This article examines how minimal genome research mobilizes philosophical concepts such as minimality and essentiality. Following a historical approach the article aims to uncover what function this terminology plays and which problems are raised by them. Specifically, four historical moments are examined, linked to the work of Harold J. Morowitz, Mitsuhiro Itaya, Eugene Koonin and Arcady Mushegian, and J. Craig Venter. What this survey shows is a historical shift away from historical questions about life or descriptive questions about specific organisms (...) towards questions that explore biological possibilities: what are possible forms of minimal genomes, regardless of whether they exist in nature? Moreover, it highlights a fundamental ambiguity at work in minimal genome research between a universality claim and a standardization claim: does a minimal genome refer to the minimal gene set for any organism whatsoever? Or does it refer rather to a gene set that will provide stable, robust and predictable behaviour, suited for biotechnological applications? Two diagnoses are proposed for this ambiguity: a philosophical diagnosis of how minimal genome research either misunderstands the ontology of biological entities or philosophically misarticulates scientific practice. Secondly, a historical diagnosis that suggests that this ambiguity is part of a broader shift towards technoscience. (shrink)

A gene is considered essential when its loss of function results in a deleterious phenotype, hugely reducing the organism's viability or fitness. However, the link between the essentiality of a gene and its degree of polymorphism is unclear. In this review, we show that there is a place for a certain degree of variability, even for essential genes. We first study the role of infectious diseases in the prevalence of genetic disorders among humans: balancing selection has (...) selected harmful variants due to the selective pressure of pathogens because the heterozygous carrier can resist them. Then we show that the environment can induce adaptation of species by rapidly evolving genes. We also study the role of positive selection on speciation, particularly upon genes of the immune, reproductive and nervous systems. Finally, we highlight the role of regulatory sequences in changes in morphology between species and adaptation to the environment within species. (shrink)

This paper begins by examining several potentially unethical recent marketing practices. Since most marketing managers face ethical dilemmas during their careers, it is essential to study the moral consequences of these decisions. A typology of ways that managers might confront ethical issues is proposed. The significant organizational, personal and societal costs emanting from unethical behavior are also discussed. Both relatively simple frameworks and more comprehensive models for evaluating ethical decisions in marketing are summarized. Finally, the fact that organizational commitment (...) to fostering ethical marketing decisions can be accomplished by top management leadership, codes of ethics, ethics seminars/programs and ethical audits is examined. (shrink)

In a very literarily complicated setting, Frater Taciturnus sets a remark about Hamlet not being a Christian tragedy. After unpeeling that literary setting and noting that Taciturnus' remark aims more at Jacob Börne than at Shakespeare, the paper shows how Frater Taciturnus' remark calls into question the religious project of a certain danish author. For, Taciturnus' primary concern is to show that religious drama is not possible, or at least "ought not be." This general law applies to Hamlet as well, (...) and if Shakespeare was attempting a religious drama he a) shouldn't have because such a thing is essentially undramatizable, and b) failed because he did not begin (which would be possible) by showing the hero's religious presuppositions. Frater Taciturnus himself has given considerable thought to the extent and the manner in which the religious can be represented; in fact the letter to the reader is his proof of how perfectly his own narrative, "Guilty/Not Guilty," was constructed with precisely these problems in mind. The play is not the thing that Taciturnus is really interested in, nor is he interested in the playwright's intentions, he considers that the play's the thing that catches out Börne's misunderstanding of the religious, and it is this field—in particular, that area where the religious life and literary art intersect, that is the brother's interest and forte. But if Taciturnus is correct in his criticism of Börne, it should be impossible for S. Kierkegaard to produce a religious authorship as well. (shrink)

This paper is a response to the preceding papers. It is maintained that American business is failing to live up to its obligations to society. One reason for this is acceptance of what De George calls the Myth of Amoral Business. Businessmen believe that morality is either not applicable to business or that business has a special morality of its own. Several arguments are advanced to show why this is not true. A second reason business is failing to fulfill its (...) obligations is that egoism seems to be an essential feature of capitalism. Harrington believes that this should be changed, but that attempts to change it are bringing about a more collectivist society. Kirk sees no need for change because he believes capitalism the best possible economic system. It is argued in reply that they are both mistaken because their analyses are based on outmoded ideologies which impede rather than aid us in solving problems caused by the irresponsibility of business. (shrink)

A central feature of the Covid-19 pandemic is state differences. Some state Governors closed all but essential businesses, others did not. In some states, most of the population wore face coverings when in public; in other states, <50% wore face coverings. According to journalists, these differences were symptomatic of a politically polarized America. The Big 5 personality factors also cluster at the state level. For example, residents of Utah score high on Conscientiousness and low on Neuroticism, whereas residents of (...) Massachusetts and Connecticut show the opposite pattern. In state-level regressions that controlled for partisan political allegiances, Conscientiousness was a significant predictor of the stringency of state Covid-19 restrictions, whereas Openness was a significant predictor of mask wearing. A number of the predictors were strongly correlated with each other. For example, the correlation coefficient linking Openness with the percentage of Democratic state legislators was r = 0.53. Commonality regression partitions the explained variance between the amount that is unique to each predictor and the amount that is shared among subsets of correlated predictors. This approach revealed that the common variance shared by Conscientiousness, Openness and partisan politics accounted for 34% of the state differences in Covid-19 policy and 35% of the state differences in mask wearing. The results reflect the importance of personality in how Americans have responded to the Covid-19 pandemic. (shrink)

Prefaced by an argument that the ancients understood mimesis as fundamental to being human, and art as therefore essential to human moral and intellectual development, this book starts from the problematic status of the (happily ending) Iphigenia in Poetics. How Aristotle must explicate tragedy to hold Iphigenia as the best thus sets up the exploration of comedy. Chapter two shows that comedy aims at the catharsis of desire and sympathy. This analysis is then applied in detail to Aristophanes’ Acharnians, (...) Shakespeare’s As You Like It and Stoppard’s Arcadia, exhibiting the cross-cultural application of the theory which Aristotle would expect. (shrink)

There is a growing call for greater public involvement in establishing science and technology policy, in line with democratic ideals. A variety of public participation procedures exist that aim to consult and involve the public, ranging from the public hearing to the consensus conference. Unfortunately, a general lack of empirical consideration of the quality of these methods arises from confusion as to the appropriate benchmarks for evaluation. Given that the quality of the output of any participation exercise is difficult to (...) determine, the authors suggest the need to consider which aspects of the process are desirable and then to measure the presence or quality of these process aspects. To this end, a number of theoretical evaluation criteria that are essential for effective public participation are specified. These comprise two types: acceptance criteria, which concern features of a method that make it acceptable to the wider public, and process criteria, which concern features of the process that are liable to ensure that it takes place in an effective manner. Future research needs to develop instruments to measure these criteria more precisely and identify the contextual and environmental factors that will mediate the effectiveness of the different participation methods. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Reviewed by:Mimesis: Culture, Art, SocietyGene FendtMimesis: Culture, Art, Society, by Gunter Gebauer and Christoph Wulf; translated by Don Reneau; 400 pp. Berkeley: University of California Press, 1995, $45.00 cloth, $18.00 paper.The purpose of this book is to develop “a historical reconstruction of important phases in the development of mimesis” (p. 1) from a brief discussion of its pre-Platonic Greek significance through contemporary thinkers. It is, then, not strictly a (...) philosophical text, as are most of the texts and authors the book takes up. It is, however, a significant effort in the history of ideas, and as such it is shot through with traces of the traditional tropes, shaping power, ideology, and even social relations of that discipline, particularly as it is practiced in the venerable school of German scholarship. That is, the structure, tone, and argument of the book are shaped mimetically. This book’s problematic is, then, not simply historical, as Republic’s problem with the poets is not simply philosophical. Rather, both books partake of mimesis, even while each one aims to criticize or set forth the concept’s historical development.Let this stand as notice of a deep philosophical problem with the method of historical criticism. In fairness we should note that the authors are not unconscious of their difficulty here: “The fact that mimesis cannot be represented without the use of mimetic processes poses the fundamental problem of theory formation in reference to our object. What is the relation between the representational and the represented world? Is the representation of representation structurally equivalent to simple representation?” (p. 21). The authors hope to moot the power of those questions, if not the questions themselves, by attending “first of all to representations of mimesis found in texts best selected for that purpose and only afterward begin to offer considerations of a more generalizing nature” (p. 21). Their reasoning and choice of texts here is the traditional trope of the discipline: a mimema. Among other things, this methodos requires that the authors treat Girard as developing a “literary critical examination of [mimesis in] nineteenth and twentieth century novels” (p. 359n1) and a “new ordering of nineteenth century social relations” (p. 235), rather than, as he claims, a comprehensive anthropological thesis. At least, this method requires treating the former as essential, and the latter as less justifiable, for if Girard’s anthropological thesis about mimesis were justifiable a history of the idea of mimesis would be merely a heresiology. This problem can be restated mutatis mutandis for such thinkers as Plato and Augustine, whose theses—if they have theses—about mimesis are deeply anthropological.Two further questions arise early on and remain at the end. If, as the authors hold (and show), “the concept of mimesis necessarily loses its intellectual centrality with the rise of rational thought,” so much so that “the field of art, which comes to be regarded in the process as autonomous, undergoes a complete and fundamental restructuring” (p. 3), must we not begin to [End Page 199] suspect—as recent philosophers like Derrida attempt to show—that there is a dialectical relationship between the intentional, truth-functional relations of modern rational thought and the mimetic, unformalizable and “ambivalent” (pp. 2–3) processes of mimesis? Rather than conclude that “the question what is mimesis? is one which demonstratively leads to error” (p. 309), does it not begin to seem that intentional representation, as most visible in science, and mimetic assimilations, as most obviously effective in art, are together the necessary dialectical elements of culture, art and science? While it seems that the rise of rational scientific thought pushes mimesis to the social fringes of the arts, isn’t scientific activity and writing still just as much subject, and just as much a product, of the power of mimesis as art? Similarly art is just as bound as science to “probability” or “the convincing impossibility,” to recall Aristotle. This idea is not entirely foreign to the book; it appears subliminally as a plausible explication of the work of theorists like Benjamin and Adorno (pp. 267–93).The third difficulty is a question about selection. As in Auerbach’s renowned precursor, Wulf... (shrink)

Two popular models of trustworthiness have garnered support over the years. One has postulated three aspects of trustworthiness as state-based antecedents to trust. Another has been interpreted to comprise two aspects of trustworthiness. Empirical data shows support for both models, and debate remains as to the theoretical and practical reasons researchers may adopt one model over the other. The present research aimed to consider this debate by investigating the factor structure of trustworthiness. Taking items from two scales commonly employed to (...) assess trustworthiness, we leveraged structural equation modeling to explore which theoretical model is supported by the data in an organizational trust context. We considered an array of first-order, second-order, and bifactor models. The best-fitting model was a bifactor model comprising one general trustworthiness factor and ability, benevolence, and integrity grouping factors. This model was determined to be essentially unidimensional, though this is qualified by the finding that the grouping variables accounted for significant variance with for several organizational outcome criteria. These results suggest that respondents typically employ a general factor when responding to items assessing trustworthiness, and researchers may be better served treating the construct as unidimensional or engaging in scale parceling of their models to reflect this response tendency more accurately. However, the substantial variance accounted by the grouping variables in hierarchical regression suggest there may be contexts in which it would be acceptable to consider the theoretical factors of ability, benevolence, and integrity independent of general trustworthiness. (shrink)

Genes cannot be selfish or unselfish, any more than atoms can be jealous, elephants abstract or biscuits teleological. This should not need mentioning, but Richard Dawkins's book The Selfish Gene has succeeded in confusing a number of people about it, including Mr J. L. Mackie. What Mackie welcomes in Dawkins is a new, biological-looking kind of support for philosophic egoism. If this support came from Dawkins's producing important new facts, or good new interpretations of old facts, about animal life, (...) this could be very interesting. Dawkins, however, simply has a weakness for the old game of Brocken-spectre moralizing—the one where the player strikes attitudes on a peak at sunrise, gazes awe-struck at his gigantic shadow on the clouds, and reports his observations as cosmic truths. He is an uncritical philosophic egoist in the first place, and merely feeds the egoist assumption into his a priori biological speculations, only rarely glancing at the relevant facts of animal behaviour and genetics, and ignoring their failure to support him. There is nothing empirical about Dawkins. Critics have repeatedly pointed out that his notions of genetics are unworkable. I shall come to this point later, but I shall not begin with it, because, damning though it is, it may seem to some people irrelevant to his main contention. It is natural for a reader to suppose that his over-simplified drama about genes is just a convenient stylistic device, because it seems obvious that the personification of them must be just a metaphor. Indeed he himself sometimes says that it is so. But in fact this personification, in its literal sense, is essential for his whole contention; without it he is bankrupt. His central point is that the emotional nature of man is exclusively self-interested, and he argues this by claiming that all emotional nature is so. Since the emotional nature of animals clearly is not exclusively selfinterested, nor based on any long-term calculation at all, he resorts to arguing from speculations about the emotional nature of genes, which he treats as the source and archetype of all emotional nature. This strange convoluted drama must be untwisted before the full force of the objections from genetics can be understood. (shrink)

Six essential genes located near the mouse albino locus have been identified as required during specific periods of development. Amongst these six, each is required either during the preimplantation stages of development, at specific times during gastrulation, within 12 hrs after birth or during juvenile development. These genes were identified as a result of extensive genetic complementation analysis using embryos homozygous for the albino deletions. Although, in principal, the associated developmental abnormalities could result from loss of multiple genes, the (...) deletion phenotype in one case is identical to that induced by chemical mutagenesis. These results indicate that the abnormalities observed in deletion homozygotes may result from single gene loss. The deletions have proven useful not only as genetic tools to localize the position of the genes, but also as molecular entry points to the regions containing these genes. The current methodology being used to isolate candidate genes from the albino region is also reviewed here. (shrink)

Gene therapy and gene editing are revolutionising the treatment of genetic diseases, most notably haematological disorders. This paper evaluates the use of both techniques in hereditary blood disorders. Many studies have been conducted in this field, especially with gene therapy, with very promising results in diseases such as haemophilia, certain haemoglobinopathies and Fanconi anaemia. The application of these techniques in clinical practice and the foreseeable development of these approaches in the coming years suggest that it might be (...) useful to evaluate the results achieved thus far. It is also essential to reflect on the possible bioethical concerns raised by the use of both techniques, especially in terms of safety issues for patients, potential side effects, treatment duration, accessibility and cost of treatment, and the heritability of genetic changes produced if germline cells are used. (shrink)

Acknowledgments 1. Culture Is Essential 2. Culture Exists 3. Culture Evolves 4. Culture Is an Adaptation 5. Culture Is Maladaptive 6. Culture and Genes Coevolve 7. Nothing about Culture Makes Sense except in the Light of Evolution.

'It's all in the genes'. Is this true, and if so, _what_ is all in the genes? _Genes: A Philosophical Inquiry_ is a crystal clear and highly informative guide to a debate none of us can afford to ignore. Beginning with a much-needed overview of the relationship between science and technology, Gordon Graham lucidly explains and assesses the most important and controversial aspects of the genes debate: Darwinian theory and its critics, the idea of the 'selfish' gene, evolutionary psychology, (...) memes, genetic screening and modification, including the risks of cloning and 'designer' babies. He considers areas often left out of the genes debate, such as the environmental risks of genetic engineering and how we should think about genes in the wider context of debates on science, knowledge and religion. Gordon Graham asks whether genetic engineering might be introducing God back into the debate and whether the risks of a brave new genetic world outweigh the potential benefits. Essential reading for anyone interested in science, technology, and philosophy, _Genes: A Philosophical Inquiry_ is ideal for those wanting to find out more about the ethical implications of genetics and the future of biotechnology. (shrink)

Genes are gained and lost over the course of evolution. A recent study found that over 1,800 new genes have appeared during primate evolution and that an unexpectedly high proportion of these genes are expressed in the human brain. But what are the molecular functions of newly evolved genes and what is their impact on an organism's fitness? The acquisition of new genes may provide a rich source of genetic diversity that fuels evolutionary innovation. Although gene manipulation experiments are (...) not feasible in humans, studies in model organisms, such as Drosophila melanogaster, have shown that new genes can quickly become integrated into genetic networks and become essential for survival or fertility. Future studies of new genes, especially chimeric genes, and their functions will help determine the role of genetic novelty in the adaptation and diversification of species. (shrink)

The fine‐structure analyses of the nopaline synthase (nos) promoter which is active constitutively in a wide range of plant tissues reveal that a portion of the upstream essential region for maximal transcription is a potential Z‐DNA‐forming element. Z‐DNA sequences are found in almost all plant‐promoter regions, suggesting that these structural elements may play important roles in plant gene expression.

The strength of a slippery slope argument is a matter of some dispute. Some see it as a reasonable argument pointing out what probably or inevitably follows from adopting some practice, others see it as essentially a fallacious argument. However, there seems to be a tendency emerging to say that in many cases, the argument is not actually fallacious, although it may be unsubstantiated. I shall not try to settle this general discussion, but merely seek to assess the strength of (...) the slippery slope argument applied to human gene therapy. The structure of my argument will be the following. First, I shall distinguish between three different versions of the slippery slope argument; two logical versions and an empirical one. Next, I will address human gene therapy in terms of each of the three versions, partly relying on slippery slope arguments against this practice that have already surfaced in the literature. I shall argue that neither version pulls through. The logical versions fail primarily because relevant distinctions can be made between different uses of gene therapy, contrary to what the proponents of the arguments claim. The empirical version fails because there seems to be no evidence supporting the claim that we shall in fact slide down the slope if we engage in gene therapy, and because if we accepted the conclusion that we should not allow gene therapy on the basis of the empirical argument, we should have to make very far-reaching and undesirable modifications in health care in general, in order to be consistent. Or at least so I shall argue. (shrink)

In this article I critically examine Adam Moore’s claim that the threshold for overriding intangible property rights and privacy rights is higher, in relation to genetic enhancement techniques and sensitive personal information, than is commonly suggested. I argue that Moore fails to see how important advances in genetic research are to social justice. Once this point is emphasised one sees that the issue of how formidable overriding these rights are is open to much debate. There are strong reasons, on grounds (...) of social justice, for thinking the importance of such rights is likely to be diminished in the interests of ensuring a more just distribution of genes essential to pursuing what John Rawls calls a person’s ”rational plan of life’. (shrink)

Heterogeneous nuclear ribonucleoprotein U (HNRNPU) is a nuclear protein that plays a crucial role in various biological functions, such as RNA splicing and chromatin organization. HNRNPU/scaffold attachment factor A (SAF‐A) activities are essential for regulating gene expression, DNA replication, genome integrity, and mitotic fidelity. These functions are critical to ensure the robustness of developmental processes, particularly those involved in shaping the human brain. As a result, HNRNPU is associated with various neurodevelopmental disorders (HNRNPU‐related neurodevelopmental disorder, HNRNPU‐NDD) characterized by (...) developmental delay and intellectual disability. Our research demonstrates that the loss of HNRNPU function results in the death of both neural progenitor cells and post‐mitotic neurons, with a higher sensitivity observed in the former. We reported that HNRNPU truncation leads to the dysregulation of gene expression and alternative splicing of genes that converge on several signaling pathways, some of which are likely to be involved in the pathology of HNRNPU‐related NDD. (shrink)

Human cooperation is highly unusual. We live in large groups composed mostly of non-relatives. Evolutionists have proposed a number of explanations for this pattern, including cultural group selection and extensions of more general processes such as reciprocity, kin selection, and multi-level selection acting on genes. Evolutionary processes are consilient; they affect several different empirical domains, such as patterns of behavior and the proximal drivers of that behavior. In this target article, we sketch the evidence from five domains that bear on (...) the explanatory adequacy of cultural group selection and competing hypotheses to explain human cooperation. Does cultural transmission constitute an inheritance system that can evolve in a Darwinian fashion? Are the norms that underpin institutions among the cultural traits so transmitted? Do we observe sufficient variation at the level of groups of considerable size for group selection to be a plausible process? Do human groups compete, and do success and failure in competition depend upon cultural variation? Do we observe adaptations for cooperation in humans that most plausibly arose by cultural group selection? If the answer to one of these questions is “no,” then we must look to other hypotheses. We present evidence, including quantitative evidence, that the answer to all of the questions is “yes” and argue that we must take the cultural group selection hypothesis seriously. If culturally transmitted systems of rules (institutions) that limit individual deviance organize cooperation in human societies, then it is not clear that any extant alternative to cultural group selection can be a complete explanation. (shrink)

The pseudoscience of evolutionary psychology purports to explain human behaviors by reference to an ancestral environment (essentially, a hunting‐gathering way of life) in which we evolved. Contemporary human behaviors are allegedly governed directly by genes that reflect adaptation to this environment by natural selection. However, the evolutionary process is much more complex than this reductionist approach implies, and adaptation cannot involve the fine‐tuning of structures or behaviors within individuals or species: natural selection can only affect entire organisms, not their components. (...) Similarly, genetic processes are too complex to admit this simplistic view. Instead, our flexible, complex human behaviors probably represent an emergent acquisition. (shrink)

The relationship of genes, genomes, the organism and the environment where development takes place can be explained in two dramatically different ways. The two views are characterized as ,,program theory' and ,,systemic theory' of DNA. The first assumes that genetic information is encoded in DNA and preexists development. Environmental influences are treated as conditions for adequate gene expression, sometimes as selective conditions for different developmental pathways. The second assumes that genetic information that makes a difference in development is generated (...) in the developmental contexts themselves. Environment, according to this account, matters per se, as a distinct kind of causes in developmental systems. The laboratory, a place where person-independent reproducibility of observations is enacted, may act as a selective epistemological factor that makes the program approach more viable than the systemic. Other reasons for the inclination of 20th Century's genetics towards the program view however are rooted in an a priori metaphysical tradition that placed DNA in the role of the essential causa formalis for ontogeny. German Die Beziehung zwischen Genen, Genomen, Organismen und der Umwelt, in der die Entwicklung stattfindet, kann auf zwei dramatisch verschiedene Weisen erklärt werden. Diese beiden Ansichten werden charakterisiert als ,,ProgrammTheorie und als ,,systemische Theorie der DNA. Die erstere nimmt an, dass genetische Information in der DNA codiert ist und vor der Entwicklung schon existiert. Umwelteinfl-üsse werden als Bedingungen für eine adequate Gen expression behandelt, manche als selektive Bedingungen für die Auswahl zwischen verschiedenen Entwicklungswegen. Die zweite Ansicht nimmt an, dass genetische Information, die in der Entwicklung einen Unterschied macht, in den Kontexten der Entwicklung erst erzeugt wird. Die Umwelt ist gemäss diesem Ansatz per se wichtig, als eine eigene Art von Ursachen in sich entwickelnden Systemen. Das Laboratorium, ein Ort, in dem die personenunabhängige Reproduzierbarkeit von Beobachtungen inszeniert wird, kann als ein selek tiver epistemologischer Faktor angesehen werden, der die Programm-Sicht des Genoms favorisiert. Andere Gründe für die Neigung der Genetik des 20. Jahrhunderts zur Programm-Theorie liegen aber in einer metaphysischen Tradi tion, die der DNA die Rolle der essentiellen causa formalis für die Ontogenese verliehen hat. (shrink)

The placenta invades the adjacent uterus and controls the maternal immune system, like a cancer invades surrounding organs and suppresses the local immune response. Intriguingly, placental and cancer cells are globally hypomethylated and share an epigenetic phenomenon that is not well understood – they fail to silence repetitive DNA sequences that are silenced in healthy somatic cells. In the placenta, hypomethylation of retrotransposons has facilitated the evolution of new genes essential for placental function. In cancer, hypomethylation is thought to (...) contribute to activation of oncogenes, genomic instability, and retrotransposon unsilencing; the latter, we postulate, is possibly the most important consequence. Activation of placental retrotransposon-derived genes in cancer underpins our hypothesis that hypomethylation of these genes drives cancer cell invasion. This alludes to an interesting paradox, that while placental retrotransposon-derived genes are essential for promoting early hominid life, the same genes promote disease-susceptibility and death through cancer. Placental and cancer cells fail to silence retrotransposons that are normally silenced in healthy tissues. This has created new genes that are essential for placental function, yet they are also expressed in cancer. We hypothesize that active retrotransposons are a double-edged sword, contributing both adaptive and deleterious functions to biology. (shrink)

Almost every human disease has both a genetic and an environmental component. Even a classical inherited condition such as hemophilia can be influenced by external factors—in fact, most of the pathogenic effects of the mutation can be avoided by judicious injections of clotting factor, leading to a nearly normal life expectancy. For infectious diseases, often considered as essentially environmental, there are well-documented inherited differences in susceptibility, one of the most striking being the resistance to HIV infection of homozygous carriers of (...) the delta-32 mutation in the CCR5 gene (Dragic et al. 1996). Nevertheless, a number of conditions are “mostly genetic,” others “mostly environmental,” while many .. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Kennedy Institute of Ethics Journal 10.3 (2000) 265-281 [Access article in PDF] Scope Note 39 Genes, Patents, and Bioethics-Will History Repeat Itself? Susan Cartier Poland Gene patenting--the very notion sounds absurd! How can anyone claim to have invented the genes with which one is born? To make matters worse, genetic makeup precedes birth, meaning the existence of the invention predates the existence of the inventor. So, do we (...) really own our genes, or do they belong to our parents, or our governments, or a Supreme Being? Ownership is only one bioethical issue involved in gene patenting. But before looking at the issues, some essential and basic terms must be understood, namely genes and patents. Genes In his book On the Origin of Species, published in 1859, the biologist Charles Darwin proposed a theory called "natural selection," whereby living things changed over time or evolved through generations due to competition and variation. By experimenting with the garden pea in the 1860s, Gregor Mendel, a monk and accomplished horticulturalist, provided the mechanism of inheritance supporting the natural selection theory of his contemporary Darwin. That mechanism is the gene, or, as Mendel described it, a discrete "factor." The gene has also been defined as "the fundamental unit of heredity" (United States 1987, p. 157). Each individual has two copies of a gene, one from each parent, but that individual passes down to offspring only one of the two copies. Because of Mendel, the gene has become a scientific concept and the basis of a new scientific field: genetics.David C. Page (2000) of the Whitehead Institute for Biomedical Research at the Massachusetts Institute of Technology explained today's terms for genetics structures using an analogy taken from the home. In his view, the cell is a kitchen, the genome is a shelf in the kitchen, the chromosome is a cookbook on the shelf, the gene is a recipe in the cookbook, and a base-pair (either adenine with thymine or guanine with cytosine) is a single letter in the recipe. A protein, the [End Page 265] working molecule blueprinted by a gene, is a dish ready to eat, and an ingredient in the dish is an amino acid, which is a building block of the protein as specified by a string of base-pairs.Colin Tudge (1993), a British science journalist, would disagree with Page's description of the gene as a recipe. A recipe is like a blueprint: both are directions that precede the work. But a gene is not passive according to Tudge; it actively administers the cell's work, and it also responds to cellular events (Aldridge 1996).The current focus of scientific research and funding is on the gene and the completion of the sequencing of all the genes that comprise the human genome, portrayed in the press as a race between the U.S. government's Human Genome Project and the private corporation Celera Genomics. The real action, however, is at the protein level. The gene only holds the information to produce a protein; it is the three-dimensional shaped protein that does the work. In order to produce energy, eliminate waste, and perform other functions specific to a cell or tissue, proteins must bind, thus creating "biological pathways." Proteins bind (or not) and detach as a function of their shapes, which are determined by their precise chemical composition as spelled out in their genetic code. IBM will spend the next five years making one computer, Blue Gene, that will then take an entire year to come up with the chemical map for only one protein (Gillis 2000). It is estimated that there are about 40,000 proteins in the human body.Despite these overwhelming numbers, modern biology has been able to achieve significant results within the Human Genome Project's 15-year time frame, from 1990 to 2005. The genetic map was completed in 1993; the physical map was completed in 1995; and the genetic sequence is expected to be completed in 2002, with 97 to 99 percent completed as of 26 June 2000. This... (shrink)

This chapter discusses some of the practical consequences of the recent and evolving situation in both science and industry, and forecasts how altering the law might affect each. It considers at least three possibilities: (1) justice demands eradicating patenting genes no matter what the consequences, (2) justice and economic efficiency demand altering the current system to meet both concerns, or (3) the economic effects of altering or eradicating the present system outweigh both the concerns of justice or economic efficiency, and (...) so the status quo should be maintained. The chapter explores each of these possibilities with an eye toward actually proposing rational public policy scenarios that could be adopted. Open Source essentially amounts to the ideal methods of the sciences applied to products in the marketplace. DNA in its natural state is the object of discovery and therefore the domain of science. (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)

Singapore has a highly developed economy and has been recognized to have one of the best business environments in Asia. Her success is based largely on focused developments of key industries in traded services and manufacturing sectors. The challenge for Singapore is to utilize her small human resource to transform the present economy to a more knowledge‐intensive economy. Singapore has recently embarked on the ambitious goal of developing Biomedical Sciences as an industry. Educating the government and the public on various (...) aspects of this new industry was identified as one of the essential steps towards this goal. The challenge was to inspire non‐biologists to embrace the life sciences. This review describes how a series of workshops were developed to address the needs and the challenges of educating the public and the government. BioEssays 25:913–917, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

Recent discoveries in life sciences evidenced that changes in the composition of the microbiome and epigenetics represent two essential mechanisms at the basis of the biological evolution, since both allow a rapid change of the phenotype in response to both environmental and internal stimuli. Surprisingly, in the age of genomics we are discovering that each organism (and its evolution) cannot be explained by genes alone. The microbiome and the epigenetic machinery are frequently described as completely separate mechanisms, but actually (...) symbionts may act as epigenetic sources of heritable variation so that genomes, epigenomes and microbiomes are not independent traits, but a tripartite driver of the biological evolution of all organisms. (shrink)

Hematopoiesis is the complex developmental process through which undifferentiated, pluripotent, hematopoietic stem cells come to generate mature, functional blood cells. This process is regulated in large part by specific transcription factors that control expression of genes necessary for the developmental sequence. Leukemias represent one form of disruption of this normal developmental process, and studies over the past few years have shown that many of the genes that underlay leukemogenesis are also essential for normal hematopoiesis. In an interesting recent example, (...) Song et al.(1) demonstrate that haploinsufficiency of the AML1 gene is the genetic basis of a form of familial thrombocytopenia which predisposes the affected individuals to the development of acute myeloid leukemia. Here we summarize Song's paper and current information describing the interesting dosage effects of this gene and other members of its gene family. BioEssays 22:214–218, 2000. © 2000 John Wiley & Sons, Inc. (shrink)

Deciding whether to grant an expanded access request for a child whose sibling is enrolled in a gene therapy trial involves a number of complex factors: considering the best interests of the child, the psychosocial and economic impact on the family, and the concerns and obligations of researchers. Despite the challenges in coming to a substantively fair outcome in cases of discordant eligibility, creating a procedurally fair decision-making process to adjudicate requests is essential.

: The following comments on Paul Root Wolpe's article "If I Am Only My Genes, What Am I? Genetic Essentialism and a Jewish Response" address (1) his presentation of the relationship between science and culture or religion as unimodal; (2) his misconception of the Jewish view of the physical corpus; and (3) his essential question of genetic determinism by examining the traditional Jewish view of the spiritual aspects of the human.

The members of the Six gene family were identified as homologues of Drosophila sine oculis which is essential for compound-eye formation. The Six proteins are characterized by the Six domain and the Six-type homeodomain, both of which are essential for specific DNA binding and for cooperative interactions with Eya proteins. Mammals possess six Six genes which can be subdivided into three subclasses, and mutations of Six genes have been identified in human genetic disorders. Characterization of Six genes (...) from various animal phyla revealed the antiquity of this gene family and roles of its members in several different developmental contexts. Some members retain conserved roles as components of the Pax-Six-Eya-Dach regulatory network, which may have been established in the common ancestor of all bilaterians as a toolbox controlling cell proliferation and cell movement during embryogenesis. Gene duplications and cis-regulatory changes may have provided a basis for diverse functions of Six genes in different animal lineages. (shrink)

In the mouse, at least 16 genes regulate vesicle trafficking to specialized lysosome‐related organelles, including platelet dense granules and melanosomes. Fourteen of these genes have been identified by positional cloning. All 16 mouse mutants are models for the genetically heterogeneous human disease, Hermansky–Pudlak Syndrome (HPS). Five HPS genes encode known vesicle trafficking proteins. Nine genes are novel, are found only in higher eukaryotes and encode members of three protein complexes termed BLOCs (Biogenesis of Lysosome‐related Organelles Complexes). Mutations in murine HPS (...) genes, which encode protein co‐members of BLOCs, produce essentially identical phenotypes. In addition to their well‐known effects on pigmentation, platelet function and lysosome secretion, HPS genes control a wide range of physiological processes including immune recognition, neuronal functions and lung surfactant trafficking. Studies of the molecular functions of HPS proteins will reveal important details of vesicle trafficking and may lead to therapies for HPS. BioEssays 26:616–628, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

Genetic studies have revealed that the antagonistic interplay between PcG and TrxG/MLL complexes is essential for the proper maintenance of vertebrate Hox gene expression in time and space. Hox genes must be silenced in totipotent embryonic stem cells and, in contrast, rapidly activated during embryogenesis. Here we discuss some recently published articles1-4 that propose a novel mechanism for the induction of Hox gene transcription. These studies report a new family of histone demethylases that remove H3K27me3/me2 repressive marks (...) at Hox promoters during differentiation of stem cells. Though the overall importance of these enzymes for proper embryogenesis was demonstrated, their precise role in Hox gene epigenetic regulation during development still remains to be firmly established. BioEssays 30:199–202, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

In a recent article, Marilyn Baffoe-Bonnie offers three arguments for conducting CRISPR/Cas9 biotechnology research to cure sickle-cell disease (SCD) based on addressing historical and current injustices in SCD research and care. I show that her second and third arguments suffer from roughly the same defect, which is that they really argue for something else rather than for conducting CRISPR/Cas9 research in particular. For instance, the second argument argues that conducting this gene therapy research would improve the relationship between SCD (...) sufferers (who are mostly of African descent) and health care providers. But really what is essential in improving this relationship is for those providers to genuinely care and be concerned, and this could be lacking even with the CRISPR research being done. Indeed, this relationship could be improved even without that research being done, as long as there is genuine concern. Thus, this argument actually argues for the need for genuine concern. As for the third argument, one (of two) problems arises because it claims that CRISPR research for SCD should be pursued because the benefits would be shared by even non-research-participants, as non-participants would be encouraged. However, this argues for any research for SCD, not for CRISPR research in particular. I conclude that a better justice-based argument will use only Baffoe-Bonnie’s first argument, which is based on historic neglect of an actual cure for SCD (going beyond merely management or transplant therapies). (shrink)

Autonomous transposable elements, generally considered as junk and selfish, encode transposition proteins that can bind, copy, break, join or degrade nucleic acids as well as process or interact with other proteins. Such a repertoire of activities might be of interest for the host cell. There is indeed substantial evidence that mobile DNA can serve as a dynamic reservoir for new cellular functions. Transposable element genes encoding transposase, integrase, reverse transcriptase as well as structural and envelope proteins have been repeatedly recruited (...) by their host during evolution in most eukaryotic lineages. Such domesticated sequences protect us against infections, are necessary for our reproduction, allow the replication of our chromosomes and control cell proliferation and death; others are essential for plant development. Many new candidates for domesticated sequences have been revealed by sequencing projects. Their functional analysis will uncover new aspects of evolutionary alchemy, the turning of junk into gold within genomes. BioEssays 28: 913–922, 2006. © 2006 Wiley periodicals, Inc. (shrink)

We advance two objections to the selfish gene theory formulated by Richard Dawkins, which states that natural selection operates on genetic replicators. These objections target three of the essential features of the theory. The first feature is the exclusivity that the theory ascribes to genetic replicators as objects of natural selection. We call it “the exclusivity clause”. The second and third features correspond to two criteria that genetic replicators must satisfy for Dawkins’ theory to hold. We call them (...) “the stability criterion” and “the fidelity criterion”. The first objection we advance is that, given the findings of transgenerational epigenetics, genetic replicators do not appear to satisfy the exclusivity clause and some of them do not seem to meet the stability criterion. The second objection is that the existence of the molecular phenomena known as alternative splicing and trans-splicing seems to entail that many genetic replicators do not satisfy neither the stability criterion nor the fidelity criterion. (shrink)

The global food system exhibits dizzying complexity, with interaction among social, economic, biological, and technological factors. Opposition to the first generation of plants and animals transformed through rDNA-enabled gene transfer has been a signature episode in resistance to the forces of industrialization and globalization in the food system. Yet agricultural scientists continue to tout gene technology as an essential component in meeting future global food needs. An ethical analysis of the debate over gene technologies reveals the (...) details that matter. On the one hand, alternative regimes for institutionalizing gene technology could mitigate injustices suffered by politically marginalized and economically disadvantaged actors in the food system, especially smallholding farmers in less industrialized economies. On the other hand, GMO opposition has been singularly effective in mobilizing citizens of affluent countries against policies and practices that lie at the heart of these same injustices. As part of the roundtable, “Ethics and the Future of the Global Food System,” this essay argues that charting a middle course that realizes the benefits of gene technology while blocking its use in the perpetration of unjust harms may require a more detailed grasp of intricacies in the food system than even motivated bystanders are willing to develop. (shrink)

DNA methylation is a repressive epigenetic modification that is essential for development and its disruption is widely implicated in disease. Yet, remarkably, ablation of DNA methylation in transgenic mouse models has limited impact on transcriptional states. Across multiple tissues and developmental contexts, the predominant transcriptional signature upon loss of DNA methylation is the de‐repression of a subset of germline genes, normally expressed in gametogenesis. We recently reported loss of de novo DNA methyltransferase DNMT3B resulted in up‐regulation of germline genes (...) and impaired syncytiotrophoblast formation in the murine placenta. This defect led to embryonic lethality. We hypothesize that de‐repression of germline genes in the Dnmt3b knockout underpins aspects of the placental phenotype by interfering with normal developmental processes. Specifically, we discuss molecular mechanisms by which aberrant expression of the piRNA pathway, meiotic proteins or germline transcriptional regulators may disrupt syncytiotrophoblast development. (shrink)

This article presents the results of a study that investigates the way in which carriers of a mutation on the BRCA1 or the BRCA2 gene, associated with a high risk of breast and ovarian cancer, make their reproductive decisions. Using semi-structured interviews, the study explored the way in which these persons reflected on the acceptability of taking the risk of transmitting this mutation to the next generation, the arguments they used in favor or against taking that risk, and in (...) the light of these arguments, their opinion on the acceptability of preimplantation genetic diagnosis (PGD) as a reproductive option. The findings suggest that when carriers are planning to have a(nother) child, they are mainly concerned by the risk of transmitting ‘much more than a gene’: essentially painful experiences not only with respect to health, such as undergoing cancer surveillance or combatting one’s own illness, but also with regards to family life, such as witnessing the illness and death of a close relative, encountering difficulties in finding a partner or reconsidering one’s plans to have a family. As for opinions concerning the acceptability of PGD as a reproductive option, opinions about personal recourse were varied but all expressed the understanding that PGD should be made available to those persons who consider it their best option. (shrink)

This paper deals with the interrelationship between causal explanation and methodology in a relatively young discipline in biology: epigenetics. Based on cases from molecular and ecological epigenetics, I show that James Woodward’s interventionist account of causation captures essential features about how epigeneticists using highly diverse methods, i.e. laboratory experiments and purely observational studies, think about causal explanation. I argue that interventionism thus qualifies as a useful unifying explanatory approach when it comes to cross-methodological research efforts. It can act as (...) a guiding rationale (i) to link causal models in molecular biology with statistical models derived from observational data analysis and (ii) to identify test-criteria for reciprocal transparent studies in different fields of research, which is a shared issue across the sciences.Este artículo trata de la relación entre explicaciones causales y metodología en una disciplina biológica relativamente joven, la epigenética. Basándome en casos de la epigenética molecular y ecológica, muestro que la concepción intervencionista de la causalidad desarrollada por James Woodward capta algunos rasgos esenciales del modo en que los epigenetistas conciben la explicación causal usando métodos sumamente diversos: e.g., experimentos de laboratorio o estudios observacionales. Defiendo que el intervencionismo es útil como aproximación unificadora a la explicación cuando se trata de empresas investigadoras transdisciplinares. Puede servir como guía para (i) conectar los modelos causales en biología molecular con los modelos estadísticos derivados del análisis de datos observacionales y (ii) para identificar criterios de prueba para estudios recíprocos en diferentes ámbitos de investigación, un problema de interés común en diferentes ciencias. (shrink)

: With the advent of the Genetic Age comes a unique new set of problems and ethical decisions. There is a tendency to take the scientific developments presented by modern genetics at face value, as if the science itself were value-neutral and not influenced by cultural and religious images. One example of the fallout of the Genetic Age is the development of a "genetic self," the idea that our essential selfhood lies in our genes. It is important to understand (...) the assumptions of the Genetic Age, the development of genetic selfhood, and the broader cultural trends and assumptions that underlie modern genetic thinking. It is equally important, however, to shape a reaction to the concept of a genetic self. Judaism has long carried on a unique discussion about the nature of selfhood in different times and places and about the relation of the corporeal self to the essential self. Insights from Judaism therefore may help to craft a reaction to the modern genetic self that incorporates the best of modern genetics as well as the integrity of a more transcendent selfhood. (shrink)

Embryonic development combines paradoxical properties: it has great precision, it is usually conducted at breakneck speed and it is flexible on relatively short evolutionary time scales, particularly at early stages. While these features appear mutually exclusive, we consider how they may be reconciled by the properties of key early regulatory networks. We illustrate these ideas with the network that controls development of endoderm progenitors. We argue that this network enables precision because of its intrinsic stability, self propagation and dependence on (...) signalling. The network enables high developmental speed because it is rapidly established by maternal inputs at multiple points. In turn these properties confer flexibility on an evolutionary time scale because they can be initiated in many ways, while buffering essential progenitor cell populations against changes in their embryonic environment on both evolutionary and developmental time scales. Although stable, these networks must be capable of rapid dissolution as cell differentiation progresses. While we focus on the core early endodermal network of vertebrates, we argue that these properties are likely to be general in early embryonic stem cell populations, such as mammalian ES cells. BioEssays 30:757–765, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

Existing empirical research often do not explain which concepts about genetics underlie the assumption that genetic information is deemed important for donor-conceived offspring. This study focused on how donor-conceived individuals following anonymous sperm donation give meaning to and make sense of genes and genetics. Analysis is based on focus groups and interviews with adult donor-conceived offspring. Findings suggest that genes are part of their specific context of being donor-conceived but also play a role in daily life. Genes make sense on (...) an individual level and a relational level, both on parent-child as sibling-level. On an individual level they were perceived as (1) a biological starting package, (2) their own unique combination and (3) as a reference point. On a relational level, genes were seen as (1) “person-al”, (2) connecting and (3) locating individuals. This information is essential for those supporting/counseling donor conceived offspring and families as well as for policy-members. (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)

Circadian rhythm abnormalities in bipolar disorder have led to a search for genetic abnormalities in circadian "clock genes" associated with BD. However, no significant clock gene findings have emerged from genome-wide association studies. At least three factors could account for this discrepancy: complex traits are polygenic, the organization of the clock is more complex than previously recognized, and/or genetic risk for BD may be shared across multiple illnesses. To investigate these issues, we considered the clock gene network at (...) three levels: essential "core" clock genes, upstream circadian clock modulators, and downstream clock controlled genes. Using relaxed thresholds for GWAS statistical significance, we determined the rates of clock vs. control genetic associations with BD, and four additional illnesses that share clinical features and/or genetic risk with BD. Then we compared the results to a set of lithium-responsive genes. Associations with BD-spectrum illnesses and lithium-responsiveness were both enriched among core clock genes but not among upstream clock modulators. Associations with BD-spectrum illnesses and lithium-responsiveness were also enriched among pervasively rhythmic clock-controlled genes but not among genes that were less pervasively rhythmic or non-rhythmic. Our analysis reveals previously unrecognized associations between clock genes and BD-spectrum illnesses, partly reconciling previously discordant results from past GWAS and candidate gene studies. (shrink)