Gene Concepts

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)

Causation has multiple distinct meanings in genetics. One reason for this is meaning slippage between two concepts of the gene: Mendelian and molecular. Another reason is that a variety of genetic methods address different kinds of causal relationships. Some genetic studies address causes of traits in individuals, which can only be assessed when single genes follow predictable inheritance patterns that reliably cause a trait. A second sense concerns the causes of trait differences within a population. Whereas some single genes can (...) be said to cause population-level differences, most often these claims concern the effects of many genes. Polygenic traits can be understood using heritability estimates, which estimate the relative influences of genetic and environmental differences to trait differences within a population. Attempts to understand the molecular mechanisms underlying polygenic traits have been developed, although causal inference based on these results remains controversial. Genetic variation has also recently been leveraged as a randomizing factor to identify environmental causes of trait differences. This technique—Mendelian randomization—offers some solutions to traditional epidemiological challenges, although it is limited to the study of environments with known genetic influences. (shrink)

The teleosemantic theory of representational content is held by some philosophers to imply that genes carry semantic information about whole-organism phenotypes. In this paper, I argue that this position is not supported by empirical findings. I focus on one of the most elaborate defenses of this position: Shea’s view that genes represent whole-organism phenotypes. I distinguish between two ways of individuating genes in contemporary biological science as possible vehicles of representational content—as molecular genes and as difference-maker genes. I show that (...) given either of these ways of individuating genes, genes fail to meet conditions which the teleosemantic theory requires an entity to meet if that entity is to qualify as a representational vehicle that represents a whole-organism phenotype. The considerations I present against Shea’s view generalize to other attempts to use the teleosemantic theory in support of the claim that genes represent whole-organism phenotypes. (shrink)

Darwinian evolutionary theory has two key terms, variations and biological selection, which finally lead to survival of the fittest variant. With the rise of molecular genetics, variations were explained as results of error replications out of the genetic master templates. For more than half a century, it has been accepted that new genetic information is mostly derived from random error-based events. But the error replication narrative has problems explaining the sudden emergence of new species, new phenotypic traits, and genome innovations (...) as a sudden single event. Meanwhile, it is recognized that errors cannot explain the evolution of genetic information, genetic novelty, and complexity. Now, empirical evidence establishes the crucial role of non-random genetic content editors, such as viruses, diversity generating retroelements, and other RNA networks, to produce new genetic information, complex regulatory control, inheritance vectors, genetic identity, immunity, new sequence space, evolution of complex organisms, and evolutionary transitions. (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)

Review of: Sophia Roosth, Synthetic: How Life Got Made (University of Chicago Press, 2017); and Andrew S. Balmer, Katie Bulpin, and Susan Molyneux-Hodgson, Synthetic Biology: A Sociology of Changing Practices (Palgrave Macmillan, 2016).

In the last few years, the lack of a unitary notion of gene across biological sciences has troubled the philosophy of biology community. However, the debate on this concept has remained largely historical or focused on particular cases presented by the scientific empirical advancements. Moreover, in the literature there are no explicit and reasonable arguments about why a philosophical clarification of the concept of gene is needed. In our paper, we claim that a philosophical clarification of the concept of gene (...) does not contribute to biology. Unlike the question, for example, “What is a biological function?”, we argue that the question “What is a gene?” could be answered by means of empirical research, in the sense that biologists' labour is enough to shed light on it. (shrink)

As many of the papers in this Special Symposium Issue discuss, by the 21st century we have moved well beyond the notion of a gene as a single particulate unit coding for a given protein, or especially a single phenotypic trait. Yet notions of genes as some kind of single, particulate entity still persist, especially in textbooks and writings about genetics for the general public. To understand this disjunct between the professional geneticist’s view of genes and their complex interactions, and (...) the more widespread public understanding of genes as distinct entities, I thought it might be useful to look back 150 years or more to the origins of the gene concept, to the origins of Mendelian genetics itself .. (shrink)

Huang and Bargh’s definition of goals is ambiguous between ‘specific goals’ – the end-state of a token action I am about to perform – and ‘unspecific goals’ – the end-state of an action-type (without specifying how this would be achieved). The analogy with selfish genes pushes the authors towards the former interpretation, but the latter would provide a more robust theoretical framework.

Much of the book is aimed at persuading the reader that genes are not ‘the prime movers in all biological processes’ and that ‘postgenomic genes’ are better understood in a functional sense, as ‘things an organism can do with its genome.' With the main argument in place, the authors examine its impact on a number of philosophical debates. I will discuss three of them: causation, information, and reduction.

This paper examines causal theories of reference with respect to how plausible an account they give of non-physical natural kind terms such as ‘gene’ as well as of the truth of the associated theoretical claims. I first show that reference fixism for ‘gene’ fails. By this, I mean the claim that the reference of ‘gene’ was stable over longer historical periods, for example, since the classical period of transmission genetics. Second, I show that the theory of partial reference does not (...) do justice to some widely held realist intuitions about classical genetics. This result is at loggerheads with the explicit goals usually associated with partial theories of reference, which is to defend a realist semantics for scientific terms. Thirdly, I show that, contrary to received wisdom and perhaps contrary to physics and chemistry, neither reference fixism nor partial reference are necessary in order to hold on to scientific realism about biology. I pinpoint the reasons for this in the nature of biological kinds, which do not even remotely resemble natural kinds (i.e., Lockean real essences) as traditionally conceived. (shrink)

Personalized genomics companies (PG; also called ‘direct-to-consumer genetics’) are businesses marketing genetic testing to consumers over the Internet. While much has been written about these new businesses, little attention has been given to their roles in science communication. This paper provides an analysis of the gene concept presented to customers and the relation between the information given and the science behind PG. Two quite different gene concepts are present in company rhetoric, but only one features in the science. To explain (...) this, we must appreciate the delicate tension between PG, academic science, public expectation, and market forces. (shrink)

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

This article is arranged around two general claims and a thought experiment. I begin by suggesting that the genome should be studied as a developmental system, and that genes supervene on genomes (rather than the other way around). I move on to present a thought experiment that illustrates the implications a dynamic view of the genome has for central concepts in biology, in particular the information content of the genome, and the notion of responses to stress.

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)

Although much has been learned about hereditary mechanisms since Gregor Mendel’s famous experiments, gene concepts have always remained vague, notwithstanding their central role in biology. During over hundred years of genetic research, gene concepts have often and dynamically changed to accommodate novel experimental findings, without ever providing a generally accepted definition of the ‘gene.’ Yet, the distinction between ‘regulatory genes’ and ‘structural genes’ has remained a common theme in modern gene concepts since the definition of the operon-model. This distinction is (...) now challenged by recent findings which suggest that, at least in eukaryotes, structural genes may in many situations have a regulatory function that is independent of the function of the gene product (protein or non-coding RNA molecule). This brief paper discusses these new findings and some possible implications for the notion of the ‘regulatory gene.’. (shrink)

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)

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)

For at least a century it has been known that multiple factors play a role in the development of complex traits, and yet the notion that there are genes “for” such traits, which traces back to Mendel, is still widespread. In this paper, we illustrate how the Mendelian model has tacitly encouraged the idea that we can explain complexity by reducing it to enumerable genes. By this approach many genes associated with simple as well as complex traits have been identified. (...) But the genetic architecture of biological traits, or how they are made, remains largely unknown. In essence, this reflects the tension between reductionism as the current “modus operandi” of science, and the emerging knowledge of the nature of complex traits. Recent interest in systems biology as a unifying approach indicates a reawakened acceptance of the complexity of complex traits, though the temptation is to replace “gene for” thinking by comparably reductionistic “network for” concepts. Both approaches implicitly mix concepts of variants and invariants in genetics. Even the basic question is unclear: what does one need to know to “understand” the genetic basis of complex traits? New operational ideas about how to deal with biological complexity are needed. (shrink)

Neurobiological disorders have diverse manifestations and symptomology. Neurodegenerative disorders, such as Alzheimer's disease, manifest late in life and are characterized by, among other symptoms, progressive loss of synaptic markers. Developmental disorders, such as autism spectrum, appear in childhood. Neuropsychiatric and affective disorders, such as schizophrenia and major depressive disorder, respectively, have broad ranges of age of onset and symptoms. However, all share uncertain etiologies, with opaque relationships between genes and environment. We propose a 'Latent Early-life Associated Regulation' (LEARn) model, positing (...) latent changes in expression of specific genes initially primed at the developmental stage of life. In this model, environmental agents epigenetically disturb gene regulation in a long-term manner, beginning at early developmental stages, but these perturbations might not have pathological results until significantly later in life. The LEARn model operates through the regulatory region (promoter) of the gene, specifically through changes in methylation and oxidation status within the promoter of specific genes. The LEARn model combines genetic and environmental risk factors in an epigenetic pathway to explain the etiology of the most common, that is, sporadic, forms of neurobiological disorders. (shrink)

In recent years geneticists have witnessed many significant observations which have seriously shaken the traditional concept of the gene. These specifically include the facts that (1) the boundaries of transcriptional units are far from clear; in fact, whole chromosomes if not the whole genome seem to be continuums of genetic transcription, (2) many examples of gene fusion are known, (3) likewise many examples of so-called encrypted genes are known in the organelle genomes of microbial eukaryotes and in prokaryotes, and (4) (...) in addition to the structure of the gene, its functional status can also be inheritable, and, further, (5) epigenetic extra-genomic modes of inheritance, called genetic restoration, seem to be a rather common phenomenon, meaning that organisms can sometimes rewrite their DNA on the basis of RNA messages inherited from generations past. I will briefly review these observations and discuss the difficulties of defining the gene, and then formulate a new view, which is called the relational or systemic concept of the gene. It has to be noted that genes assume their information content characteristics in the Shannonian sense as nucleotide sequences of DNA (or RNA). However, on the basis of this we cannot say anything about their information content in the semantic sense. The semantic information content of genes is context-dependent. Genes namely assume their biochemical characteristics usually only within living cells, their developmental characteristics only within living organisms, and their evolutionary characteristics only within populations of living organisms. (shrink)

The discursive explosion that was provoked by the new genetics could support the impression that the ethical and social problems posed by the new genetics are somehow exceptional in their very nature. According to this view we are faced with special ethical and social problems that create a challenge so fundamental that the special label of genethics is needless to justify. The historical account regarding the evolution of the gene concepts could serve us to highlight the limits of what we (...) know about genes and what we can do with genes. The widespread notion about the exceptionality of genetic knowledge and its applicative possibilities is hardly justifiable and leads to misunderstandings regarding the conceptualization of the ethical and social problems we might face. Following a more realistic interpretation of the role of genes in human life we might avoid a whole set of fictive dilemmas and counterproductive regulatory efforts in bioethics. Bioethical discourse should move from the gene-centered scientific discourse toward the more sophisticated and complex discourses where human development represented as a matter of complex interactions between genomes and environments, between genes, educational factors, nutritional regimes, and other different developmental resources. If a gene is seen as one among the different developmental resources that are shaping a given human trait then both genethics and genetic exceptionalism could hardly be represented as a justified approach in discussing the ethical and social problems of genetics. (shrink)

Richard Goldschmidt famously rejected the notion of atomic and corpuscular genes, arranged on the chromosome like beads-on-a-string. I provide an exegesis of Goldschmidt’s intuition by analyzing his repeated and extensive use of metaphorical language and analogies in his attempts to convey his notion of the nature of the genetic material and specifically the significance of chromosomal pattern. The paper concentrates on Goldschmidt’s use of metaphors in publications spanning 1940-1955. -/- .

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.

David Papineau (2003; 2005) has discussed the relationship between social learning and the family of postulated evolutionary processes that includes ‘organic selection’, ‘coincident selection’, ‘autonomisation’, ‘the Baldwin effect’ and ‘genetic assimilation’. In all these processes a trait which initially develops in the members of a population as a result of some interaction with the environment comes to develop without that interaction in their descendants. It is uncontroversial that the development of an identical phenotypic trait might depend on an interaction with (...) the environment in one population and not in another. For example, some species of passerine songbirds require exposure to species-typical songs in order to reproduce those songs whilst others do not. Hence we can envisage a species beginning with one type of developmental pathway and evolving the other type. If, however, the successive evolution of these two developmental pathways were a mere coincidence, selection first favoring the ability to acquire the trait and later, quite independently, favoring the ability to develop it autonomously, then this would not be a distinctive kind of evolutionary process, but merely two standard instances of natural selection. George Gaylord Simpson pointed this out in the paper that gave us the term ‘Baldwin effect’ (Simpson, 1953). The real interest of the Baldwin effect and its relatives lies in the mechanisms which might link the evolution of the two developmental pathways, so that acquiring the trait through interaction with the environment makes it more likely that later generations will evolve the ability to acquire the same trait without that interaction. (shrink)

Book Review: What Genes Can’t Do By Lenny Moss .

Book review of Lenny Moss, What Genes Can’t Do. Cambridge, MA: MIT Press , 256 pp. -/- Many philosophers of science will have encountered the core distinction between two different gene concepts found in What Genes Can’t Do. Moss argues that contemporary uses of the term ‘gene’ that denote an information bearing entity result from the conflation of two concepts (‘Gene-P’ and ‘Gene-D’).

Current knowledge about the variety and complexity of the processes that allow regulated gene expression in living organisms calls for a new understanding of genes. A ‘postgenomic’ understanding of genes as entities constituted during genome expression is outlined and illustrated with specific examples that formed part of a survey research instrument developed by two of the authors for an ongoing empirical study of conceptual change in contemporary biology.

In this book review essay, Justus discusses The Birth of the Mind: How a Tiny Number of Genes Creates the Complexities of Human Thought (2004) by Gary Marcus. The review opens by contrasting the common architectural-blueprint metaphor for the genome with an alternative: the if-then statements of a computer program. The former leads to a seeming “gene shortage” problem while the latter are better suited to representing the cascades of genetic expression that give rise to exponential genotype-phenotype relationships. The essay (...) then develops three conceptual issues of interest to cognitive scientists in light of this small, data-compressed genome: (1) distinguishing dissociations in the developmental process from the domain-specificity of the resulting mental representations, (2) the observation that no gene is specific to a mental representation, a cortical region, or even the nervous system, and (3) the complications that a small number of genes present to the adaptationist programme in evolutionary psychology. The review concludes by questioning the utility of the Swiss Army knife as a metaphor for cognitive development and evolution. (shrink)

What should philosophers of science accomplish when they analyze scientific concepts and interpret scientific knowledge? What is concept analysis if it is not a description of the way scientists actually think? I investigate these questions by using Hans Reichenbach's account of the descriptive, critical, and advisory tasks of philosophy of science to examine Karola Stotz and Paul Griffiths' idea that poll-based methodologies can test philosophical analyses of scientific concepts. Using Reichenbach's account as a point of departure, I argue that philosophy (...) of science should identify and clarify epistemic virtues and describe scientific knowledge in relation to these virtues. The role of concept analysis is to articulate scientific concepts in ways that help reveal epistemic virtues and limitations of particular sciences. This means an analysis of the gene concept should help clarify the explanatory power and limitations of gene-based explanations, and should help account for the investigative utility and biases of gene-centered sciences. I argue that a philosophical analysis of gene concept that helps achieve these critical aims should not be rejected on the basis of poll-based studies even if such studies could show that professional biologists don't actually use gene terminology in precise ways corresponding to the philosophical analysis. (shrink)

Darwin's ideas on variation, heredity, and development differ significantly from twentieth-century views. First, Darwin held that environmental changes, acting either on the reproductive organs or the body, were necessary to generate variation. Second, heredity was a developmental, not a transmissional, process; variation was a change in the developmental process of change. An analysis of Darwin's elaboration and modification of these two positions from his early notebooks (1836-1844) to the last edition of the /Variation of Animals and Plants Under Domestication/ (1875) (...) complements previous Darwin scholarship on these issues. Included in this analysis is a description of the way Darwin employed the distinction between transmission and development, as well as the conceptual relationship he saw between heredity and variation. This paper is part of a larger project comparing commitments regarding variation during the latter half of the nineteenth century. (shrink)

Over the decades, there has been substantial empirical evidence showing that the unity of species cannot be maintained by gene flow. The biological species concept is inconclusive on this point. The suggestion is made that the unity of species is maintained rather by selection constantly spreading new alleles throughout the species, or bygene circulation. There is a lack in conceptual distinction between gene flow and gene circulation which lies at the heart of the problem. The concept of gene circulation also (...) sheds some new light on the problem of typology and on such a broad concept as evolution. A new species definition is proposed. (shrink)