Biologists and historians often present natural history and molecular biology as distinct, perhaps conflicting, fields in biological research. Such accounts, although supported by abundant evidence, overlook important areas of overlap between these areas. Focusing upon examples drawn particularly from systematics and molecular evolution, I argue that naturalists and molecular biologists often share questions, methods, and forms of explanation. Acknowledging these interdisciplinary efforts provides a more balanced account of the development of biology during the post-World War II era.

This paper investigated the part played by collaborative practices in chaneling the work of prominent biochemists into the development of molecular biology. The RNA collaborative network that emerged in the 1960s in France encompassed a continuum of activities that linked laboratories to policy-making centers. New institutional frameworks such as the DGRST committees were instrumental in establishing new patterns of funding, and in offering arenas for multidisciplinary debates and boundary assessment. It should be stressed however, that although this collaborative network (...) was based on centralized initiatives aimed at developing molecular biology as a new biological specialty, it operated above all as a nexus of practices. The main argument of this paper is that the central allocation of funds and resources, exemplified by the DGRST operation, actually enhanced the creation of a self-conscious community of biochemists turned molecular biologists by virtue of an increased circulation of tools, skills, and results that took place within the RNA network and a few analogous systems of exchange.Having hands on “things” viewed as identical for all practical purposes was a potent factor in changing the experimental systems and their meanings. Limited but shared means of doing helped to reduce uncertainties, change representations, and turn contingent decisions into meaningful choices. The collaborative enterprises then resulted in personal contacts and the transfer of skills and materials, which gradually incorporated the biochemical tools into systems producing facts relevant to molecular biology as defined by its early practitioners. In that sense, networking was a regulatory process that stabilized new research objects and acculturated French biochemists.The mere existence of such a collaborative network also changed the scale of the disciplining process. Collaborations may have been started for contingent motives, but multiple exchanges resulted in the emergence of a new collective, and amplified small displacements. Collaborations, however, worked both ways, and the RNA network may be viewed as an efficient “trading-post.” An unexpected outcome of the development of a conversion zone is the fact that, by the late 1960s, the former biochemists dominated the “new” world of molecular biology — both in terms of research habits, since interests in structural studies dominated the field, and in terms of institutional initiatives such as the creation of laboratories and institutes for molecular biology.As an example of the cognitive displacements achieved by the network, I have focused here on the stabilization of “messenger RNA” as a new biological entity. This process illustrates the role of “boundary objects” and other mediating innovations in the development of disciplinary structures. Students of science trained in the symbolic interactionism tradition have proposed that “boundary objects” enhance the multiple interactions between heterogeneous social worlds: they are robust enough to enhance unity, but plastic enough to be manipulated in different social and cultural contexts.81 Within the emerging network, messenger RNA was a weakly structured “genetic information carrier” in common use, but it could, at the same time, be a strongly structured “macromolecular structure” adapted to practical and local uses. Consequently, messenger RNA favored the association of groups of heterogeneous scientists with backgrounds and interests in medical biochemistry, genetics, physical chemistry, organic chemistry, and so forth. This contrast between general and local uses was also instrumental in integrating the manipulation of things and the negotiation of aims. In contrast to transfer RNAs, which in the French context remained objects for chemical (and mainly structural) studies, messenger RNA became a key component of the new culture of “genetic information”. Messenger RNA was a loose theoretical entity described as a “genetic information carrier” in the policy-making documents, while operational but tacit and more conflicting definitions prevailed at the bench. In other words, messenger RNA was not only a classical “boundary object” but also a “flag object,” which tightened the collaborative network by mediating between the DGRST offices and the laboratories. (shrink)

This paper is the result of the research I undertook at Lancaster University with a Marie Curie Fellowship during the academic years 2000‐2002. The objective of this research was to study the limits and the challenges of the analogy between molecular geneticists’ work and hackers’ activities. By focusing on this analogy I aim to explore the different ethical and philosophical issues surrounding new genetics and its IPR regulations. The paper firstly will show the philosophical background lying behind the proposed (...) analogy and analyses the sense in which we can talk of geneticists as “hackers.” It will provide grounds for the analogy by exploring some of the techniques used by geneticists; in particular it will focus on the so‐called Shotgun method for genomic sequencing. After having provided reasons for the proposed analogy I will claim that the open source philosophy used in the computer field would be a good way to regulate research in the genetics and in pharmaceutical field too. The open source philosophy would provide fair distribution of research opportunities around the globe with the shift from patenting to copyright in sensitive fields such as genetics. (shrink)

'Structure' and 'function' are both ambiguous terms. Discriminating different meanings of these terms sheds light on research and explanatory practice in molecular biology, as well as clarifying central theoretical concepts in the life sciences like the sequence-structure-function relationship and its corresponding scientific "dogmas". The overall project is to answer three questions, primarily with respect to proteins: What is structure? What is function? What is the relation between structure and function? The results of addressing these questions lead to an answer (...) to the title question, what the statement 'structure determines function' means. (shrink)

The ancient, interlinked questions about the role of chance in the living world and the origins of life, gained new relevance with the development of molecular biology in the twentieth century. In 1970, French molecular biologist Jacques Monod, joint winner of the 1965 Nobel Prize in Physiology or Medicine, devoted a popular book on modern biology and its philosophical implications to these questions, which was quickly translated into English as _Chance and Necessity_. Nine years later, Belgian thermodynamicist (...) Ilya Prigogine, 1977 winner of the Nobel Prize in Chemistry, published a popular book on the history and philosophy of natural sciences with Belgian philosopher Isabelle Stengers. Translated into English under the title _Order out of Chaos_ and widely discussed, the whole book can be seen as a response to Monod on these biological and philosophical questions. This study will trace this intellectual controversy between two Nobel Prize winners defending two opposing scientific and philosophical visions of the living world, rooted in two different scientific disciplines. (shrink)

BackgroundThis study presents an empirical investigation of the ethical reasoning and ethical issues at stake in the daily work of physicians and molecular biologists in Denmark. The aim of this study was to test empirically whether there is a difference in ethical considerations and principles between Danish physicians and Danish molecular biologists, and whether the bioethical principles of the American bioethicists Tom L. Beauchamp and James F. Childress are applicable to these groups.MethodThis study is based on 12 semi-structured (...) interviews with three groups of respondents: a group of oncology physicians working in a clinic at a public hospital and two groups of molecular biologists conducting basic research, one group employed at a public university and the other in a private biopharmaceutical company.ResultsIn this sample, the authors found that oncology physicians and molecular biologists employed in a private biopharmaceutical company have the specific principle of beneficence in mind in their daily work. Both groups are motivated to help sick patients. According to the study, molecular biologists explicitly consider nonmaleficence in relation to the environment, the researchers' own health, and animal models; and only implicitly in relation to patients or human subjects. In contrast, considerations of nonmaleficence by oncology physicians relate to patients or human subjects. Physicians and molecular biologists both consider the principle of respect for autonomy as a negative obligation in the sense that informed consent of patients should be respected. However, in contrast to molecular biologists, physicians experience the principle of respect for autonomy as a positive obligation as the physician, in dialogue with the patient, offers a medical prognosis based upon the patients wishes and ideas, mutual understanding, and respect. Finally, this study discloses utilitarian characteristics in the overall conception of justice as conceived by oncology physicians and molecular biologists from the private biopharmaceutical company. Molecular biologists employed at a public university are, in this study, concerned with allocation, however, they do not propose a specific theory of justice.ConclusionThis study demonstrates that each of the four bioethical principles of the American bioethicists Tom L. Beauchamp & James F. Childress – respect for autonomy, beneficence, nonmaleficence and justice – are reflected in the daily work of physicians and molecular biologists in Denmark. Consequently, these principles are applicable in the Danish biomedical setting. (shrink)

This article presents results from a qualitative empirical investigation of how Danish oncology physicians and Danish molecular biologists experience the principle of respect for autonomy in their daily work.

This article presents results from an empirical investigation of the role and importance of ethics in the daily work of Danish oncologyphysicians and Danish molecular biologists. The study is based on 12 semi-structured interviews with three groups of respondents: a group of oncology physicians working in a clinic at a public hospital and two groups of molecular biologists conducting basic research, one group employed at a public university and the other in a private biopharmaceutical company.We found that oncology (...) physicians consider ethical evaluation as part of their daily work. They discuss how to treat patients in groups and they have interdisciplinary seminars. In contrast, molecular biologists employed at the university do not think that basic research causes significant ethical problems, they do not talk about ethics in their daily work and they do not want to prioritise seminars on ethics. Molecular biologists employed in a private biopharmaceutical company do not think that basic research causes significant ethical problems, but the private company prioritises ethical evaluation. If the company behaves unethical, they will be punished by the consumers and by the investors in the last end. In general, oncology physicians working in the clinic experience a closer relationship between their daily work and ethical problems concerning human beings than molecular biologists conducting basic research. (shrink)

This last result leads, rather naturally, to some concluding observations and a series of questions for further investigation. These case studies show that in all of the sites examined, the institutionalization of molecular biology as a “discipline” was primarily driven by the need to separate groups of practitioners with divergent but overlapping interests within the local context. Thus molecular biology was contingently separated from agricultural or medical biochemistry, virology, work on the physiology of nucleic acids, and so forth (...) for contingent local institutional reasons. This makes it even more pressing to try to understand how molecular biology came to be delimited on a larger scale. How did it come to be a discipline with specific intellectual content (or did it?), including some problems, tools, and practices and excluding others? How did it gain authority as the forefront biological science by the mid-1960s? We need to understand the ways in which the tensions between different practices, projects, aims, understandings of the goals of molecular biology, and so on were resolved, on what scale and in what venues, so that something approximating the political character of a discipline, rather than a federation, was achieved. If these case studies provide a sound starting point, it will nevertheless prove difficult to answer the interconnected questions implicit here satisfactorily.One means of getting at such questions that should prove of considerable interest is to examine carefully the work of those who were widely cited in the papers of the late fifties through the mid-seventies by the people now considered major founders of molecular biology. By studying the contributions of those who are now omitted in the standard histories and recollections, we will gain a clearer sense of the possibilities that were open as molecular biology took shape. It is already widely recognized that the contributions of a number of biochemists have been given short shrift, but (as the example of Ernest Gale in Rheinberger's study illustrates) there are a great many more figures whose line of work were then crucial but who are now overlooked.6 To understand both what molecular biology was at the time of its early institutionalization and what is has become, it will be enormously helpful to understand at what point the definition or ideology “hardened” and the grounds for inclusion and exclusion of individuals and lines of work were reformed. Studies of this sort are appropriate in many other areas as well, of course; in general, they should different histories, political standing, and institutional bases of those disciplines in their national cultures. It is likely (but a matter for investigation!) that such differences influenced the opportunities for introducing new bench practices, if in no other way than by delimiting the niches within which certain practices could be initiated.7 And since new practices can fail to achieve their objectives, can transform the direction of work and disciplinary allegiances of their practitioners, can lead to only routine results, or can open up important new vistas, the character of the available niches from which to work can prove to have a strong influence on the direction that new work takes if and when it starts to flourish. A key aspect of this problematic (not yet adequately studied, I believe) is the problem of drawing boundaries between different kinds of work and determining where each should fit among established disciplines and/or within some new construct. To the extent that an “international” solution is ultimately achieved to such problems, it must surely be achieved in light of initially different ways of dealing with it in different countries.Underlying work of the sort we have been exploring is the thorny problem of how best to contextualize the work being studied. This, I believe, is one of the major historiographic problems that we must face in the history of science. It is by no means a new problem, of course, but a particularization of the age-old problem of the (seeming) overdetermination of historical events. If we deal with local cultures, to understand how they develop and their fate we need to understand their location within larger cultures. But it is utterly unclear how to draw appropriate boundaries on the relevant larger culture(s). As even this brief discussion has shown, institutional cultures, the cultures of sponsoring agencies, “the” culture of science (or of biological science, physical science, etc., as appropriate), and national cultures all can provide relevant contexts, all can occasionally determine the fate of work undertaken in a particular local context. The potentially intractable problem of delimiting the boundaries of investigation looms large here, but it is one that must be faced explicity if we are to profit fully from the enormously stimulating investigations of local cultures exemplified in the four papers published in this symposium. My own view is that we have no abstract standard available for determining which boundaries are appropriate to a given study, and, indeed, that no single contextualization is adequate to the examination of any given case, but that, nonetheless, we can (at least sometimes) distinguish useful and explanatory delimitations of the larger context from others that prove to be misleading.Against this background, I hope that the four papers published in this special issue will stimulate the readers of the JHB to carry out similar studies—that is, studies that seek to characterize and contextualize local experimental cultures —over a wide range of cases. I also hope that some of those who take up this challenge will deal with the larger questions raised by the need to find a way of balancing different, sometimes competing, contextualizations of such studies. The fact that any given case requires multiple contextualizations, resulting in multifaceted representations no one of which is alone adequate, will surely land us in fascinating, hopefully fruitful and productive, controversies. (shrink)

Comparative genomics has proven a fruitful approach to acquire many functional and evolutionary insights into core cellular processes. Here it is argued that in order to perform accurate and interesting comparative genomics, one first and foremost has to be able to recognize, postulate, and revise different evolutionary scenarios. After all, these studies lack a simple protocol, due to different proteins having different evolutionary dynamics and demanding different approaches. The authors here discuss this challenge from a practical (what are the observations?) (...) and conceptual (how do these indicate a specific evolutionary scenario?) viewpoint, with the aim to guide investigators who want to analyze the evolution of their protein(s) of interest. By sharing how the authors draft, test, and update such a scenario and how it directs their investigations, the authors hope to illuminate how to execute molecular evolution studies and how to interpret them. Also see the video abstract here https://youtu.be/VCt3l2pbdbQ. (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)

This article looks at Deleuze and Guattari's understanding of molecular biology, focusing particularly on their reading of two highly influential works by the eminent French molecular biologists François Jacob and Jacques Monod, La logique du vivant and Le hasard et la nécessité. In these two works, Jacob and Monod present the significance of molecular biology in broadly reductionist terms. What is more, the lac operon model of gene regulation that they propose serves to reinforce the so-called Central (...) Dogma of molecular biology, according to which information passes from DNA to RNA to proteins, with no reverse route. However, Deleuze and Guattari discover intensive potentials within the descriptions of molecular biology offered by both writers. It is argued that Jacob's work in particular, as it has developed in the years since the publication of La logique du vivant in 1970, has itself developed these intensive potentials. (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 first part of this paper has shown that the development of regulatory genetics and the lactose operon model stemmed from laboratory cultures rooted in local traditions. A "physiological" culture may be recognized in the Pasteurian context. The institutional continuity provided the basis for a tenuous link between Pasteur, Lwoff, and Monod. My claim is that the "national" value of regulatory and physiological genetics is an artifact produced in the course of the legitimization process accompanying the institutionalisation of the discipline. (...) In the 1960s, the lactose operon model was turned into a "flag-object," a symbol of the new culture. The work done by the Pasteurian group became therefore the most important, if not the only, exemplar of molecular biology in France.The second part o f the paper described the origins of general patterns that dominated the building of molecular biology in France. The study of the relationships between molecular biologists and biochemists or immunologists revealed the existence of alternatives to the development of operon research, or to the convergence with molecular biology. Both examples uncover specific paths leading to achievements that might be viewed as international trends: the expansion of RNA and translation studies, and the development of cellular immunology. They illustrate two possible patterns of linking local settings and disciplinary traditions: an oligopolistic situation where a few groups or one institution dominate an entire field, and the emergence of "collective" trends through collaboration networks or schools. (shrink)

Biologists employ a suggestive metaphor to describe the complexities of molecular interactions within cells and embryos: cytological components are said to be part of “ecosystems” that integrate them in a complex network of relations with many other entities. The aim of this essay is to scrutinize the molecular ecosystem, a metaphor that, despite its longstanding history, has seldom be articulated in detail. I begin by analyzing some relevant analogies between the cellular environment and the biosphere. Next, I discuss (...) the applicability of the molecular ecosystem concept in actual scientific practice. (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)

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)

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)

ArgumentThis paper explores the connection between the epistemic and the “political” dimensions of the metaphor of information during the early days of the study of Molecular Evolution. While preserving some of the meanings already documented in the history of molecular biology, the metaphor acquired a new, powerful use as a substitute for “history.” A rhetorical analysis of Emilé Zuckerkandl's paper, “Molecules as Documents of Evolutionary History,” highlights the ways in which epistemic claims on the validity and superiority of (...) molecular evidence for evolution were intimately connected with authority issues in evolutionary biology. The debate is situated within the framework of the battle for resources between traditional evolutionists and molecular biologists at the beginning of the 1960s. The architects of evolutionary synthesis questioned the idea that molecular characters constitute “cleaner” and “more direct” evidence of evolution. Nevertheless, the information discourse constituted a productive space for the development of a new research program that, paradoxically, has made explicit the limitations of the information metaphor in reconstructing life's history. (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)

A crucial part of the knowledge of molecular biologists is procedural knowledge, that is, knowledge of how to do things in laboratories. Procedural knowledge of molecular biologists involves both perceptual-motor skills and cognitive skills. We discuss such skills required in performing the most commonly used molecular biology techniques, namely, Polymerase Chain Reaction and gel electrophoresis. We argue that procedural knowledge involved in performing these techniques is more than just knowing their protocols. Creative exploration and experience are essential (...) for the acquisition of procedural knowledge in molecular biology. With enough experience, molecular biologists make intuitive judgments without recourse to analytical reasoning. We propose that procedural knowledge is intuitive recognition of the patterns of one's environment that are the most relevant for making a decision or acting appropriately. Finally, we argue that knowledge of molecular biologists requires an integration of procedural knowledge and propositional knowledge. (shrink)

Mammalian hibernation is characterized by profound reductions in metabolism, oxygen consumption and heart rate. As a result, the animal enters a state of suspended animation where core body temperatures can plummet as low as −2.9°C. Not only can hibernating mammals survive these physiological extremes, but they also return to a normothermic state of activity without reperfusion injury or other ill effects. This review examines recent findings on the genes, proteins and small molecules that control the induction and maintenance of hibernation (...) in mammals. The molecular events involved with remodeling metabolism, inducing hypothermia and maintaining organ function are discussed and considered with respect to analogous processes in non‐hibernating mammals such as mice and humans. The advent of sequenced genomes from three distantly related hibernators, a bat, hedgehog and ground squirrel, provides additional opportunities for molecular biologists to explore the mechanistic aspects of this biological adaptation in greater detail. BioEssays 29:431–440, 2007. © 2007 Wiley Periodicals, Inc. (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)

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 paper investigates what molecular biology has done for our understanding of the gene. I base a new account of the gene concept of classical genetics on the classical dogma that gene differences cause phenotypic differences. Although contemporary biologists often think of genes in terms of this concept, molecular biology provides a second way to understand genes. I clarify this second way by articulating a molecular gene concept. This concept unifies our understanding of the molecular basis (...) of a wide variety of phenomena, including the phenomena that classical genetics explains in terms of gene differences causing phenotypic differences. (shrink)

Until the 1930s Germany had been the international leader in biochemistry, chemistry, and areas of biology. After WWII, however, molecular biology as a new interdisciplinary scientific enterprise was scarcely represented in Germany for almost 20 years. Three major reasons for the low performance of molecular biology are discussed: first, the forced emigration of Jewish scientists after 1933, which not only led to the expulsion of future distinguished molecular biologists, but also to a strong decline of ''dynamic biochemistry'', (...) a field which contributed greatly to molecular biology. Second, German university structures that strongly impeded interdisciplinary research. Third, the international isolation and self-isolation of German scientists that was a major obstacle to the implementation of new fields of research developed elsewhere. Despite the fact that there was no official boycott against Germany as there had been after WWI and despite the Cold War policy of integrating Germans into the West, as a consequence of National Socialism and WWI for many years only very few German scientists gained access to the international community of molecular biologists. Max Delbruck played an important role in helping the Germans establish modern, mostly molecular, biology because he retained strong connections to Germany. Most importantly, it required a new generation of young scientists who had received part of their training in the US to establish modern molecular biology at German universities and Max Planck Institutes. (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 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)

In 1926, Haldane published an essay titled 'On Being the Right Size' in which he argued that the structure, function, and behavior of an organism are strongly conditioned by the physical forces that exert the greatest impact at the scale at which it exists. This chapter puts Haldane’s insight to work in the context of contemporary cell and molecular biology. Owing to their minuscule size, cells and molecules are subject to very different forces than macroscopic organisms. In a sense, (...) macroscopic and microscopic entities inhabit different “worlds”: the former is ruled by gravity and inertia, whereas the latter is governed by Brownian motion. One implication is that we should be extremely skeptical of models and analogies that seek to explain properties of microscopic entities by appealing to properties of macroscopic ones. Unfortunately, this is precisely what the appeal to engineering metaphors in molecular biology attempts to do. Molecular biologists routinely resort to such metaphors because they are familiar and intuitively intelligible. But if our machines were the size of molecules it would be impossible for them to function the way they do. It follows that we should avoid distorting biological reality by construing it in engineering terms. In this chapter I examine four key metaphors in molecular biology – “genetic program,” “cellular circuitry,” “molecular machine,” and “molecular motor” – and I argue that their deficiencies derive from their neglect of scale. I also try to explain why many biologists today appear to have forgotten the importance of scale that Haldane drew attention to in his essay. I suggest that the reason has to do with the influence of Schrödinger’s argument in 'What is Life?' regarding the stability of the gene. (shrink)

A recurrent theme in ethnomethodological research is that of instructed actions. Contrary to the classic traditions in the social and cognitive sciences, which attribute logical priority or causal primacy to instructions, rules, and structures of action, ethnomethodologists investigate the situated production of actions which enable such formulations to stand as adequate accounts. Consequently, a recitation of formal structures can not count as an adequate sociological description, when no account is given of the local production ofwhat those structures describe. The natural (...) sciences can be described as a domain of practical action in whichthe use of methods enables the intersubjective reproduction of naturalistic observations and experiments. As numerous sociological studies of laboratory practices have shown, the achievement of intersubjective order cannot be reduced to formal methods; instead, it arises from the work of custom-fitting relevant methods to the local circumstances of the research. In this paper we discuss a possible extension of this idea to cover two intertwined aspects of molecular biology: (1) the work of following instructions on how to perform routine laboratory procedures, and (2) the relationship between cellular orders and the encoded instructions contained in the DNA molecule. We suggest that a classic conception of scientific action is implied by the way formal instructions are treated as a primary basis, both for molecular biologists' actions and the cellular functions they study, and we envision an ethnomethodological alternative to those conceptions of social and biological order. (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)

“I myself was forced to call myself a molecular biologist because when inquiring clergymen asked me what I did, I got tired of explaining that I was a mixture of crystallographer, biophysicist, biochemist, and geneticist.” Thus explained Francis Crick, who with James Watson discovered in 1953 the double helical structure of DNA, the genetic material..

Recent controversy about the use of the vertebrate fossil record for external calibration of molecular clocks centers on two issues, the number of dates used for calibration and the reliability of the fossil calibration date. Viewing matters from a palaeontological perspective, we propose three qualitative, phylogenetic criteria that can be used within a comparative framework for the selection of well-constrained calibration dates from the vertebrate fossil record. On the basis of these criteria, we identify three highly suitable new fossil (...) calibration dates for molecular clock estimates: the lungfish–tetrapod split (between 419 and 408 Ma), the bird–crocodile split (between 251 and 243 Ma), and the alligator–caiman split (between 71 and 66 Ma). Together with our previously suggested bird–lizard split (between 252 and 257 Ma), these four fossil dates span a range of very different ages. They are, in our opinion, more suitable for molecular clock calibration than the traditionally used mammal–bird split, which is less well constrained. We plea for closer interactions between paleontologists and molecular biologists in studying the timescale of vertebrate evolution. BioEssays 27:1069–1075, 2005. © 2005 Wiley Periodicals, Inc. (shrink)

It was no accident that the first neuroscience community, the Neurosciences Research Program (NRP), took shape in the 1960s at MIT, the birthplace of cybernetics. Francis O. Schmitt, known as the founding father of the NRP, was a famous biologist and an avid reader of cybernetics. Focusing on the intellectual and institutional context that Schmitt was situated in, this article unveils the way that the brain was conceptualized as a distinct object, requiring the launch of a new research community (...) in the US. In doing so, this article moves beyond the dominant narratives on the triumph of molecularization of the brain at the beginning of neuroscience. Instead, it argues that what brought researchers together in the name of neuroscience was not just a molecule but an aspiration to develop biological theories of the brain/mind, which resonated with biologists in a postwar context and was materialized through support for basic research. The article highlights the tension over the computerization and molecularization of the brain, which shaped the interdisciplinary gathering of neuroscientists in the context of growing interest in basic research. Thereby, this article reveals the rise of theoretical concerns in brain science that reflect the distinct desires and concerns of biologists in the US at an intellectual and institutional level. By revisiting the launch of the NRP with a focus on Schmitt, the article sheds light on the historical contingencies in launching the new community as neuroscience in the US and their meaning for the locality and transiency of (inter)disciplinarity in brain science. (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)

From the mid-1960s onwards, a set of Spanish molecular biology research groups emerged in Spain. The factors contributing to this included: the return of a group of molecular biologists from their postdoctoral period abroad, the negotiations for the return of Spanish-born Nobel prize winner Severo Ochoa from New York, the negotiations for Spanish membership in the European Conference of Molecular Biology, and national policy towards university reform. As a result, the early molecular biologists’ research groups began (...) to be recognised as research schools by Spanish authorities and postgraduate courses and new research centres for molecular biology were set up. Foreign influence in the whole process was crucial. (shrink)

In The Logic of Life, François Jacob reconstructed the history of heredity from the seventeenth century to the present, emphasizing the role of physics in the development of biology. Quantum mechanics provided questions, methods, and techniques to molecular biologists. In the 1960s, physics also provided the organizational model. Jacob worked on the creation of the European Molecular Biology Laboratory, on the model of CERN (European Organization for Nuclear Research). I argue that reflection on the relation between molecular (...) biology and physics played a part in the making of The Logic of Life. Between the mid-1960s and the early 1970s, Jacob focused on relations between the “genealogy” of his molecular biology work and the development of physics at scientific, institutional, and historical levels. He thus brought molecular biology to the attention of a larger public, following the history of the Institut Pasteur, whose public mission had to be reaffirmed to grant its survival. With The Logic of Life, Jacob became an influential intellectual who engaged with scholars in human sciences. He promoted his view of the development of molecular biology as a model for a possible new discipline: bioanthropology. (shrink)

From the mid-1960s onwards, a set of Spanish molecular biology research groups emerged in Spain. The factors contributing to this included: the return of a group of molecular biologists from their postdoctoral period abroad, the negotiations for the return of Spanish-born Nobel prize winner Severo Ochoa from New York, the negotiations for Spanish membership in the European Conference of Molecular Biology, and national policy towards university reform. As a result, the early molecular biologists' research groups began (...) to be recognised as research schools by Spanish authorities and postgraduate courses and new research centres for molecular biology were set up. Foreign influence in the whole process was crucial. (shrink)

Occam’s razor refers to the idea that among competing explanations the simplest should be preferred. This principle has been understood and defended in different ways. Some systems biologists argue that traditional molecular biology is misguided because it relies on an unjustified application of Occam’s razor. I analyze which version of the principle is relevant in this context and ask whether the allegation stands up to scrutiny by looking at actual research. I defend the traditional approach by arguing that its (...) use of Occam’s razor is innocuous and by showing that systems biology heavily relies on considerations of simplicity as well. (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)