Is knowledge in the natural sciences discovered or constructed? For objectivists, scientific knowledge is discovered through investigations into a mind-independent, natural world. For constructivists, such knowledge is produced through negotiations among members of a professional guild. I examine the clash between the two positions and propose that scientific knowledge is the concurrent outcome from investigations into a natural world and from consensus reached through negotiations of a professional guild. Specifically, I introduce the general methodological notion, instituting science, which incorporates both (...) the discovery and the construction processes in the generation of scientific knowledge. To that end, I use a case study from the biomedical sciences to illustrate the notion. I conclude with a discussion of how this methodological notion helps to address the debate between objectivists and constructivists over the generation of scientific knowledge, and of how it compares with others who have also attempted to address the debate. (shrink)

In this article, I introduce the notion of horizon for scientific practice (HSP), representing limits or boundaries within which scientists ply their trade, to facilitate analysis of scientific discovery and progress. The notion includes not only constraints that delimit scientific practice, e.g. of bringing experimentation to a temporary conclusion, but also possibilities that open up scientific practice to additional scientific discovery and to further scientific progress. Importantly, it represents scientific practice as a dynamic and developmental integration of activities to investigate (...) and analyze the natural world. I use the discovery of the clotting factor, thrombin, and the experiments conducted by the Johns Hopkins physiologist, William Howell, on the enzymatic nature of thrombin to illustrate the notion of HSP. In a concluding section, I compare the notion of HSP to other notions for scientific practice proposed in the history and philosophy of science literature. (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)

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)

During the 1960s, Howard M. Temin (1934-1994), dared to advocate a "heretical" hypothesis that appeared to be at variance with the central dogma of molecular biology, understood by many to imply that information transfer in nature occurred only from DNA to RNA. Temin's provirus hypothesis offered a simple explanation of both virus replication and viral-induced cancer and stated that Rous sarcoma virus, an RNA virus, is replicated via a DNA intermediate. Popular accounts of this scientific episode, written after the discovery (...) of an RNA-directed DNA polymerase in 1970, tend to describe the reaction to his proposition as ardent opposition. Typically these accounts use a 'molecular biology' standpoint emphasizing the central dogma's part in its rejection. In this article, however, this episode will be examined from a joint perspective of virology and experimental cancer research. From this perspective it is clear that Temin's work was well within the epistemological and methodological boundaries of virology and cancer research. Still, scientists did have reasons to doubt the provirus hypothesis, but these do not seem to be good enough to either justify an account that portrays Temin as a renegade or his ideas as heretical. (shrink)

Stem cell biology is driven by experiment. Its major achievements are striking experimental productions: "immortal" human cell lines from spare embryos (Thomson et al. 1998); embryo-like cells from "reprogrammed" adult skin cells (Takahashi and Yamanaka 2006); muscle, blood and nerve tissue generated from stem cells in culture (Lanza et al. 2009, and references therein). Well-confirmed theories are not so prominent, though stem cell biologists do propose and test hypotheses at a profligate rate. 1 This paper aims to characterize the role (...) of experiment in stem cell biology, so as to answer the following question: how do experiments contribute to our knowledge of stem cells and related phenomena? The .. (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)