Discussion of partial grounds that aren't parts of full grounds; definition of full grounding in terms of partial grounding.

: The medical and clinical promise of stem cell research is widely heralded, but moral judgments about it collide. This article takes general stock of such judgments and offers one specific resolution. It canvasses a spectrum of value judgments on sources, complicity, adult stem cells, and public and private contexts. It then examines how debates about abortion and stem cell research converge and diverge. Finally, it proposes to extend the principle of "nothing is lost" to current debates. This extension links (...) historic discussions of the ethics of direct killing with unprecedented possibilities that in vitro fertilization procedures yield. A definite normative region to inhabit is located, within a larger range of rival value judgments. The creation of embryos for research purposes only should be resisted, yet research on "excess" embryos is permissible by virtue of an appeal to the "nothing is lost" principle. (shrink)

The Ethical Journalist Praise for the Third Edition of The Ethical Journalist “A riveting examination of journalism ethics, updated for the seismic change that is now an industry constant. The Ethical Journalist is written to fortify journalism students, but real-life examples of everything from faked photographs to reporting on presidential lies make it valuable to all of us who care about the news.” ANN MARIE LIPINSKI, CURATOR OF THE NIEMAN FOUNDATION AT HARVARD UNIVERSITY AND FORMER EDITOR OF THE CHICAGO TRIBUNE (...) Praise for the Earlier Editions “The book is superb — the definitive work on journalism ethics and practices. It should be a basic text in every school of journalism.” GENE ROBERTS, FORMER EXECUTIVE EDITOR OF THE PHILADELPHIA INQUIRER AND FORMER MANAGING EDITOR OF THE NEW YORK TIMES “At a time when the internet has turned journalism inside out and blown up long-held traditions, the need for media ethics is even more critical. This is the book to help guide students and the rest of us through the revolution.” ALICIA C. SHEPARD, FORMER NPR OMBUDSMAN The third edition of The Ethical Journalist is a comprehensive examination of current issues in the field of journalism ethics, researched and written by four journalists with experience in both the newsroom and the classroom. It gives students and professionals the tools they need to navigate the challenges of journalism today, first explaining the importance of ethics in journalism and then putting a decision-making strategy to work. The text is supplemented by case studies and essays, and two companion websites provide additional materials for educators and a forum for all users to discuss new topics in journalism ethics as they arise. (shrink)

Imprecise definition of key terms in the “public participation” domain have hindered the conduct of good research and militated against the development and implementation of effective participation practices. In this article, we define key concepts in the domain: public communication, public consultation, and public participation. These concepts are differentiated according to the nature and flow of information between exercise sponsors and participants. According to such an information flow perspective, an exercise’s effectiveness may be ascertained by the efficiency with which (...) full, relevant information is elicited from all appropriate sources, transferred to all appropriate recipients, and combined to give an aggregate/consensual response. Key variables that may theoretically affect effectiveness—and on which engagement mechanisms differ—are identified and used to develop a typology of mechanisms. The resultant typology reveals four communication, six consultation, and four participation mechanism classes. Limitations to the typology are discussed, and future research needs identified. (shrink)

The concept of public participation is one of growing interest in the UK and elsewhere, with a commensurate growth in mechanisms to enable this. The merits of participation, however, are difficult to ascertain, as there are relatively few cases in which the effectiveness of participation exercises have been studied in a structured manner. This seems to stem largely from uncertainty in the research community as to how to conduct evaluations. In this article, one agenda for conducting evaluation research that might (...) lead to the systematic acquisition of knowledge is presented. This agenda identifies the importance of defining effectiveness and of operationalizing one’s definition. The article includes analysis of the nature of past evaluations, discussion of potential difficulties in the enactment of the proposed agenda, and discussion of some potential solutions. (shrink)

The Affymetrix GeneChip is a popular microarray platform for genome‐wide expression profiling and has been widely used in functional genomics especially in the classification of cancers. Due to the updating of genome data, much of the genome information with which the chips were designed is out‐of‐date and it has been reported that many of the genes/transcripts on the chips differ from their original definition when mapping the probes to the new genome information. Dai et al. have reported that the (...) updated definition can cause as much as 30–50% discrepancy in the genes selected as differentially expressed on a heart tissue expression profiling dataset. Understanding the nature of this difference is therefore very important for the utilization of the data. In this work, with a large cancer dataset as an example, we compared two major definitions and investigated their effects on classification, clustering, discovery of differentially expressed genes and gene‐set‐based analysis. Results show that the two definitions agree well on clustering and classification results but genes and gene sets discovered as differentially expressed or enriched can be very different. Discoveries based on the Affymetrix definition can cover most of those based on the new definition, but tend to have more false positives. BioEssays 28: 739–746, 2006. © 2006 Wiley Periodicals, Inc. (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)

Sightings of the revolutionary comet that appeared in the skies of evolutionary biology in 1976—the selfish gene—date back to the 19th and early 20th centuries. It became generally recognized that genes were located on chromosomes and compete with each other in a manner consistent with the later appellation “selfish.” Chromosomes were seen as disruptable by the apparently random “cut and paste” process known as recombination. However, each gene was only a small part of its chromosome. On a statistical (...) basis a gene should escape disruption for many generations. This led George Williams and Richard Dawkins to a new definition of the gene, differing from conventional biochemical definitions in that there were no consistent genic boundaries. There had been no previous sightings of another revolutionary, albeit less verbally spectacular, comet that appeared in 1975—the homostability principle of Akiyoshi Wada. Each gene has a base composition “accent” that distinguishes it from its neighbors. We now see that recombination can be triggered by the shift in base composition at genic boundaries. Hence, the Williams-Dawkins definition approaches the conventional definitions. (shrink)

Sightings of the revolutionary comet that appeared in the skies of evolutionary biology in 1976—the selfish gene—date back to the 19th and early 20th centuries. It became generally recognized that genes were located on chromosomes and compete with each other in a manner consistent with the later appellation “selfish.” Chromosomes were seen as disruptable by the apparently random “cut and paste” process known as recombination. However, each gene was only a small part of its chromosome. On a statistical (...) basis a gene should escape disruption for many generations. This led George Williams and Richard Dawkins to a new definition of the gene, differing from conventional biochemical definitions in that there were no consistent genic boundaries. There had been no previous sightings of another revolutionary, albeit less verbally spectacular, comet that appeared in 1975—the homostability principle of Akiyoshi Wada. Each gene has a base composition “accent” that distinguishes it from its neighbors. We now see that recombination can be triggered by the shift in base composition at genic boundaries. Hence, the Williams-Dawkins definition approaches the conventional definitions. (shrink)

We outline three very different concepts of the gene—instrumental, nominal, and postgenomic. The instrumental gene has a critical role in the construction and interpretation of experiments in which the relationship between genotype and phenotype is explored via hybridization between organisms or directly between nucleic acid molecules. It also plays an important theoretical role in the foundations of disciplines such as quantitative genetics and population genetics. The nominal gene is a critical practical tool, allowing stable communication between bioscientists (...) in a wide range of fields grounded in well-defined sequences of nucleotides, but this concept does not embody major theoretical insights into genome structure or function. The post-genomic gene embodies the continuing project of understanding how genome structure supports genome function, but with a deflationary picture of the gene as a structural unit. This final concept of the gene poses a significant challenge to conventional assumptions about the relationship between genome structure and function, and between genotype and phenotype. (shrink)

What is a gene? Does it represent a natural kind, or is it just a tool for genomics? A clear answer to these questions has been challenged by postgenomic discoveries. In response, I will argue that the gene can be deemed a natural kind as it satisfies some requirements for genuine kindhood. Specifically, natural kinds are projectible categories in our best scientific theories, and they represent nodes in the causal network of the world (as in Khalidi. Natural Categories (...) and Human Kinds: Classification in the Natural and Social Sciences. Cambridge University Press, Cambridge, 2013; Khalidi. Synthese 195: 1379–1396, 2018; Khalidi. Are Sexes Natural Kinds, In: Dasgupta S, Weslake B (eds) Current Controversies in Philoso-phy of Science. Routledge, New York, 2020; Khalidi. Philos Sci 88:1–21, 2021). In Sect. 2, I will present a brief history of the gene and the controversy over its status. In Sect. 3, I will introduce the account of natural kinds considered in this paper. In Sect. 4, I will first present the relevant definition of genes and how they can be classified. Then, I will argue that the gene can be considered a natural kind as it satisfies the criteria for natural kindhood. Section 5 concludes. (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)

This paper describes one complete and one ongoing empirical study in which philosophical analyses of the concept of the gene were operationalized and tested against questionnaire data obtained from working biologists to determine whether and when biologists conceive genes in the ways suggested. These studies throw light on how different gene concepts contribute to biological research. Their aim is not to arrive at one or more correct 'definitions' of the gene, but rather to map out the variation (...) in the gene concept and to explore its causes and its effects. (shrink)

This article challenges the view of disability presented by Harris in his article, “Is gene therapy a form of eugenics?”1 It is argued that his definition of disability rests on an individual model of disability, where disability is regarded as a product of biological determinism or “personal tragedy” in the individual. Within disability theory this view is often called “the medical model” and it has been criticised for not being able to deal with the term “disability”, but only (...) with impairment. The individual model of disability presupposes a necessary causal link between a certain condition in the individual and disablement. The shortcomings of such a view of disability are stated and it is argued that in order to have an adequate ethical discourse on gene therapy perspectives from disability research need to be taken into consideration. (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)

Formal principles governing best practices in classification and definition have for too long been neglected in the construction of biomedical ontologies, in ways which have important negative consequences for data integration and ontology alignment. We argue that the use of such principles in ontology construction can serve as a valuable tool in error-detection and also in supporting reliable manual curation. We argue also that such principles are a prerequisite for the successful application of advanced data integration techniques such as (...) ontology-based multi-database querying, automated ontology alignment and ontology-based text-mining. These theses are illustrated by means of a case study of the Gene Ontology, a project of increasing importance within the field of biomedical data integration. (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)

Progress in genetic and reproductive technology now offers us the possibility of choosing what kinds of children we do and don't have. Should we welcome this power, or should we fear its implications? There is no ethical question more urgent than this: we may be at a turning-point in the history of humanity. The renowned moral philosopher and best-selling author Jonathan Glover shows us how we might try to answer this question, and other provoking and disturbing questions to which it (...) leads. Surely parents owe it to their children to give them the best life they can? Increasingly we are able to reduce the number of babies born with disabilities and disorders. But there is a powerful new challenge to conventional thinking about the desirability of doing so: this comes from the voices of those who have these conditions. They call into question the very definition of disability. How do we justify trying to avoid bringing people like them into being? In 2002 a deaf couple used sperm donated by a friend with hereditary deafness to have a deaf baby: they took the view that deafness is not a disability, but a difference. Starting with the issues raised by this case, Jonathan Glover examines the emotive idea of 'eugenics', and the ethics of attempting to enhance people, for non-medical reasons, by means of genetic choices. Should parents be free, not only to have children free from disabilities, but to choose, for instance, the colour of their eyes or hair? This is no longer a distant prospect, but an existing power which we cannot wish away. What impact will such interventions have, both on the individuals concerned and on society as a whole? Should we try to make general improvements to the genetic make-up of human beings? Is there a central core of human nature with which we must not interfere? This beautifully clear book is written for anyone who cares about the rights and wrongs of parents' choices for their children, anyone who is concerned about our human future. Glover handles these uncomfortable questions in a controversial but always humane and sympathetic manner. (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)

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)

Although epistasis is at the center of the Fisher-Wright debate, biologists not involved in the controversy are often unaware that there are actually two different formal definitions of epistasis. We compare concepts of genetic independence in the two theoretical traditions of evolutionary genetics, population genetics and quantitative genetics, and show how independence of gene action (represented by the multiplicative model of population genetics) can be different from the absence of gene interaction (represented by the linear additive model of (...) quantitative genetics). The two formulations converge with weak selection but not with strong selection or, for multiple loci, when the aggregated interaction terms are not negligible. As a result of the different formulations of gene interaction, the presence or absence of linkage disequilibrium,/D/, does not necessarily indicate the presence or absence of fitness epistasis. Indeed, linkage disequilibrium is generated in ‘additive’ models in quantitative genetics whenever two (or more) loci experience simultaneous selection. As a research strategy, it is often practical, for theoretical or experimental reasons, to minimize gene interaction by assuming independence of gene action in regard to fitness, or by assuming linear additive effects of multiple loci on a phenotype. However, minimizing the role of epistasis in theoretical investigations hinders our understanding of the origins of diversity and the evolution of complex phenotypes. (shrink)

Enormous phylogenetic variation exists in the number and sizes of introns in protein‐coding genes. Although some consideration has been given to the underlying role of the population‐genetic environment in defining such patterns, the influence of the intracellular environment remains virtually unexplored. Drawing from observations on interactions between co‐transcriptional processes involved in splicing and mRNA 3′‐end formation, a mechanistic model is proposed for splice‐site recognition that challenges the commonly accepted intron‐ and exon‐definition models. Under the suggested model, splicing factors that (...) outcompete 3′‐end processing factors for access to intronic binding sites concurrently favor the recruitment of 3′‐end processing factors at the pre‐mRNA tail. This hypothesis sheds new light on observations such as the intron‐mediated enhancement of gene expression and the negative correlation between intron length and levels of gene expression. (shrink)

Auxin, a class of plant hormones which affects a wide array of growth and developmental processes including cell elongation and cell division, alters gene expression in a very rapid, selective, and dramatic way. The relative level of some mRNAs decreases several fold, while that of other mRNAs increases many fold. These changes are mediated, at least in some cases, by very fast (within 5–10 min) modulation by auxin of transcription as measured by run‐off transcription assays using nuclei isolated from (...) control and auxin‐treated tissues. Rapid turnover of mRNAs following auxin treatment also contributes to large changes in steady state concentration in some cases. The data are suggestive of multiple and complex mechanisms of regulation of expression of those genes which have been studied, using cloned cDNAs for direct quantitation of mRNA steady state levels and relative transcription rates. While there is no definitive evidence that auxin‐regulated gene expression mediates any of the growth responses effected by auxin, several lines of evidence are supportive of a very close relationship between these processes. The working hypothesis is that there is a causal relationship between the effects of auxin on gene expression and at least some of the physiological and growth responses to auxin. (shrink)

How can researchers use race, as they do now, to conduct health-care studies when its very definition is in question? The belief that race is a social construct without “biological authenticity” though widely shared across disciplines in social science is not subscribed to by traditional science. Yet with an interdisciplinary approach, the two horns of the social construct/genetics dilemma of race are not mutually exclusive. We can use traditional science to provide a rigorous framework and use a social-science approach (...) so that “invisible” factors are used to adjust the design of studies on an as-needed basis. One approach is to first observe health-care outcomes and then categorize the outcomes, thus removing genetic differences as racial proxies from the design of the study. From the outcomes, we can then determine if there is a pattern of conceivable racial categories. If needed, we can apply dynamic notions of race to acknowledge bias without prejudice. We can use them constructively to improve outcomes and reduce racial disparities. Another approach is nearly identical but considers race not at all: While analyzing outcomes, we can determine if there are biological differences significant enough to identify classifications of humans. That is, we look for genetic patterns in the outcomes and classify only those patterns. There is no attempt to link those patterns to race. (shrink)

Despite widespread and worldwide efforts to eradicate vector-borne diseases such as malaria, these diseases continue to have an enormous negative impact on public health. For this reason, scientists are working on novel control strategies, such as gene drive technologies (GDTs). As GDT research advances, researchers are contemplating the potential next step of conducting field trials. An important point of discussion regarding these field trials relates to who should be informed, consulted, and involved in decision-making about their design and launch. (...) It is generally argued that community members have a particularly strong claim to be engaged, and yet, disagreement and lack of clarity exist about how this “community” should be defined and delineated. In this paper, we shed light on this “boundary problem”: the problem of determining how boundaries of inclusion and exclusion in (GDT) community engagement should be drawn. As our analysis demonstrates, the process of defining and delineating a community is itself normative. First, we explicate why it is important to define and delineate the community. Second, we demonstrate that different definitions of community are used and intermingled in the debate on GDTs, and argue in favor of distinguishing geographical, affected, cultural, and political communities. Finally, we propose initial guidance for deciding who should (not) be engaged in decision-making about GDT field trials, by arguing that the definition and delineation of the community should depend on the rationale for engagement and that the characteristics of the community itself can guide the effective design of community engagement strategies. (shrink)

This chapter offers a review of standard views about the requirements for natural selection to shape evolution and for the sorts of ‘units’ on which selection might operate. It then summarizes traditional arguments for genic selectionism, i.e., the view that selection operates primarily on genes (e.g., those of G. C. Williams, Richard Dawkins, and David Hull) and traditional counterarguments (e.g., those of William Wimsatt, Richard Lewontin, and Elliott Sober, and a diffuse group based on life history strategies). It then offers (...) a series of responses to the arguments, based on more contemporary considerations from molecular genetics, offered by Carmen Sapienza. A key issue raised by Sapienza concerns the degree to which a small number of genes might be able to control much of the variation relevant to selection operating on such selectively critical organs as hearts. The response to these arguments suggests that selection acts on many levels at once and that sporadic selection, acting with strong effects, can act successively on different key traits (and genes) while maintaining a balance among many potentially conflicting demands faced by organisms within an evolving lineage. (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)

Recombinant DNA technology will soon allow physicians an opportunity to carry out both somatic cell- and Germ-Line gene therapy. While somatic cell gene therapy raises no new ethical problems, gene therapy of gametes, fertilized eggs or early embryos does raise several novel concerns. The first issue discussed here relates to making a distinction between negative and positive eugenics; the second issue deals with the evolutionary consequences of lost genetic diversity. In distinguishing between positive and negative eugenics, the (...) concept of malady is applied as a definitional criterion for identifying genetic disorders that could qualify for Germ-Line therapy. Because gene replacement techniques are currently unavailable for humans, and because even if they were possible the number of people involved would be quite small, the loss of diversity concern seems moot. Finally, we dissuss the issue of iatrogenic disorders associated with gene therapy and discuss several ‘real world considerations.’. (shrink)

Protein turnover (PT) has been formally defined only in equilibrium conditions, which is ill‐suited to quantify PT during dynamic processes that occur during embryogenesis or (extra) cellular signaling. In this Hypothesis, we propose a definition of PT in an out‐of‐equilibrium regime that allows the quantification of PT in virtually any biological context. We propose a simple mathematical and conceptual framework applicable to a broad range of available data, such as RNA sequencing coupled with pulsed‐SILAC datasets. We apply our framework (...) to a published dataset and show that stimulation of mouse dendritic cells with LPS leads to a proteome‐wide change in PT. This is the first quantification of PT out‐of‐equilibrium, paving the way for the analysis of biological systems in other contexts. (shrink)

Developments in the sequencing of whole genomes and in simultaneously surveying many thousands of transcription and translation products of specific cells have ushered in a conceptual revolution in genetics that rationally introduces top-down, holistic analyses. This emphasized the futility of attempts to reduce genes to structurally discrete entities along the genome, and the need to return to Johannsen's definition of a gene as 'something' that refers to an invariant entity of inheritance and development. We may view genes either (...) as generic terms for units of inheritance whose referents are pragmatic ad hoc and context-dependent, or as (epistemologically) representing entities of cell functions. It is cellular functions that determine the structural referents along the DNA. Structures that happened to secure specific functions that were essential for or conducive to the survival of cells were selected for. With natural selection being the etiological background of genes as functions, genes obtain again their theoretical role as intervening variables, abstractive variables that purely 'summarize' characters. The importance of DNA sequences is that of all possible phenotypes these are the most basic ones from which we can read off the genotype directly. (shrink)

Mouse models of human genetic disorders provide a valuable resource for investigating the pathogenesis of genetic disease and for testing potential therapies. The high degree of resolution of linkage mapping in the mouse allows mutant phenotypes to be mapped precisely which, combined with the accurate definition of areas of homology between the mouse and human genomes, greatly facilitates the identification of mouse models. We describe here mouse models of human single gene disorders dividing them into three categories depending (...) on the information available; phenotypic similarities, comparative mapping and identification of the underlying genetic lesion. (shrink)

This chapter contains sections titled: Introduction Natural Selection Operates within Genomes without Regard for Phenotypic Effect Selective Forces, Heritable Variation, and the Definition of Function Natural Selection Can, and Does, Act on the Products of Individual Genes Natural Selection Can Act Directly on Genes Themselves What Are the Limitations on the Unit of Selection Being “the Gene”? The “Complexity” Argument: Do Complex Phenotypes Require Complex Explanations? Do “Epigenes/Epialleles” Provide a “Non‐genetic” Source of Heritable Variation Upon Which Natural Selection (...) May Act? Summary Points: The Usual Unit of Selection Is the Gene Postscript: Counterpoint Note References. (shrink)

The classical view of the gene prevailing during the 1910s and 1930s comprehended the gene as the indivisible unit of genetic transmission, genetic recombination, gene mutation and gene function. The discovery of intragenic recombination in the early 1940s led to the neoclassical concept of the gene, which prevailed until the 1970s. In this view the gene or cistron, as it was now called, was divided into its constituent parts, the mutons and recons, materially identified (...) as nucleotides. Each cistron was believed to be responsible for the synthesis of one single mRNA and concurrently for one single polypeptide. The discoveries of DNA technology, beginning in the early 1970s, have led to the second revolution in the concept of the gene in which none of the classical or neoclassical criteria for the definition of the gene hold strictly true. These are the discoveries concerning gene repetition and overlapping, movable genes, complex promoters, multiple polyadenylation sites, polyprotein genes, editing of the primary transcript, pseudogenes and gene nesting. Thus, despite the fact that our comprehension of the structure and organization of the genetic material has greatly increased, we are left with a rather , open and general concept of the gene. This article discusses past and present contemplations of genes, genomes, genotypes and phenotypes as well as the most recent advances of the study of the organization of genomes. (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.

La doctrine de l'État de Cari Schmitt, souvent délaissée au profit d'autres facettes de son œuvre, constitue pourtant le lieu où s'incarnent ses théories du politique et de la Constitution. Le juriste allemand y consigne les bouleversements institutionnels traversés par l'Allemagne au XXe siècle. En 1914, il pense encore l'État dans sa conformité à la légalité, alors qu'à la chute de l'Empire, il ne considère les organes étatiques que dans leur usage de la décision et leur aptitude à affronter les (...) situations d'exception. Dans une perspective inédite, à partir d'une étude systématique de ses écrits relatifs à l'État, cet ouvrage relie la théologie politique de Schmitt, son anti-individualisme, comme sa définition singulière du politique, à ses propositions de refonte des institutions. La reconstitution de sa doctrine de l'État éclaire d'un jour nouveau l'affrontement entre ses partisans et ses adversaires et explique, malgré les compromissions avérées de Cari Schmitt avec le nazisme, la persistance de sa pensée dans la vie intellectuelle après Nuremberg. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Reviewed by:Changing Human Nature: Ecology, Ethics, Genes, and God by James C. PetersonDolores L. ChristieChanging Human Nature: Ecology, Ethics, Genes, and God James C. Peterson Grand Rapids, Mich.: Eerdmans, 2010. 259 pp. $18.00Grounding himself in the Christian tradition, James Peterson argues for the moral efficacy of human genetic manipulation. Interpreting intentional intervention as part of human stewardship rather than as a wrongful interference with some divine plan, he takes (...) on the sticky questions, making critical distinctions, for example, between cure and enhancement or welcoming children as they come and making them “better.” Not neglecting future implications of current tinkering with human biology, even in such taboo areas as gamete selection, he contends that engineering a baby free of harmful genes (for example, Tay-Sachs or Down syndrome) not only makes that person better, but it also eliminates an ongoing burden to family, to society, and perhaps to future generations. Treading gingerly among the sacred cows of some Christian ethicists, he advocates the implanting of selected embryos free of unwanted genes; in his view, embryos are not yet persons.Peterson considers serious concerns such as eugenics projects and racial bias but offers standards to address them. He contends that intentionally increasing choices for our children is not only acceptable but also praiseworthy. What parents would not optimize the educational and social opportunities for their child, even without the child’s consent? Interventions should be safe, offer genuine improvement, increase the recipient’s capacity, and make the best use of limited resources. Peterson is not so naive that he does not recognize that technology does not always make us better. He recognizes, too, that his standards do not eliminate risk.Fair enough, but the issue of what “improvement” may mean to the individual as well as to the greater community remains somewhat ambiguous. Peterson suggests that broadening the decision making among a variety of professional and individual cohorts would help, but his argument is not totally persuasive. In sum, Peterson’s treatment falls short of offering a totally satisfying standard for determining which characteristics should be manipulated and which should be accepted. Nor does he demonstrate definitively how a [End Page 187] Christian perspective would contribute to sorting out possible choices. Does the deaf parents’ desire for their child to be deaf like them constitute an instance where intervention should not be attempted? Can the disparate cohorts he suggests as arbiters rise above their own biases? Does Christianity and its belief system offer answers? Readers—even readers who call themselves Christian—will likely be persuaded that genetic intervention is a good, and even compatible with their religious perspective. Nonetheless, they will harbor lingering doubts about how the questions can best be solved, who should solve them, and how Christian belief helps sort among the possibilities. In his closing comments Peterson appears to agree.The book is rich in research and in provocative ideas. It is an exciting book. It is a readable and enlightened contribution to the professional conversation on gene therapy. Peterson’s research is extensive, his argumentation balanced. His attempt to locate the question within the Christian tradition is laudable. Happily, Peterson eschews a creationist approach to world and human origins. Unhappily, his approach to the scriptural text is not always nuanced. His assertion that Jesus himself was different biologically from other human beings (132) seems a stretch. If one takes the passages of Jesus’s biological origins literally, as apparently does the author, what happens to the assertion that Jesus is like other human beings “in all things but sin”? And where did Jesus get the Y chromosomes? While he persuades the reader that genetic intervention is compatible with a Christian worldview, Peterson does not offer—at least in this reviewer’s view—an adequate criterion for navigating this new world of the possible.Dolores L. ChristieJohn Carroll UniversityCopyright © 2013 Society of Christian Ethics... (shrink)

Speciation is an aspect of evolutionary biology that has received little philosophical attention apart from articles mainly by biologists such as Mayr (1988). The role of speciation as a terminus a quo for the individuality of species or in the context of punctuated equilibrium theory has been discussed, but not the nature of speciation events themselves. It is the task of this paper to attempt to bring speciation events into some kind of general scheme, based primarily upon the work of (...) Sergey Gavrilets on adaptive landscapes, using migration rate, or gene flow, as the primary scale, and concluding that adaptive and drift explanations are complementary rather than competing. I propose a distinction between intrinsic and extrinsic selection, and the notion of reproductive reach and argue that speciation modes should be discriminated in terms of gene flow, the nature of selection maintaining reproductive reach, and whether the predominant cause is selective or stochastic. I also suggest that the notion of an adaptive “quasispecies” for asexual species is the primitive notion of species, and that members of reproductively coherent sexual species are additionally coadapted to their mating partners. (shrink)

The notion of information puts the human, the animal and the vegetable all on the same plane, and tends to dissolve the previous specificities of these categories. DNA, in this way, is fetishized. Also, the notion of information, and of the gene, has moved from the domain of expert or technical culture to become a part of mass culture: a development that has important social consequences. The human body is seen as a prototype that needs to be tested or (...) rectified (a consequence of the notion of ‘bad’ genes). From prenatal testing to the courtroom, it is implicitly around the notion a ‘life worth living’ (that is to say, of good morphological or genetic quality) that intense debates have arisen concerning the status of the body, of illness and of disability. Genetics is becoming part of the social environment, and it is setting itself up as a form of secular religion, with fundamentalist overtones. This article will analyse the anthropological shifts that have grown up around these new definitions of the human. (shrink)

We defend a realistic attitude towards biological species. We argue that two species are not different species because they differ in intrinsic features, be they phenotypic or genomic, but because they are separated with regard to gene flow. There are no intrinsic species essences. However, there are relational ones. We argue that bearing a gene flow relation to conspecifics may serve as the essence of a species. Our view of the species as a Gene-Flow Community differs from (...) Mayr’s definition of the species as a reproductive community. In a reproductive community, each organism is able to successfully reproduce with each other. However, there are species in which geographically distant organisms lost their ability to successfully reproduce, due to strong genetic adaptations to the respective local environmental conditions. Despite this loss of the ability to mutually reproduce, they are still bound by gene flow via continuous intermediate populations. This replacement of Mayr’s notion of an interbreeding potential as a criterion for species membership has important implications for the treatment of populations in allopatry and sympatry. (shrink)

Computational drug repositioning has been proven as a promising and efficient strategy for discovering new uses from existing drugs. To achieve this goal, a number of computational methods have been proposed, which are based on different data sources of drugs and diseases. These methods approach the problem using either machine learning- or network-based models with an assumption that similar drugs can be used for similar diseases to identify new indications of drugs. Therefore, similarities between drugs and between diseases are usually (...) used as inputs. In addition, known drug-disease associations are also needed for the methods as prior information. It should be noted that those associations are still not well established due to the fact that many of marketed drugs have been withdrawn and this could affect the outcome of the methods. In this study, we propose a novel method named RLSDR to find new uses of drugs. More specifically, it relies on a semi-supervised learning model, Regularized Least Square, thus it does not require definition of non-drug-disease associations as previously proposed machine learning-based methods. In addition, the similarity between drugs measured by chemical structures of drug compounds and the similarity between diseases which share phenotypes can be represented in a form of either similarity network or similarity matrix as inputs of the method. Moreover, instead of using a gold-standard set of known drug-disease associations, we construct an artificial set of the associations based on known disease-gene and drug-target associations. Experiment results demonstrate that RLSDR achieves better prediction performance on the artificial set of drug-disease associations than that on the gold-standard ones in terms of area under the Receiver Operating Characteristic curve. In addition, it outperforms two representative network-based methods irrespective of the prior information of drug-disease associations. Novel indications for a number of drugs are also identified and validated by evidences from a different data resource. (shrink)

Three recent genome‐wide studies in mice and humans have produced the most definitive map to date of genomic imprinting (gene expression that depends on parental origin) by incorporating multiple tissue types and developmental stages. Here, we explore the results of these studies in light of the kinship theory of genomic imprinting, which predicts that imprinting evolves due to differential genetic relatedness between maternal and paternal relatives. The studies produce a list of imprinted genes with around 120–180 in mice and (...) ∼100 in humans. The studies agree on broad patterns across mice and humans including the complex patterns of imprinted expression at loci like Igf2 and Grb10. We discuss how the kinship theory provides a powerful framework for hypotheses that can explain these patterns. Finally, since imprinting is rare in the genome despite predictions from the kinship theory that it might be common, we discuss evolutionary factors that could favor biallelic expression. (shrink)