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)

Philosophers of experiment have acknowledged that experiments are often more than mere hypothesis-tests, once thought to be an experiment's exclusive calling. Drawing on examples from contemporary biology, I make an additional amendment to our understanding of experiment by examining the way that `wide' instrumentation can, for reasons of efficiency, lead scientists away from traditional hypothesis-directed methods of experimentation and towards exploratory methods.

Starting with some illustrative examples, I develop a systematic account of a specific type of experimentation--an experimentation which is not, as in the "standard view", driven by specific theories. It is typically practiced in periods in which no theory or--even more fundamentally--no conceptual framework is readily available. I call it exploratory experimentation and I explicate its systematic guidelines. From the historical examples I argue furthermore that exploratory experimentation may have an immense, but hitherto widely neglected, epistemic significance.

This paper argues, first, that recent studies of experimentation, most notably by Deborah Mayo, provide the conceptual resources to describe scientific discovery's early stages as error-probing processes. Second, it shows that this description yields greater understanding of those early stages, including the challenges that they pose, the research strategies associated with them, and their influence on the rest of the discovery process. Throughout, the paper examines the phenomenon of "chemical hormesis" (i.e., anomalous low-dose effects from toxic chemicals) as a case (...) study that is important not only for the biological sciences but also for contemporary public policy. The resulting analysis is significant for at least two reasons. First, by elucidating the importance of discovery's earliest stages, it expands previous accounts by philosophers such as William Wimsatt and Lindley Darden. Second, it identifies the discovery process as yet another philosophical topic on which the detailed studies of the "new experimentalists" can shed new light. (shrink)

: The increasing attention on experiment in the last two decades has led to important insights into its material, cultural and social dimensions. However, the role of experiment as a tool for generating knowledge has been comparatively poorly studied. What questions are asked in experimental research? How are they treated and eventually resolved? And how do questions, epistemic situations, and experimental activity cohere and shape each other? In my paper, I treat these problems on the basis of detailed studies of (...) research practice. After presenting several cases from the history of electricity—Dufay, Ampère, and Faraday—I discuss a specific type of experiment—the "exploratory experiment"—and analyze how it works in concept formation. I argue that a fuller understanding of experiment can only be achieved by intertwining historical and philosophical perspectives in such a way that the very separation of the two become questioable. (shrink)

It is considered in some quarters that hypothesis‐driven methods are the only valuable, reliable or significant means of scientific advance. Data‐driven or ‘inductive’ advances in scientific knowledge are then seen as marginal, irrelevant, insecure or wrong‐headed, while the development of technology—which is not of itself ‘hypothesis‐led’ (beyond the recognition that such tools might be of value)—must be seen as equally irrelevant to the hypothetico‐deductive scientific agenda. We argue here that data‐ and technology‐driven programmes are not alternatives to hypothesis‐led studies in (...) scientific knowledge discovery but are complementary and iterative partners with them. Many fields are data‐rich but hypothesis‐poor. Here, computational methods of data analysis, which may be automated, provide the means of generating novel hypotheses, especially in the post‐genomic era. BioEssays 26:99–105, 2004. © 2003 Wiley Periodicals, Inc. (shrink)

There has been relatively little effort to provide a systematic overview of different forms of exploratory experimentation (EE). The present paper examines the growing subdiscipline of nanotoxicology and suggests that it illustrates at least four ways that researchers can engage in EE: searching for regularities; developing new techniques, simulation models, and instrumentation; collecting and analyzing large swaths of data using new experimental strategies (e.g., computer-based simulation and "high-throughput" instrumentation); and structuring an entire disciplinary field around exploratory research agendas. In order (...) to distinguish these and other activities more effectively, the paper proposes a taxonomy that includes three dimensions along which types of EE vary: (1) the aim of the experimental activity, (2) the role of theory in the activity, and (3) the methods or strategies employed for varying experimental parameters. (shrink)