The rapidly changing field of genetics affects society through advances in health-care and through implications of genetic research. This study addresses the impacts of new genetic discoveries and technologies on different segments of today's society. The book begins with a chapter on genetic complexity, and subsequent chapters discuss moral and ethical questions arising from today's genetics from the perspectives of health care professionals, the media, the general public, special interest groups and commercial interests.

This text addresses the problems of complex systems in understanding natural phenomena and the behaviour of systems related to human activity, from a science and humanities perspective. It discusses molecular behaviour and structures, and offers examples of ecological and environmental modelling.

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

In 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)

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)

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)

It is proposed that the controlling system of the nerve cell is a molecular quantum device with an inner point of view. For the description of such a system it is necessary to create new science.

Whether or not quantum physics can account for molecular structure is a matter of considerable controversy. Three of the problems raised in this regard are the problems of molecular structure. We argue that these problems are just special cases of the measurement problem of quantum mechanics: insofar as the measurement problem is solved, the problems of molecular structure are resolved as well. In addition, we explore one consequence of our argument: that claims about the reduction or emergence (...) of molecular structure cannot be settled independently of the choice of a particular resolution to the measurement problem. Specifically, we consider how three standard putative solutions to the measurement problem inform our under- standing of a molecule in isolation, as well as of chemistry’s relation to quantum physics. (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)

I am honored to have been invited to participate in this Workshop on Comparative Studies of Building Molecular Biology, with a discussion of Japanese experiences in constructing a science — in this case, the discipline of molecular biology. As I understand it, the construction of a science must be equivalent to building a new culture. My having given this title to my paper suggests that I have enough knowledge about the subject to perhaps even extrapolate its (...) course into the future — which I do not. What I do have is a sincere admiration of my old friends and colleagues, in Japan and elsewhere, who together tried to build a new science of molecular biology in Japan. (shrink)

Preparative and analytical methods developed by separation scientists have played an important role in the history of molecular biology. One such early method is gel electrophoresis, a technique that uses various types of gel as its supporting medium to separate charged molecules based on size and other properties. Historians of science, however, have only recently begun to pay closer attention to this material epistemological dimension of biomolecular science. This paper substantiates the historiographical thread that explores the relationship (...) between modern laboratory practice and the production of scientific knowledge. It traces the historical development of gel electrophoresis from the mid-1940s to the mid-1960s, with careful attention to the interplay between technical developments and disciplinary shifts, especially the rise of molecular biology in this time-frame. Claiming that the early 1950s marked a decisive shift in the evolution of electrophoretic methods from moving boundary to zone electrophoresis, I reconstruct various trajectories in which scientists such as Oliver Smithies sought out the most desirable solid supporting medium for electrophoretic instrumentation. Biomolecular knowledge, I argue, emerged in part from this process of seeking the most appropriate supporting medium that allowed for discrete molecular separation and visualization. The early 1950s, therefore, marked not only an important turning point in the history of separation science, but also a transformative moment in the history of the life sciences as the growth of molecular biology depended in part on the epistemological access to the molecular realm available through these evolving technologies. (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)

Preparative and analytical methods developed by separation scientists have played an important role in the history of molecular biology. One such early method is gel electrophoresis, a technique that uses various types of gel as its supporting medium to separate charged molecules based on size and other properties. Historians of science, however, have only recently begun to pay closer attention to this material epistemological dimension of biomolecular science. This paper substantiates the historiographical thread that explores the relationship (...) between modern laboratory practice and the production of scientific knowledge. It traces the historical development of gel electrophoresis from the mid-1940s to the mid-1960s, with careful attention to the interplay between technical developments and disciplinary shifts, especially the rise of molecular biology in this time-frame. Claiming that the early 1950s marked a decisive shift in the evolution of electrophoretic methods from moving boundary to zone electrophoresis, I reconstruct various trajectories in which scientists such as Oliver Smithies sought out the most desirable solid supporting medium for electrophoretic instrumentation. Biomolecular knowledge, I argue, emerged in part from this process of seeking the most appropriate supporting medium that allowed for discrete molecular separation and visualization. The early 1950s, therefore, marked not only an important turning point in the history of separation science, but also a transformative moment in the history of the life sciences as the growth of molecular biology depended in part on the epistemological access to the molecular realm available through these evolving technologies. (shrink)

The general perception of how innovative assisted reproductive technologies are introduced is through a carefully controlled series of experiments in an animal model, such as the mouse. Only after the technique has been proven can one consider confirmatory studies on mammals closely related to humans, such as rhesus monkeys or other nonhuman primates. With this background of a peer-reviewed body of well-established published data, there is sufficient foundation and rationale to propose a clinical investigation to a responsible human subjects institutional (...) review board. IRBs weigh the benefits and risks of the new methods to human subjects, and then consider the appropriate informed consent procedures for the particular case. Only after a large number of clinical studies are performed at multiple sites and are peer reviewed can the efficacy and safety of the innovative approach be clearly evaluated. At that time, the potential therapy can be responsibly offered to suitable beneficiaries. (shrink)

The general perception of how innovative assisted reproductive technologies are introduced is through a carefully controlled series of experiments in an animal model, such as the mouse. Only after the technique has been proven can one consider confirmatory studies on mammals closely related to humans, such as rhesus monkeys or other nonhuman primates. With this background of a peer-reviewed body of well-established published data, there is sufficient foundation and rationale to propose a clinical investigation to a responsible human subjects institutional (...) review board. IRBs weigh the benefits and risks of the new methods to human subjects, and then consider the appropriate informed consent procedures for the particular case. Only after a large number of clinical studies are performed at multiple sites and are peer reviewed can the efficacy and safety of the innovative approach be clearly evaluated. At that time, the potential therapy can be responsibly offered to suitable beneficiaries. (shrink)

_Philosophy of Molecular Medicine: Foundational Issues in Theory and Practice_ aims at a systematic investigation of a number of foundational issues in the field of molecular medicine. The volume is organized around four broad modules focusing, respectively, on the following key aspects: What are the nature, scope, and limits of molecular medicine? How does it provide explanations? How does it represent and model phenomena of interest? How does it infer new knowledge from data and experiments? The essays (...) collected here, authored by prominent scientists and philosophers of science, focus on a handful of mainstream topics in the philosophical literature, such as _causation_, _explanation_, _modeling_, and _scientific inference_. These previously unpublished contributions shed new light on these traditional topics by integrating them with problems, methods, and results from three prominent areas of contemporary biomedical science: _basic research_, _translational_ and _clinical research_, and _clinical practice_. (shrink)

Senior molecular geneticists were interviewed about their perceptions of the ethical and social implications of genetic knowledge. Inductive analysis of these interviews identified a number of strategies through which the scientists negotiated their moral responsibilities as they participated in generating knowledge that presents difficult ethical questions. These strategies included: further analysis and application of scientific method; clarification of multiple roles; negotiation with the public through public debate, institutional processes of funding, ethics committees and legislation; and personal responsibility.

Much of the recent philosophical debate on causation and causal explanation in the biological and biomedical sciences has focused on the notion of mechanism. Mechanisms, their nature and epistemic roles have been tackled by a range of so-called neo-mechanistic theories, and widely discussed. Without denying the merits of this approach, our paper aims to show how lately it has failed to give proper credit to processes, which are central to the field, especially of contemporary molecular biology. Processes can be (...) summed up in the notion of ‘pathway’, which is far from being just equivalent to that of ‘mechanism’ and has a profound epistemological and explanatory relevance. It is argued that an adequate consideration of pathways impels some rethinking of scientific explanation in molecular biology, namely its functional and contextual features. A number of examples are given to suggest that the focus of philosophical attention in this disciplinary field should shift from the notion of mechanism to the notion of pathway. (shrink)

One of the most plausible and widely discussed examples of strong emergence is molecular structure. The only detailed account of it, which has been very influential, is due to Robin Hendry and is formulated in terms of downward causation. This paper explains Hendry’s account of the strong emergence of molecular structure and argues that it is coherent only if one assumes a diachronic reflexive notion of downward causation. However, in the context of this notion of downward causation, the (...) strong emergence of molecular structure faces three challenges that have not been met and which have so far remained unnoticed. First, the putative empirical evidence presented for the strong emergence of molecular structure equally undermines supervenience, which is one of the main tenets of strong emergence. Secondly, it is ambiguous how the assumption of determinate nuclear positions is invoked for the support of strong emergence, as the role of this assumption in Hendry’s argument can be interpreted in more than one way. Lastly, there are understandings of causation which render the postulation of a downward causal relation between a molecule’s structure and its quantum mechanical entities, untenable. (shrink)

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

The 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)

Molecular biology is a relatively new and very successful branch of science but currently it faces challenges posed by very complex issues that cannot be addressed by a traditional reductionist approach. However, despite its origins in the providential shift of some theoretical physicists to biology, currently molecular biology is immersed in a blind trend in which high-throughput technology, able to generate trillions of data, is becoming the leading edge of a discipline that has traded rational and critical (...) thinking for computer power, data crunching and statistics in hope of finding, once more, its way. However, the complex questions facing MB may only be solved by a paradigm shift in the causal way of thinking, so that complex, emergent, non-linear phenomena may be effectively understood in top-down and not in bottom-up terms. (shrink)

Philosophical discussion of molecular and developmental biology began in the late 1960s with the use of genetics as a test case for models of theory reduction. With this exception, the theory of natural selection remained the main focus of philosophy of biology until the late 1970s. It was controversies in evolutionary theory over punctuated equilibrium and adaptationism that first led philosophers to examine the concept of developmental constraint. Developmental biology also gained in prominence in the 1980s as part of (...) a broader interest in the new sciences of self-organization and complexity. The current literature in the philosophy of molecular and developmental biology has grown out of these earlier discussions under the influence of twenty years of rapid and exciting growth of empirical knowledge. Philosophers have examined the concepts of genetic information and genetic program, competing definitions of the gene itself and competing accounts of the role of the gene as a developmental cause. The debate over the relationship between development and evolution has been enriched by theories and results from the new field of 'evolutionary developmental biology'. Future developments seem likely to include an exchange of ideas with the philosophy of psychology, where debates over the concept of innateness have created an interest in genetics and development. (shrink)

Recent work on gene concepts has been influenced by recognition of the extent to which RNA transcripts from a given DNA sequence yield different products in different cellular environments. These transcripts are altered in many ways and yield many products based, somehow, on the sequence of nucleotides in the DNA. I focus on alternative splicing of RNA transcripts (which often yields distinct proteins from the same raw transcript) and on 'gene sharing', in which a single gene produces distinct proteins with (...) the exact same amino acid sequence. These are instances of molecular pleiotropy, in which distinct molecules are derived from a single putative gene. In such cases the cellular and external environments play major roles in determining which protein is produced. Where there is molecular pleiotropy, alternative gene concepts are naturally deployed; molecular epigenesis (revision of sequence-based information by altering molecular conformations or by action of non-informational molecules) plays a major role in orderly development. These results show that gene concepts in molecular biology do, and should, have both structural and functional components. They also show the need for a plurality of gene concepts and reveal fundamental difficulties in stabilizing gene concepts solely by reference to nucleotide sequence. (shrink)

I attempt to characterize the relationship of classical experimental embryology (CEE) and molecular developmental biology and compare it to the much-discussed case of classical genetics. These sciences are treated here as discovery practices rather than as definitive forms of knowledge. I first show that CEE had some causal knowledge and hence was able to answer specific why?-questions. A paradigm was provided by the case of eye induction, perhaps CEE’s greatest success. The case of the famous Spemann-Mangold organizer is more (...) difficult. I argue that before the advent of molecular biology, knowledge of its causal role in development was very limited. As a result, there was no functional definition of the concept of organizer. I argue that, like the classical gene concept, it is best viewed as an operational concept. This means that an account of reduction such as Kim’s functional reduction, which is still a mainstay in scientific metaphysics, cannot work in these cases. Nonetheless, again like in the classical gene case, the operational concepts of CEE played an important heuristic role in the discovery of molecules involved in morphogenesis and cell differentiation. This was made possible by what I call inter-level investigative practices. These are practices that combine experimental manipulations targeting two (or more) different levels. I conclude that the two sciences are more closely related via their experimental practices than by any inter-level explanatory relations. (shrink)

Historians agree that the second half of the twentieth century saw widespread changes in the structure of biological science in universities. This shift was, and continues to be, characterized by the de-differentiation of nineteenth and early twentieth century disciplines, with increasing emphasis on the methods and authority of molecular fields. Yet we currently lack appreciation of the dynamics that underpinned these changes, and of their tangible effects on the working practices of those involved. In this article we examine (...) the wholesale reform of biological science at the University of Manchester, England, that occurred in two successive steps in 1986 and 1993. We examine how reform was enabled by economic and political factors, as staff seized upon national pressures; in so doing, we emphasize how this reform was shaped by a generational view of the biological sciences as a one field, unified by molecular techniques. We assess how the success of these reforms was tied to new management policies that rewarded research activity in molecular fields, and refigured teaching as a punishment for research inactivity. We close by showing how our analysis fits amongst, and can contribute to, ‘big picture’ debates in the history and sociology of knowledge. (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)

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).

This paper examines processes of translation through which molecular genetic technologies and practices are incorporated into environmental health research and regulation. Specifically, it considers how scientists, risk assessors, and regulators have used genetically modified mouse models to translate across scientific disciplines, articulate emergent molecular forms, standards, and practices with the extant? gold standard,? and establish roles for molecular knowledge in risk assessment and regulation. Noting variation both within and between regulatory agencies in responses to data from these (...) models, the article describes also the role of public-private networks and their effects on professional and institutional imperatives which shape regulators? responses to the potential applications of these models. The conclusions address the importance of translation for understanding the wider implications of the molecularization of environmental health science. (shrink)

The paper argues against the central dogma and its interpretation by C. Kenneth Waters and Alex Rosenberg. I argue that certain phenomena in the regulation of gene expression provide a break with the central dogma, according to which sequence specificity for a gene product must be template derived. My thesis of 'molecular epigenesis' with its three classes of phenomena, sequence 'activation', 'selection', and 'creation', is exemplified by processes such as transcriptional activation, alternative cis- and trans-splicing, and RNA editing. It (...) argues that other molecular resources share the causal role of genes; the sequence specificity for the linear sequence of any gene product is distributed between the coding sequence, cis-acting sequences, trans-acting factors, environmental signals, and the contingent history of the cell (thesis of distributed causal specificity). I conclude that the central dogma has unnecessarily restricted genetic research to the sequencing of protein-coding genes, unilinear pathway analyses, and the focus on exclusive specificity. (shrink)

By their own account, physicalists are committed to the claim that physics is causally complete, or closed. The claim is presented as an empirical one. However, detailed and explicit empirical arguments for the claim are rare. I argue that molecular models are a key source of evidence but that, on closer inspection, they do not support the completeness claim.

This paper focuses on the consolidation of Molecular Evolution, a field originating in the 1960s at the interface of molecular biology, biochemistry, evolutionary biology, biophysics and studies on the origin of life and exobiology. The claim is made that Molecular Evolution became a discipline by integrating different sorts of scientific traditions: experimental, theoretical and comparative. The author critically incorporates Timothy Lenoir’s treatment of disciplines , as well as ideas developed by Stephen Toulmin on the same subject. On (...) their account disciplines are spaces where the social and epistemic dimensions of science are deeply and complexly interwoven. However, a more detailed account of discipline formation and the dynamics of an emerging disciplinary field is lacking in their analysis. The present essay suggests focusing on the role of scientific concepts in the double configuration of disciplines: the social/political and the epistemic order. In the case of Molecular Evolution the concepts of molecular clock and informational molecules played a central role, both in differentiating molecular from classical evolutionists, and in promoting communication between the different sorts of traditions integrated in Molecular Evolution. The paper finishes with a reflection on the historicity of disciplines, and the historicity of our concepts of disciplines. (shrink)