Although the concept of ‘true infinity’ is undoubtedly central to Hegel's philosophy, the Anglophone rehabilitation of Hegel as a post-Kantian critical philosopher has avoided any sustained interpretive confrontation with the concept. In this paper, I provide a revisionary reconstruction of Hegelian true infinity by engaging with Martin Hägglund's argument in This Life (2019) for the centrality of finitude to Hegel's philosophy. For Hägglund, Hegel's philosophy effects a ‘secular reconciliation’ with finitude by demonstrating that our mortality is not a negative condition (...) to be overcome; rather, mortality is constitutive of rational social agency or ‘spiritual life’. While Hägglund's interpretive emphasis on finitude prima facie occludes a consideration of the concept of true infinity, I show that Hägglund's understanding of spiritual life in terms of the dynamic of self-maintenance implicitly articulates a revisionary understanding of true infinity as instantiated in and through the activity of finite living rational beings. More specifically, I show that Hägglund's understanding of finitude as constitutive of spiritual life is grounded in three closely interrelated Hegelian meta-concepts, all of which Hegel derives in the second chapter of the Logic (‘Existence’): (a) the distinction between abstract and determinate negation; (b) the form of individuality as constituted through determinate negation; and (c) true infinity as the form of individuality understood in explicitly processual terms. I thus ground a deflationary interpretation of true infinity in Hegel's logical account of determinate individuality, and at the same time, contribute to This Life's ongoing critical reception by articulating its Hegelian logical infrastructure. (shrink)

Presented in six principal analytic chapters with supporting appendices, this book explores the role of Islam in precipitating Europe's twelfth century commercial renaissance. Employing the classic analytic techniques of economics, Gene Heck determines that medieval Europe's feudal interregnum was largely caused by indigenous governmental business regulation and not by shifts in international trade patterns. He then proceeds by demonstrating how Islamic economic precepts provided the ideological rationales that empowered medieval Europe to escape its three-centuries-long experiment in "Dark Age economics" (...) ― in the process, providing the West with its archetypic tools of capitalism. While treatises such as Maxime Rodinson's excellent book, Islam and Capitalism, document the capitalistic nature of the Islamic economic system, in applying modern economic method to medieval orientalist historiography, this work is unique in capturing both the evolution and the impact of the system's role in forging medieval history. (shrink)

Camus is defined by many as an absurdist philosopher of revolt. The Plague, however, shows him working rigorously through a well-known division between ancient and modern ethics concerning the relation of reason, feeling and happiness. For Aristotle, the virtues are stable dispositions including affective and intellectual elements. For Kant, one’s particular feelings are either that from which we must abstract to judge moral worth, or are a constant hindrance to proper moral activity. Further, Kant claims “habit belongs to the physical (...) nature of the determination of the will,” which seems to imply habit cannot be a moral determination at all. A related disagreement regards virtue and happiness. Aristotle’s happiness is “an activity of the soul in accord with virtue.” For Kant and other moderns, happiness is an ideal of imagination, “a maximum of well-being in my present, and in every future, state,” all the elements of which “are without exception empirical.” Thus happiness seems more the constant counterweight to moral action than its fulfillment. Kant and Aristotle agree, however, in their judgment of many characters and actions, as is illustrated in The Plague. The novel provides realistic insights into a philosophical agreement between these supposed oppositions. In particular, I show how both philosophers would agree in their judgements concerning both the relative goodness and relative happiness of Joseph Grand and Raymond Rambert. The illustration of this agreement proves Camus is valorizing a traditional ethic. (shrink)

The target article emphasizes the relationship between a matching law-based theory of addiction and the disease model of addiction. In contrast, this response emphasizes the relationship between the matching law theory and other behavioral approaches to addiction. The basic difference, I argue, is that the matching law specifies that choice is governed by local reinforcement rates. In contrast, economics says that overall reinforcement rate controls choice, and for other approaches there are other measures or no clear prediction at all. The (...) response also differs from the target article in that there is more emphasis on the finding that stimulus conditions determine whether choice is under local or overall reinforcement rate control. (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)

The attitudes of the American public toward the environmental movement may be undergoing change as the economic crunch continues and energy shortages reoccur. The principles underlying the environmental movement need to be defined and examined carefully to determine what makes sense for our changing conditions. In this paper an attempt is made to express the two primary ethical principles which have evolved from environmental thinking and, in turn, have influenced the directions taken by the movement. It is argued that these (...) principles must not be accepted uncritically, but rather must be analyzed and subsequently modified to become compatible with more traditional ethical thinking. Such a synthesis is attempted in the paper. The modified principles can provide valuable guidance as we make difficult decisions which can influence the future path of life on Earth. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Reviewed by:Prophetic Evangelicals: Envisioning a Just and Peaceable Kingdom ed. by Bruce Ellis Benson, Malinga Elizabeth Berry, and Peter Goodwin Heltzel, and: Bearing True Witness: Truthfulness in Christian Practice by Craig HoveyGuenther “Gene” HaasReview of Prophetic Evangelicals: Envisioning a Just and Peaceable Kingdom EDITED BY BRUCE ELLIS BENSON, MALINGA ELIZABETH BERRY, AND PETER GOODWIN HELTZEL Grand Rapids, MI: Eerdmans, 2012. 225 pp. $35.00Review of Bearing True Witness: Truthfulness (...) in Christian Practice CRAIG HOVEY Grand Rapids, MI: Eerdmans, 2011. 258 pp. $27.00Christian thought and practice in North America—especially in the evangelical world—has undergone significant changes in recent years. Prophetic Evangelicals and Bearing True Witness deal with two areas where this is evident: first, the attention many evangelicals are now giving to social justice and peace and, second, their determination to witness to the truth about Christ in a manner consistent with the Christian gospel. Prophetic evangelicals is the name the editors apply to a new generation of evangelicals who believe that the gospel of Christ requires a commitment to proclaim and embody “the just and peaceable kingdom” (2). These evangelicals view Jesus as inaugurating “a new social order that is a radical alternative to the order of empire” (7).This trend among evangelicals to move beyond the preaching of the gospel in a narrow sense (over against the liberals’ emphasis on social justice) is the culmination of a trend that has been happening since the publication in 1947 of Carl Henry’s The Uneasy Conscience of Modern Fundamentalism. What is new about many younger evangelicals in recent decades is their embrace of the Anabaptist perspective on justice and peace. It is clear in the introductory and concluding chapters by the editors—with their appeals to John Howard Yoder and Stanley Hauerwas and their references to the “cultural captivity” of the church—that this is the trend they have in mind. One also reads hints of liberation theology in the editors’ references to the needs of the people being “holy” (12), to God’s being on the side of—and the gospel always being in favor of—the “least” (47), and to a critique of “the order of empire” (7). Of course, [End Page 221] non-Anabaptist evangelicals are also concerned with these themes as part of their commitment to justice and peace. But it is the distinctive emphasis of this book—with some exceptions among the contributors—that it highlights the ways Anabaptist evangelicals are prophetic.The chapters consist of expositions on the following biblical themes: creation, shalom, justice, kingdom, news, Mary, the cross, church, freedom, reconciliation, resurrection, and hope. The authors include a wide range of evangelicals: from a Kuyperian (Vincent Bacote on creation) to a committed Anabaptist (David Gushee on shalom), to postcolonial Christians (Gabriel Salguero on the cross, and Raymond Alfred on freedom). Although the term is slippery, the inclusion of two contributors raises the question about who the editors consider to be an “evangelical”: Helen Slessarov-Jamir (on justice) agrees with her students’ desire not to learn theology from “dead white men” (77) and embraces religious pluralism (85); Pamela Lightsey (on reconciliation) embraces liberalism and liberation theology and calls herself a “womanist theologian” (169).The chapters contain a diversity of contributions in length and quality. Some are good, short expositions of themes: creation (Bacote), kingdom (Christian Collins Winn), Mary—actually about suffering—(Ruth Padilla DeBorst), church (John Franke), and resurrection (Cherith Fee Nordling). Gushee’s chapter contains a good exposition of the Anabaptist view of shalom, along with typical sweeping statements about the “Constantinian compromise” and the evangelical compromise with the state (72). Two chapters deserve special recognition. Chris Boesel’s chapter, “News,” is an excellent account of the Christian call to justice as part of the full goodness of the gospel. He criticizes both liberal-progressive and evangelical-conservative assumptions about the church’s mission and calls for a “recovering evangelical faith” that pursues justice with repentance, humility, and a reliance on the Holy Spirit. Telford Work’s chapter, “Hope,” also articulates a perceptive critique of the activism of both the Christian Right and the Christian Left. Rejecting all alignments with worldly power, he calls on the... (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)

The concept of “public participation” is currently one of great interest to researchers and policy makers. In response to a perceived need for greater public involvement in decision making and policy formation processes on the part of both policymakers and the general public, a variety of novel mechanisms have been developed, such as the consensus conference and citizens jury, to complement traditional mechanisms, such as the public meeting. However, the relative effectiveness of the various mechanisms is unclear, as efforts at (...) evaluation have been sparse. In this article, the authors describe an evaluation of a two-day “deliberative conference” on the topic of radiation dose assessment. The authors detail the evaluation framework that they adopt and describe the instruments that they have developed to determine the attainment of the evaluationcriteria stipulated in that framework. They then describe the participation exercise that they have evaluated. Finally, they apply the instruments to assess the effectiveness of the exercise, and discuss the results and their implications for the conduct of evaluations and the use of this particular participation mechanism. (shrink)

Before September 11, 2001, a mass-casualty terrorist attack on American soil was generally considered a remote possibility. Similarly, before October 4, 2001—the first confirmed case of anthrax caused by intentional release — widespread bioterrorism seemed implausible. Among the arguments that such a biological artack was unlikely included: the lack of a historical precedent; the technological and organizational challenges to acquiring and weaponizing a biological agent; and the almost universal moral opprobrium that would certainly accompany the use by terrorists of such (...) a weapon. In the wake of September 11th and October 4th, however, many are reconsidering the likelihood of a large-scale bioterrorist attack against civilians.The Centers for Disease Control and Prevention defines bioterrorism as the intentional release of viruses, bacteria, or toxins for the purpose of harming or killing civilian. One measurement of the public health system's level of bioterrorism preparedness is the quality and distribution of laws mandating the reporting of diseases caused by certain biological agents. (shrink)

Before September 11, 2001, a mass-casualty terrorist attack on American soil was generally considered a remote possibility. Similarly, before October 4, 2001—the first confirmed case of anthrax caused by intentional release — widespread bioterrorism seemed implausible. Among the arguments that such a biological artack was unlikely included: the lack of a historical precedent; the technological and organizational challenges to acquiring and weaponizing a biological agent; and the almost universal moral opprobrium that would certainly accompany the use by terrorists of such (...) a weapon. In the wake of September 11th and October 4th, however, many are reconsidering the likelihood of a large-scale bioterrorist attack against civilians.The Centers for Disease Control and Prevention defines bioterrorism as the intentional release of viruses, bacteria, or toxins for the purpose of harming or killing civilian. One measurement of the public health system's level of bioterrorism preparedness is the quality and distribution of laws mandating the reporting of diseases caused by certain biological agents. (shrink)

The pathway that controls sexual fate in the nematode Caenorhabditis elegans has been well characterized at the molecular level. By identifying differences between the sex‐determination mechanisms in C. elegans and other nematode species, it should be possible to understand how complex sex‐determining pathways evolve. Towards this goal, orthologues of many of the C. elegans sex regulators have been isolated from other members of the genus Caenorhabditis. Rapid sequence evolution is observed in every case, but several of the orthologues appear (...) to have conserved sex‐determining roles. Thus extensive sequence divergence does not necessarily coincide with changes in pathway structure, although the same forces may contribute to both. This review summarizes recent findings and, with reference to results from other animals, offers explanations for why sex‐determining genes and pathways appear to be evolving rapidly. Experimental strategies that hold promise for illuminating pathway differences between nematodes are also discussed. BioEssays 25: 221–231, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

Mouse embryo cells, primed to differentiate with the hypomethylating agent 5‐azacytidine (5‐aza‐CR), provide an excellent model system in which cellular differentiation can be studied at the molecular level. An inherent advantage of this system is the availability of clonal populations of cells representative of the non‐differentiated precursor, those whose determinative state is that of a specific lineage, and the end stage, phenotypically mature cell. Analysis of these cultures at the cellular and molecular level will advance our understanding of requirements for (...) and the mechanism of action of growth modulators as well as the necessity for controlled expression of certain proto‐oncogenes. At a more fundamental level, the system can be used to identify, isolate and characterize genes whose expression alters the phenotypic fate of cells. (shrink)

Until recently, sex determination in mammals has often been described as a male determination process, with male differentiation being the active and dominant pathway, and only in its absence is the passive female pathway followed. This picture has been challenged recently with the discovery that the gene encoding R-spondin1 is mutated in human patients with female-to-male sex reversal.((1)) These findings might place R-spondin1 in the exceptional position of being the female-determining gene in mammals. In this review, (...) possible roles of R-spondin1 during sex determination as well as questions arising from this study will be discussed. (shrink)

It may be possible, one day, to use gene therapy to treat diseases whose genetic defects have been discerned. Because many genes responsible for inherited eye disorders within the retina have been identified, diseases of the eye are prime candidates for this form of therapy. The eye also has the advantage of being highly accessible with altered immunological properties, important considerations for easy delivery of virus and avoidance of systemic immune responses. Currently, adenovirus, adeno‐associated virus and lentivirus have been (...) used to successfully transfer genetic material to retinal pigment epithelium and photoreceptor cells. By harnessing therapeutic genes to these viruses, researchers have been able to demonstrate rescue in rodent models of retinitis pigmentosa, providing evidence that this form of therapy can be effective in delaying photoreceptor cell death. Future challenges include confirming therapeutic effects in animal models with eyes more anatomically similar to those of humans and demonstrating long‐term rescue with minimal toxicity. BioEssays 23:662–668, 2001. © 2001 John Wiley & Sons, Inc. (shrink)

How does neuronal activity give rise to cognitive capacities? To address this question, neuroscientists hypothesize about what neurons “represent,” “encode,” or “compute,” and test these hypotheses empirically. This process is similar to the assessment of hypotheses in other fields of science and as such is subject to the same limitations and difficulties that have been discussed at length by philosophers of science. In this paper, we highlight an additional difficulty in the process of empirical assessment of hypotheses that is unique (...) to the cognitive sciences. We argue that, unlike in other scientific fields, comparing hypotheses according to the extent to which they explain or predict empirical data can lead to absurd results. Other considerations, which are perhaps more subjective, must be taken into account. We focus on one such consideration, which is the purposeful function of the neurons as part of a biological system. We believe that progress in neuroscience critically depends on properly addressing this difficulty. (shrink)

Over 10 years ago, Pax‐6 was shown to play an evolutionarily conserved role in controlling eye formation from Drosophila to humans.1 Since then, the identification of an entire cascade of conserved eye determination genes has brought a new understanding to the developmental relationship between the insect compound eye and the vertebrate camera eye.2 Additional studies are now beginning to suggest that even late aspects of eye development, including cell type specification, also share common molecular machinery. In this commentary, I (...) will discuss some of these findings, with a particular focus on the recent study by Dyer et al.3 describing a novel role for the Prox1 transcription factor in specifying horizontal cells in the mouse retina. As Prospero, the Drosophila homolog of Prox1, also participates in retinal cell specification, these data provide a forum for asking new questions concerning pathways that may regulate retinogenesis across evolution. BioEssays 25:921–925, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

Pioneering molecular work on chelicerate visual system development in the horseshoe crab Limulus polyphemus surprised with the possibility that this process may not depend on the deeply conserved retinal determination function of Pax6 transcription factors. Genomic, transcriptomic, and developmental studies in spiders now reveal that the arthropod Pax6 homologs eyeless and twin of eyeless act as ancestral determinants of the ocular head segment in chelicerates, which clarifies deep gene regulatory and structural homologies and recommends more unified terminologies (...) in the comparison of arthropod visual systems. Following this phylotypic stage, chelicerate visual system development differs fundamentally from other arthropods during the compartmentalization of the ocular segment in that eye and optic neuropil primordia originate independently from each other. Comparative analyses of this phase identified further gene regulatory homologies but also major differences, most notably the possibly compensatory replacement of Pax6 by Pax2 in lateral eye specification. Also see the video abstract here: https://youtu.be/Hdfr3z5kEXU. (shrink)

Vallortigara & Rogers (V&R) propose a fundamental role of the environment in determining population-level lateralisation and suggest that genes play no primary function in this phenomenon. Here I argue that genes involved in the coordination of visceral organ laterality and in coupling of different forms of lateralisation do play a role in the control of lateralisation within the population.

Genetic and lifestyle factors contribute to cognitive ageing. However, the extent to which the public attribute changes in thinking skills to either genetic or lifestyle factors is largely unknown. This may be important if it impacts engagement in activities deemed beneficial to thinking skills. This study, therefore, explored people’s beliefs about determinants of cognitive ageing and whether those beliefs were associated with engagement in potentially beneficial behaviours. Data were collected through a United Kingdom-wide survey of people aged 40 and over. (...) Participants completed questions about their beliefs regarding cognitive ageing, and specifically the extent to which they believed lifestyle or genetic factors influence those changes, and their engagement in specific behaviours that may be cognitively beneficial. Responses from 3,130 individuals were analysed using chi-square tests of independence, principal component analysis and ANCOVAs to investigate whether their attribution of genetic or lifestyle determinants were associated with their beliefs about cognitive ageing and their participation in brain health-related behaviours. Most respondents believed genes and lifestyle contribute equally to age-related changes in cognitive skills. Respondents who believed genetic factors were more influential were less likely to expect cognitive skills might be improved or maintained with age, less sure what behaviours might be associated with brain health, and less likely to engage in behaviours comprising mental challenge/novelty supported as beneficial for brain health. From this United Kingdom-wide survey about beliefs regarding potential determinants of cognitive ageing, some of our respondents’ views were not aligned with the findings from ageing research. It is important for the public to know how to keep their brains healthy. Our results indicate a need for clearer messaging highlighting the role of lifestyle factors for brain health. (shrink)

Conceptual developments have defined concrete questions about the timing and precise location of cellular pattern formation. Plants in general, and the trichomes of Arabidopsis in particular, are remarkably suited for research on these problems. Genetic analysis requires the quantitative characterizations of the developmental processes by which patterning occurs. Larkin et al.(1) have provided measures of the non‐random distances between trichomes. They have also obtained evidence about the cell lineages leading to trichome development, and this evidence constrains the possible role of (...) intracellular programs. Continued genetic analysis may call for the identification of mutations that are expressed only during development and whose effects are corrected before the phenotype matures. (shrink)

The signal for sex determination in the nematode Caenorhabditis elegans is the ratio between the number of × chromosomes and the number of sets of autosomes (the X/A ratio). Animals with an X/A ratio of 0.67 (a triploid with two × chromosomes) or less are males. Animals with an X/A ratio of 0.75 or more are hermaphrodites. Thus, diploid males have one × chromosome and diploid hermaphrodites have two × chromosomes. However, the difference in X‐chromosome number between the sexes (...) is not reflected in general levels of X‐linked gene expression because of the phenomenon of dosage compensation. In dosage compensation, X‐linked gene expression appears to be ‘turned down’ in 2X animals to the 1X level of expression. An intriguing and unexplained finding is that mutations and X‐chromosome duplications that elevate X‐linked gene expression also feminize triploid males. One way that this relationship between sex determination and X‐linked gene expression may be operating is discussed. (shrink)

Hereditary retinal degeneration due to mutations in visual genes may be amenable to therapeutic interventions that modulate, either positively or negatively, the amount of protein product. Some of the proteins involved in phototransduction are rapidly moved by a lightdependent mechanism between the inner segment and the outer segment in rod photoreceptor cells, and this phenomenon is important in phototransduction.

Cellular 3D structures, for example, organoids, are an excellent model for studying and developing treatments for various diseases, including hereditary ones. Therefore, they are increasingly being used in biomedical research. From the point of view of safety and efficacy, recombinant adeno‐associated viral (rAAV) vectors are currently most in demand for the delivery of various transgenes for gene replacement therapy or other applications. The delivery of transgenes using rAAV vectors to various types of organoids is an urgent task, however, it (...) is associated with a number of problems that are discussed in this review. Cellular heterogeneity and specifics of cultivation of 3D structures determine the complexity of rAAV delivery and are sometimes associated with low transduction efficiency. This review surveys the main ways to solve emerging problems and increase the efficiency of transgene delivery using rAAVs to organoids. A clear understanding of the stage of development of the organoid, its cellular composition and the presence of surface receptors will allow obtaining high levels of organoid transduction with existing rAAV vectors. (shrink)

Male superiority in mathematical ability (along with female superiority in verbal fluency) may reflect the operation of an X-Y homologous gene (the right-shift-factor) influencing the relative rates of development of the cerebral hemispheres. Alleles at the locus on the Y chromosome will be selected at a later mean age than alleles on the X, and only by females.

After a vertebrate dies, many of its organ systems, tissues, and cells remain functional while its body no longer works as a whole. We define this state as the “twilight of death” − the transition from a living body to a decomposed corpse. We claim that the study of the twilight of death is important to ethical, legal and medical science. We examined gene expression at the twilight of death in the zebrafish and mouse reaching the conclusion that apparently (...) thousands of transcripts significantly increase in abundance from life to several hours/days postmortem relative to live controls. Transcript dynamics of different genes provided “proof-of-principle” that models accurately predict an individual's elapsed-time-of-death. While many transcripts were associated with survival and stress compensation, others were associated with epigenetic factors, developmental control, and cancer. Future studies are needed to determine whether the high incidence of cancer in transplant recipients is due to the postmortem processes in donor organs. In organismal death, some organ systems, tissues and cells remain functional while the body no longer works as a whole. In the “twilight of death” − the transition from a living body to a decomposed corpse − thousands of gene transcripts increase in abundance relative to live controls. (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)

Gene replacement therapy holds great promise in the treatment of many genetic CNS disorders. This commentary discusses the feasibility of gene replacement therapy in the unique context of the retina, with regard to: (1) the genetics of retinal neoplasia and degeneration, (2) available gene transfer technology, and (3) potential gene delivery vehicles.

To discern the ethical issues involved incurrent gene therapy research, to explore theproblems inherent in possible future genetherapies, and to encourage debate within thescientific community about ethical questionsrelevant to both, we surveyed American Societyof Human Genetics scientists who engage inhuman genetics research. This study of theopinions of U.S. scientific experts about theethical issues discussed in the literature ongene therapy contributes systematic data on theattitudes of those working in the field as wellas elaborative comments. Our survey finds thatrespondents are highly (...) supportive of thepotential use of somatic cell gene therapy tocure serious diseases in adults and children aswell as prospective offspring. A clearmajority, however, believe that using suchgenetic techniques for enhancement purposes isunacceptable. Delineating the line betweendisease/disorder and improvement/enhancementposes a problem not easily resolved and oneconducive to the growth of slippery-slopeapprehensions. The majority of respondents alsoadvocate germ-line therapy, in theory at least,and under similar restrictions, but theyrecognize the roadblock that the existence ofunanticipated negative consequences currentlypresents. Another complex matter involvestrying to determine appropriate reasons forchoosing target diseases for research, forwhich the dichotomy between rare single-geneand common multifactorial diseases reveals anongoing dilemma. (shrink)

types of application of genetic engineering for the insertion of genes into humans. The scientific requirements and the ethical issues associated with each type are discussed. Somatic cell gene therapy is technically the simplest and ethically the least controversial. The first clinical trials will probably be undertaken within the next year. Germ line gene therapy will require major advances in our present knowledge and it raises ethical issues that are now being debated. In order to provide guidelines for (...) determining when germ line gene therapy would be ethical, the author presents three criteria which should be satisfied prior to the time that a clinical protocol is attempted in humans. Enhancement genetic engineering presents significant, and troubling, ethical concerns. Except where this type of therapy can be justified on the grounds of preventive medicine, enhancement engineering should not be performed. The fourth type, eugenic genetic engineering, is impossible at present and will probably remain so for the foreseeable future, despite the widespread media attention it has received. Keywords: genetic engineering, somatic cells, germ cells, enhancement, eugenics, humanhood CiteULike Connotea Del.icio.us What's this? (shrink)

Advances in genetic technology in general and medical genetics in particular will enable us to intervene in the process of human biological development which extends from zygotes and embryos to people. This will allow us to control to a great extent the identities and the length and quality of the lives of people who already exist, as well as those we bring into existence in the near and distant future. Genes and Future People explores two general philosophical questions, one metaphysical, (...) the other moral: (1) How do genes, and different forms of genetic intervention (gene therapy, genetic enhancement, presymptomatic genetic testing of adults, genetic testing of preimplantation embryos), affect the identities of the people who already exist and those we bring into existence? and (2) How do these interventions benefit or harm the people we cause to exist in the near future and those who will exist in the distant future by satisfying or defeating their interest in having reasonably long and disease-free lives? Genes and Future People begins by explaining the connection between genes and disease, placing genetic within a framework of evolutionary biology. It then discusses such topics as how genes and genetic intervention influence personal identity, what genetic testing of individuals and the knowledge resulting from it entails about responsibility to others who may be at risk, as well as how gene therapy and genetic enhancement can affect the identities of people and benefit or harm them. Furthermore, it discusses various moral aspects of cloning human beings and body parts. Finally, it explores the metaphysical and moral implications of genetic manipulation of the mechanisms of aging to extend the human life span.The aim Genes and Future People is to move philosophers, bioethicists, and readers in general to reflect on the extent to which genes determine whether we are healthy or diseased, our identities as persons, the quality of our lives, and our moral obligations to future generations of people. (shrink)

Though the target article is not without fertile suggestions, at least two problems limit its overall validity: (1) the extended gene-culture coevolutionary framework is not an alternative to standard evolutionary theory; (2) the proposed model does not explain how much time is necessary for selective pressure to determine the stabilization of a new aspect of the genotype.

A common view is that species occupy a unique position on the Tree of Life. Evaluating this claim requires an understanding of what the Tree of Life represents. The Tree represents history, but there are at least three biological levels that are often said to have genealogies: species, organisms, and genes. Here I focus on defending the plausibility of a gene-based account of the Tree. This leads to an account of species that are determined by gene genealogies. On (...) this view, an exclusive group is a group of organisms that forms a clade for a higher proportion of the genome than any conflicting clade. Taxa occupy a unique position in what can be called the ‘primary concordance tree’. But each gene has its own historical ‘Tree of Life’. I conclude by arguing that both organismal pedigrees with their corresponding Tree as well as gene genealogies and their trees are objectively real and play important, but different, roles in biological practice. (shrink)

One of our most brilliant evolutionary biologists, Richard Lewontin has also been a leading critic of those--scientists and non-scientists alike--who would misuse the science to which he has contributed so much. In The Triple Helix, Lewontin the scientist and Lewontin the critic come together to provide a concise, accessible account of what his work has taught him about biology and about its relevance to human affairs. In the process, he exposes some of the common and troubling misconceptions that misdirect and (...) stall our understanding of biology and evolution.The central message of this book is that we will never fully understand living things if we continue to think of genes, organisms, and environments as separate entities, each with its distinct role to play in the history and operation of organic processes. Here Lewontin shows that an organism is a unique consequence of both genes and environment, of both internal and external features. Rejecting the notion that genes determine the organism, which then adapts to the environment, he explains that organisms, influenced in their development by their circumstances, in turn create, modify, and choose the environment in which they live.The Triple Helix is vintage Lewontin: brilliant, eloquent, passionate, and deeply critical. But it is neither a manifesto for a radical new methodology nor a brief for a new theory. It is instead a primer on the complexity of biological processes, a reminder to all of us that living things are never as simple as they may seem. (shrink)

Despite its importance, the linkage between genetic and cultural evolution has until now been little explored. An understanding of this linkage is needed to extend evolutionary theory so that it can deal for the first time with the phenomena of mind and human social history. We characterize the process of gene-culture coevolution, in which culture is shaped by biological imperatives while biological traits are simultaneously altered by genetic evolution in response to cultural history. A case is made from both (...) theory and evidence that genetic and cultural evolution are inseverable, and that the human mind has tended to evolve so as to bias individuals toward certain patterns of cognition and choice rather than others. With the aid of mathematical models we trace the coevolutionary circuit: The genes prescribe structure in developmental pathways that lay down endocrine and neural systems, imposing regularities in the development of cognition and behavior; these regularities translate upward into holistic patterns of culture, which can be predicted in the form of probability density distributions ; natural selection acts within human history to favor certain epigenetic rules over others; and the selection alters the frequencies of the underlying genes. The effects of genetic and cultural changes reverberate throughout the circuit and are consequently tested with the passage of each life cycle. In addition to modeling gene-culture coevolution, we apply methods from island biogeography and information theory to examine the cultural capacity of the genes, the factors determining the magnitude of cultural diversity, and the possible reasons for the uniqueness of the human achievement. (shrink)

Diseases causing inherited retinal degeneration in humans, such as retinitis pigmentosa and macular dystrophy, are genetically heterogeneous and clinically diverse. More than 40 genes causing retinal degeneration have been mapped to specific chromosomal sites; of these, at least 10 have been cloned and characterized. Mutations in two proteins, rhodopsin and peripherin/RDS, account for approximately 35% of all cases of autosomal dominant retinitis pigmentosa and a lesser fraction of other retinal conditions. This target article reviews the genes and (...) mutations causing retinal degeneration and proposes mechanisms whereby specific mutations lead to particular clinical consequences, that is, the relationship between genotype and phenotype. Retinitis pigmentosa and macular dystrophy are genetically heterogeneous diseases that cause retinal degeneration in humans and often result in severe visual impairment or blindness. Although many of the genes causing these diseases have not been identified, three photoreceptor-specific proteins have been implicated: rhodopsin, peripherin/RDS, and the P-subunit of rod phosphodiesterase. Mutations in the genes for these three proteins can cause either dominant retinitis pigmentosa, recessive retinitis pigmentosa, dominant congenital stationary night blindness, or dominant macular degeneration. Why this multiplicity of clinical phenotypes? Our target article summarizes the genetic and biochemical background to this question and proposes a number of possible explanations. Discussion focuses mainly on 73 distinct disease-causing mutations of rhodopsin. We feel that rhodopsin and other photoreceptor proteins can serve as model systems for unraveling the connection between genotype and phenotype, not only for inherited retinal diseases but for other degenerative disorders as well. (shrink)

Polyphenic differences between individuals arise not through differences at the genome level but as a result of specific cues received during development. Polyphenisms often involve entire suites of characters, as shown dramatically by the polyphenic castes found in many social insect colonies. An understanding of the genetic architecture behind polyphenisms provides a novel means of studying the interplay between genomes, gene expression and phenotypes. Here we discuss polyphenisms and molecular genetic tools now available to unravel their developmental bases in (...) insects. We focus on several recent studies that have tracked gene-expression patterns during social insect caste determination. BioEssays 23:62–68, 2001. Published 2001 John Wiley & Sons, Inc. (shrink)

In this paper, I explore the “expressivist critique” of the use of prenatal testing to select against the birth of persons with impairments. I begin by setting out the expressivist critique and then highlighting, through an investigation of an influential objection to this critique, the ways in which both critics and proponents of the use of technologies of genetic selection negotiate a difficult set of dilemmas surrounding the relationship between genes and identity. I suggest that we may be able to (...) advance the debate about these technologies by becoming more aware of the ways in which this debate is itself in part a political contestation over this relationship. Ultimately, I will argue, the real force of the expressivist objection lies in its capacity to draw our attention to political questions about the role of the state and about relationships between different social groups rather than between parents and prospective children. That is to say, crucial issues, when evaluating the force of this criticism, turn out to be: the nature of the institutions which determine how decisions about prenatal selection are made; and how we think of each other, that is, what we take to be the defining characteristics of human beings. Paradoxically, arguments about the ethics of the “sorting society”, both supportive and critical, are an important arena in which these institutions and these ideas about identity are contested and shaped. An increased awareness of the reflexive nature of the process of debating these issues may assist us in better negotiating them. (shrink)

Despite its importance, the linkage between genetic and cultural evolution has until now been little explored. An understanding of this linkage is needed to extend evolutionary theory so that it can deal for the first time with the phenomena of mind and human social history. We characterize the process of gene-culture coevolution, in which culture is shaped by biological imperatives while biological traits are simultaneously altered by genetic evolution in response to cultural history. A case is made from both (...) theory and evidence that genetic and cultural evolution are inseverable, and that the human mind has tended to evolve so as to bias individuals toward certain patterns of cognition and choice rather than others. With the aid of mathematical models we trace the coevolutionary circuit: The genes prescribe structure in developmental pathways that lay down endocrine and neural systems, imposing regularities in the development of cognition and behavior; these regularities translate upward into holistic patterns of culture, which can be predicted in the form of probability density distributions ; natural selection acts within human history to favor certain epigenetic rules over others; and the selection alters the frequencies of the underlying genes. The effects of genetic and cultural changes reverberate throughout the circuit and are consequently tested with the passage of each life cycle. In addition to modeling gene-culture coevolution, we apply methods from island biogeography and information theory to examine the cultural capacity of the genes, the factors determining the magnitude of cultural diversity, and the possible reasons for the uniqueness of the human achievement. (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)