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.

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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 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)

‘‘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)

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)

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)

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 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 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)

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)

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)

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 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)

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)

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

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)

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)

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)

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)

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)

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)

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)

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)

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)