Kenneth Waters and Marcel Weber argue that the joint use of distinct gene concepts and the transfer of knowledge between classical and molecular analyses in contemporary scientific practice is possible because classical and molecular concepts of the gene refer to overlapping chromosomal segments and the DNA sequences associated with these segments. However, while pointing in the direction of coreference, both authors also agree that there is a considerable divergence between the actual sequences that count as genes (...) in classical genetics and molecular biology. The thesis advanced in this paper is that the referents of classical and molecular gene concepts are coextensive to a higher degree than admitted by Waters and Weber, and therefore coreference can provide a satisfactory account of the high level of integration between classical genetics and molecular biology. In particular, I argue that the functional units/cistrons identified by classical techniques overlap with functional elements entering the composition of molecular transcription units, and that the precision of this overlap can be improved by conducting further experimentation. (shrink)

How to interpret the “molecular gene” concept is discussed in this paper. I argue that the architecture of biological systems is hierarchical and multi-layered, exhibiting striking similarities to that of modern computers. Multiple layers exist between the genotype and system level property, the phenotype. This architectural complexity gives rise to the intrinsic complexity of the genotype-phenotype relationships. The notion of a gene being for a phenotypic trait or traits lacks adequate consideration of this complexity and has (...) limitations in explaining the genotype-phenotype relationships. I explore ways toward an integrative interpretation of the gene in the context of multi-layered biological systems. A gene, I argue, should be interpreted as a functional unit that is responsible for the trans-generation passage of the capacity to dynamically produce a biochemical activity or biochemical activities. At the molecular level, a gene is a genetic unit, a stretch of DNA sequence, which dictates the behavior and the dynamic production of the encoded cellular component(s). Embedded in a gene’s quadruple DNA code are the regulatory signals, such as those for RNA splicing and/or editing, as well as for transcription factor binding. A regulatory signal can be recognized by the gene expression machinery in one state, but not in another. The confusion caused by RNA splicing, editing, and a gene’s selective tissue distribution pattern is addressed. Instead of a context-dependent definition of the gene, I argue for the view that it is the same gene displaying multiple meanings, subject to differential interpretation by the cellular machinery in different states. In other words, the same gene gives rise to different products and expression levels under different conditions. (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)

This chapter contains section titled: Introduction The Gene in Classical Genetics The Gene in Molecular Genetics The Gene in Evolution and Development Conclusion: Genes, Genomics, and Reduction Acknowledgement References Further Reading.

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)

The purpose of this article is to update and defend syntax-based gene concepts. I show how syntax-based concepts can and have been extended to accommodate complex cases of processing and gene expression regulation. In response to difficult cases and causal parity objections, I argue that a syntax-based approach fleshes out a deflationary concept defining genes as genomic sequences and organizational features of the genome contributing to a phenotype. These organizational features are an important part of accepted (...) class='Hi'>molecular explanations, provide the theoretical basis for a large number of experimental techniques and practical applications, and play a crucial role in in annotating the genome, deriving predictions and constructing bioinformatics models. (shrink)

In light of scientific advances such as genomics, predictive diagnostics, genetically engineered agriculture, nuclear transfer cloning, and the manipulation of stem cells, the idea that genes carry predetermined molecular programs or blueprints is pervasive. Yet new scientific discoveries—such as rna transcripts of single genes that can lead to the production of different compounds from the same pieces of dna—challenge the concept of the gene alone as the dominant factor in biological development. Increasingly aware of the tension between (...) certain empirical results and interpretations of those results based on the orthodox view of genetic determinism, a growing number of scientists urge a rethinking of what a gene is and how it works. In this collection, a group of internationally renowned scientists present some prominent alternative approaches to understanding the role of dna in the construction and function of biological organisms. Contributors discuss alternatives to the programmatic view of dna, including the developmental systems approach, methodical culturalism, the molecular process concept of the gene, the hermeneutic theory of description, and process structuralist biology. None of the approaches cast doubt on the notion that dna is tremendously important to biological life on earth; rather, contributors examine different ideas of how dna should be represented, evaluated, and explained. Just as ideas about genetic codes have reached far beyond the realm of science, the reconceptualizations of genetic theory in this volume have broad implications for ethics, philosophy, and the social sciences. Contributors. Thomas Bürglin, Brian C. Goodwin, James Griesemer, Paul Griffiths, Jesper Hoffmeyer, Evelyn Fox Keller, Gerd B. Müller, Eva M. Neumann-Held, Stuart A. Newman, Susan Oyama, Christoph Rehmann-Sutter, Sahotra Sarkar, Jackie Leach Scully, Gerry Webster, Ulrich Wolf. (shrink)

The present paper discusses Kitcher’s framework for studying conceptual change and progress. Kitcher’s core notion of reference potential is hard to apply to concrete cases. In addition, an account of conceptual change as change in reference potential misses some important aspects of conceptual change and conceptual progress. I propose an alternative framework that focuses on the inferences and explanations supported by scientific concepts. The application of my approach to the history of the gene concept offers a better account (...) of the conceptual progress that occurred in the transition from the Mendelian to the molecular gene than Kitcher’s theory. (shrink)

Thomas Kuhn described the progress of science as comprising occasional paradigm shifts separated by interludes of ‘normal science’. The paradigm that has held sway since the inception of molecular biology is that genes (mainly) encode proteins. In parallel, theoreticians posited that mutation is random, inferred that most of the genome in complex organisms is non‐functional, and asserted that somatic information is not communicated to the germline. However, many anomalies appeared, particularly in plants and animals: the strange genetic phenomena of (...) paramutation and transvection; introns; repetitive sequences; a complex epigenome; lack of scaling of (protein‐coding) genes and increase in ‘noncoding’ sequences with developmental complexity; genetic loci termed ‘enhancers’ that control spatiotemporal gene expression patterns during development; and a plethora of ‘intergenic’, overlapping, antisense and intronic transcripts. These observations suggest that the original conception of genetic information was deficient and that most genes in complex organisms specify regulatory RNAs, some of which convey intergenerational information. Also see the video abstract here: https://youtu.be/qxeGwahBANw. (shrink)

Advances in molecular biological research in the latter half of the twentieth century have made the story of the gene vastly complicated: the more we learn about genes, the less sure we are of what a gene really is. Knowledge about the structure and functioning of genes abounds, but the gene has also become curiously intangible. This collection of essays renews the question: what are genes? Philosophers, historians and working scientists re-evaluate the question in this volume, (...) treating the gene as a focal point of interdisciplinary and international research. It will be of interest to professionals and students in the philosophy and history of science, genetics and molecular biology. (shrink)

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

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)

The discussion presents a framework of concepts that is intended to account for the rationality of semantic change and variation, suggesting that each scientific concept consists of three components of content: 1) reference, 2) inferential role, and 3) the epistemic goal pursued with the concept’s use. I argue that in the course of history a concept can change in any of these components, and that change in the concept’s inferential role and reference can be accounted for (...) as being rational relative to the third component, the concept’s epistemic goal. This framework is illustrated and defended by application to the history of the gene concept. It is explained how the molecular gene concept grew rationally out of the classical gene concept despite a change in reference, and why the use and reference of the contemporary molecular gene concept may legitimately vary from context to context. (shrink)

Genes in Development is a collection of 13 stimulating essays on "post genomic" approaches to the concept of the gene. At the risk of caricaturing some complex balances, the contributors tend to be skeptical about genetic determinism, the central dogma of molecular biology, reductionism, genes as programs and the concept of the gene as a DNA sequence. They tend to like emergent properties, complexity theory, the parity thesis for developmental resources, developmental systems theory, and membranes. (...) But within this broad weltanschauung the essays in Genes in Development vary widely in their interests and emphases––from the history of twentieth century genetics to the social and ethical issues raised by contemporary genetics––which makes for an attractive and valuable collection. (shrink)

Particularly, but not exclusively, in Germany, concerns are uttered as to the consequences of modern biotechnological advances and their range of applications in the field of human genetics. Whereas the proponents of this research are mainly focussing on the possible knowledge that could be gained by understanding the causes of developmental processes and of disease on the molecular level, the critics fear the beginnings of a new eugenics movement. Without claiming a logical relationship between genetic sciences and eugenics movements, (...) it is nevertheless suggested in this article that a connection between both can become established when the distinction between scientifically validated statements on one hand and guiding hypotheses and assumptions on the other hand is blurred, as is observed particularly when scientists report their results to the public. This claim is demonstrated in comparisons between the current state of scientific knowledge on the role of genes in development and causation of diseases, and the way this is presented to the public. It is required that a debate on biotechnology should include reflections on the validity of claims made by scientists. (shrink)

While the definition of the ‘genotype’ has undergone dramatic changes in the transition from classical to molecular genetics, the definition of the ‘phenotype’ has remained for a long time within the classical framework. In addition, while the notion of the genotype has received significant attention from philosophers of biology, the notion of the phenotype has not. Recent developments in the technology of measuring gene-expression levels have made it possible to conceive of phenotypic traits in terms of levels of (...) gene expression. We demonstrate that not only has this become possible but it has also become an actual practice. This suggests a significant change in our conception of the phenotype: as in the case of the ‘genotype’, phenotypes can now be conceived in quantitative and measurable terms on a comprehensive molecular level. We discuss in what sense gene expression profiles can be regarded as phenotypic traits and whether these traits are better described as a novel concept of phenotype or as an extension of the classical concept. We argue for an extension of the classical concept and call for an examination of the type of extension involved. (shrink)

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

Currently there are persistent doubts about the meaning and contributions of the gene concept, mostly related to its interpretation as a stretch of DNA encoding a single functional product, i.e., the classical molecular gene concept. There is, however, much conceptual variation around genes, leading to important difficulties in genetics teaching. We investigated whether and how conceptual variation related to the gene concept and gene function models is present in school science and what (...) potential problems it may bring to genetics teaching and learning. Here, we report results on how ideas about genes and gene function are treated in textbooks and appear in students’ views and, also, about a teaching strategy for improving higher education students’ understanding of scientific models and conceptual variation around genes and their functions. (shrink)

The concept of the gene has been the central organizing theme of 20th century biology. Biology has become increasingly influential both for philosophers seeking a naturalized basis for epistemology, ethics, and the understanding of the mind, as well as for the human sciences generally. The central task of this work is to get the story right about genes and in so doing provide a critical and enabling resourse for use in the further pursuit of human self-understanding. ;The work (...) begins with a wide-ranging historical reconstruction and conceptual analysis of the meaning of "the gene" that results in defining and distinguishing two different "genes". Each of these can be seen as an heir to one of the two major historical trends in explaining the source of biological order---preformationism and epigenesis. The preformationist gene predicts phenotypes but only on an instrumental basis where immediate medical and/or economic benefits can be had. The gene of epigenesis , by contrast, is a developmental resource that provides templates for RNA and protein synthesis but has in itself no determinate relationship to organismal phenotypes. The seemingly prevalent idea that genes constitute information for traits is based, I argue, upon an unwarranted conflation of these two senses which is in effect held together by rhetorical glue. Beyond this historical, conceptual, and rhetorical inquiry the bulk of the dissertation then concerns itself with an empirically up-to-date analysis of the cell and molecular basis of biological order and of the pathological loss of same. In each of these chapters I structure my analysis with the idea in mind that the "conflated" view can be held empirically accountable. Major touchpoints in this work include the ideas of I. Kant, J. Blumenbach, K. E. von Baer, J. Muller, R. Virchow, W. Johannsen, R. Falk, J. Sapp, E. Schrodinger, M. Delbruick, G. Gamow, R. Doyle, L. Kay, S. Kauffman, E. Jablonka, J. Rothman, K. Yamamoto, P. Rous, H. Temin, J. M. Bishop, H. Harris, E. Stanbridge, D. L. Smithers, B. Vogelstein, E. Farber and H. Rubin. (shrink)

Definitions of the term gene typically superimpose molecular genetics onto Mendelism. What emerges are persistent attempts to regard the gene as a unit of structure and/or function, language that creates multiple meanings for the term and fails to acknowledge the diversity of gene architecture. I argue that coherence at the molecular level requires abandonment of the classical unit concept and recognition that a gene is constructed from an assemblage of domains. Hence, a domain (...) set (1) conforms more closely to empirical evidence for genetic organization of DNA regions capable of transcription and (2) has ontological properties lacking in the traditional unit definition. (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)

There is at present uneasiness about the conceptual basis of genetics. The gene concept has become blurred and there are problems with the distinction between genotype and phenotype. In the present paper I go back to their role in the creation of modern genetics in the early twentieth century. The terms were introduced by the Danish botanist and geneticist Wilhelm Johannsen in his big textbook of 1909. Historical accounts usually concentrate on this book and his 1911 paper “The (...) Genotype Conception of Heredity.” His bean selection experiment of 1900–1903 is generally assumed to be the source of his genotype theory. The present paper examines the scientific context and meaning of this experiment, how it was received, and how the genotype theory became securely established by the early 1910s. I argue in conclusion that the genotype/phenotype distinction, which provides the empirical basis for Johannsen's gene, was scientifically well founded when introduced and still is. Keith Baverstock's criticism does not consider the force of the bean selection experiment at the time and as a paradigm for following investigations of heredity. (shrink)

The unit of selection is the concept of that ‘something’ to which biologists refer when they speak of an adaptation as being ‘for the good of’ something. Darwin identified the organism as the unit of selection because for him the ‘struggle for existence’ was an issue among individuals. Later on it was suggested that, in order to understand the evolution of social behavior, it is necessary to argue that groups, and not individuals, are the units of selection. The last (...) addition to this debate was the formulation by Dawkins, in 1976, that the genes themselves are the units of selection while organisms are merely the temporary receptacles and vehicles for such genes. Thus, the preposterous dissolution of the organism into genes and the proteins coded by such genes has been introduced in the evolutionary discourse by neglecting that the explanations for biological phenomena can be either synchronic or diachronic, depending on the phenomenon to be explained. Therefore explanations in molecular biology are synchronic while evolutionary biology needs diachronic explanations. Nevertheless, for ultra-Darwinians such as Dawkins, efficient replication is all that biology is about. Here I develop an argument in order to show that there is nothing in molecular and cell biology that might support such a contention and that the idea of the gene as the unit of selection is incompatible with the evident evolution of biological complexity. (shrink)

In their Bioessays review ‘Current views of collagen degradation’, Gillian Murphy and John Reynolds gave an outline of the molecular structure of the members of the collagen family and described their traditional role in providing stable tissue frameworks.1 This short review considers the relationship between the different members of that family and what gene structure reveals about their evolution. Mutation of the collagen structural genes has been discovered in patients suffering from brittle‐bone syndrome and other inherited connective tissue (...) disorders, and here I attempt to rationalize these results into an overall concept of collagen gene mutation and evolution. (shrink)

The Neo‐Darwinian concept of natural selection is plausible when one assumes a straightforward causation of phenotype by genotype. However, such simple 1:1 mapping must now give place to the modern concepts of gene regulatory networks and gene expression noise. Both can, in the absence of genetic mutations, jointly generate a diversity of inheritable randomly occupied phenotypic states that could also serve as a substrate for natural selection. This form of epigenetic dynamics challenges Neo‐Darwinism. It needs to incorporate (...) the non‐linear, stochastic dynamics of gene networks. A first step is to consider the mathematical correspondence between gene regulatory networks and Waddington's metaphoric ‘epigenetic landscape’, which actually represents the quasi‐potential function of global network dynamics. It explains the coexistence of multiple stable phenotypes within one genotype. The landscape's topography with its attractors is shaped by evolution through mutational re‐wiring of regulatory interactions – offering a link between genetic mutation and sudden, broad evolutionary changes. (shrink)

In this paper, rather than focusing on genes as an organising concept around which historical considerations of theory and practice in genetics are elucidated, we place genetic markers at the heart of our analysis. This reflects their central role in the subject of our account, livestock genetics concerning the domesticated pig, Sus scrofa. We define a genetic marker as a element existing in different forms in the genome, that can be identified and mapped using a variety of quantitative, classical (...) and molecular genetic techniques. The conjugation of pig genome researchers around the common object of the marker from the early-1990s allowed the distinctive theories and approaches of quantitative and molecular genetics concerning the size and distribution of gene effects to align in projects to populate genome maps. Critical to this was the nature of markers as ontologically inert, internally heterogeneous and relational. Though genes as an organising and categorising principle remained important, the particular concatenation of limitations, opportunities, and intended research goals of the pig genetics community, meant that a progressively stronger focus on the identification and mapping of markers rather than genes per se became a hallmark of the community. We therefore detail a different way of doing genetics to more gene-centred accounts. By doing so, we reveal the presence of practices, concepts and communities that would otherwise be hidden. (shrink)

Contrary to Mendel, who introduced hybridization as a methodology for the study of selected discrete traits, de Vries conceived of organisms to be composed of discrete traits. This introduced into genetic research the dialectics of reductive analysis of genes as instrumental variables versus that of genes as the material atoms of heredity. The latter conception gained support with the analysis of mutations and eventually with high resolution analysis at the genetic and biochemical levels, as achieved in fungi and later in (...) bacteria and their viruses. Attempts to reduce "classical" genetics to "molecular" genetics turned out to be futile. However, this did not necessarily imply that these were two distinct theoretical approaches. On the contrary, it is argued that molecular genetics is an extension of phenomenological deduction, rather than being induction from molecular (DNA) causes to effects. Although conceptually systems direct development, methodologically individual inputs must be studied. (shrink)

The dialectic discourse of the ‘gene’ as the unit of heredity deduced from the phenotype, whether an intervening variable or a hypothetical construct, appeared to be settled with the presentation of the molecular model of DNA: the gene was reduced to a sequence of DNA that is transcribed into RNA that is translated into a polypeptide; the polypeptides may fold into proteins that are involved in cellular metabolism and structure, and hence function. This path turned out to (...) be more bewildering the more the regulation of products and functions were uncovered in the contexts of integrated cellular systems. Philosophers struggling to define a unified concept of the gene as the basic entity of genetics confronted those who suggested several different ‘genes’ according to the conceptual frameworks of the experimentalists. Researchers increasingly regarded genes de facto as generic terms for describing their empiric data, and with improved DNA-sequencing capacities these entities were as a rule bottom-up nucleotide sequences that determine functions. Only recently did empiricists return to discuss conceptual considerations, including top-down definitions of units of function that through cellular mechanisms select the DNA sequences which comprise ‘genomic-footprints’ of functional entities. (shrink)

The aim of this dissertation is to provide an analysis of central concepts in philosophy of science from the perspective of current molecular and developmental research. Each chapter explores the ways in which particular phenomena or discoveries in molecular biology influences our philosophical understanding of the nature of scientific knowledge. The introductory prologue draws some general connections between the various threads, which revolve around two central themes: causation and explanation. Chapter Two identifies a particular type of causal relation (...) which is widespread across the sciences, but cannot be straightforwardly accommodated by extant accounts of causation and causal explanation. Chapter Three explores how the form of redundant causality identified in the previous chapter plays an important role in causal explanation, by making the effect stable and robust. Chapter Four offers a novel perspective on the debate over biological reductionism by distinguishing between different paradigms of molecular explanation. Chapter Five provides a philosophical analysis of the so-called "Developmental Synthesis" of evolutionary and developmental biology, and suggests a general account of scientific unification grounded in the notion of explanatory relevance. Chapter Six offers an account of dispositional properties inspired by mechanisms of gene regulation, according to which dispositions are not properties of entities, but properties that describe the behavior of abstract idealized models. Finally, Chapter Seven scrutinizes the concept of the molecular ecosystem, a metaphor frequently employed by biologists to describe cellular interactions, but seldom articulated in detail. (shrink)

Advancing the reductionist conviction that biology must be in agreement with the assumptions of reductive physicalism (the upward hierarchy of causal powers, the upward fixing of facts concerning biological levels) A. Rosenberg argues that downward causation is ontologically incoherent and that it comes into play only when we are ignorant of the details of biological phenomena. Moreover, in his view, a careful look at relevant details of biological explanations will reveal the basic molecular level that characterizes biological systems, defined (...) by wholly physical properties, e.g., geometrical structures of molecular aggregates (cells). In response, we argue that contrary to his expectations one cannot infer reductionist assumptions even from detailed biological explanations that invoke the molecular level, as interlevel causal reciprocity is essential to these explanations. Recent very detailed explanations that concern the structure and function of chromatin—the intricacies of supposedly basic molecular level—demonstrate this. They show that what seem to be basic physical parameters extend into a more general biological context, thus rendering elusive the concepts of the basic level and causal hierarchy postulated by the reductionists. In fact, relevant phenomena are defined across levels by entangled, extended parameters. Nor can the biological context be explained away by basic physical parameters defining molecular level shaped by evolution as a physical process. Reductionists claim otherwise only because they overlook the evolutionary significance of initial conditions best defined in terms of extended biological parameters. Perhaps the reductionist assumptions (as well as assumptions that postulate any particular levels as causally fundamental) cannot be inferred from biological explanations because biology aims at manipulating organisms rather than producing explanations that meet the coherence requirements of general ontological models. Or possibly the assumptions of an ontology not based on the concept of causal powers stratified across levels can be inferred from biological explanations. The incoherence of downward causation is inevitable, given reductionist assumptions, but an ontological alternative might avoid this. We outline desiderata for the treatment of levels and properties that realize interlevel causation in such an ontology. (shrink)

One observes regulation at every biological level. Organisms, cells, and biochemical processes operate efficiently, normally wasting neither material nor energy, and adjusting their functions to external influences. Nature evidently has evolved mechanisms specifically dedicated to regulation at many levels. What is the molecular basis of this control?In the 1950s these molecular control mechanisms began to be explored seriously. The discoveries of feedback inhibition of enzyme activity were important because they gave an initial example of how regulation is achieved (...) at the molecular level. We showed that certain enzymes are composed of two parts, one for catalysis and another distinct part present only to regulate this catalysis. Catalytic activity can be either stimulated or inhibited when a small molecule in the environment combines with the enzyme's regulatory site. In particular, a final product of a metabolic pathway generates a feedback loop which automatically limits its own excessive production, by combining with the regulatory site of an early enzyme in that pathway. Later studies showed that catalytic and regulatory structures of some enzymes could be separated physically.The discovery of regulatory sites and their interaction with molecules unrelated to their substrates was the basis for the generalized allosteric concept. This concept extends the regulatory site idea to a wide variety of processes such as control of gene expression, hormone action, and cellular growth. (shrink)

“Challenging the utility of polygenic scores for social science” is a compelling but limited critique. Phenotypic development is sensitive to both initial conditions and all subsequent states – from conception to senescence. Thus, gene-centric analyses are misleading (and often meaningless) because gene products are transformed, and their phenotypic ‘effects' combined and attenuated with successive propagations from molecular and cellular contexts to organismal and social environments.

Contrary to the common-sense view and positivist aspirations, scientific concepts are often imprecise. Many of these concepts are ambiguous, vague, or have an under-specified meaning. In this paper, I discuss how imprecise concepts promote integration in biology and thus benefit science. Previous discussions of this issue focus on the concepts of molecular gene and evolutionary novelty. The concept of molecular gene helps biologists integrate explanatory practices, while the notion of evolutionary novelty helps them integrate research (...) questions into an interdisciplinary problem New directions in the philosophy of science, Springer, Dordrecht, 2014). In what follows, I compare molecular gene and evolutionary novelty to another imprecise concept, namely biological lineage. This concept promotes two other types of scientific integration: it helps biologists integrate theoretical principles and methodologies into different areas of biology. The concept of biological lineage facilitates these types of integration because it is broad and under-specified in ways that the concepts of molecular gene and evolutionary novelty are not. Hence, I use the concept of biological lineage as a case study to reveal types of integration that have been overlooked by philosophers. This case study also shows that even very imprecise concepts can be beneficial to scientific practice. (shrink)

One of the defining features of the classical gene was its position. In molecular genetics, positions are defined instead as nucleotide numbers and there is no clear correspondence with its classical counterpart. However, the classical gene position did not simply disappear with the development of the molecular approach, but survived in the lab associated to different genetic practices. The survival of classical gene position would illustrate Waters’ view about the practical persistence of the genetic approach (...) beyond reductionism and anti-reductionist claims. We show instead that at the level of laboratory practices there are also reductive processes, operating through the rise and fall of different techniques. Molecular markers made the concept of classical gene position practically dispensable, leading us to rethink whether it had any causal role or was just a mere heuristic. (shrink)

We discuss the role of linguistic metaphors as a cognitive frame for the understanding of genetic information processing. The essential similarity between language and genetic information processing has been recognized since the very beginning, and many prominent scholars have noted the possibility of considering genes and genomes as texts or languages. Most of the core terms in molecular biology are based on linguistic metaphors. The processing of genetic information is understood as some operations on text – writing, reading and (...) editing and their specification (encoding/decoding, proofreading, transcription, translation, reading frame). The concept of gene reading can be traced from the archaic idea of the equation of Life and Nature with the Book. Thus, the genetics itself can be metaphorically represented as some operations on text (deciphering, understanding, code-breaking, transcribing, editing, etc.), which are performed by scientists. At the same time linguistic metaphors portrayed gene entities also as having the ability of reading. In the case of such “bio-reading” some essential features similar to the processes of human reading can be revealed: this is an ability to identify the biochemical sequences based on their function in an abstract system and distinguish between type and its contextual tokens of the same type. Metaphors seem to be an effective instrument for representation, as they make possible a two-dimensional description: biochemical by its experimental empirical results and textual based on the cognitive models of comprehension. In addition to their heuristic value, linguistic metaphors are based on the essential characteristics of genetic information derived from its dual nature: biochemical by its substance, textual (or quasi-textual) by its formal organization. It can be concluded that linguistic metaphors denoting biochemical objects and processes seem to be a method of description and explanation of these heterogeneous properties. (shrink)

The gene regulation function (GRF) provides an operational description of a promoter behavior as a function of the concentration of one of its transcriptional regulators. Behind this apparently trivial definition lies a central concept in biological control: the GRF provides the input/output relationship of each edge in a transcriptional network, independently from the molecular interactions involved. Here we discuss how existing methods allow direct measurement of the GRF, and how several trade‐offs between scalability and accuracy have hindered (...) its application to relatively large networks. We discuss the theoretical and technical requirements for obtaining the GRF. Based on these requirements, we introduce a simplified and easily scalable method that is able to capture the significant parameters of the GRF. The GRF is able to predict the behavior of a simple genetic circuit, illustrating how addressing the quantitative nature of gene regulation substantially increases our comprehension on the mechanisms of gene control. (shrink)

We discuss the role of linguistic metaphors as a cognitive frame for the understanding of genetic information processing. The essential similarity between language and genetic information processing has been recognized since the very beginning, and many prominent scholars have noted the possibility of considering genes and genomes as texts or languages. Most of the core terms in molecular biology are based on linguistic metaphors. The processing of genetic information is understood as some operations on text – writing, reading and (...) editing and their specification (encoding/decoding, proofreading, transcription, translation, reading frame). The concept of gene reading can be traced from the archaic idea of the equation of Life and Nature with the Book. Thus, the genetics itself can be metaphorically represented as some operations on text (deciphering, understanding, codebreaking, transcribing, editing, etc.), which are performed by scientists. At the same time linguistic metaphors portrayed gene entities also as having the ability of reading. In the case of such “bio-reading” some essential features similar to the processes of human reading can be revealed: this is an ability to identify the biochemical sequences based on their function in an abstract system and distinguish between type and its contextual tokens of the same type. Metaphors seem to be an effective instrument for representation, as they make possible a two-dimensional description: biochemical by its experimental empirical results and textual according to the cognitive models of comprehension. In addition to their heuristic value, linguistic metaphors are based on the essential characteristics of genetic information derived from its dual nature: biochemical by its substance, textual (or quasitextual) by its formal organization. It can be concluded that linguistic metaphors denoting biochemical objects and processes seem to be a method of description and explanation of these heterogeneous properties. (shrink)

“Evolvability,” writes Evelyn Fox Keller, “refers to the capacity to generate any kind of heritable phenotypic variation upon which selection can act” . Whether one considers genes or organisms, the potential to adapt and evolve, to respond flexibly to a changing environment, is now recognized by many biologists as itself a trait actively favored by natural selection. Keller correctly presents this idea as an antidote to an old notion of genetic stability. She seems not to appreciate how well it applies (...) to her own subject.The Century of the Gene is Keller's latest collection of linked essays, six tidy, intelligent shovelfuls from her ongoing effort to undermine the claims of mainstream molecular biology and to substitute from the scientific margins an alternative interpretation. This project stems from her philosophical biography of the geneticist Barbara McClintock, published in 1983. In her Nobel speech, also from 1983, McClintock wrote of the genome as a dynamic “sensitive organ of the cell,” responsive, flexible, and interacting with the environment. For half a century, McClintock had railed at biologists that genes must be studied not as autonomous, independently acting units but rather as parts of an exquisite whole, acting in concert. Keller celebrated this in McClintock's work, though many have read Keller as applying to this view of nature a gloss of feminism that McClintock rejected. More recently, among other projects, Keller has criticized the “master molecule” concept in biology, examined the use of metaphor in science, and celebrated Christiane Nüsslein‐Vollhard's studies in developmental biology. Through it all, she maintains a fascination with gender and with language as shapers of scientific thought.Here Keller explores what she sees as the divergent histories of studies of genes and use of the term “gene.” While scientists continue to talk of genes much as they have done for a century now—as stable, discrete units directing the activities of the cell and the development of the organism—the molecular biology of the last forty years has seen a breaking down of the boundaries of the gene, physically, chemically, and physiologically. Keller begins by attacking the notion of genetic stability—whence the introductory quotation about evolvability. Next she explores the idea of genetic regulation, the fact that genes do not make anything, nor do they literally control anything. The molecular biologist's version of the chicken‐and‐egg problem is: Which comes first—proteins or genes? Proteins read the DNA that provides the instructions to make more proteins. Keller argues for chickens.The most important idea in the book is Keller's distinction between a developmental program and a genetic program. The former is a sequence of ontological steps in the life of an organism; it does not presuppose that all steps in the program are encoded in genes or that all steps are determined prior to the beginning of development. Developmental programs may be derived empirically, independently of genetic analysis. In contrast, the genetic program is a more recent idea that does locate the program instructions in the nucleus in the fertilized egg. For Keller, genetic programs carry implications of determinism, a restriction of vision in our attempts to understand nature.The term “gene,” Keller concludes, has outlived its utility. Molecular biologists no longer work with anything so discrete as genes. Their own data, she argues, show that genes and genomes are flexible, modular, and interactive. Keller wishes for, but does not offer, a new term or set of terms that would better reflect current understanding of genetics and development.If biologists have shown that the gene concept is outmoded, why don't they know it? Keller's answer is that the biologists have not yet recognized the implications of their own results; their language lags behind their knowledge. Eventually, she believes, either they will drop the term “gene” or biology must suffocate in its shell. Yet the changes she describes have been under way for decades and biology shows no signs of slowing. Keller recognizes this, and in the conclusion she briefly acknowledges the obvious solution to the conundrum: that biology continues to grow because of, not despite, this linguistic flexibility. This important idea deserves fuller treatment.As with the gene in nature, so with the word “gene” in the scientific lexicon: its very evolvability is selected for, a crucial trait that ensures its survival. (shrink)

We discuss the role of linguistic metaphors as a cognitive frame for the understanding of genetic information processing. The essential similarity between language and genetic information processing has been recognized since the very beginning, and many prominent scholars have noted the possibility of considering genes and genomes as texts or languages. Most of the core terms in molecular biology are based on linguistic metaphors. The processing of genetic information is understood as some operations on text – writing, reading and (...) editing and their specification (encoding/decoding, proofreading, transcription, translation, reading frame). The concept of gene reading can be traced from the archaic idea of the equation of Life and Nature with the Book. Thus, the genetics itself can be metaphorically represented as some operations on text (deciphering, understanding, codebreaking, transcribing, editing, etc.), which are performed by scientists. At the same time linguistic metaphors portrayed gene entities also as having the ability of reading. In the case of such “bio-reading” some essential features similar to the processes of human reading can be revealed: this is an ability to identify the biochemical sequences based on their function in an abstract system and distinguish between type and its contextual tokens of the same type. Metaphors seem to be an effective instrument for representation, as they make possible a two-dimensional description: biochemical by its experimental empirical results and textual based on the cognitive models of comprehension. In addition to their heuristic value, linguistic metaphors are based on the essential characteristics of genetic information derived from its dual nature: biochemical by its substance, textual (or quasi-textual) by its formal organization. It can be concluded that linguistic metaphors denoting biochemical objects and processes seem to be a method of description and explanation of these heterogeneous properties. (shrink)

Genomes are defined by their primary sequence. The functional properties of genomes, however, are determined by far more complex mechanisms and depend on multiple layers of regulatory control processes. A key emerging contributor to genome function is the architectural organization of the cell nucleus. The spatial and temporal behavior of genomes and their regulatory proteins are now being recognized as important, yet still poorly understood, control mechanisms in genome function. Combined cell biological, molecular and computational analysis of architectural aspects (...) of genome function has added a further dimension to the investigation of some of the most fundamental cellular processes including transcription and maintenance of genome integrity. The complete elucidation of the contribution that nuclear architecture makes to gene expression will be required to fully understand physiological processes such as differentiation, development and disease at the cellular level. Here I give an overview of some of the emerging concepts in the study of in vivo genome organization and function. BioEssays 27:477–487, 2005. Published 2005 Wiley Periodicals, Inc. (shrink)

1900 was a remarkable year for science. Several ground-breaking events took place, in physics, biology and psychology. Planck introduced the quantum concept, the work of Mendel was rediscovered, and Sigmund Freud published The Interpretation of Dreams . These events heralded the emergence of completely new areas of inquiry, all of which greatly affected the intellectual landscape of the 20 th century, namely quantum physics, genetics and psychoanalysis. What do these developments have in common? Can we discern a family likeness, (...) a basic affinity between them, so that we can use the one to deepen our understanding of the other? One common denominator is that they open up realms of inquiry that are significantly different from the world of everyday experience, namely the realm of elementary particles, of genes and genomes, and of the unconscious. But to what extent can we meaningfully argue, for instance, that the genome is the biological unconscious, and the unconscious the psychic genome? To address these questions, I will build on the work of two key intellectual figures who have explored the affinities of these developments in depth, namely Erwin Schrödinger (a quantum physicist and avid reader of Schopenhauer who initiated molecular biology) and Jacques Lacan (who reframed the specificity of psychoanalysis with the help of 20 th century science: the era of structural linguistics, but also of quantum physics, molecular biology, bioinformatics and DNA). (shrink)

The scientific reasoning strategies used to discover a new concept in a scientific domain were investigated in two studies. An innovative task in which subjects discover new concepts in molecular biology was used. This task was based upon one set of experiments that Jacob and Monod used to discover how genes are controlled, and for which they were awarded the Nobel prize. In the two studies reported in this article, subjects were taught some basic facts and experimental techniques (...) in molecular biology, using a simulated molecular genetics laboratory on a computer. Following their initial training, they were then asked to discover how genes are controlled by other genes. In Study 1, subjects found no evidence that was consistent with their initial hypothesis. Subjects then set one of two goals for conducting experiments and evaluating data. One goal was to search for evidence consistent with the current hypothesis (and they did not attend to the features of discrepant findings); none of the subjects who only had this goal succeeded at discovering how the genes were controlled. Other subjects in Study 1 used a different goal: Upon noticing evidence inconsistent with their current hypothesis, these subjects set a new goal of attempting to explain the cause of the discrepant findings. Using this goal, a subset of these subjects discovered the correct solution to the problem. Study 2 was conducted to test the hypothesis that subjects' goals of finding evidence consistent with their current hypothesis blocks consideration of alternate hypotheses and generation of new goals, it was predicted that if subjects could achieve their initial goal of discovering evidence consistent with their current hypothesis, they would then attend to particular features of discrepant evidence and solve the problem. To test this prediction, an additional mechanism of genetic control that was consistent with subjects' initial goal was added to the genes. Here, subjects had to discover two mechanisms of control: one mechanism consistent with their current hypothesis, and one inconsistent with their hypothesis. Twice as many subjects reached the correct solution in Study 2 than in Study 1. The findings of the two studies indicate that goals provide a powerful constraint on the cognitive processes underlying scientific reasoning and that the types of goals that are represented determine many of the reasoning errors that subjects make. (shrink)

First the ‘Weismann barrier’ and later on Francis Crick’s ‘central dogma’ of molecular biology nourished the gene-centric paradigm of life, i.e., the conception of the gene/genome as a ‘central source’ from which hereditary specificity unidirectionally flows or radiates into cellular biochemistry and development. Today, due to advances in molecular genetics and epigenetics, such as the discovery of complex post-genomic and epigenetic processes in which genes are causally integrated, many theorists argue that a gene-centric conception of (...) the organism has become problematic. Here, we first explore the causal implications of the following two central dogma-related issues: (1) widespread reverse transcription—arguing for an extension from ‘DNA-genome’ to RNA-encompassing ‘NA-genome’ and, thus, from traditional DNA-centrism to a broader ‘NA-centrism’; and (2) the absence of a mechanism of reverse translation—arguing for the ‘structural primacy’ of NA-sequence over protein in cellular biochemistry. Secondly, we explore whether this latter conclusion can be extended to a ‘functional primacy’ of NA-sequence over protein in cellular biochemistry, which would imply a limited kind of ‘gene/NA-centrism’ confined to the subcellular level of NA/protein-based biochemistry. Finally, we explore the conditions—and their (non)fulfilment—for a more generalised form of gene-centrism extendable to higher levels of biological organisation. We conclude that the higher we go in the biological hierarchy, the more dubious gene-centric claims become. (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)

Between November 30th and December 2nd, 2015, the Jacques Loeb Centre for the History and Philosophy of the Life Sciences at Ben-Gurion University of the Negev in Beer Sheva held its Eighth International Workshop under the title “From Genome to Gene: Causality, Synthesis and Evolution”. Eric Davidson, the founder of the concept of developmental Gene Regulatory Networks, had regularly attended the previous meetings, and his participation in this one was expected, but he suddenly passed away 3 months (...) before. In this paper, we provide an introduction and overview on five papers that were presented at the workshop and examine the importance of genomes and gene regulatory networks in extant biology, developmental biology, evolutionary biology and medicine, as well as a collection of remembrances of Eric Davidson, of his personality as well as of his scientific contributions. Historical perspectives are provided, and the ethical issues raised by the new tools developed to modify the genome are also discussed. (shrink)

The applicability of Nagel's concept of theory reduction, and related concepts of reduction, to the reduction of genetics to molecular biology is examined using the lactose operon in Escherichia coli as an example. Geneticists have produced the complete nucleotide sequence of two of the genes which compose this operon. If any example of reduction in genetics should fit Nagel's analysis, the lactose operon should. Nevertheless, Nagel's formal conditions of theory reduction are inapplicable in this case. Instead, it is (...) argued that genetics has been partially reduced to molecular biology in the sense of token-token reduction. (shrink)

Genetic information is becoming increasingly used in modern life, extending beyond medicine to familial history, forensics and more. Following this expansion of use, the effect of genetic information on people’s identity and ultimately people’s quality of life is being explored in a host of different disciplines. While a multidisciplinary approach is commendable and necessary, there is the potential for the multidisciplinarity to produce conceptual misconnection. That is, while experts in one field may understand their use of a term like ‘ (...) class='Hi'>gene’, ‘identity’ or ‘information’ for experts in another field, the same term may link to a distinctly different concept. These conceptual misconnections not only increase inefficiency in complex organisational practices, but can also have important ethical, legal and social consequences. This paper comes at the problem of conceptual misconnection by clarifying different uses of the terms ‘gene’, ‘identity’ and ‘information’. I start by looking at three different conceptions of the gene; the Instrumental, the Nominal and the Postgenomic Molecular. Secondly, a taxonomy of four different concepts of identity is presented; Numeric, Character, Group and Essentialised, and their use is clarified. A general concept of Information is introduced, and finally three distinct kinds of information are described. I then introduce Concept Creep as an ethical problem that arises from conceptual misconnections. The primary goal of this paper is to reduce the potential for conceptual misconnection when discussing genetic identity and genetic information. This is complimented by three secondary goals—1) to clarify what a conceptual misconnection is, 2) to explain why clarity of use is particularly important to discussions of genes, identity and information and 3) to show how concept creep between different uses of genetic identity and genetic information can have important ethical outcomes. (shrink)

If the question ``What is a gene?'' proves to be worth asking it must be able to elicit an answer which both recognizes and address the reasons why the concept of the gene ever seemed to be something worth getting excited about in the first place as well analyzing and evaluating the latest develops in the molecular biology of DNA. Each of the preceding papers fails to do one of these and sufferrs the consequences. Where Rolston (...) responds to the apparent failure of molecular biology to make good on the desideratum of the classical gene by veering off into fanciful talk about ``cybernetic genes,'' Griffiths and Stotz lose themselves in the molecular fine print and forget to ask themselves why ``genes'' should be of any special interst anyway. (shrink)

The use of informational terms is widespread in molecular and developmental biology. The usage dates back to Weismann. In both protein synthesis and in later development, genes are symbols, in that there is no necessary connection between their form (sequence) and their effects. The sequence of a gene has been determined, by past natural selection, because of the effects it produces. In biology, the use of informational terms implies intentionality, in that both the form of the signal, and (...) the response to it, have evolved by selection. Where an engineer sees design, a biologist sees natural selection. (shrink)

We discuss the impact of horizontal gene transfer (HGT) on phylogenetic reconstruction and taxonomy. We review the power of HGT as a creative force in assembling new metabolic pathways, and we discuss the impact that HGT has on phylogenetic reconstruction. On one hand, shared derived characters are created through transferred genes that persist in the recipient lineage, either because they were adaptive in the recipient lineage or because they resulted in a functional replacement. On the other hand, taxonomic patterns (...) in microbial phylogenies might also be created through biased gene transfer. The agreement between different molecular phylogenies has encouraged interpretation of the consensus signal as reflecting organismal history or as the tree of cell divisions; however, to date the extent to which the consensus reflects shared organismal ancestry and to which it reflects highways of gene sharing and biased gene transfer remains an open question. Preferential patterns of gene exchange act as a homogenizing force in creating and maintaining microbial groups, generating taxonomic patterns that are indistinguishable to those created by shared ancestry. To understand the evolution of higher bacterial taxonomic units, concepts usually applied in population genetics need to be applied. (shrink)