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)

My paper draws on examples from molecular biology, the details of which I have developed elsewhere (Rheinberger 1992, 1993, 1995, 1997). Here, I can give only a brief outline of my argument. Reduction of complexity is a prerequisite for experimental research. To make sense of the universe of living beings, the modern biologist is bound to divide his world into fragments in which parameters can be defined, quantities measured, qualities identified. Such is the nature of any "experimental system." Ontic complexity (...) has to be reduced in order to make experimental research possible. The complexity of the research object, however, is epistemically retained in the rich context of an experimental landscape, where the eruption of "volcanic systems" can change the scenery dramatically as the result of particular, unprecedented findings. (shrink)

The “Human Brain Project” (HBP) is a large-scale European neuroscience and information communication technology (ICT) project that has been a matter of heated controversy since its inception. With its aim to simulate the entire human brain with the help of supercomputing technologies, the HBP plans to fundamentally change neuroscientific research practice, medical diagnosis, and eventually the use of computers itself. Its controversial nature and its potential impacts render the HBP a subject of crucial importance for critical studies of science and (...) society. In this paper, we provide a critical exploratory analysis of the potential mid- to long-term impacts the HBP and its ICT infrastructure could be expected to have, provided its agenda will indeed be implemented and executed to a substantive degree. We analyse how the HBP aspires to change current neuroscientific practice, what impact its novel infrastructures could have on research culture, medical practice and the use of ICT, and how, given a certain degree of successful execution of the project’s aims, potential clinical and methodological applications could even transform society beyond scientific practice. Furthermore, we sketch the possibility that research such as that projected by the HBP may eventually transform our everyday world, even beyond the scope of the HBP’s explicit agenda, and beyond the isolated ‘application’ of some novel technological device. Finally, we point towards trajectories for further philosophical, historical and sociological research on the HBP that our exploratory analysis might help to inspire. Our analysis will yield important insights regardless of the actual success of the HBP. What we drive at, for the most part, is the broader dynamics of scientific and technological development of which the HBP agenda is merely one particularly striking exemplification. (shrink)

Philosophers of science turned to historical case studies in part in response to Thomas Kuhn's insistence that such studies can transform the philosophy of science. In this issue Joseph Pitt argues that the power of case studies to instruct us about scientific methodology and epistemology depends on prior philosophical commitments, without which case studies are not philosophically useful. Here I reply to Pitt, demonstrating that case studies, properly deployed, illustrate styles of scientific work and modes of argumentation that are not (...) well handled by currently standard philosophical analyses. I illustrate these claims with exemplary findings from case studies dealing with exploratory experimentation and with interdisciplinary cooperation across sciences to yield multiple independent means of access to theoretical entities. The latter cases provide examples of ways that scientists support claims about theoretical entities that are not available in work performed within a single discipline. They also illustrate means of correcting systematic biases that stem from the commitments of each discipline taken separately. These findings illustrate the transformative power of case study methods, allow us to escape from the horns of Pitt's "dilemma of case studies," and vindicate some of the post-Kuhn uses to which case studies have been put. (shrink)

A longstanding philosophical premise perceives simplicity as a desirable attribute of scientific theories. One of several raised justifications for this notion is that simple theories are more likely to indicate the true makeup of natural systems. Qualitatively parsimonious hypotheses and theories keep to a minimum the number of different postulated entities within a system. Formulation of such ontologically simple working hypotheses proved to be useful in the experimental probing of narrowly defined bio systems. It is less certain, however, whether qualitatively (...) parsimonious theories are effective indicators of the true nature of complex biological systems. This paper assesses the success of ontologically simple theories in envisaging the makeup of three complex systems in bacteriology, immunology, and molecular biology. Evidence shows that parsimonious theories completely misconstrued the actual ontologically complex constitutions of the three examined systems. Since evolution and selective pressures typically produce ontologically intricate rather than simple bio systems, qualitatively parsimonious theories are mostly inapt indicators of the true nature of complex biological systems. (shrink)

This article concerns itself with the reception of Rous' 1911 discovery of what later came to be known as the Rous Sarcoma Virus (RSV). Rous made his discovery at the Rockefeller Institute for Medical Research which had been primarily established to conduct research into infectious diseases. Rous' chance discovery of a chicken tumor led him to a series of conjectures about cancer causation and about whether cancer could have an extrinsic cause. Rous' finding was received with some scepticism by the (...) scientific community that held that cancer was not infectious and favored explanations which located the origins of cancer in the inner mechanism of the cell. After 4 years of unsuccessful effort to isolate and further determine the virus Rous felt compelled to discontinue his work on cancer viruses. When 55 years later, the significance of Rous's discovery was attested by the award of the Nobel Prize, it opened up debates about the issues of delayed recognition and scientific reputation. This article also considers why Rous' hypothesis of a viral origin of cancer could not be incorporated into the existing body of knowledge about cancer before the 1950s. (shrink)

Attention to scientific practice offers a novel response to philosophical queries about how conceptual understanding is empirically accountable. The locus of the issue is thereby shifted, from perceptual experience to experimental and fieldwork interactions. More important, conceptual articulation is shown to be not merely ?spontaneous? and intralinguistic, but instead involves a establishing a systematic domain of experimental operations. The importance of experimental practice for conceptual understanding is especially clearly illustrated by cases in which entire domains of scientific investigation were first (...) made accessible to articulated conceptual understanding. We thereby see more clearly how experimental systems themselves, and not merely the theories and models they make possible, have an intentional directedness and ?representational? import. (shrink)

Biology deals, notoriously, with complex systems. In discussing biological methodology, all three papers in this symposium honor the complexity of biological subject matter by preferring models and theories built to reflect the details of complex systems to models based on broad general principles or laws. Rheinberger's paper, the most programmatic of the three, provides a framework for the epistemology of discovery in complex systems. A fundamental problem is raised for Rheinberger's epistemology, namely, how to understand the referential continuity of the (...) theoretical terms and concepts employed in typical case studies involving complex systems. (shrink)

Scientific hypotheses may either predict particular unknown facts or accommodate previously-known data. Although affirmed predictions are intuitively more rewarding than accommodations of established facts, opinions divide whether predictive hypotheses are also epistemically superior to accommodation hypotheses. This paper examines the contribution of predictive hypotheses to discoveries of several bio-molecular systems. Having all the necessary elements of the system known beforehand, an abstract predictive hypothesis of semiconservative mode of DNA replication was successfully affirmed. However, in defining the genetic code whose biochemical (...) basis was unclear, hypotheses were only partially effective and supplementary experimentation was required for its conclusive definition. Markedly, hypotheses were entirely inept in predicting workings of complex systems that included unknown elements. Thus, hypotheses did not predict the existence and function of mRNA, the multiple unidentified components of the protein biosynthesis machinery, or the manifold unknown constituents of the ubiquitin–proteasome system of protein breakdown. Consequently, because of their inability to envision unknown entities, predictive hypotheses did not contribute to the elucidation of cation theories remained the sole instrument to explain complex bio-molecular systems, the philosophical question of alleged advantage of predictive over accommodative hypotheses became inconsequential. (shrink)

During the first years of the post-war era, many French scientists travelled in the United States. As they looked for a reference to be used in rebuilding their own scientific landscape, their diaries say as much about the rise of the American biomedical complex as they do about their perception of research in the country. In order to illustrate how the French biologists adopted, competed with, or challenged the American model and how transatlantic exchanges played a critical role in the (...) molecularization of the life sciences, this paper presents three trajectories of laboratories. These include the services respectively led by P. Lépine and J. Monod at the Pasteur Institute, and G. Schapira’s biochemical research unit at the Hôpital des Enfants Malades. The three studies document the massive transatlantic circulation of materials, techniques, instruments, and people during the scientific reconstruction. The reconstruction however produced highly differentiated characters each operating in his own niche: the biotechnological inventor, the neo-clinician, and the fundamental biologist. The comparison situates the rise of molecular biology within the context of a rapidly expanding biomedical research system. It will help in understanding how, in contrast to the American situation, a logic of “demedicalization” became in France a means for developing biology at the molecular level. (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)

This article concerns itself with the reception of Rous’ 1911 discovery of what later came to be known as the Rous Sarcoma Virus. Rous made his discovery at the Rockefeller Institute for Medical Research which had been primarily established to conduct research into infectious diseases. Rous’ chance discovery of a chicken tumor led him to a series of conjectures about cancer causation and about whether cancer could have an extrinsic cause. Rous’ finding was received with some scepticism by the scientific (...) community that held that cancer was not infectious and favored explanations which located the origins of cancer in the inner mechanism of the cell. After 4 years of unsuccessful effort to isolate and further determine the virus Rous felt compelled to discontinue his work on cancer viruses. When 55 years later, the significance of Rous’s discovery was attested by the award of the Nobel Prize, it opened up debates about the issues of delayed recognition and scientific reputation. This article also considers why Rous’ hypothesis of a viral origin of cancer could not be incorporated into the existing body of knowledge about cancer before the 1950s. (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)

Since the practice turn, the role technologies play in the production of scientific knowledge has become a prominent topic in science studies. Much existing scholarship, however, either limits technology to merely mechanical instrumentation or uses the term for a wide variety of items. This article argues that technologies in scientific practice can be understood as a result of past scientific knowledge becoming sedimented in materials, like model organisms, synthetic reagents or mechanical instruments, through the routine use of these materials in (...) subsequent research practice. The proposed theoretical interpretation of technology is examined through a case where a model organism—Drosophila melanogaster—acted as a technology for investigating a contested biological effect of a mechanical instrument: Hermann J. Muller’s experiments on X-ray mutagenicity in the 1920s. The article reconstructs how Muller employed two synthetic Drosophila stocks as tests for measuring X-rays’ capacity to cause genetic aberration. It argues that past scientific knowledge sedimented in the Drosophila stocks influenced Muller’s perception of X-ray-induced mutation. It further describes how Muller’s concept of X-ray mutagenicity sedimented through the adoption of X-ray machines as a ready-made resource for producing mutants by other geneticists, for instance George Beadle and Edward Tatum in their experiments on Neurospora crassa, despite ongoing disputes surrounding Muller’s conclusions. Technological sedimentation is proposed as a potential explanation why sedimentation and disputation may often coexist in the history of science. (shrink)