Historically, hypotheses failed in most cases to correctly forecast the workings of complex biological systems. Francis Crick’s adaptor hypothesis, however, stands out as an exceptional case of a confirmed abstract prediction. This hypothesis presciently anticipated the existence of RNA adaptors that function as bridges between amino acids and the chemically different nucleic acid template for proteins. Crick conjectured that the adaptors are enzymatically charged with cognate amino acids, they bind to complementary protein-coding nucleic acid, and their liberated amino acids are (...) incorporated into growing protein chains. Independently from and concomitantly with Crick’s hypothesis, Mahlon Hoagland and Paul Zamecnik conducted experiments with no guiding theory that culminated in discoveries of the actual adaptors, transfer RNA (tRNA) molecules, and their amino acids charging enzymes. This paper traces the parallel histories of Crick’s adaptor hypothesis and of the experimental discovery of tRNA and compares their relative impacts on the scientific community. Remarkably, despite the brilliance of Crick’s confirmed prognostication, it had marginal impact on practicing scientists. Conversely, Hoagland and Zamecnik’s experimental discoveries and their evidence-based model of protein synthesis had immediate and enduring impact. I discuss possible explanations for the different impacts of the theoretical prediction and experimental identifications of the same entities. (shrink)

Berichte zur Wissenschaftsgeschichte, Volume 45, Issue 3, Page 415-427, September 2022.

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)

In the early twentieth century, Tatsuo Aida in Japan, Øjvind Winge in Denmark, Richard Goldschmidt in Germany, and Calvin Bridges in the United States all developed different experimental systems to study the genetics of sex reversal. These locally specific experimental systems grounded these experimenters’ understanding of sex reversal as well as their interpretation of claims regarding experimental results and theories. The comparison of four researchers and their experimental systems reveals how those different systems mediated their understanding of genetic phenomena, and (...) influenced their interpretations of sex reversal. (shrink)

The ArgumentIn the first part of this paper, issues concerning an “epistemology of time” are raised. The Derridean theme of the historial movement of a trace is connected to Prigogine's notion of an operator-time. It is suggested that both conceptions can be used to characterize the dynamics of experimental systems in contemporary science. It is argued that such systems have, to speak with Hacking, “a life of their own” and that this is precisely the reason for their inherent unpredictability.In the (...) second part, a case from the history of virology and cytomorphology is presented. The movement of a particular experimental system is followed in its peculiar tension between deferring and becoming different—i.e., between the persistence of a problem and the vagaries of its successive transformations. They are rendered possible by novel technical implementations, but they are not determined in any meaningful sense on a mere technological level.In conclusion, a point is made for a deconstructive approach to the history of science. (shrink)

The ArgumentThis paper focuses on the opening of a discursive space: the emergence of informational and scriptural representations of life and their self-negating consequences for the construction of biological meaning. It probes the notion of writing and the book of life and shows how molecular biology's claims to a status of language and texuality undermines its own objective of control. These textual significations were historically contingent. The informational representations of heredity and life were not an outcome of the internal cognitive (...) momentum of molecular biology; they were not a logical necessity of the unravelling of the base-pairing of the DNA double-helix. They were transported into molecular biology still within the protein paradigm of the gene in the 1940s and permeated nearly every discipline in the life and social sciences. These information-based models, metaphors, linguistic, and semiotic tools which were central to the formulation of the genetic code were transported into molecular biology from cybernetics, information theory, electronic computing, and control and communication systems — technosciences that were deeply embedded with the military experiences of world war II and the Cold War. The information discourse thus became fixed in molecular biology not because it worked in the narrow epistemic sense (it did not), but because it positioned molecular biology within postwar discourse and culture, perhaps within the transition to a post-modern information-based society. (shrink)

In this paper, I revisit a problem in immunology and molecular genetics that I had first tried to understand some philosophical implications of over twenty years ago. At that time, some immunologists such as Mel Cohn at the Salk Institute, referred to it as the GOD problem, which was the acronym forGeneratorOfDiversity (also see Cohn's more recent discussion in his 1994, 41-48). In the early 1970s there were three or four different theories that had been proposed to account for the (...) way in which antibody diversity is generated and considerable argument among the proponents of the different approaches to the problem (see Cohn, 1994). In 1971-72 I attempted to assess the strengths and weaknesses of the competing theories of antibody diversity from the perspective of a “logic of comparative theory evaluation” that had seemed to work reasonably well in physics (Schaffner, 1970), and I drafted an essay that ultimately sided with one of those theories (somatic mutation). (shrink)

The ArgumentMost historians of science share the conviction that the incorporation of the corpuscular theory into seventeenth-century chemistry was the beginning of modern chemistry. My thesis in this paper is that modern chemisty started with the concept of the chemicl compound, which emerged at the end of the seventeenth and the beginning of the eighteenth century, without any signifivant influence of the corpuscular theory. Rather the historical reconstruction of the emergence of this concept shows that it resulted from the reflection (...) on the chemical operations in the sixteenth-century metallurgy and seventeenth-century pharmacy. I argue that the reversibility of these operations and their understanding as crafts (metallurgy) or chemical arts (pharmacy) were decisive factors for the emergence of the first ideas about chemical compounds in the seventeenth-century pharmaceutical works written by pharmaceutically trained authors, influenced by the Paracelsian image of nature. There is a direct line of descent from these authors to E.F.Geoffroy (1675–1742), who integrated the first scattered ideas of chemical compound into a general concept comprising chemical artefacts as well as natural bodies. (shrink)

The ArgumentWhat kind of objects are computer programs used for simulation purposes in scientific settings? The current investigation treats a special case. It focuses on “event generators,” the program packages that particle physicists construct and use to simulate mechanisms of particle production. The paper is an attempt to bring the multiplex and unfolding character of such knowledge objects to the fore: Multiple meanings and functions are embodied in the object and can be drawn out selectively according to the requirements of (...) a work setting. The object's conceptual complexity governs its application in some contexts, while the object is considered a mere “black box,” transparent and ready-to-hand, in others. These two poles span a full spectrum of object aspects, functions, and conceptions. Event generators are ideas turned into software, testing grounds for models, just a tool to study the performance of a detector, etc. The object's multiplex nature is submitted to negotiation among different actors. (shrink)

The paper tries to show that an evolutionary perspective helps us to address what is called the adaptation problem, that is, the remarkable coherence, and seemingly successful design, existing between our cognitive tools and the phenomena of the material world. It argues that a fine-grained description of the structure and function of experimental techniques—as a special type amongst evolving scientific practices—is a condition for a better understanding and, ultimately, an explanation of how adaptation among the heterogeneous elements of experimental knowledge (...) is attained. Some apparently contradictory features of techniques, such as their high context-dependency and their capabilities to reproduce and diversify outside their original contexts, are addressed with the help of the concepts of technical variation and the historical entrenchment of phenomena in techniques. In order to do so, a case-study on the construction of satellite-DNA and the evolution of nucleic acid hybridization, a research project carried out by Roy J. Britten and his colleagues in the 1960s, is presented in detail. This case illustrates the close relationship existing between the evolution of techniques and the stabilization of phenomena in experimental biology. (shrink)

This article argues that understanding everyday practices in neurobiological labs requires us to take into account a variety of different action positions: self-conscious social actors, technical artifacts, conscious organisms, and organisms being merely alive. In order to understand the interactions among such diverse entities, highly differentiated conceptual tools are required. Drawing on the theory of the German philosopher and sociologist Helmuth Plessner, the paper analyzes experimenters as self-conscious social persons who recognize monkeys as conscious organisms. Integrating Plessner’s ideas into the (...) stock of concepts used in science and technology studies provides richer descriptions of laboratory life. In particular, this theory allows an understanding of a crucial feature of neurobiological brain research: the construction of the brain as the epistemic object of brain research. As such, the brain must be isolated from the acting and interacting organism in a complicated process. (shrink)

The history of what we call molecular biology today is not just the story of DNA. Molecular biology emerged from and was supported by a multiplicity of widely scattered, differently embedded, and loosely, if at all connected experimental systems for characterizing living beings to the level of biologically relevant macromolecules. By implementing different modes of technical analysis, these systems created a new space of representation in which the central concepts of molecular biology gradually became articulated. The paper describes the establishment (...) of the rat liverin vitro protein synthesis system of Paul Zamecnik and his group a the Collis P. Huntington Memorial Hospital of Harvard University between 1947 and 1952. Insofar as such systems orient the research activity, they may also prove helpful for the orientation of the historian. Experimental systems „have a life of their own. (shrink)

H. B. D. Kettlewell's (1955, 1956) classic field experiments on industrial melanism in polluted and unpolluted settings using the peppered moth, Biston betularia, are routinely cited as establishing that the melanic (dark) form of the moth rose in frequency downwind of industrial centers because of the cryptic advantage dark coloration provides against visual predators in soot-darkened environments. This paper critiques three common myths surrounding these investigations: (1) that Kettlewell used a model that identified crypsis as the only selective force responsible (...) for the spread of the melanic gene, (2) that Kettlewell's field experiments alone established that selection for crypsis was the most important factor in the spread of melanic forms, and (3) that Kettlewell's investigations in an unpolluted wood near Dorset constituted a control for his earlier Birmingham studies (contra Hagen 1993, 1996). This analysis further identifies two features that distinguish manipulative experiments in evolutionary biology from experiments in other contexts. First, experiments in evolutionary biology rest on a wealth of information provided by strictly observational ecological studies; in the absence of such information experiments in evolutionary biology make no sense. Second, there is a trade-off between how much control investigators have over the conditions being studied and how informative the results of the experiment will be with regard to natural populations. (shrink)

: The main contribution of this paper for social studies of scientific practice is to use and further elaborate the concept of experimental system. It is expanded from mere epistemic concerns to also incorporate the built-in practicality and societal relevance of scientific research. For this, an analysis of object construction by a potato-biotechnology research group is presented. The group's object of activity is conceptualized as a dual one comprising both the epistemic and applied objectives. The application object points to the (...) virus-resistant cultivated potato under construction, the epistemic object to the knowledge on the virus-resistance mechanism. Two major phases of the group's work are perceived as distinct experimental systems. The transition between them is analysed in terms of a gradual evolution characterised by network collaboration, ad hoc improvization, resistance, opportunism and informal interaction. (shrink)

Berichte zur Wissenschaftsgeschichte, Volume 45, Issue 3, Page 415-427, September 2022.

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)

In 1928, a German zoologist and philosopher named Helmuth Plessner published a book titled Die Stufen des Organischen und der Mensch: Einleitung in die philosophische Anthropologie. Almost a 100 years later, Jos de Mul has edited a collection of 26 new essays on Plessner’s text, titled Plessner’s Philosophical Anthropology: Perspectives and Prospects. The volume offers a variety of advanced discussions of its theme. In this review essay of de Mul’s collection, I provide a critical overview of the contents of the (...) new volume and some speculations on the possible motives and future directions of the current “Plessner renaissance.”. (shrink)

Berichte zur Wissenschaftsgeschichte, Volume 45, Issue 3, Page 332-343, September 2022.

Berichte zur Wissenschaftsgeschichte, Volume 45, Issue 3, Page 332-343, September 2022.

H. B. D. Kettlewell's (1955, 1956) classic field experiments on industrial melanism in polluted and unpolluted settings using the peppered moth, Biston betularia, are routinely cited as establishing that the melanic (dark) form of the moth rose in frequency downwind of industrial centers because of the cryptic advantage dark coloration provides against visual predators in soot-darkened environments. This paper critiques three common myths surrounding these investigations: (1) that Kettlewell used a model that identified crypsis as the only selective force responsible (...) for the spread of the melanic gene, (2) that Kettlewell's field experiments alone established that selection for crypsis was the most important factor in the spread of melanic forms, and (3) that Kettlewell's investigations in an unpolluted wood near Dorset constituted a control for his earlier Birmingham studies (contra Hagen 1993, 1996). This analysis further identifies two features that distinguish manipulative experiments in evolutionary biology from experiments in other contexts. First, experiments in evolutionary biology rest on a wealth of information provided by strictly observational ecological studies; in the absence of such information experiments in evolutionary biology make no sense. Second, there is a trade-off between how much control investigators have over the conditions being studied and how informative the results of the experiment will be with regard to natural populations. (shrink)

ArgumentFilm scholars have long posed the question of the specificity of the film medium and the apparatus of cinema, asking what is unique to cinema, how it constrains and enables filmmakers and audiences in particular ways that other media do not. This question has rarely been considered in relation to scientific film, and here it is posed within the specific context of cell biology: What does the use of time-based media such as film coupled with the microscope allow scientists to (...) experience that other visualization practices do not? Examining three episodes in the twentieth-century study of the cell, this article argues that the apparatus of microcinematography constitutes what might be thought of as a technical portal to another world, a door that determines the experience of the world that lies on the other side of it. In this case, the design of apparatuses to capture time-lapsed images enabled the acceleration of cellular time, bringing it into the realm of human perception and experience. Further, the experience of the cellular temporal world was part of a distinct kind of cell biology, one that was focused on behavior rather than structure, focused on the relation between cells, and between the cell and its milieu rather than on cell-intrinsic features such as chromosomes or organelles. As such, the instruments and technical design of the microcinematographic apparatus may be understood as a kind of materialized epistemology, the history of which can elucidate how cinema was and is used to produce scientific knowledge. (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)

As recent studies in economic and financial sociology have underscored, calculation is central to economic practices. While some sociological accounts locate the performance of calculation within individual ability, networks of human agents or their cultural embeddedness, studies operating on the background of the sociology of (scientific) knowledge conceive of calculation as situated in the practice of the participants engaged, the technological tools used and their requirements. The article explores this point further, using a distinction which can be traced back to (...) Heidegger’s notion of Gestell (enframing): the ‘calculation of something’ and the ‘calculation with something’ are analysed taking the practices of risk management departments of big international banks as an example. It is argued that, through the use of calculation tools, the corporate clients are constituted anew and that written documents which are the outcome of this process constitute a social prosthesis for remote communication taking place between subsidiaries and the headquarters of international banks. (shrink)