates transitions from genetics to genomics and systems biology, and it shows how diverse configurations of research practice are related to major scientific advances. (shrink)

We employ a pragmatic model of inquiry to distinguish the epistemological character of exploratory experimentation. Exploratory experimentation is not constituted by any intrinsic characteristics of an episode of experimentation but depends on the context and aims of the experiment and the ways in which these shape decisions about how the experimental inquiry is to be conducted: its tasks, resources, and aims, as well as the critical assessment of all of these. To demonstrate the usefulness of our pragmatist model, we apply (...) it to the contrast between two kinds of searches for new physics at the Large Hadron Collider. Some searches are exploratory while others target specific Beyond Standard Model hypotheses, but this contrast can be understood only by considering the relations between these searches, their aims, and the way that these aims shape their respective experimental parameters and procedures. Our approach provides a model for establishing the epistemological significance of details of experimental practice. (shrink)