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)

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)

In this article, I examine various aspects of the application of Heidegger's motif of interpretative articulation (the core phenomenological motif of existential analytic) to the constitutional analysis of meaningful objects in scientific research that are contextually ready-to-hand. It is my contention that not only the concepts of the ‘fore-structure of understanding’ and the ‘as-structure of interpretation’, but also the extended concepts of the ‘hermeneutic fore-structure of meaning constitution’ and ‘characteristic hermeneutic situation’ are the keys to understanding the interpretative nature of (...) scientific research. The paper applies the constitutional analysis of hermeneutic phenomenology to several phenomena of scientific research—constitution of meaningful objects, situational fulfilment of a domain's general project, production of a domain's thematically given objects, implementation of readable technologies to what is contextually ready-to-hand, reading hypothetical theoretical objects, and exegetical textualizing within interrelated practices. The study is supplied with exemplary illustrations from enzymology and biochemistry. The correlation between a domain's interpretative articulation and the appropriation of research possibilities within the research everydayness is addressed. Special attention is paid to the belief in and reading of intracellular enzymes as hypothetical theoretical objects. (shrink)

This article examines to what extent a particular case of cross-disciplinary research in the 1930s was structured by mechanistic reasoning. For this purpose, it identifies the interfield theories that allowed biologists and chemists to use each other’s techniques and findings, and that provided the basis for the experiments performed to identify plant growth hormones and to learn more about their role in the mechanism of plant growth. In 1930, chemists and biologists in Utrecht and Pasadena began to cooperatively study plant (...) growth. I will argue that these researchers decided to join forces because they believed to rely on each other’s findings and methods to solve their research problems adequately. In the course of the cooperation, organic chemists arrived at isolating plant growth hormones by using a test method developed in plant physiology. This achievement, in turn, facilitated biologists’ investigation of the mechanism of plant growth. Researchers eventually believed to have the means to study the relation between a substance’s molecular structure and its physiological activity. The way they conceptualized the problem of identifying hormones and unraveling the mechanism of plant growth, as well as their actual research actions are compatible with the new mechanists’ account of mechanism research. The study illustrates that focusing on researchers’ mechanistic reasoning can contribute considerably to explaining the structure of cross-disciplinary research projects. (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)

Aron Arthur Moscona was an Israeli-American developmental biologist whose name is associated with research on cell interactions during embryonic development. His appearance on the international scene dates back to a paper published in 1952, while he was working, together with his wife Haya Sobel Moscona, at the Strangeways Research Laboratory of Cambridge. Together they demonstrated that cells from previously dissociated chick tissues undergo histiotypical and organotypical aggregation in vitro. From 1952 to 1997, Moscona focused his research on cell recognition mechanisms, (...) ultimately demonstrating the role of transmembrane proteins in cellular adhesiveness, tissue segregation, and organ tridimensional assemblage during development. However, who was Aron Moscona before 1952 and what brought him to developmental biology? A Polish Jew who immigrated to Mandatory Palestine in 1933, Moscona belonged to the first generation of biologists formed in the newly established Zoology Department of the Hebrew University. With a particular focus on the Israeli context, the paper reconstructs the evolution of Moscona’s scientific thought by emphasizing the cultural and experimental context of his training and early research at the Hebrew University. The aim is to investigate how local scientific traditions influenced Moscona’s eventual research as well as enabled the relevant experimental innovation he contributed to the field of developmental biology and pathology. The paper can be read both as a scientific biography of Aron Moscona and as a preliminary contribution to the historiography of embryology in the Mandatory Palestine/Israeli context. (shrink)

In 1971, Günter Blobel and David Sabatini proposed a novel and quite speculative schematic model to describe how proteins might reach the proper cellular location. According to their proposal, proteins destined to be secreted from the cell contain a “signal” to direct their release. Despite the fact that Blobel and Sabatini presented their signal hypothesis as a “beautiful idea” not grounded in experimental evidence, they received criticism from other scientists who opposed such speculation. Following the publication of the 1971 model, (...) Blobel persisted in conducting experiments and revising the model to incorporate new data. In fact, over the period of 1975–1984, Blobel and colleagues published five subsequent schematic models of the signal hypothesis, each revised based on new laboratory evidence. I propose that the original 1971 model can be viewed as an epistemic creation. Additionally, analysis of the subsequent schematic diagrams over the period of 1975–1984 allows one to track Blobel’s changing conception of an epistemic object over time. Furthermore, the entire series of schematic diagrams presented by Blobel from 1971 to 1984 allow one to visualize the initial conception and subsequent reworking of a scientific theory. In 1999, Blobel was awarded the Nobel Prize in Physiology or Medicine for his work on the signal hypothesis, which was ultimately supported by experimental evidence gathered after the speculative model was published. (shrink)