In the 1950s–60s biochemists searched intensively for a series of high-energy molecules in the cell. Although we now believe that these molecules do not exist, biochemists claimed to have isolated or identified them on at least sixteen occasions. The episode parallels the familiar eighteenth-century case of phlogiston, in illustrating how error is not simply the loss of facts but, instead, must be actively constructed. In addition, the debates surrounding each case demonstrate how revolutionary-scale disagreement is sometimes resolved by differentiating or (...) partitioning empirical domains, rather than by replacement of one theory by another. (shrink)

Philosophers have committed sins while studying science, it is said – philosophy of science focused on physics to the detriment of biology, reconstructed idealizations of scientific episodes rather than attending to historical details, and focused on theories and concepts to the detriment of experiments. Recent generations of philosophers of science have tried to atone for these sins, and by the 1980s the exculpation was in full swing. Marcel Weber’s Philosophy of Experimental Biology is a zenith mea culpa for philosophy of (...) science: it carefully describes several historical examples from twentieth century biology to address both ‘old’ philosophical topics, like reductionism, inference, and realism, and ‘new’ topics, like discovery, models, and norms. Biology, experiments, history – at last, philosophy of science, free of sin. (shrink)

A biochemical pathway is a sequence of chemical reactions in a biological organism. Such pathways specify mechanisms that explain how cells carry out their major functions by means of molecules and reactions that produce regular changes. Many diseases can be explained by defects in pathways, and new treatments often involve finding drugs that correct those defects. This paper presents explanation schemas and treatment strategies that characterize how thinking about pathways contributes to biomedical discovery. It discusses the significance of pathways for (...) understanding the nature of diseases, explanations, and theories. (shrink)

It is often claimed that there can be no such thing as a logic of scientific discovery, but only a logic of verification. By 'logic of discovery' is usually meant a normative theory of discovery processes. The claim that such a normative theory is impossible is shown to be incorrect; and two examples are provided of domains where formal processes of varying efficacy for discovering lawfulness can be constructed and compared. The analysis shows how one can treat operationally and formally (...) phenomena that have usually been dismissed with fuzzy labels like 'intuition' and 'creativity'. (shrink)

Semmelweis’s discovery of the cause of puerperal fever around the middle of the 19th century counts among the paradigm cases of scientific discovery. For several decades, philosophers of science have used the episode to illustrate, appraise and compare views of proper scientific methodology.Here I argue that the episode can be profitably reexamined in light of two cognate notions: causal reasoning and mechanisms. Semmelweis used several causal reasoning strategies both to support his own and to reject competing hypotheses. However, these strategies (...) have gone unappreciated in the existing literature. I show that a causal reasoning approach makes sense of the multitude of tables in Semmelweis’s main text, which in later editions were often abridged because they appeared redundant.Moreover, the existing literature tends to focus on Semmelweis’s clinical intervention and on the extent to which it alone confirms his theoretical conclusions. This neglects Semmelweis’s efforts to show by animal experiments that his clinical results are in agreement with a demonstrable mechanism of puerperal fever pathogenesis. I argue that the full evidential force of Semmelweis’s argument can only be appreciated if both his clinical and his laboratory investigations are taken into account. (shrink)

Mitchell's formulation of the chemiosmotic theory of oxidative phosphorylation in 1961 lacked any experimental support for its three central postulates. The path by which Mitchell reached this theory is explored. A major factor was the role of Mitchell's philosophical system conceived in his student days at Cambridge. This system appears to have become a tacit influence on his work in the sense that Polanyi understood all knowledge to be generated by an interaction between tacit and explicit knowing. Early in his (...) life Mitchell had evolved a simple philosophy based on fluctoids, fluctids and statids which was developed in a thesis submitted for the Ph.D. at the University of Cambridge, England. This aspect of his work was rejected by the examiners and became a tacit element in his intellectual development. It is argued from his various publications that this philosophy can be traced as an underlying theme behind much of Mitchell's theoretical writing in the 50's leading, through his notion of vectorial metabolism, to the formulation and amplification of the chemiosmotic theory in the sixties. This philosophy formed the basis for Mitchell of his understanding of biological systems and gave him his unique approach to cell biology. (shrink)

The origins of oxidative phosphorylation, initially known as aerobic phosphorylation, grew out of three research areas of muscle metabolism, creatine phosphorylation, aerobic metabolism of lactic acid in muscle, and studies on the nature and role of adenosine triphosphate . Much of this work centred round the laboratory of Otto Meyerhof, and most of those contributing to the study of aerobic phosphorylation were influenced by that laboratory: particularly Lipmann and also Ochoa. The work of Engelhardt on ATP levels in blood also (...) appears to have been influenced by the studies of Meyerhof’s laboratory. However, with the work of Kalckar, influenced by Lipmann, biochemists began to realise the potential importance of the process. This was confirmed and extended by Belitzer and Ochoa and the theoretical contribution of Lipmann. Thus it is not easy to identify a single point that marked the initiation of studies in this field.The early work was based on the use of tissue homogenates and cells but ultimately this approach limited research possibilities. The development of techniques based on mitochondria opened up new possibilities and brought this first phase of the study of oxidative phorphorylation to a close. (shrink)

Historians of biology have argued that much of the dynamics of experimental disciplines such as genetics or molecular biology can be understood from studying experimental systems and model organisms alone . Such accounts contrast sharply with more traditional philosophies of science which viewed scientific research essentially as a process of inventing and testing theories. I present a case from the history of biochemistry which can be viewed from both the experimental systems perspective and from the methodology of theory testing. I (...) argue that not only are the two perspectives fully compatible, but they are both necessary for a complete account of the research process. (shrink)

The concept of mechanism is analyzed in terms of entities and activities, organized such that they are productive of regular changes. Examples show how mechanisms work in neurobiology and molecular biology. Thinking in terms of mechanisms provides a new framework for addressing many traditional philosophical issues: causality, laws, explanation, reduction, and scientific change.

Proponents of mechanistic explanation all acknowledge the importance of organization. But they have also tended to emphasize specificity with respect to parts and operations in mechanisms. We argue that in understanding one important mode of organization—patterns of causal connectivity—a successful explanatory strategy abstracts from the specifics of the mechanism and invokes tools such as those of graph theory to explain how mechanisms with a particular mode of connectivity will behave. We discuss the connection between organization, abstraction, and mechanistic explanation and (...) illustrate our claims by looking at an example from recent research on so-called network motifs. (shrink)

In the years 1919 to 1923, Otto Warburg published four papers that were to revolutionise the field of photosynthesis. In these articles, he introduced a number of new techniques to measure the rate of photosynthesis, put forward a new model of the mechanism and added a completely new perspective to the topic by attempting to establish the process’s efficiency in terms of the light quantum requirement. In this paper I trace the roots of Warburg’s series of contributions to photosynthesis research (...) by exploring three different contexts of inspiration: Warburg’s own research into cell respiration, his father’s work on the quantum yield of photochemical reactions in general and the photosynthesis work carried out by Richard Willstätter and Arthur Stoll. When these influences are considered together, it becomes clear that Warburg implemented a Building Block Strategy in his research: rather than inventing his photosynthesis model from scratch, he availed himself of fragments from other contexts, which he then recombined in a new and innovative way. This way of working is considered to be standard practice in scientific research. (shrink)

How do novel scientific concepts arise? In Creating Scientific Concepts, Nancy Nersessian seeks to answer this central but virtually unasked question in the problem of conceptual change. She argues that the popular image of novel concepts and profound insight bursting forth in a blinding flash of inspiration is mistaken. Instead, novel concepts are shown to arise out of the interplay of three factors: an attempt to solve specific problems; the use of conceptual, analytical, and material resources provided by the cognitive-social-cultural (...) context of the problem; and dynamic processes of reasoning that extend ordinary cognition. Focusing on the third factor, Nersessian draws on cognitive science research and historical accounts of scientific practices to show how scientific and ordinary cognition lie on a continuum, and how problem-solving practices in one illuminate practices in the other. (shrink)

Between 1940 and 1970 pioneers in the new field of cell biology discovered the operative parts of cells and their contributions to cell life. They offered mechanistic accounts that explained cellular phenomena by identifying the relevant parts of cells, the biochemical operations they performed, and the way in which these parts and operations were organised to accomplish important functions. Cell biology was a revolutionary science but in this book it also provides fuel for yet another revolution, one that focuses on (...) the very conception of science itself. Laws have traditionally been regarded as the primary vehicle of explanation, but in the emerging philosophy of science it is mechanisms that do the explanatory work. Bechtel emphasises how mechanisms were discovered, focusing especially on the way in which new instruments made these inquiries possible. He also describes how new journals and societies provided institutional structure to this new enterprise. (shrink)

I highlight a category of experiment-what I am calling 'demonstrations'-that differs in justificatory mode and argumentative role from the more familiar 'crucial tests'. 'Tests' are constructed such that alternative results are equally and symmetrically informative; they help discriminate between alternative solutions within a problem-field, where questions are shared. 'Demonstrations' are notably asymmetrical (for example, "failures" are often not telling), yet they are effective, if not "crucial," in interparadigm dispute, to legitimate questions themselves. The Ox-Phos Controversy in bioenergetics serves as an (...) integral case study. (shrink)

Several diagrams and tables from review articles during the Ox-Phos Controversy serve as an occasion to assess the nature of competition in models of theory choice in science. Many models follow "Super-Bowl" principles of polar, either-or, winner-take-all competition. A significant alternative highlighted by this episode, however, is the differentiation of domains. Incommensurability and the partial divergence of overlapping domains serve both as signals and context for shifting frameworks of competition. Appropriate strategies may thus help researchers diagnose the status of competition (...) and shape their research accordingly. (shrink)