Advances in molecular biology have generally been taken to support the claim that biology is reducible to chemistry. I argue against that claim by looking in detail at a number of central results from molecular biology and showing that none of them supports reduction because (1) their basic predicates have multiple realizations, (2) their chemical realization is context-sensitive and (3) their explanations often presuppose biological facts rather than eliminate them. I then consider the heuristic and (...) confirmational implications of irreducibility and argue that purely biochemical approaches are likely to be unsound and to be unable to confirm an important range of statements. I conclude by sketching criteria for scientific unity that do not entail reducibility and yet leave an important place for identifying underlying mechanisms. Molecular biology, properly understood, provides an excellent paradigm of non-reductive unity between different explanatory levels. (shrink)

The intellectual origins of molecular biology are usually traced back to the 1930s. By contrast, molecular biology acquired a social reality only around 1960. To understand how it came to designate a community of researchers and a professional identity, I examine the creation of the first institutes of molecular biology, which took place around 1960, in four European countries: Germany, the United Kingdom, France, and Switzerland. This paper shows how the creation of these institutes (...) was linked to the results of post-war economic reconstruction. Then, it compares how the promoters of these different institutional projects delimited the goals of their discipline, reflected on its history, and suggested how research should be organised. I show how they carefully positioned their new discipline within the emerging national science policy discourse of the 1950s, and aligned it with the current vision of scientific modernity. In particular, I discuss how they articulated the meaning of molecular biology with respect to five common themes: the role of physics in the atomic age, the relations between fundamental research and medical applications, the ‘Americanisation’ of scientific research, the value of science in the reconstruction of national identities, and the drive towards interdisciplinary research. This paper thus demonstrates that beyond the local and national accounts there is a European history of molecular biology. (shrink)

Ongoing empirical discoveries in molecular biology have generated novel conceptual challenges and perspectives. Philosophers of biology have reacted to these trends when investigating the practice of molecular biology and contributed to scientific debates on methodological and conceptual matters. This article reviews some major philosophical issues in molecular biology. First, philosophical accounts of mechanistic explanation yield a notion of explanation in the context of molecular biology that does not have to rely on (...) laws of nature and comports well with molecular discovery. Second, reductionism continues to be debated and increasingly be rejected by scientists. Philosophers have likewise moved away from reduction toward integration across fields or integrative explanations covering several levels of organization. Third, although the gene concept has undergone substantial transformation and even fragmentation, it still enjoys widespread use by molecular biologists, which has prompted philosophers to understand the empirical reasons for this. At the same time, it has been argued the notion of ‘genetic information’ is largely an empty metaphor, which generates the illusion of explanatory understanding without offering an adequate explanation of molecular and developmental mechanisms. (shrink)

This book is a collection of papers which reflect the recent trends in the philosophy and history of molecular biology. It brings together historians, philosophers, and molecular biologists who reflect on the discipline's emergence in the 1950's, its explosive growth, and the directions in which it is going. Questions addressed include: (i) what are the limits of molecular biology? (ii) What is the relation of molecular biology to older subdisciplines of biology, (...) especially biochemistry? (iii) Are there theories in molecular biology? (iv) If so, how are these theories structured? (v) What role did information theory play in the rise of molecular biology? The book will open the way for many future researchers. (shrink)

I offer a defense, albeit a qualified one, of machine analogies in biology, focusing on molecular contexts. The defense is rooted in my prior work (Levy in Philosopher’s Imprint 14(6), 2014), which construes the machine machine-likeness of a system as a matter of the extent to which it exhibits an internal division of labor. A concrete aim is to shore up the notion of molecular biological machines, paying special attention to processive molecular motors, such as Kinesin. (...) But I will also try to show how the division of labor account gives us guidance more broadly, both about where and why machine analogies can be expected to prove helpful and about their limitations. (shrink)

The question that probably emerges when the title of this work is read is if it is possible to establish any relation between philosophy and a scientific discipline such as molecular biology. The common opinion, shared even by many renowned biologists and philosophers, is that each of these disciplines has got its own without taking into account the results of the other. However, the relation between science and philosophy is nowadays one of the most challenging topics, (...) where philosophers and biologists meet and each other to better understand what life is and how it works. Philosophical concepts such as information, causality, semiotics and function can be seen as instruments for a philosophical approach to biological topics. The aim of this work is to see if, studying a biological example in depth, there are elements that fit with the informational paradigm that is proposed as a philosophical framework. Biology has been considered as a discipline in which objects can be reduced to the laws of physics and chemistry. A different approach can be seen in this work. The philosophy of Charles Sanders Peirce can help us to see biological systems as informational systems, where molecules are more than their chemical structure, indeed, the cell can deal with them from a semiotic point of view; that is, treating them as signs that stand for other molecules or processes, allowing the system to canalize all this information to its own benefit. (shrink)

Some real life processes, including molecular ones, are context-sensitive, in the sense that their outcome depends on side conditions that are most of the times difficult, or impossible, to express fully in advance. In this paper, we survey and discuss a logical account of context-sensitiveness in molecular processes, based on a kind of non-classical logic. This account also allows us to revisit the relationship between logic and philosophy of science (and philosophy of biology, in particular).

In recent years the number of scholarly publications devoted to Kant's theory of biology has rapidly growing, with particular attention being given to Kant's thoughts about the concepts of teleology, function, organism, and their respective roles in scientific practice. Moving from these recent studies, and distancing itself from their mostly evolutionary background, the main aim of the present paper is to suggest an original "cognitive turn" in the interpretation of Kant's theory of biology. More specifically, the Authors will (...) trace a connection between some Kantian theses about the “peculiar” or special nature of the human mind, advanced in the Critique of the Power of Judgement, and some specific epistemological issues pertaining to the research practice of contemporary molecular biology. (shrink)

In this paper, I defend the agent/patient distinction against critics who argue that causal interactions are symmetrical. Specifically, I argue that there is a widespread type of causal interaction between distinct entities, resulting in a type of ontological asymmetry that provides principled grounds for distinguishing agents from patients. The type of interaction where the asymmetry is found is when one of the entities undergoes a change in kind, structure, powers, or intrinsic properties as a result of the interaction while the (...) other does not. Interactions of this type are widespread in molecular biology and chemistry. I focus specifically on (i) the actions of enzymes on substrates and (ii) water molecules breaking the bonds of polarized molecules. Finally, I respond to objections by laying out and to a limited extent defending three commitments of my account: emergent entities and powers, realism about chemical kinds or structures, and the assumption of the agent/patient distinction in functional attributions in biology. (shrink)

After the discovery of the structure of DNA in 1953, scientists working in molecular biology embraced reductionism—the theory that all complex systems can be understood in terms of their components. Reductionism, however, has been widely resisted by both nonmolecular biologists and scientists working outside the field of biology. Many of these antireductionists, nevertheless, embrace the notion of physicalism—the idea that all biological processes are physical in nature. How, Alexander Rosenberg asks, can these self-proclaimed physicalists also be antireductionists? (...) With clarity and wit, Darwinian Reductionism navigates this difficult and seemingly intractable dualism with convincing analysis and timely evidence. In the spirit of the few distinguished biologists who accept reductionism—E. O. Wilson, Francis Crick, Jacques Monod, James Watson, and Richard Dawkins—Rosenberg provides a philosophically sophisticated defense of reductionism and applies it to molecular developmental biology and the theory of natural selection, ultimately proving that the physicalist must also be a reductionist. (shrink)

The intellectual origins of molecular biology are usually traced back to the 1930s. By contrast, molecular biology acquired a social reality only around 1960. To understand how it came to designate a community of researchers and a professional identity, I examine the creation of the first institutes of molecular biology, which took place around 1960, in four European countries: Germany, the United Kingdom, France, and Switzerland. This paper shows how the creation of these institutes (...) was linked to the results of post-war economic reconstruction. Then, it compares how the promoters of these different institutional projects delimited the goals of their discipline, reflected on its history, and suggested how research should be organised. I show how they carefully positioned their new discipline within the emerging national science policy discourse of the 1950s, and aligned it with the current vision of scientific modernity. In particular, I discuss how they articulated the meaning of molecular biology with respect to five common themes: the role of physics in the atomic age, the relations between fundamental research and medical applications, the 'Americanisation' of scientific research, the value of science in the reconstruction of national identities, and the drive towards interdisciplinary research. This paper thus demonstrates that beyond the local and national accounts there is a European history of molecular biology. (shrink)

The new mechanistic philosophy is divided into two largely disconnected projects. One deals with a metaphysical inquiry into how mechanisms relate to issues such as causation, capacities and levels of organization, while the other deals with epistemic issues related to the discovery of mechanisms and the intelligibility of mechanistic representations. Tudor Baetu explores and explains these projects, and shows how the gap between them can be bridged. His proposed account is compatible both with the assumptions and practices of experimental (...) design in biological research, and with scientifically accepted interpretations of experimental results. (shrink)

In recent decades the expression "molecular biology" has progressively disappeared from journals, and no longer designates new chairs or departments. This begs the question: does it mean that molecular biology is dead, and has been displaced by new emerging disciplines such as systems biology and synthetic biology? Maybe its reductionist approach to living phenomena has been substituted by one that is more holistic. The situation, undoubtedly, is far less simple. To appreciate better what has (...) happened it is necessary to acknowledge the following: the intial project of molecular biologists was not a reductionist one, but an attempt to naturalize the phenomena of life by using the epistemological principles of physics as a model; and, it is necessary to distinguish the early stages of molecular biology, and the later aggregating process which gave it its present characteristics. Only one of these characteristics, the importance of the informational vision, has been seriously challenged in recent years. But it is obvious that the ambition of most early molecular biologists to discover simple rules and principles explaining all of biological facts has vanished. The pendulum has now moved toward the study of the diversity generated by a long evolutionary history. (shrink)

Despite the transformation in biological practice and theory brought about by discoveries in molecular biology, until recently philosophy of biology continued to focus on evolutionary biology. When the Human Genome Project got underway in the late 1980s and early 1990s, philosophers of biology -- unlike historians and social scientists -- had little to add to the debate. In this landmark collection of essays, Sahotra Sarkar broadens the scope of current discussions of the philosophy (...) of biology, viewing molecular biology as a unifying perspective on life that complements that of evolutionary biology. His focus is on molecular biology, but the overriding question behind these papers is what molecular biology contributes to all traditional areas of biological research.Molecular biology -- described with some foresight in a 1938 Rockefeller Foundation report as a branch of science in which "delicate modern techniques are being used to investigate ever more minute details" -- and its modeling strategies apparently argue in favor of physical reductionism. Sarkar's first three chapters explore reductionism -- defending it, but cautioning that reduction to molecular interactions is not necessarily a reduction to genetics. The next sections of the book discuss function, exploring how functional explanations pose a problem for reductionism; the informational interpretation of biology and how it interacts with reductionism; and the tension between the unifying framework of molecular biology and the received framework of evolutionary theory. The concluding chapter is an essay in the emerging field of developmental evolution, exploring what molecular biology may contribute to the transformation of evolutionary theory as evolutionary theory takes into account morphogenetic development. (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)

Understanding how scientific activities use naming stories to achieve disciplinary status is important not only for insight into the past, but for evaluating current claims that new disciplines are emerging. In order to gain a historical understanding of how new disciplines develop in relation to these baptismal narratives, we compare two recently formed disciplines, systems biology and genomics, with two earlier related life sciences, genetics and molecular biology. These four disciplines span the twentieth century, a period in (...) which the processes of disciplinary demarcation fundamentally changed from those characteristic of the nineteenth century. We outline how the establishment of each discipline relies upon an interplay of factors that include paradigmatic achievements, technological innovation, and social formations. Our focus, however, is the baptism stories that give the new discipline a founding narrative and articulate core problems, general approaches and constitutive methods. The highly plastic process of achieving disciplinary identity is further marked by the openness of disciplinary definition, tension between technological possibilities and the ways in which scientific issues are conceived and approached, synthesis of reductive and integrative strategies, and complex social interactions. The importance – albeit highly variable – of naming stories in these four cases indicates the scope for future studies that focus on failed disciplines or competing names. Further attention to disciplinary histories could, we suggest, give us richer insight into scientific development. (shrink)

During the past few decades, philosophers of biology have debated the issue of reductionism versus anti-reductionism, with both sides often claiming a ‘pluralist’ position. However, both sides also tend to focus on a single research paradigm, which analyzes living things in terms of certain macromolecular components. I offer a case study where biologists pursue other analytic pathways, in a tradition of quantitative genetics that originates with the initially purely mathematical theories of R. A. Fisher, J. B. S. Haldane, and (...) Sewall Wright in the 1930s. Aster Models offers a class of statistical models designed for studying the fitness of plant and animal populations, by integrating the measurements of separate, sequential, non-normally distributed fitness components in novel ways. Their work generates important theoretical and practical results that do not require elaboration by molecular biology, and thus serves as a counterexample to the claims of philosophers whose ‘pluralism’ still harbors reductionist assumptions. (shrink)

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

The Medical Research Council Laboratory of Molecular Biology (formerly the Medical Research Council Unit for the Study of Molecular Structure of Biological Systems) in Cambridge (England) played a key role in the postwar history of molecular biology. The paper, focussing on the early history of the institution, aims to show that the creation of the laboratory and the making of molecular biology were part of a new scientific culture set in place after World (...) War II. In five interlinked parts it deals with the institutional creation of the MRC unit dedicated to the crystallographic analysis of biological molecules; the attraction of postwar biophysics, the heading under which the work of the unit initially fell; the people who joined the laboratory and their appropriation of new technologies, in particular the electronic computer for protein crystal structure determination; the cultural appeal of postwar crystallography, as exemplified in the use of crystal structure diagrams for a wide series of consumer goods at the Festival of Britain in 1951 and the display of molecular models at the Brussels World's Fair in 1958, a key site for the presentation of science and its role in the postwar world. (shrink)

In a recent essay in this journal, John Maynard Smith argues that the often expressed idea that the genome is the repository of meaningful information is not merely a heuristically useful metaphor. Instead, he contends, it is a central idea in contemporary microbiology. While I am in general agreement with Maynard Smith on this issue, his account suffers, I believe, from using an inappropriate concept of ‘information.’ One result of this is that the concept of genomic information becomes burdened by (...) a conceptual load that the biological facts cannot support. When, however, the appropriate concept of information is used, then these burdens are shed, and the result is an account that is in substantial agreement with the heart of Maynard Smith's thesis. (shrink)

The Medical Research Council Laboratory of Molecular Biology in Cambridge played a key role in the postwar history of molecular biology. The paper, focussing on the early history of the institution, aims to show that the creation of the laboratory and the making of molecular biology were part of a new scientific culture set in place after World War II. In five interlinked parts it deals with the institutional creation of the MRC unit dedicated (...) to the crystallographic analysis of biological molecules; the attraction of postwar biophysics, the heading under which the work of the unit initially fell; the people who joined the laboratory and their appropriation of new technologies, in particular the electronic computer for protein crystal structure determination; the cultural appeal of postwar crystallography, as exemplified in the use of crystal structure diagrams for a wide series of consumer goods at the Festival of Britain in 1951 and the display of molecular models at the Brussels World’s Fair in 1958, a key site for the presentation of science and its role in the postwar world. (shrink)

Molecular biologists use different kinds of reasoning strategies for different tasks, such as hypothesis formation, experimental design, and anomaly resolution. More specifically, the reasoning strategies discussed in this paper may be characterized as (1) abstraction-instantiation, in which an abstract skeletal model is instantiated to produce an experimental system; (2) the systematic scan, in which alternative hypotheses are systematically generated; and (3) modular anomaly resolution, in which components of a model are stated explicitly and methodically changed to generate alternative changes (...) to resolve an anomaly. This work grew out of close observation over a period of six months of an actively functioning molecular genetics laboratory. (shrink)

The convergence of developmental biology — embryology — and molecular biology was one of the major scientific events of the last decades of the twentieth century. The transformation of developmental biology by the concepts and methods of molecular biology has already been described. Less has been told on the reciprocal transformation of molecular biology on contact with higher organisms. The transformation of molecular biology occurred at the end of a deep (...) crisis which affected this discipline in the sixties and seventies and which led to a cruel criticism of the preexisting models of gene regulation. Numerous new, sometimes heterodox, models were proposed to describe the level at which gene regulation took place and its underlying mechanisms. The crisis resolved itself at the beginning of the eighties with the rapid accumulation of results from genetic engineering techniques and, above all, a displacement of the descriptive level from the molecule to the cell. This displacement gave molecular biologists the 'explanandum' which had been cruelly lacking during their initial study of higher organisms. The new molecular cell biology is an interfield explanation of living phenomena, relating a description and an interpretation localized at different levels of organization. (shrink)

This paper is devoted to an examination of the discovery, characterization, and analysis of the functions of microRNAs, which also serves as a vehicle for demonstrating the importance of exploratory experimentation in current (post-genomic) molecular biology. The material on microRNAs is important in its own right: it provides important insight into the extreme complexity of regulatory networks involving components made of DNA, RNA, and protein. These networks play a central role in regulating development of multicellular organisms and illustrate (...) the importance of epigenetic as well as genetic systems in evolution and development. The examination of these matters yields principled arguments for the historicity of the functions of key biological molecules and for the indispensability of exploratory experimentation in contemporary molecular biology as well as some insight into the complex interplay between exploratory experimentation and hypothesis-driven science. This latter result is not only important for philosophy of science, but also of practical importance for the evaluation of grant proposals, although the elaboration of this latter claim must be left for another occasion. (shrink)

This paper proposes an experiment-based methodology for both classical genetics and molecular biology by integrating Lindley Darden’s mechanism-centered approach and C. Kenneth Waters’s phenomenon-centered approach. We argue that the methodology basing on experiments offers a satisfactory account of the development of the two biological disciplines. The methodology considers discovery of new mechanisms, investigation of new phenomena, and construction of new theories together, in which experiments play a central role. Experimentation connects the three type of conduct, which work as (...) both ends and means, occurring in a circular way and constituting an overall process of scientific practice from classical genetics to molecular biology. (shrink)

I have not attempted to provide here an analysis of the methodology of molecular biology or molecular genetics which would demonstrate at what specific points a more reductionist aim would make sense as a research strategy. This, I believe, would require a much deeper analysis of scientific growth than philosophy of science has been able to provide thus far. What I have tried to show is that a straightforward reductionist strategy cannot be said to be follwed (...) in important cases of theory development in molecular biology, and that in at least one important case, the Jacob-Monod operon theory, the methodology followed was more biological than chemical. It should be noted in closing, however, that since biological systems are thought by molecular biologists to be nothing but chemical systems, in the long run detailed investigations of such systems will be in full accord with the dictates suggested by the general reduction model. (shrink)

In 1809--the year of Charles Darwin's birth--Jean-Baptiste Lamarck published Philosophie zoologique, the first comprehensive and systematic theory of biological evolution. The Lamarckian approach emphasizes the generation of developmental variations; Darwinism stresses selection. Lamarck's ideas were eventually eclipsed by Darwinian concepts, especially after the emergence of the Modern Synthesis in the twentieth century. The different approaches--which can be seen as complementary rather than mutually exclusive--have important implications for the kinds of questions biologists ask and for the type of research they conduct. (...) Lamarckism has been evolving--or, in Lamarckian terminology, transforming--since Philosophie zoologique's description of biological processes mediated by "subtle fluids." Essays in this book focus on new developments in biology that make Lamarck's ideas relevant not only to modern empirical and theoretical research but also to problems in the philosophy of biology. Contributors discuss the historical transformations of Lamarckism from the 1820s to the 1940s, and the different understandings of Lamarck and Lamarckism; the Modern Synthesis and its emphasis on Mendelian genetics; theoretical and experimental research on such "Lamarckian" topics as plasticity, soft (epigenetic) inheritance, and individuality; and the importance of a developmental approach to evolution in the philosophy of biology. The book shows the advantages of a "Lamarckian" perspective on evolution. Indeed, the development-oriented approach it presents is becoming central to current evolutionary studies--as can be seen in the burgeoning field of Evo-Devo. Transformations of Lamarckism makes a unique contribution to this research. (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)

Abstraction and idealization are the two notions that are most often discussed in the context of assumptions employed in the process of model building. These notions are also routinely used in philosophical debates such as that on the mechanistic account of explanation. Indeed, an objection to the mechanistic account has recently been formulated precisely on these grounds: mechanists cannot account for the common practice of idealizing difference-making factors in models in molecular biology. In this paper I revisit the (...) debate and I argue that the objection does not stand up to scrutiny. This is because it is riddled with a number of conceptual inconsistencies. By attempting to resolve the tensions, I also draw several general lessons regarding the difficulties of applying abstraction and idealization in scientific practice. Finally, I argue that more care is needed only when speaking of abstraction and idealization in a context in which these concepts play an important role in an argument, such as that on mechanistic explanation. (shrink)

An assessment is offered of the recent debate on information in the philosophy of biology, and an analysis is provided of the notion of information as applied in scientific practice in molecular genetics. In particular, this paper deals with the dependence of basic generalizations of molecular biology, above all the 'central dogma', on the socalled 'informational talk'. It is argued that talk of information in the 'central dogma' can be reduced to causal claims. In that (...) respect, the primary aim of the paper is to consider a solution to the major difficulty of the causal interpretation of genetic information: how to distinguish the privileged causal role assigned to nucleic acids, DNA in particular, in the processes of replication and protein production. A close reading is proposed of Francis H. C. Crick's On Protein Synthesis and related works, to which we owe the first explicit definition of information within the scientific practice of molecular biology. (shrink)

The philosophical debate around the impact of machine learning in science is often framed in terms of a choice between AI and classical methods as mutually exclusive alternatives involving difficult epistemological trade-offs. A common worry regarding machine learning methods specifically is that they lead to opaque models that make predictions but do not lead to explanation or understanding. Focusing on the field of molecular biology, I argue that in practice machine learning is often used with explanatory aims. More (...) specifically, I argue that machine learning can be tightly integrated with other, more traditional, research methods and in a clear sense can contribute to insight into the causal processes underlying phenomena of interest to biologists. One could even say that machine learning is not the end of theory in important areas of biology, as has been argued, but rather a new beginning. I support these claims with a detailed discussion of a case study involving gene regulation by microRNAs. (shrink)

In his [1], David Berlinski explores, among other things, both what could be called a “sophisticated” and a “basic” analogy between languages and the genetic code. The basic analogy stems from the observation that the relationship between English and “Morse” appears to be formally similar to the relationship between DNA and protein. That is, just as sentences of the English language can be encoded into Morse, sequences of bases within strands of DNA are “transcribed” into polypeptides. To some, this “basic” (...) analogy. (shrink)

The recent historiography of molecular biology features key technologies, instruments and materials, which offer a different view of the field and its turning points than preceding intellectual and institutional histories. Radioisotopes, in this vein, became essential tools in postwar life science research, including molecular biology, and are here analyzed through their use in experiments on bacteriophage. Isotopes were especially well suited for studying the dynamics of chemical transformation over time, through metabolic pathways or life cycles. Scientists (...) labeled phage with phosphorus-32 in order to trace the transfer of genetic material between parent and progeny in virus reproduction. Initial studies of this type did not resolve the mechanism of generational transfer but unexpectedly gave rise to a new style of molecular radiobiology based on the inactivation of phage by the radioactive decay of incorporated phosphorus-32. These ‘suicide experiments’, a preoccupation of phage researchers in the mid-1950s, reveal how molecular biologists interacted with the traditions and practices of radiation geneticists as well as those of biochemists as they were seeking to demarcate a new field. The routine use of radiolabels to visualize nucleic acids emerged as an enduring feature of molecular biological experimentation. (shrink)

An assessment is offered of the recent debate on information in the philosophy of biology, and an analysis is provided of the notion of information as applied in scientific practice in molecular genetics. In particular, this paper deals with the dependence of basic generalizations of molecular biology, above all the ‘central dogma’, on the so-called ‘informational talk’ (Maynard Smith [2000a]). It is argued that talk of information in the ‘central dogma’ can be reduced to causal (...) claims. In that respect, the primary aim of the paper is to consider a solution to the major difficulty of the causal interpretation of genetic information: how to distinguish the privileged causal role assigned to nucleic acids, DNA in particular, in the processes of replication and protein production. A close reading is proposed of Francis H. C. Crick's On Protein Synthesis (1958) and related works, to which we owe the first explicit definition of information within the scientific practice of molecular biology. Introduction 1.1 The basic questions of the information debate 1.2 The causal interpretation (CI) of biological information and Crick's ‘central dogma’ Crick's definitions of genetic information The main requirement for (CI) Types of causation in molecular biology 4.1 Structural causation in molecular biology 4.2 Nucleic acids as correlative causal factors The ‘central dogma’ without the notion of information Concluding remarks This is a new version of this article as there were errors in the abstract and full text in the previous version. (shrink)

Traditional approaches to theory structure and theory change in science do not fare well when confronted with the practice of certain fields of science. We offer an account of contemporary practice in molecular biology designed to address two questions: Is theory change in this area of science gradual or saltatory? What is the relation between molecular biology and the fields of traditional biology? Our main focus is a recent episode in molecular biology, the (...) discovery of enzymatic RNA. We argue that our reconstruction of this episode shows that traditional approaches to theory structure and theory change need considerable refinement if they are to be defended as generally applicable. 1This paper emerged from discussions between us, and we are both equally responsible for its errors. We would like to thank Yvonne Paterson for helpful comments. (shrink)

This paper is about the interaction and the intertwinement between history of science as a historical process and history of science as the historiography of this process, taking molecular biology as an example. In the first part, two historical shifts are briefly characterized that appear to have punctuated the emergence of molecular biology between the 1930s and the 1980s, one connected to a new generation of analytical apparatus, the other to properly molecular tools. The second (...) part concentrates on the historiography of this development. Basically, it distinguishes three phases. The first phase was largely dominated by accounts of the actors themselves. The second coincided with the general ‘practical turn’ in history of science at large, and today’s historical appropriations of the molecularization of the life sciences appear to be marked by the changing disciplinary status of the science under review. In a closing remark, an argument is made for differentiating between long-range, middle-range and short-range perspectives in dealing with the history of the sciences. (shrink)

Since the 1930s, scientists studying the neurological disease scrapie had assumed that the infectious agent was a virus. By the mid 1960s, however, several unconventional properties had arisen that were difficult to reconcile with the standard viral model. Evidence for nucleic acid within the pathogen was lacking, and some researchers considered the possibility that the infectious agent consisted solely of protein. In 1982, Stanley Prusiner coined the term `prion' to emphasize the agent's proteinaceous nature. This infectious protein hypothesis was denounced (...) by many scientists as `heretical'.This two-part essay asks why the concept of an infectious protein was considered controversial. Some biologists justified their evaluation of this hypothesis on the grounds that an infectious protein contradicted the `central dogma of molecular biology'. Others referred to vague theoretical constraints such as molecular biology's `theoretical structure' or `framework'. Examination of the objections raised by researchers reveals exactly what generalizations were being challenged by a protein model of infection.This two-part survey of scrapie and prion research reaches several conclusions: A theoretical framework is present in molecular biology, exerting its influence in hypothesis formation and evaluation; This framework consists of several related, yet separable, generalizations or `elements', including Francis Crick's Central Dogma and Sequence Hypothesis, plus notions concerning infection, replication, protein synthesis, and protein folding; The term `central dogma' has stretched beyond Crick's original 1958 definition to encompass at least two other `framework elements': replication and protein synthesis; and From the study of scrapie and related diseases, biological information has been delineated into at least two classes: sequential and what I call `conformational'.In Part I of this essay, a brief review of the central dogma was given, and the developments in scrapie research from 1965 to 1972 were traced. This section summarized many of the puzzling, non-virus-like properties of the scrapie agent. Alternative hypotheses to the viral explanation were presented, including early versions of a protein-only hypothesis. Part II of this essay will follow the developments in scrapie and prion research from the mid-1970s through 1991. The growing prominence of a protein-only model of infection will be countered by continued objections from many researchers to a pathogen devoid of nucleic acid. These objections will help illuminate those generalizations in molecular biology that were indeed challenged by a protein-only model of infection. (shrink)