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)

In this paper I present a historiography of the recent emergence of philosophy of chemistry. Special attention is given to the interest in this domain in Eastern Europe before the collapse of the USSR. It is shown that the initial neglect of the philosophy of chemistry is due to the unanimous view in philosophy and philosophy of science that only physics is a proper science (to put in Kant's words). More recently, due to the common though incorrect assumption that chemistry (...) can in principle be reduced to physics, the neglect continued, even when interest in sciences such as biology and psychology entered more strongly in philosophy of science. It is concluded that chemistry is an autonomous science and is perhaps a more typical science than physics. (shrink)

: Errors in science range along a spectrum from those relatively local to the phenomenon (usually easily remedied in the laboratory) to those more conceptually derived (involving theory or cultural factors, sometimes quite long-term). One may classify error types broadly as material, observational, conceptual or discoursive. This framework bridges philosophical and sociological perspectives, offering a basis for interfield discourse. A repertoire of error types also supports error analytics, a program for deepening reliability through strategies for regulating and probing error.

Incommensurability of scientific theories, as conceived by Thomas Kuhnand Paul Feyerabend, is thought to be a major or even insurmountable obstacletothe empirical comparison of these theories. I examine this problem in light ofaconcrete case from the history of experimental biology, namely the oxidativephosphorylation controversy in biochemistry (ca. 1961-1977). After a briefhistorical exposition, I show that the two main competing theories which werethe subject of the ox-phos controversy instantiate some of the characteristicfeatures of incommensurable theories, namely translation failure,non-corresponding predictions, and different (...) claims about what kinds ofentitiesexist in the world. By examining how the controversy was eventually resolved, Ithen show that at least this pair of incommensurable theories couldneverthelessbe empirically compared. (shrink)

Developing models of biological mechanisms, such as those involved in respiration in cells, often requires collaborative effort drawing upon techniques developed and information generated in different disciplines. Biochemists in the early decades of the 20th century uncovered all but the most elusive chemical operations involved in cellular respiration, but were unable to align the reaction pathways with particular structures in the cell. During the period 1940-1965 cell biology was emerging as a new discipline and made distinctive contributions to understanding the (...) role of the mitochondrion and its component parts in cellular respiration. In particular, by developing techniques for localizing enzymes or enzyme systems in specific cellular components, cell biologists provided crucial information about the organized structures in which the biochemical reactions occurred. Although the idea that biochemical operations are intimately related to and depend on cell structures was at odds with the then-dominant emphasis on systems of soluble enzymes in biochemistry, a reconceptualization of energetic processes in the 1960s and 1970s made it clear why cell structure was critical to the biochemical account. This paper examines how numerous excursions between biochemistry and cell biology contributed a new understanding of the mechanism of cellular respiration. (shrink)

Thomas Kuhn had little to say about scientific change in biological science, and biologists are ambivalent about how applicable his framework is for their disciplines. We apply Kuhn’s account of paradigm change to evolutionary microbiology, where key Darwinian tenets are being challenged by two decades of findings from molecular phylogenetics. The chief culprit is lateral gene transfer, which undermines the role of vertical descent and the representation of evolutionary history as a tree of life. To assess Kuhn’s relevance to this (...) controversy, we add a social analysis of the scientists involved to the historical and philosophical debates. We conclude that while Kuhn’s account may capture aspects of the pattern of an episode of scientific change, he has little to say about how the process of generating new understandings is occurring in evolutionary microbiology. Once Kuhn’s application is limited to that of an initial investigative probe into how scientific problem-solving occurs, his disciplinary scope becomes broader. (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 evolution of sexual reproduction is a striking case of explanatory pluralism, meaning that one needs to refer to more than one explanation in order to adequately account for it. I develop the concept a domain of phenomena in order to analysis this pluralism. Pluralism exists when a phenomenon can be included in more that one homogeneous domain or in a heterogeneous domain. I argue that in some cases domain partitioning can be used to decrease pluralism, but that in the (...) case of sex domains are overlapping and interconnecting, or in other words bear an orthogonal relationship to one another, and hence cannot be partitioned in such a way as to eliminate pluralism. (shrink)

In the 1950s and 1960s, the search for the mechanism of oxidative phosphorylation by biochemists paralleled the description of mitochondrial form by George Palade and Fritiof Sjöstrand using electron microscopy. This paper explores the extent to which biochemists studying oxidative phosphorylation took mitochondrial form into account in the formulation of hypotheses, design of experiments, and interpretation of results. By examining experimental approaches employed by the biochemists studying oxidative phosphorylation, and their interactions with Palade, I suggest that use of mitochondrial form (...) as a guide to experimentation and interpretation varied considerably among investigators. Most notably, Peter Mitchell, whose chemiosmotic hypothesis was ultimately the basis of the correct mechanism of oxidative phosphorylation, incorporated crucial aspects of mitochondrial form into his model that others failed to recognize. I discuss these historical observations in terms of the background and training of the biochemists, as well as a proposed heuristic of form, whose use may increase the possibility that biologically meaningful molecular mechanisms will be discovered. (shrink)

We investigate the context of discovery of two significant achievements of twentieth century biochemistry: the chemiosmotic mechanism of oxidative phosphorylation and the dark reaction of photosynthesis. The pursuit of these problems involved discovery strategies such as the transfer, recombination and reversal of previous causal and mechanistic knowledge in biochemistry. We study the operation and scope of these strategies by careful historical analysis, reaching a number of systematic conclusions: even basic strategies can illuminate “hard cases” of scientific discovery that go far (...) beyond simple extrapolation or analogy; the causal–mechanistic approach to discovery permits a middle course between the extremes of a completely substrate-neutral and a completely domain-specific view of scientific discovery; the existing literature on mechanism discovery underemphasizes the role of combinatorial approaches in defining and exploring search spaces of possible problem solutions; there is a subtle interplay between a fine-grained mechanistic and a more coarse-grained causal level of analysis, and both are needed to make discovery processes intelligible. (shrink)

The term ‘cell’, in addition to designating fundamental units of life, has also been applied since the nineteenth century to technical apparatuses such as fuel and galvanic cells. This paper shows that such technologies, based on the electrical effects of chemical reactions taking place in containers, had a far-reaching impact on the concept of the biological cell. My argument revolves around the controversy over oxidative phosphorylation in bioenergetics between 1961 and 1977. In this scientific conflict, a two-level mingling of technological (...) culture, physical chemistry and biological research can be observed. First, Peter Mitchell explained the chemiosmotic hypothesis of energy generation by representing cellular membrane processes via an analogy to fuel cells. Second, in the associated experimental scrutiny of membranes, material cell models were devised that reassembled spatialized molecular processes in vitro. Cells were thus modelled both on paper and in the test tube not as morphological structures but as compartments able to perform physicochemical work. The story of cells and membranes in bioenergetics points out the role that theories and practices in physical chemistry had in the molecularization of life. These approaches model the cell as a ‘topology of molecular action’, as I will call it, and it involves concepts of spaces, surfaces and movements. They epitomize an engineer’s vision of the organism that has influenced diverse fields in today’s life sciences. (shrink)

In his pioneering sociological theory, which makes phenomenological concepts fruitful for the social sciences, Alfred Schütz has laid foundations for a characterization of an manifold of distinct domains of experience. My aim here is to further develop this pluralist theory of experience by buttressing and extending the elements of diversity that it includes, and by eliminating or minimizing lingering imbalances among the domains of experience. After a critical discussion of the criterion-catalogue Schütz develops for the purpose of characterizing different cognitive (...) styles, I move on to examine its application to one special style, the lifeworld. I appeal, on the one hand, to Husserl's characterization of the lifeworld as a world of perception, and on the other hand to the layer-model of the lifeworld developed by Schütz and Thomas Luckmann. A consequence of this approach is that the lifeworld appears as a socially definable context that is detached from other experiences but on an equal footing with them with respect to their claim of validity. The term "lifeworld" does not denote a category that encompasses culture or nature but refers to a delimited action-space. Finally, I draw upon Schütz' s criterion-catalogue to characterize two domains of experience outside of the lifeworld, which play a central role for the process of differentiation of experience in modernity and for the phenomenological analysis of types of experience: experimental science and subjectivity. (shrink)

In the same year, 1961, Peter D. Mitchell and Robert R.J.P. Williams both put forward hypotheses for the mechanism of oxidative phosphorylation in mitochondria and photophosphorylation in chloroplasts. Mitchell's proposal was ultimately adopted and became known as the chemiosmotic theory. Both hypotheses were based on protons and differed markedly from the then prevailing chemical theory originally proposed by E.C. Slater in 1953, which by 1961 was failing to account for a number of experimental observations. Immediately following the publication of Williams's (...) hypothesis and before his own was published, Mitchell initiated a correspondence. Examination of the letters shows the development of a dispute based on the validity of the proposals, who should have priority and particularly whether Mitchell had drawn on Williams's work without acknowledgement. We have concluded that Mitchell's proposals were original although it is evident that prior to the correspondence Williams had considered and rejected a proposition similar to Mitchell's theory. However, a major cause of the dispute was the difference in disciplinary backgrounds of Mitchell, a microbial biochemist and Williams, a chemist. (shrink)

: This paper is concerned with the claim that epistemic terms and categories are historical entities. The starting point is the observation that recent attempts at historical studies of epistemic terms fail to bridge the gap between history and philosophy proper. I examine whether, and how, it is possible to forge a closer link between historical and philosophical aspects of conceptual analysis. The paper explores possible links by analyzing aspects of the concept of error. A "pragmatic" and a "mentalist" notion (...) of error are identified in current philosophical studies of error: according to the latter, errors can be ascribed only to mental operations, according to the former, errors can also be ascribed to things and processes. The paper then draws on historical accounts of optical instruments to highlight certain presuppositions and implications of these two uses of the term. Contextual features and trans-contextual structures of the notion of error are distinguished. In conclusion, I argue that an intimate link between history and philosophy of science can be forged by an analysis ofthe development of conceptual arrangements which allows for trans- contextual structural aspects while drawing attention to the contextual epistemological and scientific conditions of their re-arrangement. (shrink)

The aim of this paper is twofold. First, I want to show how hermeneutics can help philosophy of science to focus not only on explanation but also on understanding of meaning as an important part of science. Second, I want to argue that philosophy of science can improve the hermeneutic vision of understanding: a great part of what we call interpretations is in fact explanations of a pre-established meaning. Hence interpretation in the sense of explanation is ‘objective’ as long as (...) the interpretation reflects such a pre-established meaning. At the end I illustrate this point by presenting an interpretation of Botticelli's painting "The Mystical Nativity.". (shrink)

The history of biochemistry and molecular biology is replete with examples of erroneous theories that persisted for considerable lengths of time before they were rejected. This paper examines patterns of dissolution of three such erroneous hypotheses: The idea that nucleic acids are tetrads of the four nucleobases (‘the tetranucleotide hypothesis’); the notion that proteins are collinear with their encoding genes in all branches of life; and the hypothesis that proteins are synthesized by reverse action of proteolytic enzymes. Analysis of these (...) cases indicates that amassed contradictory empirical findings did not prompt critical experimental testing of the prevailing theories nor did they elicit alternative hypotheses. Rather, the incorrect models collapsed when experiments that were not purposely designed to test their validity exposed new facts. (shrink)

Paul Boyer shared a Nobel Prize in 1997 for his work on the mechanism of ATP synthase. His earlier work, though (which contributed indirectly to his triumph), included major errors, both experimental and theoretical. Two benchmark cases offer insight into how scientists err and how they deal with error. Boyer's work also parallels and illustrates the emergence of bioenergetics in the second half of the twentieth century, rivaling achievements in evolution and molecular biology.

Attempts to solve the puzzling problem of oxidative phosphorylation led to four very different hypotheses each of which suggested a different view of the ATP synthase, the phosphorylating enzyme. During the 1960s and 1970s evidence began to accumulate which rendered Peter Mitchell’s chemiosmotic hypothesis, the novel part of which was the proton translocating ATP synthase (ATPase), a plausible explanation. The conformational hypothesis of Paul Boyer implied an enzyme where ATP synthesis was driven by the energy of conformational changes in the (...) respiratory proteins. This was finally abandoned as an explanation of the overall process. Nevertheless the conformational understanding of the enzyme became an acceptable proposal during the early 1970s and eventually led Boyer to a view of the enzyme that incorporated both hypotheses. The correspondence between Mitchell and Boyer, both Nobel laureates, exposes their different approaches to both this enzyme and to the hypotheses of oxidative phosphorylation and illuminates a key step in the development of bioenergetics. In particular Boyer was suspicious of proton gradients, because he could not envisage a chemical mechanism for the synthesis of ATP, while Mitchell distrusted conformational arguments because he believed the proton must act vectorially at the active site of the enzyme. This resulted in two different views of the mechanisms operating in this enzyme. Ultimately while Boyer was able to marry the two approaches, Mitchell retained his insistence on the role of the proton at the active site and was thus unable to give significance to Boyer’s conformational ideas. The underlying issues in this debate are discussed particularly with reference to the differing styles of Boyer and Mitchell and the influence of molecular biology, especially the development of protein technology. (shrink)