The importance of viruses as model organisms is well-established in molecular biology and Max Delbrück’s phage group set standards in the DNA phage field. In this paper, I argue that RNA phages, discovered in the 1960s, were also instrumental in the making of molecular biology. As part of experimental systems, RNA phages stood for messenger RNA, genes and genome. RNA was thought to mediate information transfers between DNA and proteins. Furthermore, RNA was more manageable at the bench than DNA due (...) to the availability of specific RNases, enzymes used as chemical tools to analyse RNA. Finally, RNA phages provided scientists with a pure source of mRNA to investigate the genetic code, genes and even a genome sequence. This paper focuses on Walter Fiers’ laboratory at Ghent University and their work on the RNA phage MS2. When setting up his Laboratory of Molecular Biology, Fiers planned a comprehensive study of the virus with a strong emphasis on the issue of structure. In his lab, RNA sequencing, now a little-known technique, evolved gradually from a means to solve the genetic code, to a tool for completing the first genome sequence. Thus, I follow the research pathway of Fiers and his ‘RNA phage lab’ with their evolving experimental system from 1960 to the late 1970s. This study illuminates two decisive shifts in post-war biology: the emergence of molecular biology as a discipline in the 1960s in Europe and of genomics in the 1990s. (shrink)

Fred Sanger, the inventor of the first protein, RNA and DNA sequencing methods, has traditionally been seen as a technical scientist, engaged in laboratory bench work and not interested at all in intellectual debates in biology. In his autobiography and commentaries by fellow researchers, he is portrayed as having a trajectory exclusively dependent on technological progress. The scarce historical scholarship on Sanger partially challenges these accounts by highlighting the importance of professional contacts, institutional and disciplinary moves in his career, spanning (...) from 1940 to 1983. This paper will complement such literature by focusing, for the first time, on the transition of Sanger’s sequencing strategies from degrading to copying the target molecule, which occurred in the late 1960s as he was shifting from protein and RNA to DNA sequencing, shortly after his move from the Department of Biochemistry to the Laboratory of Molecular Biology, both based in Cambridge (UK). Through a reinterpretation of Sanger’s papers and retrospective accounts and a pioneering investigation of his laboratory notebooks, I will claim that sequencing shifted from the working procedures of organic chemistry to those of the emergent molecular biology. I will also argue that sequencing deserves a history in its own right as a practice and not as a technique subordinated to the development of molecular biology or genomics. My proposed history of sequencing leads to a reappraisal of current STS debates on bioinformatics, biotechnology and biomedicine. (shrink)

Causal selection has to do with the distinction we make between background conditions and “the” true cause or causes of some outcome of interest. A longstanding consensus in philosophy views causal selection as lacking any objective rationale and as guided, instead, by arbitrary, pragmatic, and non-scientific considerations. I argue against this position in the context of causal selection for disease traits. In this domain, causes are selected on the basis of the type of causal control they exhibit over a disease (...) of interest. My analysis clarifies the principled rationale that guides this selection and how it involves both pragmatic and objective considerations, which have been overlooked in the extant literature. (shrink)

RESUMENEl desarrollo embriológico es un fenómeno que ha inspirado la especulación filosófica desde temprano en la historia del pensamiento. Desde los tiempos de Aristóteles dos modelos conceptuales antitéticos se han utilizado tradicionalmente para comprender la embriogénesis: o el embrión posee ya una forma o estructura, o ésta se forma de nuevo en cada generación. Nuestro objetivo en este artículo es mostrar que el contraste entre la posición preformacionista y epigenética persiste a pesar de los formidables avances teóricos y experimentales de (...) la biología del desarrollo contemporánea. El preformacionismo y la epigénesis han perfeccionado constantemente sus posiciones en el curso de la historia con el fin de responder a los retos conceptuales de la época. Este continuo proceso de transformación ha dado lugar a una convergencia parcial entre las dos posiciones. Sin embargo, vamos a argumentar que, a pesar de los esfuerzos por conciliar ambas posturas, esta antinomia, que se erige como una de las más fundamentales de la biología, no será fácil de superar. ABSTRACTThe process of development of the embryo has inspired philosophical speculation since the advent of Western thought. Since the time of Aristotle two antithetical conceptual models have traditionally been used to understand embryogenesis: either form or structure is preformed in the embryo or it is newly formed with each generation. Our aim in this article is to show that the contrast between the pre-formationist and epigenetic positions persists despite the formidable theoretical and experimental advances of contemporary developmental biology. Pre-formationism and epigenesis have constantly refined their positions in the course of history in order to answer the conceptual challenges of each epoch. This process of continuous transformation has resulted in a partial convergence of the two positions. However, we shall argue that, despite the partial successes of this process of continuous convergence, one of the most fundamental antinomies in biology persists. (shrink)

Griffiths and Stotz’s Genetics and Philosophy: An Introduction offers a very good overview of scientific and philosophical issues raised by present-day genetics. Examining, in particular, the questions of how a “gene” should be defined and what a gene does from a causal point of view, the authors explore the different domains of the life sciences in which genetics has come to play a decisive role, from Mendelian genetics to molecular genetics, behavioural genetics, and evolution. In this review, I highlight what (...) I consider as the two main theses of the book, namely: genes are better conceived as tools; genes become causes only in a context. I situate these two theses in the wider perspective of developmental systems theory. This leads me to emphasize that Griffiths and Stotz reflect very well an on going process in genetics, which I call the “epigenetization” of genetics, i.e., the growing interest in the complex processes by which gene activation is regulated. I then make a factual objection, which is that Griffiths and Stotz have almost entirely neglected the perspective of ecological developmental biology, and more precisely recent work on developmental symbioses, and I suggest that this omission is unfortunate in so far as an examination of developmental symbioses would have considerably strengthened Griffiths and Stotz’s own conclusions. (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)

ABSTRACT. This paper contemplates Organicism and its relation with molecular and evolutionary biology. We explore whether twentieth-first century biology is returning to positions held at the beginning of the twentieth century and then abandoned. The guiding line is a history of theoretical biology in which we distinguish three periods: 1. The 20s-30s, and the Theoretical Biology Club (Needham, Woodger, and Waddington, among others); 2. An intermediate period in the 60s-70s, in which, in spite of the eclosion of the molecular and (...) evolutionary biologies, there is some recovery of organicist positions, and 3. The present post-genomic situation, which is demanding a systemic approach. (shrink)

Fred Sanger, the inventor of the first protein, RNA and DNA sequencing methods, has traditionally been seen as a technical scientist, engaged in laboratory bench work and not interested at all in intellectual debates in biology. In his autobiography and commentaries by fellow researchers, he is portrayed as having a trajectory exclusively dependent on technological progress. The scarce historical scholarship on Sanger partially challenges these accounts by highlighting the importance of professional contacts, institutional and disciplinary moves in his career, spanning (...) from 1940 to 1983. This paper will complement such literature by focusing, for the first time, on the transition of Sanger's sequencing strategies from degrading to copying the target molecule, which occurred in the late 1960s as he was shifting from protein and RNA to DNA sequencing, shortly after his move from the Department of Biochemistry to the Laboratory of Molecular Biology, both based in Cambridge (UK). Through a reinterpretation of Sanger's papers and retrospective accounts and a pioneering investigation of his laboratory notebooks, I will claim that sequencing shifted from the working procedures of organic chemistry to those of the emergent molecular biology. I will also argue that sequencing deserves a history in its own right as a practice and not as a technique subordinated to the development of molecular biology or genomics. My proposed history of sequencing leads to a reappraisal of current STS debates on bioinformatics, biotechnology and biomedicine. (shrink)

The importance of viruses as model organisms is well-established in molecular biology and Max Delbrück's phage group set standards in the DNA phage field. In this paper, I argue that RNA phages, discovered in the 1960s, were also instrumental in the making of molecular biology. As part of experimental systems, RNA phages stood for messenger RNA (mRNA), genes and genome. RNA was thought to mediate information transfers between DNA and proteins. Furthermore, RNA was more manageable at the bench than DNA (...) due to the availability of specific RNases, enzymes used as chemical tools to analyse RNA. Finally, RNA phages provided scientists with a pure source of mRNA to investigate the genetic code, genes and even a genome sequence. This paper focuses on Walter Fiers’ laboratory at Ghent University (Belgium) and their work on the RNA phage MS2. When setting up his Laboratory of Molecular Biology, Fiers planned a comprehensive study of the virus with a strong emphasis on the issue of structure. In his lab, RNA sequencing, now a little-known technique, evolved gradually from a means to solve the genetic code, to a tool for completing the first genome sequence. Thus, I follow the research pathway of Fiers and his ‘RNA phage lab’ with their evolving experimental system from 1960 to the late 1970s. This study illuminates two decisive shifts in post-war biology: the emergence of molecular biology as a discipline in the 1960s in Europe and of genomics in the 1990s. (shrink)

I describe two traditions of philosophical accounts of evidence: one characterizes the notion in terms of signs of success, the other characterizes the notion in terms of conditions of success. The best examples of the former rely on the probability calculus, and have the virtues of generality and theoretical simplicity. The best examples of the latter describe the features of evidence which scientists appeal to in practice, which include general features of methods, such as quality and relevance, and general features (...) of evidence, such as patterns in data, concordance with other evidence, and believability of the evidence. Two infamous episodes from biomedical research help to illustrate these features. Philosophical characterization of these latter features—conditions of success—has the virtue of potential relevance to, and descriptive accuracy of, practices of experimental scientists. (shrink)

Philosophy may relate to interdisciplinarity in two distinct ways On the one hand, philosophy may play an auxiliary role in the process of interdisciplinarity, typically through conceptual analysis, in the understanding that the disciplines themselves are the main epistemic players. This version of the relationship I characterise as ‘normal’ because it captures the more common pattern of the relationship, which in turn reflects an acceptance of the division of organized inquiry into disciplines. On the other hand, philosophy may be itself (...) the site for the production of interdisciplinary knowledge, understood as a kind of second-order understanding of reality that transcends the sort of knowledge that the disciplines provide, left to their own devices. This is my own position, which I dub ‘deviant’ and to which most of this article is devoted. I begin by relating the two types of interdisciplinarity to the organization of inquiry, especially their respective attitudes to the history of science. Underlying the two types are contrasting notions of what constitutes the ‘efficient’ pursuit of knowledge. This difference is further explored in terms of the organization of the university. The normal/deviant distinction was already marked in the institution’s medieval origins in terms of the difference between Doctors and Masters, respectively, an artefact of which remains in the postgraduate/undergraduate degree distinction. In the context of the history of the university, the prospects for deviant interdisciplinarity were greatest from the early sixteenth to the early nineteenth century—the period called ‘early modern’ in the philosophy curriculum. Towards the end of that period, due to Kant and the generation of idealists who followed him, philosophy was briefly the privileged site for deviant interdisciplinarity. After Hegel’s death, the mantle of deviant interdisciplinarity increasingly passed to some version of ‘biology’. I explore the ‘Natur-’ and ‘Geisteswissenschaft’ versions of that post-philosophical vision, which continue to co-exist within today’s biological science. I then briefly examine the chequered reputation of Jean-Baptiste Lamarck, someone who exemplified the promise and perils of deviant interdisciplinarity over the past 200 years. I conclude with an Epilogue that considers contemporary efforts to engage philosophy in interdisciplinary work, invoking William James as an exemplar. (shrink)

The chemical characterization of the substance responsible for the phenomenon of “transformation” of pneumococci was presented in the now famous 1944 paper by Avery, MacLeod, and McCarty. Reception of this work was mixed. Although interpreting their results as evidence that deoxyribonucleic acid (DNA) is the molecule responsible for genetic changes was, at the time, controversial, this paper has been retrospectively celebrated as providing such evidence. The mixed and changing assessment of the evidence presented in the paper was due to the (...) work’s interpretive flexibility – the evidence was interpreted in various ways, and such interpretations were justified given the neophytic state of molecular biology and methodological limitations of Avery’s transformation studies. I argue that the changing context in which the evidence presented by Avery’s group was interpreted partly explains the vicissitudes of the assessments of the evidence. Two less compelling explanations of the reception are a myth-making account and an appeal to the wartime historical context of its publication. (shrink)

This paper argues that besides mechanistic explanations, there is a kind of explanation that relies upon “topological” properties of systems in order to derive the explanandum as a consequence, and which does not consider mechanisms or causal processes. I first investigate topological explanations in the case of ecological research on the stability of ecosystems. Then I contrast them with mechanistic explanations, thereby distinguishing the kind of realization they involve from the realization relations entailed by mechanistic explanations, and explain how both (...) kinds of explanations may be articulated in practice. The second section, expanding on the case of ecological stability, considers the phenomenon of robustness at all levels of the biological hierarchy in order to show that topological explanations are indeed pervasive there. Reasons are suggested for this, in which “neutral network” explanations are singled out as a form of topological explanation that spans across many levels. Finally, I appeal to the distinction of explanatory regimes to cast light on a controversy in philosophy of biology, the issue of contingence in evolution, which is shown to essentially involve issues about realization. (shrink)

‘‘Adaptive radiation’’ is an evocative metaphor for explosive evolutionary divergence, which for over 100 years has given a powerful heuristic to countless scientists working on all types of organisms at all phylogenetic levels. However, success has come at the price of making ‘‘adaptive radiation’’ so vague that it can no longer reflect the detailed results yielded by powerful new phylogeny-based techniques that quantify continuous adaptive radiation variables such as speciation rate, phylogenetic tree shape, and morphological diversity. Attempts to shoehorn the (...) results of these techniques into categorical ‘‘adaptive radiation: yes/no’’ schemes lead to reification, in which arbitrary quantitative thresholds are regarded as real. Our account of the life cycle of metaphors in science suggests that it is time to exchange the spent metaphor for new concepts that better represent the full range of diversity, disparity, and speciation rate across all of life. (shrink)

François Jacob is known as one of the key figures in the history of molecular biology. His elaboration, together with Jacques Monod, of the operon model and the basic features of the regulation of gene expression in bacteria, as well as the concept of genetic messenger, won him the Nobel Prize in 1965. Both notions were decisive for the novel imagery of molecular genetics in which the notion of information came to stand central. From a close reading, this article tries (...) to reconstruct how the new language of molecular genetics took shape in the scientific writings of Jacob. In particular, it analyzes how the notions of regulation, information, and language came to be articulated, and how this articulation changed and underwent modulations over time. It shows that a scientific language consists of several layers and thus, as a rule, forms a hybrid structure. The time span covered reaches from the early experiments done together with Monod and Arthur Pardee between 1958 and 1960, also known as the “PaJaMo” experiment, to Jacob’s book on the history of heredity, The Logic of Life, which appeared in 1970. (shrink)

In 1958, Francis Crick distinguished the flow of information from the flow of matter and the flow of energy in the mechanism of protein synthesis. Crick’s claims about information flow and coding in molecular biology are viewed from the perspective of a new characterization of mechanisms and from the perspective of information as holding a key to distinguishing work in molecular biology from that of biochemistry in the 1950s–1970s . Flow of matter from beginning to end does not occur in (...) the protein synthesis mechanism; flow of information does. The flow of information and coding in molecular biological mechanisms are distinguished, on the one hand, from formal information theory, and, on the other, from information as used in cognitive neuroscience, where information and representation are often coupled. (shrink)

This paper discussses various concepts of biological information with particular attention being paid to genetic information.

A notion of experimental series is developed, in which experiments or experimental sets are connected through experimental suggestions arising from previous experimental outcomes. To that end, the justification of Howard Temin’s DNA provirus hypothesis is examined. The hypothesis originated with evidence from two exploratory experimental sets on an oncogenic virus and was substantiated by including evidence from three additional experimental sets. Collectively these sets comprise an experimental series and the accumulative evidence from the series was adequate to justify the hypothesis (...) by persuading the virology community of its veracity. The notion of crucial experiment is also discussed in terms of experimental series. (shrink)

We outline three very different concepts of the gene—instrumental, nominal, and postgenomic. The instrumental gene has a critical role in the construction and interpretation of experiments in which the relationship between genotype and phenotype is explored via hybridization between organisms or directly between nucleic acid molecules. It also plays an important theoretical role in the foundations of disciplines such as quantitative genetics and population genetics. The nominal gene is a critical practical tool, allowing stable communication between bioscientists in a wide (...) range of fields grounded in well-defined sequences of nucleotides, but this concept does not embody major theoretical insights into genome structure or function. The post-genomic gene embodies the continuing project of understanding how genome structure supports genome function, but with a deflationary picture of the gene as a structural unit. This final concept of the gene poses a significant challenge to conventional assumptions about the relationship between genome structure and function, and between genotype and phenotype. (shrink)

The concept of mechanism is analyzed in terms of entities and activities, organized such that they are productive of regular changes. Examples show how mechanisms work in neurobiology and molecular biology. Thinking in terms of mechanisms provides a new framework for addressing many traditional philosophical issues: causality, laws, explanation, reduction, and scientific change.

According to Kuhn's speciation analogy, scientific specialisation is fundamentally analogous to biological speciation. In this paper, we extend Kuhn's original language-centred formulation of the speciation analogy, to account for episodes of scientific specialisation centred around methodological differences. Building upon recent views in evolutionary biology about the process of speciation by genetic divergence, we will show how these methodology-centred episodes of scientific specialisation can be understood as cases of specialisation driven by value divergence. We will apply our model of specialisation by (...) value divergence to an episode of methodology-centred scientific specialisation: the emergence of molecular biology. (shrink)

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)

According to the hypothesis-generator account, valid extrapolations from a source to a target system are circular, since they rely on knowledge of relevant similarities and differences that can onl...

This essay considers how scholarly approaches to the development of molecular biology have too often narrowed the historical aperture to genes, overlooking the ways in which other objects and processes contributed to the molecularization of life. From structural and dynamic studies of biomolecules to cellular membranes and organelles to metabolism and nutrition, new work by historians, philosophers, and STS scholars of the life sciences has revitalized older issues, such as the relationship of life to matter, or of physicochemical inquiries to (...) biology. This scholarship points to a novel molecular vista that opens up a pluralist view of molecularizations in the twentieth century and considers their relevance to current science. (shrink)

The use of multiple means of determination to “triangulate” on the existence and character of a common phenomenon, object, or result has had a long tradition in science but has seldom been a matter of primary focus. As with many traditions, it is traceable to Aristotle, who valued having multiple explanations of a phenomenon, and it may also be involved in his distinction between special objects of sense and common sensibles. It is implicit though not emphasized in the distinction between (...) primary and secondary qualities from Galileo onward. It is arguably one of several conceptions involved in Whewell’s method of the “consilience of inductions” (Laudan 1971) and is to be found in several places in Peirce. (From M. Brewer and B. Collins, eds., (1981); Scientific Inquiry in the Social Sciences (a festschrift for Donald T. Campbell), San Francisco: Jossey-Bass, pp. 123–162.). (shrink)

The theory of concepts advanced in the dissertation aims at accounting for a) how a concept makes successful practice possible, and b) how a scientific concept can be subject to rational change in the course of history. Traditional accounts in the philosophy of science have usually studied concepts in terms only of their reference; their concern is to establish a stability of reference in order to address the incommensurability problem. My discussion, in contrast, suggests that each scientific concept consists of (...) three components of content: 1) reference, 2) inferential role, and 3) the epistemic goal pursued with the concept's use. I argue that in the course of history a concept can change in any of these three components, and that change in one component—including change of reference—can be accounted for as being rational relative to other components, in particular a concept's epistemic goal.This semantic framework is applied to two cases from the history of biology: the homology concept as used in 19th and 20th century biology, and the gene concept as used in different parts of the 20th century. The homology case study argues that the advent of Darwinian evolutionary theory, despite introducing a new definition of homology, did not bring about a new homology concept (distinct from the pre-Darwinian concept) in the 19th century. Nowadays, however, distinct homology concepts are used in systematics/evolutionary biology, in evolutionary developmental biology, and in molecular biology. The emergence of these different homology concepts is explained as occurring in a rational fashion. The gene case study argues that conceptual progress occurred with the transition from the classical to the molecular gene concept, despite a change in reference. In the last two decades, change occurred internal to the molecular gene concept, so that nowadays this concept's usage and reference varies from context to context. I argue that this situation emerged rationally and that the current variation in usage and reference is conducive to biological practice.The dissertation uses ideas and methodological tools from the philosophy of mind and language, the philosophy of science, the history of science, and the psychology of concepts. (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)

The issue of the conservatism of scientific research questions the nature and the role of the internal and external forces controlling the emergence of new research questions or problems, the exploration of risky directions of research, or the use of risky research methods. This issue has recently gained a new framing in connection with the growing importance of the peer-review process and of the social and economic pressures weighing on the funding of scientific research. Current literature then interrogates the external (...) and internal features that promote what are described as conservative tendencies in scientific research. In this paper, I propose to contribute to this debate by clarifying what might be internal sources of conservatism in science; that is, that are inherent to the research process itself. I distinguish two possible understandings of the sources and manifestations of this internal conservatism. I first present a representational description of the nature and origin of conservatism in science, which brings to the fore the difficulties researchers find in setting aside their conceptual framework. I then offer for consideration a larger perspective on conservatism by arguing for the existence of a practical conservatism generated by all the dimensions of scientific activities. In this framework, conservatism in science can be explained by the tendency of all practices to close in on their own local objectives. I illustrate this view by reference to an historical episode: the discovery of the chemical nature of genes by Avery. (shrink)

It has become customary to conceptualize the living cell as an intricate piece of machinery, different to a man-made machine only in terms of its superior complexity. This familiar understanding grounds the conviction that a cell's organization can be explained reductionistically, as well as the idea that its molecular pathways can be construed as deterministic circuits. The machine conception of the cell owes a great deal of its success to the methods traditionally used in molecular biology. However, the recent introduction (...) of novel experimental techniques capable of tracking individual molecules within cells in real time is leading to the rapid accumulation of data that are inconsistent with an engineering view of the cell. This paper examines four major domains of current research in which the challenges to the machine conception of the cell are particularly pronounced: cellular architecture, protein complexes, intracellular transport, and cellular behaviour. It argues that a new theoretical understanding of the cell is emerging from the study of these phenomena which emphasizes the dynamic, self-organizing nature of its constitution, the fluidity and plasticity of its components, and the stochasticity and non-linearity of its underlying processes. (shrink)

We present two case studies from contemporary biology in which we observe conflicts between established and emerging approaches. The first case study discusses the relation between molecular biology and systems biology regarding the explanation of cellular processes, while the second deals with phylogenetic systematics and the challenge posed by recent network approaches to established ideas of evolutionary processes. We show that the emergence of new fields is in both cases driven by the development of high-throughput data generation technologies and the (...) transfer of modeling techniques from other fields. New and emerging views are characterized by different philosophies of nature, i.e. by different ontological and methodological assumptions and epistemic values and virtues. This results in a kind of conflict we call “epistemic competition” that manifests in two ways: On the one hand, opponents engage in mutual critique and defense of their fundamental assumptions. On the other hand, they compete for the acceptance and integration of the knowledge they provide by a broader scientific community. Despite an initial rhetoric of replacement, the views as well as the respective audiences come to be seen as more clearly distinct during the course of the debate. Hence, we observe—contrary to many other accounts of scientific change—that conflict results in the formation of new niches of research, leading to co-existence and perceived complementarity of approaches. Our model thus contributes to the understanding of the pluralization of the scientific landscape. (shrink)

Causal selection has to do with a distinction between mere background conditions and the "true" causes of some outcome of interest. Mainstream philosophical views claim that causal selection is "groundless" in the sense that it lacks any type of principled rationale. I argue against this position in the context of biochemistry where causal factors are selected in explanations of metabolic processes. These factors are selected on the basis of a principled rationale, which is best understood in terms of the causal (...) control that they provide over an outcome of interest. (shrink)

This paper argues that the “long 1970s” (1969–1983) is an important though often overlooked period in the development of a rich landscape in the research of metabolism, development, and evolution. The period is marked by: shrinking public funding of basic science, shifting research agendas in molecular biology, the incorporation of new phenomena and experimental tools from previous biological research at the molecular level, and the development of recombinant DNA techniques. Research was reoriented towards eukaryotic cells and development, and in particular (...) towards “giant” RNA processing and transcription. We will here focus on three different models of developmental regulation published in that period: the two models of eukaryotic genetic regulation at the transcriptional level that were developed by Georgii P. Georgiev on the one hand, and by Roy Britten and Eric Davidson on the other; and the model of genetic sufficiency and evolution of regulatory genes proposed by Emile Zuckerkandl. These three cases illustrate the range of exploratory hypotheses that characterised the challenging landscape of gene regulation in the 1970s, a period that in hindsight can be labelled as transitional, between the biology at the laboratory bench of the preceding period, and the biology of genetic engineering and intensive data-driven research that followed. (shrink)

This paper considers the theoretical circumstances that urged Michel Foucault to analyse modern societies in terms of biopower. Georges Canguilhem’s account of the relations between science and the living forms an essential starting point for Foucault’s own later explorations, though the challenges posed by the molecular revolution in biology and François Jacob’s history of it allowed Foucault to extend and transform Canguilhem’s philosophy of error. Using archival research into his 1955–1956 course on “Science and Error,” I show that, for Canguilhem, (...) it is inauthentic to treat a living being as an error, even if living things are capable of making errors in the domain of knowledge. The emergent molecular biology in the 1960s posed a grave challenge, however, since it suggested that individuals could indeed be errors of genetic reproduction. The paper discusses how Canguilhem and Foucault each responded to this by examining, among other texts, their respective reviews of Jacob’s The Logic of the Living. For Canguilhem this was an opportunity to reaffirm the creativity of life in the living individual, which is not a thing to be evaluated, but the source of values. For Foucault, drawing on Jacob’s work, this was the opportunity to develop a transformed account of valuation by posing biopower as the DNA of society. Despite their disagreements, the paper examines these three authors as different iterations of a historical epistemology attuned to errancy, error, and experimentation. (shrink)

In his late years, Thomas Kuhn became interested in the process of scientific specialization, which does not seem to possess the destructive element that is characteristic of scientific revolutions. It therefore makes sense to investigate whether and how Kuhn’s insights about specialization are consistent with, and actually fit, his model of scientific progress through revolutions. In this paper, I argue that the transition toward a new specialty corresponds to a revolutionary change for the group of scientists involved in such a (...) transition. I will clarify the role of the scientific community in revolutionary changes and characterize the incommensurability across specialties as possessing both semantic and methodological aspects. The discussion of the discovery of the structure of DNA will serve both as an illustration of my main argument and as reply to one criticism raised against Kuhn—namely, that his model cannot capture cases of revolutionary yet non-disruptive episodes of scientific progress. Revisiting Kuhn’s ideas on specialization will shed new light on some often overlooked features of scientific change. (shrink)

Although molecular biology has meant different things at different times, the term is often associated with a tendency to view cellular causation as conforming to simple linear schemas in which macro-scale effects are specified by micro-scale structures. The early achievements of molecular biologists were important for the formation of such an outlook, one to which the discovery of recombinant DNA techniques, and a number of other findings, gave new life even after the complexity of genotype–phenotype
relations had become apparent. Against this (...) background we outline how a range of scientific developments and conceptual considerations can be regarded as enabling and perhaps necessitating contemporary systems approaches. We suggest that philosophical ideas have a valuable part to play in making sense of complex scientific and disciplinary issues. (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)

Frederick Griffith was an English bacteriologist at the Pathological Laboratory of the Ministry of Health in London who believed that progress in the epidemiology and control of infectious diseases would come only with more precise knowledge of the identity of the causative microorganisms. Over the years, Griffith developed and expanded a serological technique for identifying pathogenic microorganisms, which allowed the tracing of the sources of infectious disease outbreaks: slide agglutination. Yet Griffith is not remembered for his contributions to the biology (...) and epidemiology of infectious diseases so much as for discovering the phenomenon known as ‘transformation’. Griffith’s discovery, for many, was a pure case of serendipity whose biological relevance had also largely escaped him. In this paper, I argue that the key to understanding the significance of bacterial transformation – and the scientific legacy of Fred Griffith – rests not only on it initiating a cascade of events leading to molecular genetics but also on its implications for epidemiology based on the biology of host–parasite interactions. Looking at Griffith’s entire career, instead of focusing only on the transformation study, we can better appreciate the place of the latter within Griffith’s overall contributions. Presented in this way, Griffith’s experiment on bacterial transformation also ceases to appear as an anomaly, which in turn leads us to rethink some of the most prevalent historical conceptions about his work. (shrink)

What is now familiarly referred to as the ‘embryonic stem (ES) cell’ is a recent biological category whose origins lie in research into benign and malignant teratomas carried out in the 1950s, 60s and 70s. In these studies, the question of the normal or pathological character of the ES cell was a matter of considerable debate and indeed the term ES cell was often used interchangeably with that of the embryonal carcinoma (EC) cell. This article argues that the indecisiveness of (...) the entity known as the ES cell—its refusal to commit to established demarcations between the normal and the pathological—continues to haunt the field of stem cell science. Exploring the prehistory of research into ES cells, early theories of cancer (in particular the embryonal theory expounded by Julius Cohnheim) and recent theoretical critiques of the somatic mutation theory, the article not only points to a shift in understandings of the normal and the pathological but asks under what conditions such shifts are able to take place. (shrink)

This chapter provides an introduction to the study of the philosophical notions of mechanisms and causality in biology and economics. This chapter sets the stage for this volume, Mechanism and Causality in Biology and Economics, in three ways. First, it gives a broad review of the recent changes and current state of the study of mechanisms and causality in the philosophy of science. Second, consistent with a recent trend in the philosophy of science to focus on scientific practices, it in (...) turn implies the importance of studying the scientific methods employed by researchers. Finally, by way of providing an overview of each chapter in the volume, this chapter demonstrates that biology and economics are two fertile fields for the philosophy of science and shows how biological and economic mechanisms and causality can be synthesized. (shrink)

A number of areas of biology raise questions about what is of value in the natural environment and how we ought to behave towards it: conservation biology, environmental science, and ecology, to name a few. Based on my experience teaching students from these and similar majors, I argue that the field of environmental ethics has much to teach these students. They come to me with pent-up questions and a feeling that more is needed to fully engage in their subjects, and (...) I believe some exposure to environmental ethics can help focus their interests and goals. I identify three primary areas in which environmental ethics can con- tribute to their education. The first is an examination of who (or what) should be considered to be part of our moral community (i.e., the community to whom we owe direct duties). Is it humans only? Or does it include all sentient life? Or all life? Or ecosystems considered holistically? Often, readings implicitly assume one or more of these answers; the goal is to make the student more sensitive to these implicit claims and to get them to think about the different reasons that support them. The second area, related to the first, is the application of the different answers concerning the extent of the ethical community to real environmental issues and problems. Students need to be aware of how the different answers concerning the moral community can imply conflicting answers for how we should act in certain cases and to think about ways to move toward conflict resolution. The third area in which environmental ethics can contribute is a more conceptual one, focusing on central concepts such as biodiversity, sustainability, species, and ecosystems. Exploring and evaluating various meanings of these terms will make students more reflective and thoughtful citizens and biologists, sensitive to the implications that different conceptual choices make. (shrink)

The inapplicability of variations on theory reduction in the context of genetics and their irrelevance to ongoing research has led to an anti-reductionist consensus in philosophy of biology. One response to this situation is to focus on forms of reductive explanation that better correspond to actual scientific reasoning (e.g. part–whole relations). Working from this perspective, we explore three different aspects (intrinsicality, fundamentality, and temporality) that arise from distinct facets of reductive explanation: composition and causation. Concentrating on these aspects generates new (...) forms of reductive explanation and conditions for their success or failure in biology and other sciences. This analysis is illustrated using the case of protein folding in molecular biology, which demonstrates its applicability and relevance, as well as illuminating the complexity of reductive reasoning in a specific biological context. (shrink)

The historian Raphael Falk has described the gene as a ‘concept in tension’ (Falk 2000) – an idea pulled this way and that by the differing demands of different kinds of biological work. Several authors have suggested that in the light of contemporary molecular biology ‘gene’ is no more than a handy term which acquires a specific meaning only in a specific scientific context in which it occurs. Hence the best way to answer the question ‘what is a gene’, and (...) the only way to provide a truly philosophical answer to that question is to outline the diversity of conceptions of the gene and the reasons for this diversity. In this essay we draw on the extensive literature in the history of biology to explain how the concept has changed over time in response to the changing demands of the biosciences . Finally, we outline some of the conceptions of the gene current today. The seeds of change are implicit in many of those current conceptions and the future of the gene concept looks set to be at as turbulent as the past. (shrink)

Although it has not been much noticed, reproduction is the central theme of François Jacob’s important history of biology, La logique du vivant (The Logic of Life). In a book ostensibly devoted to heredity, this molecular biologist had reproduction integrate levels of organization from organisms to molecules and play a major role in each historical transition between them, not just in the influential argument for a shift “from generation to reproduction.” Moreover, I claim, La logique was the first general history (...) of (research on) reproduction. Earlier histories had tackled only aspects of generation and reproduction; none historicized the latter. Jacob’s innovation came out of the rising prominence of reproduction in neo-Darwinist studies of populations and in his own field, the cellular genetics of bacteria and their viruses, and engagement with history and philosophy of science. The discovery of bacterial “sex” enabled microbial genetics but, ironically, led Jacob to a sexless concept of reproduction. This approach molded a history that reached across the living world but slighted sex and the complexities of reproduction in multicellular organisms. Readers can learn from its strength and limitations. (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)