Recent completion of the human genome sequence is a spectacular achievement of the 20th-century biology. This achievement has opened the door for future revolutions in biological and medical sciences. By learning about the gene sequences and the individual genetic differences, scientists hope to understand the molecular basis of the normal state and the diseased state of life on one hand, and individualize medicine on the other hand. However, the human genome sequencing project was not an isolated, spectacular undertaking. Rather, it (...) was a natural extension and the culmination of the advances in the science and techniques of molecular biology. The present article is an attempt to summarize these major landmarks in the history of DNA research, beginning from the identification of “nuclein.”. (shrink)

This paper investigates continuities and changes in the definition of sickle cell disease in 1950s Brazil, taking into account that diseases have a history and are recognized as such according to the knowledge and perceptions available in a certain historical period and specific location. In the post-war era, new diagnostic tools, inheritance theories and, in particular, discussions on the concepts of race and racial relations, both nationally and internationally, were changing previous racialist and racist views. Nonetheless, the Brazilian medical interpretations (...) of sickle cell disease continued to racialize it and even use deep-rooted racist formulations to explain its symptoms or the existence of the disease. It is argued that the celebration of racial mixture and racial democracy might have concealed racist presumptions biasing the study of sickle cell disease. Although race as a biological concept gradually gave way to other genetic expressions, in Brazilian medical papers on sickle cell disease, race continued to influence the interpretation of the disease, along with the persistence of concepts of heredity through blood mixture. (shrink)

In the last few years, biologists and computer scientists have claimed that the introduction of data science techniques in molecular biology has changed the characteristics and the aims of typical outputs (i.e. models) of such a discipline. In this paper we will critically examine this claim. First, we identify the received view on models and their aims in molecular biology. Models in molecular biology are mechanistic and explanatory. Next, we identify the scope and aims of data science (machine learning in (...) particular). These lie mainly in the creation of predictive models which performances increase as data set increases. Next, we will identify a tradeoff between predictive and explanatory performances by comparing the features of mechanistic and predictive models. Finally, we show how this a priori analysis of machine learning and mechanistic research applies to actual biological practice. This will be done by analyzing the publications of a consortium—The Cancer Genome Atlas—which stands at the forefront in integrating data science and molecular biology. The result will be that biologists have to deal with the tradeoff between explaining and predicting that we have identified, and hence the explanatory force of the ‘new’ biology is substantially diminished if compared to the ‘old’ biology. However, this aspect also emphasizes the existence of other research goals which make predictive force independent from explanation. (shrink)

The Bermuda Principles for DNA sequence data sharing are an enduring legacy of the Human Genome Project. They were adopted by the HGP at a strategy meeting in Bermuda in February of 1996 and implemented in formal policies by early 1998, mandating daily release of HGP-funded DNA sequences into the public domain. The idea of daily sharing, we argue, emanated directly from strategies for large, goal-directed molecular biology projects first tested within the “community” of C. elegans researchers, and were introduced (...) and defended for the HGP by the nematode biologists John Sulston and Robert Waterston. In the C. elegans community, and subsequently in the HGP, daily sharing served the pragmatic goals of quality control and project coordination. Yet in the HGP human genome, we also argue, the Bermuda Principles addressed concerns about gene patents impeding scientific advancement, and were aspirational and flexible in implementation and justification. They endured as an archetype for how rapid data sharing could be realized and rationalized, and permitted adaptation to the needs of various scientific communities. Yet in addition to the support of Sulston and Waterston, their adoption also depended on the clout of administrators at the US National Institutes of Health and the UK nonprofit charity the Wellcome Trust, which together funded 90% of the HGP human sequencing effort. The other nations wishing to remain in the HGP consortium had to accommodate to the Bermuda Principles, requiring exceptions from incompatible existing or pending data access policies for publicly funded research in Germany, Japan, and France. We begin this story in 1963, with the biologist Sydney Brenner’s proposal for a nematode research program at the Laboratory of Molecular Biology at the University of Cambridge. We continue through 2003, with the completion of the HGP human reference genome, and conclude with observations about policy and the historiography of molecular biology. (shrink)

This paper explores multiple experimental interventions in molecular biology. By “multiple,” we mean that molecular biologists often use different modes of experimental interventions in a series of experiments for one and the same subject. In performing such a series of experiment, scientists may use different modes of interventions to realize plural goals such as testing given hypotheses and exploring novel phenomena. In order to illustrate this claim, we develop a framework of multiple modes of experimental interventions to analyze a series (...) of experiments for a single subject. Our argument begins with a brief characterization of Craver and Darden’s taxonomy of experiments, because the taxonomy they have made implies various modes of interventions. We propose to extract two interventional directions and two interventional effects from their taxonomy as the basis of classification. The vertical or inter-level direction means that an intervention is performed between different levels of organization and the horizontal or inter-stage direction means that an intervention is performed between different stages of a mechanism. Interventions may produce an excitatory or an inhibitory effect. As a consequence, we can classify modes of interventions according to different directions and effects. We illustrate our claims by doing a case study of the PaJaMo experiment, which is a series of experiments for a single subject. The final goal in this paper is to provide a taxonomy of characteristics of experimentation in which the PaJaMo experiment is adequately located. (shrink)

In the last decade, Systems Biology has emerged as a conceptual and explanatory alternative to reductionist-based approaches in molecular biology. However, the foundations of this new discipline need to be fleshed out more carefully. In this paper, we claim that a relational ontology is a necessary tool to ground both the conceptual and explanatory aspects of Systems Biology. A relational ontology holds that relations are prior—both conceptually and explanatory—to entities, and that in the biological realm entities are defined primarily by (...) the context they are embedded within—and hence by the web of relations they are part of. (shrink)

Molecular biologists exploit information conveyed by mechanistic models for experimental purposes. In this article, I make sense of this aspect of biological practice by developing Keller’s idea of the distinction between ‘models of’ and ‘models for’. ‘Models of (phenomena)’ should be understood as models representing phenomena and are valuable if they explain phenomena. ‘Models for (manipulating phenomena)’ are new types of material manipulations and are important not because of their explanatory force, but because of the interventionist strategies they afford. This (...) is a distinction between aspects of the same model. In molecular biology, models may be treated either as ‘models of’ or as ‘models for’. By analysing the discovery and characterization of restriction–modification systems and their exploitation for DNA cloning and mapping, I identify the differences between treating a model as a ‘model of’ or as a ‘model for’. These lie in the cognitive disposition of the modeller towards the model: a modeller will look at a model as a ‘model of’ if interested in its explanatory force, or as a ‘model for’ if interested in the material manipulations it can possibly afford. (shrink)

The history of twentieth-century life sciences is not exactly a new topic. However, in view of the increasingly rapid development of the life sciences themselves over the past decades, some of the well-established narratives are worth revisiting. Taking stock of where we stand on these issues was the aim of a conference in 2015, entitled “Perspectives for the History of Life Sciences”. The papers in this topical collection are based on work presented and discussed at and around this meeting. Just (...) as the conference, the collection aims at exploring fields in the history of life sciences that appear understudied, sources that have been overlooked, and novel ways of engaging with this material. The papers convened in this collection may not be representative of the field as a whole; but we feel that they do indicate some elements that have received emphasis in recent years, and may become more central in the years to come, such as the history of previously neglected contexts and domains of the life sciences, the question of continuity and change on the level of practices, the history of complexity and diversity in twentieth-century life sciences and the reconsideration of the relationship between history and philosophy of life sciences. (shrink)

Biological modalities (e.g., biological possibility, necessity and counterfactuality) play an important explanatory role in biological practice. However, biological modalities lack truth conditions and the inferential relationship between biological and other modalities is unclear. This thesis addresses these problems, first, by improving upon Daniel Dennett's Library of Mendel. Second, a family of modal logics is introduced. In the simplest model, states are interpreted as codons, the binary relation is interpreted as single substitution mutation and the valuation induces a partition of blocks (...) of codons that code for some amino acid. In addition, the proposed framework allows for a grading of biological possibility and captures various competing notions of biological possibility. Applications include a model checker and a lawless Lewis-style semantics for biological counterfactuals. In short, this thesis lays the groundwork for a theory of biological modalities. (shrink)

In the 1950s and 1960s, an interfield interaction between molecular biologists and biochemists integrated important discoveries about the mechanism of protein synthesis. This extended discovery episode reveals two general reasoning strategies for eliminating gaps in descriptions of the productive continuity of mechanisms: schema instantiation and forward chaining/backtracking. Schema instantiation involves filling roles in an overall framework for the mechanism. Forward chaining and backtracking eliminate gaps using knowledge about types of entities and their activities. Attention to mechanisms highlights salient features of (...) this historical episode while providing general reasoning strategies for mechanism discovery. (shrink)

An important strategy in the discovery of biological mechanisms involves the piecing together of experimental results from interventions. However, if mechanisms are investigated by means of ideal interventions, as defined by James Woodward and others, then the kind of information revealed is insufficient to discriminate between modular and non-modular causal contributions. Ideal interventions suffice for constructing webs of causal dependencies that can be used to make some predictions about experimental outcomes, but tell us little about how causally relevant factors are (...) organized together and how they interact with each other in order to produce a phenomenon. I argue that lab research relies on more elaborated types of interventions targeting in a controlled fashion multiple variables at the same time in order to probe the temporal organization of causally-relevant factors along distinct causal pathways and to test for non-modular interaction effects, thus providing crucial spatial-temporal constraints guiding the formulation of more detailed mechanistic explanations. (shrink)

The article addresses the issue of dynamics of science, in particular of new sciences born in twentieth century and developed after the Second World War (information science, materials science, life science). The article develops the notion of search regime as an abstract characterization of dynamic patterns, based on three dimensions: the rate of growth, the degree of internal diversity of science and the associated dynamics (convergent vs. proliferating), and the nature of complementarity. The article offers a conceptual discussion for the (...) argument that new sciences follow a different pattern than established sciences and presents preliminary evidence drawn from original data in particle physics, computer science and nanoscience. (shrink)

The majority of G protein-coupled receptors (GPCRs) self-assemble in the form dimeric/oligomeric complexes along the plasma membrane. Due to the molecular interactions they participate, GPCRs can potentially provide the framework for discriminating a wide variety of intercellular signals, as based on some kind of combinatorial receptor codes. GPCRs can in fact transduce signals from the external milieu by modifying the activity of such intracellular proteins as adenylyl cyclases, phospholipases and ion channels via interactions with specific G-proteins. However, in spite of (...) the number of cell functions they can actually control, both GPCRs and their associated signal transduction pathways are extremely well conserved, for only a few alleles with null or minor functional alterations have so far been found. This would seem to suggest that, beside a mechanism for DNA repairing, there must be another level of quality control that may help maintaining GPCRs rather stable throughout evolution. We propose here receptor oligomerization to be a basic molecular mechanism controlling GPCRs redundancy in many different cell types, and the plasma membrane as the first hierarchical cell structure at which selective categorical sensing may occur. Categorical sensing can be seen as the cellular capacity for identifying and ordering complex patterns of mixed signals out of a contextual matrix, i.e., the recognition of meaningful patterns out of ubiquitous signals. In this context, redundancy and degeneracy may appear as the required feature to integrate the cell system into functional units of progressively higher hierarchical levels. (shrink)

Knowing how introns originated should greatly enhance our understanding of the information we carry in our DNA. Gilbert’s suggestion that introns initially arose to facilitate recombination still stands, though not for the reason he gave. Reanney’s alternative, that evolution, from the early “RNA world” to today’s DNA-based world, would require the ability to detect and correct errors by recombination, now seems more likely. Consistent with this, introns are richer than exons in the potential to extrude the stem-loop structures needed for (...) the homology search that can lead to heteroduplex formation and the recognition of base mismatches. In nucleic acid sequences that were unable concomitantly to encode sufficient stem-loop potential, protein-encoding potential was constrained to arise as segments (exons) interrupted by segments rich in stem-loop potential (introns). Thus, sequences with properties that we now deem intronic are likely to have preceded the emergence of exons. (shrink)

Evolutionary systems biology (ESB) is a rapidly growing integrative approach that has the core aim of generating mechanistic and evolutionary understanding of genotype‐phenotype relationships at multiple levels. ESB's more specific objectives include extending knowledge gained from model organisms to non‐model organisms, predicting the effects of mutations, and defining the core network structures and dynamics that have evolved to cause particular intracellular and intercellular responses. By combining mathematical, molecular, and cellular approaches to evolution, ESB adds new insights and methods to the (...) modern evolutionary synthesis, and offers ways in which to enhance its explanatory and predictive capacities. This combination of prediction and explanation marks ESB out as a research manifesto that goes further than its two contributing fields. Here, we summarize ESB via an analysis of characteristic research examples and exploratory questions, while also making a case for why these integrative efforts are worth pursuing. (shrink)

The comprehension of living organisms in all their complexity poses a major challenge to the biological sciences. Recently, systems biology has been proposed as a new candidate in the development of such a comprehension. The main objective of this paper is to address what systems biology is and how it is practised. To this end, the basic tools of a systems biological approach are explored and illustrated. In addition, it is questioned whether systems biology ‘revolutionizes’ molecular biology and ‘transcends’ its (...) assumed reductionism. The strength of this claim appears to depend on how molecular and systems biology are characterised and on how reductionism is interpreted. Doing credit to molecular biology and to methodological reductionism, it is argued that the distinction between molecular and systems biology is gradual rather than sharp. As such, the classical challenge in biology to manage, interpret and integrate biological data into functional wholes is further intensified by systems biology’s use of modelling and bioinformatics, and by its scale enlargement. (shrink)

Collecting, comparing, and computing molecular sequences are among the most prevalent practices in contemporary biological research. They represent a specific way of producing knowledge. This paper explores the historical development of these practices, focusing on the work of Margaret O. Dayhoff, Richard V. Eck, and Robert S. Ledley, who produced the first computer-based collection of protein sequences, published in book format in 1965 as the Atlas of Protein Sequence and Structure. While these practices are generally associated with the rise of (...) molecular evolution in the 1960s, this paper shows that they grew out of research agendas from the previous decade, including the biochemical investigation of the relations between the structures and function of proteins and the theoretical attempt to decipher the genetic code. It also shows how computers became essential for the handling and analysis of sequence data. Finally, this paper reflects on the relationships between experimenting and collecting as two distinct "ways of knowing" that were essential for the transformation of the life sciences in the twentieth century. (shrink)

DNA methylation is a quintessential epigenetic mechanism. Widely considered a stable regulator of gene silencing, it represents a form of “molecular braille,” chemically printed on DNA to regulate its structure and the expression of genetic information. However, there was a time when methyl groups simply existed in cells, mysteriously speckled across the cytosine building blocks of DNA. Why was the code of life chemically modified, apparently by “no accident of enzyme action” (Wyatt 1951 )? If all cells in a body (...) share the same genome sequence, how do they adopt unique functions and maintain stable developmental states? Do cells remember? In this historical perspective, I review epigenetic history and principles and the tools, key scientists, and concepts that brought us the synthesis and discovery of prokaryotic and eukaryotic methylated DNA. Drawing heavily on Gerard Wyatt’s observation of asymmetric levels of methylated DNA across species, as well as to a pair of visionary 1975 DNA methylation papers, 5-methylcytosine is connected to DNA methylating enzymes in bacteria, the maintenance of stable cellular states over development, and to the regulation of gene expression through protein-DNA binding. These works have not only shaped our views on heritability and gene regulation but also remind us that core epigenetic concepts emerged from the intrinsic requirement for epigenetic mechanisms to exist. Driven by observations across prokaryotic and eukaryotic worlds, epigenetic systems function to access and interpret genetic information across all forms of life. Collectively, these works offer many guiding principles for our epigenetic understanding for today, and for the next generation of epigenetic inquiry in a postgenomics world. (shrink)

The experimental practice in contemporary molecular biology oscillates between the creativity of the researcher in tinkering with the experimental system, and the necessity of standardization of methods of inquiry. Experimental procedures, when standardized in lab protocols, might definitely be seen as actual recipes. Considering these protocols as recipes can help us understand some epistemological characteristics of current practice in molecular biology. On the one hand, protocols represent a common ground, i.e. the possibility of reproducibility, which constitutes one of the essential (...) properties for contemporary science to define an actual discovery. At the same time, however, protocols are flexible enough to be adapted by the individual researcher (within a space of maneuver given by the experimental system and by the practices that each individual discipline gives to itself) to his/her specific needs. These variations, just like the recipes, remind us that the legitimacy of an experimental practice, involves both objective and subjective constraints and it is articulated on a fuzzy background rather than a rigid and clear context. Moreover, looking at experiments according to this perspective can provide a key to understanding how different forms of science (which adopt different methodologies but which investigate the same phenomena), such as computational biology, are precisely different in the use of a different “cookbook”.Indeed, given the procedural/operational realism of biologists towards phenomena, the clash of different procedures has opened a discussion also about the nature and the meaning of the obtained results. Thus, according to the recipe-perspective that, the methodological struggle over the nature of biological phenomena (and their ways of discovery) among scientists, might be seen as a not always explicit, epistemological debate, however coming from the practice of science itself. (shrink)

This paper investigates continuities and changes in the definition of sickle cell disease in 1950s Brazil, taking into account that diseases have a history and are recognized as such according to the knowledge and perceptions available in a certain historical period and specific location. In the post-war era, new diagnostic tools, inheritance theories and, in particular, discussions on the concepts of race and racial relations, both nationally and internationally, were changing previous racialist and racist views. Nonetheless, the Brazilian medical interpretations (...) of sickle cell disease continued to racialize it and even use deep-rooted racist formulations to explain its symptoms or the existence of the disease. It is argued that the celebration of racial mixture and racial democracy might have concealed racist presumptions biasing the study of sickle cell disease. Although race as a biological concept gradually gave way to other genetic expressions, in Brazilian medical papers on sickle cell disease, race continued to influence the interpretation of the disease, along with the persistence of concepts of heredity through blood mixture. (shrink)

In this paper, rather than focusing on genes as an organising concept around which historical considerations of theory and practice in genetics are elucidated, we place genetic markers at the heart of our analysis. This reflects their central role in the subject of our account, livestock genetics concerning the domesticated pig, Sus scrofa. We define a genetic marker as a element existing in different forms in the genome, that can be identified and mapped using a variety of quantitative, classical and (...) molecular genetic techniques. The conjugation of pig genome researchers around the common object of the marker from the early-1990s allowed the distinctive theories and approaches of quantitative and molecular genetics concerning the size and distribution of gene effects to align in projects to populate genome maps. Critical to this was the nature of markers as ontologically inert, internally heterogeneous and relational. Though genes as an organising and categorising principle remained important, the particular concatenation of limitations, opportunities, and intended research goals of the pig genetics community, meant that a progressively stronger focus on the identification and mapping of markers rather than genes per se became a hallmark of the community. We therefore detail a different way of doing genetics to more gene-centred accounts. By doing so, we reveal the presence of practices, concepts and communities that would otherwise be hidden. (shrink)

This paper looks at the commodification of interferon, marketed by Hoffmann La Roche as Roferon A in 1986, as a case study that helps us understand the role of pharmaceutical industry in cancer research, the impact of molecular biology on cancer therapy, and the relationships between biotech start-ups and established pharmaceutical firms. Drawing extensively on materials from the Roche company archives, the paper traces interferon’s trajectory from observed phenomenon to product. Roche embraced molecular biology in the late 1960s to prepare (...) for the moment when the patents on some of its bestselling drugs were going to expire. The company funded two basic science institutes to gain direct access to talents and scientific leads. These investments, I argue, were crucial for Roche’s success with recombinant interferon, along with more mundane, technical and regulatory know-how held at Roche’s Nutley base. The paper analyses in some detail the development process following the initial success of cloning the interferon gene in collaboration with Genentech. It looks at the factors necessary to scale up the production sufficiently for clinical trials. Using Alfred Chandler’s concept of ‘organizational capabilities’, I argue that the process is better described as ‘mobilisation’ than as ‘translation’. (shrink)

Laboratory manuals, notebooks and instrumentation from Otto Warburg’s Institute of Cell Physiology have been discovered at the Max Planck Institute of Biochemistry. Following Warburg’s death in 1970 one of his technicians was transferred from Berlin-Dahlem to the newly founded biochemical institute at Martinsried near Munich, and brought with him these resources, which epitomize the singular position of Warburg’s work style and institute in the 1950s and 1960s. Since the technician’s skills and apparently outmoded instrumentation like the Warburg apparatus were still (...) used in the context of 1970s membrane biochemistry, this trove also documents an unexpected continuity of research within the life sciences. Moreover, the service of Warburg’s technician, which spans more than four decades, as well as the meticulous documentation of preparations and experiments, serve as a case in point for the importance of routine and rather mundane techniques in the post-war molecular life sciences. (shrink)

ZusammenfassungDie aDNA-Forschung hat die Geschichtswissenschaft erreicht. Das Anliegen dieses Beitrags ist es, Wissen über die historische Gewordenheit des epistemischen Objekts alte DNA und des überfachlichen Forschungsfeldes, das sich mit ihr befasst, in die aktuelle Diskussion über den Stellenwert molekulargenetischer Quellen und Verfahren zur Bearbeitung historischer Fragestellungen einzubringen. Über den Bezug zum gemeinsamen Wissensgegenstand DNA traten ForscherInnen und Forscher aus verschiedenen Fächern und Disziplinen der Natur-, Kultur- und Geisteswissenschaften miteinander in Kontakt. Als Zeichen der Molekularisierung der Wissenschaften und der Gesellschaft kann (...) man ansehen, dass diese Fächer sich eine molekulare Erkenntnisebene geschaffen, DNA zur Quelle für historische Fragestellungen definiert und damit für das Geschichtsbewusstsein relevant gemacht haben. Die Entwicklung dieses Forschungsfeldes seit den 1980er Jahren lässt sich mit dem Modell des Hype Cycle beschreiben. Auf dem Weg zu seinem momentanen Produktivitätsniveau erwiesen sich Kontaminationen und Authentifizierungsschwierigkeiten als die zentrale technische und methodische Herausforderung. Die Fragen, ob genetische und soziokulturelle Daten und Konzepte, DNA-Quellen, Sachgut und Schriftquellen miteinander in Bezug gesetzt werden können und dürfen, und wem die Interpretationshoheit zukommen soll, gerieten hingegen zum wichtigsten Thema der überfachlichen Debatten. (shrink)

Biomedical ontologies are considered a serious innovation for biomedical research and clinical practice. They promise to integrate information coming from different biological databases thus creating a common ground for the representation of knowledge in all the life sciences. Such a tool has potentially many implications for both basic biomedical research and clinical practice. Here I discuss how this tool has been generated and thought. Due to the analysis of some empirical cases I try to elaborate how biomedical ontologies constitute a (...) novelty also from an epistemological point of view. (shrink)

Laboratory manuals, notebooks and instrumentation from Otto Warburg’s Institute of Cell Physiology have been discovered at the Max Planck Institute of Biochemistry. Following Warburg’s death in 1970 one of his technicians was transferred from Berlin-Dahlem to the newly founded biochemical institute at Martinsried near Munich, and brought with him these resources, which epitomize the singular position of Warburg’s work style and institute in the 1950s and 1960s. Since the technician’s skills and apparently outmoded instrumentation like the Warburg apparatus were still (...) used in the context of 1970s membrane biochemistry, this trove also documents an unexpected continuity of research within the life sciences. Moreover, the service of Warburg’s technician, which spans more than four decades, as well as the meticulous documentation of preparations and experiments, serve as a case in point for the importance of routine and rather mundane techniques in the post-war molecular life sciences. (shrink)

During the 1960s, Howard M. Temin (1934-1994), dared to advocate a "heretical" hypothesis that appeared to be at variance with the central dogma of molecular biology, understood by many to imply that information transfer in nature occurred only from DNA to RNA. Temin's provirus hypothesis offered a simple explanation of both virus replication and viral-induced cancer and stated that Rous sarcoma virus, an RNA virus, is replicated via a DNA intermediate. Popular accounts of this scientific episode, written after the discovery (...) of an RNA-directed DNA polymerase in 1970, tend to describe the reaction to his proposition as ardent opposition. Typically these accounts use a 'molecular biology' standpoint emphasizing the central dogma's part in its rejection. In this article, however, this episode will be examined from a joint perspective of virology and experimental cancer research. From this perspective it is clear that Temin's work was well within the epistemological and methodological boundaries of virology and cancer research. Still, scientists did have reasons to doubt the provirus hypothesis, but these do not seem to be good enough to either justify an account that portrays Temin as a renegade or his ideas as heretical. (shrink)

Causal complexities involved in biological phenomena often generate ambiguous experimental results that may create epistemic niches for new approaches and interpretations. The exploration for new approaches may foment momentum of larger epistemological shifts, and thereby introduce the possibilities of adopting new technologies. This paper describes British molecular biologist Robin Holliday’s cell aging research from 1963 to the 1980s that transformed from simple hypothesis testing to working on various alternative and integrative approaches designed to deal with complex data. In the 1960s, (...) hoping to use biochemical investigations of cells to settle a debate about whether DNA mutations or protein errors caused aging, Holliday carried out a series of experiments with fruit flies, fungi, and human fibroblast cells. The results seemed to demonstrate that cytoplasmic protein errors caused cell aging. However, other scientists obtained contradictory results and raised issues about potential flaws in Holliday’s experiments. In the 1970s, working as the director of the Genetics Division of the National Institute for Medical Research in Mill Hill, United Kingdom, Holliday relied on available talents of his associates, including computational expertise, to explore alternative hypotheses and approaches. By the early 1980s, they had worked out an epigenetic explanation and had established integrative, evolutionary models of cell aging that incorporated both DNA mutations and protein errors as critical factors. By delineating Holliday’s research path from simply testing hypotheses to integrating multiple factors involved in aging, this paper offers an account of the difficulties in targeting molecular cause in cell aging around the 1970s, whose failures nevertheless opened up an epistemic niche for integration. (shrink)

Este artículo tiene por objetivo general indagar acerca de los procesos de institucionalización de una nueva disciplina científica. En particular, se analizan los desplazamientos que se producen entre disciplinas al emerger una nueva: la biología molecular. Se presenta en este artículo el caso del Instituto Nacional de Tecnología Agropecuaria (INTA) de Argentina, institución creada en 1956 para realizar investigaciones, innovaciones y extensionismo para el sector agropecuario. De esa manera, el trabajo presenta los cambios en las disciplinas de las que provienen (...) los investigadores del INTA, desde su creación en 1956 hasta 2010. La investigación que se presenta se centra en un análisis cuantitativo en relación a las disciplinas de origen de los investigadores que se incorporaron a la institución. Al mostrar los desplazamientos entre disciplinas, este artículo pretende contribuir al estudio sobre los conflictos entre las mismas. Pues se sugiere que la emergencia de una nueva disciplina no implica solamente la apertura de nuevas profesiones, instituciones, temas y técnicas de investigación, sino también el desplazamiento de otras anteriormente instaladas, y que tales desplazamientos estarían en la raíz de las tensiones que se registran en la institucionalización de una nueva disciplina. This article aims to investigate the process of institutionalization of a new scientific discipline. In particular, the displacements that occur between disciplines with the emergence of a new one: molecular biology. The case presented in this article is the National Institute of Agricultural Technology (INTA) of Argentina, institution created in 1956 for research, innovation and extension to the agricultural sector. Thus, the paper presents the changes in the disciplines from which INTA's researchers come, since its inception in 1956 until 2010. The research presented in this article focuses on a quantitative analysis in relation to the disciplines of origin of the researchers who joined the institution. By showing the displacements between disciplines, this article aims to contribute to the study of the conflicts between them. For it suggests that the emergence of a new discipline involves not only the opening of new professions, institutions, research subjects and techniques, but also the displacement of other previously installed. These displacements would be at the root of the tensions that occur in the institutionalization of a new discipline. (shrink)

Philosophers have traditionally conceived of discovery in terms of internal cognitive acts. Close consideration of Rosalind Franklin's role in the discovery of the DNA double helix, however, reveals some problems with this traditional conception. This article argues that defining discovery in terms of mental operations entails problematic conclusions and excludes acts that should fall within the domain of discovery. It proposes that discovery be expanded to include external acts of making visible. Doing so allows for a reevaluation of Franklin's role (...) in the discovery of the structure of DNA. (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)

This paper examines the “biotechnology problem” in the history of molecular biology, namely the alleged reinvention of a basic academic discipline looking for the logic of life, into a typical technoscientific enterprise, closely related to agriculture, medicine, and the construction of markets. The dominant STS model sees the roots of this shift in a radical change of the regime of knowledge production. The paper argues that this scheme needs to be historicized to take into account the past in our biotech (...) present. Looking at the development of breast cancer genetic testing and GMOs as examples of mounting issues of intellectual property, risk and regulation, the paper also argues that historians of biology should pay closer attention to the political, the economical and the legal changes of the last thirty years. Solving the biotech problem requires new categories. The notion of “way of regulating” is given as an example of such notions linking the local and the global. (shrink)

In this paper, I discuss the discovery of the DNA structure by Francis Crick and James Watson, which has provoked a large historical literature but has yet not found entry into philosophical debates. I want to redress this imbalance. In contrast to the available historical literature, a strong emphasis will be placed upon analysing the roles played by theory, model, and evidence and the relationship between them. In particular, I am going to discuss not only Crick and Watson's well-known model (...) and Franklin's x-ray diffraction pictures (the evidence) but also the less well known theory of helical diffraction, which was absolutely crucial to Crick and Watson's discovery. The insights into this groundbreaking historical episode will have consequences for the ‘new’ received view of scientific models and their function and relationship to theory and world. The received view, dominated by works by Cartwright and Morgan and Morrison ([1999]), rather than trying to put forth a ‘theory of models’, is interested in questions to do with (i) the function of models in scientific practice and (ii) the construction of models. In regard to (i), the received view locates the model (as an idealized, simplified version of the real system under investigation) between theory and the world and sees the model as allowing the application of the former to the latter. As to (ii) Cartwright has argued for a phenomenologically driven view and Morgan and Morrison ([1999]) for the ‘autonomy’ of models in the construction process: models are determined neither by theory nor by the world. The present case study of the discovery of the DNA structure strongly challenges both (i) and (ii). In contrast to claim (i) of the received view, it was not Crick and Watson's model but rather the helical diffraction theory which served a mediating purpose between the model and the x-ray diffraction pictures. In particular, Cartwright's take on (ii) is refuted by a comparison of Franklin's bottom-up approach with Crick and Watson's top-down approach in constructing the model. The former led to difficulties, which only a strong confidence in the structure incorporated in the model could circumvent. How to Get to the Structure 1.1 X-ray diffraction and its synthesis 1.2 Model building and Pauling's panache 1.3 The structure of proteins 1.3.1 A failed inference to the best explanation 1.3.2 The misleading 5.1 Å spot in proteins and how to get rid of it 1.3.3 Derived predictions from Pauling's alpha-helix of protein molecules The CCV Theory of Helical X-Ray Diffraction 2.1 The role of the CCV theory in the discovery of the DNA structure Killing the Helix 3.1 Appreciating all evidence—in vain Conclusion Epilogue: Chargaff's Ratios CiteULike Connotea Del.icio.us What's this? (shrink)