Transposable elements (TEs) are powerful facilitators of genome evolution, and hence of phenotypic diversity as they can cause genetic changes of great magnitude and variety. TEs are ubiquitous and extremely ancient, and although harmful to some individuals, they can be very beneficial to lineages. TEs can build, sculpt, and reformat genomes by both active and passive means. Lineages with active TEs or with abundant homogeneous inactive populations of TEs that can act passively by causing ectopic recombination are potentially fecund, adaptable, (...) and taxonate readily. Conversely, taxa deficient in TEs or possessing heterogeneous populations of inactive TEs may be well adapted in their niche, but tend to prolonged stasis and may risk extinction by lacking the capacity to adapt to change, or diversify. Because of recurring intermittent waves of TE infestation, available data indicate a compatibility with punctuated equilibrium, in keeping with widely accepted interpretations of evidence from the fossil record. We propose a general and holistic synthesis on how the presence of TEs within genomes makes them flexible and dynamic, so that genomes themselves are powerful facilitators of their own evolution. (shrink)

A common account sees the human genome sequencing project of the 1990s as a “natural outgrowth” of the deciphering of the double helical structure of DNA in the 1950s. The essay aims to complicate this neat narrative by putting the spotlight on the field of human chromosome research that flourished at the same time as molecular biology. It suggests that we need to consider both endeavors – the human cytogeneticists who collected samples and looked down the microscope and the molecular (...) biologists who probed the molecular mechanisms of gene function – to understand the rise of the human genome sequencing project and the current genomic practices. In particular, it proposes that what has often been described as the “molecularization” of cytogenetics could equally well be viewed as the turn of molecular biologists to human and medical genetics – a field long occupied by cytogeneticists. These considerations also have implications for the archives that are constructed for future historians and policy makers. (shrink)

This case is another in a series intended to highlight the new questions emerging from advances in mapping the human genome and the application of genetic findings to clinical practice. The National Human Genome Research Institute, a component of the National Institutes of Health, by law is directed to designate a portion of its annual budget to furthering understanding of the ethical, legal, and social questions emerging from research on the human genome. As part of the effort, the Institute supports (...) research by scientists and scholars around the nation with the aim of clarifying and resolving the tough ethical and research choices facing this endeavor. But recently it has launched an intramural program, which is expected to take a catalytic role in grappling with the array of issues the researchers face in carrying out investigations in human genetics. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:LettersMaxwell J. Mehlman, Susan R. Massey, Ronald M. Green, and Fred RosnerPhysicians and the Allocation of Scarce ResourcesMadam: We read with interest Dr. Pellegrino's commentary on our article in the December 1994 issue of the Kennedy Institute of Ethics Journal, and commend him for pointing out so well the different ways that law and ethics approach the issue of physician allocation of scarce resources.We wish to make one clarification. (...) Dr. Pellegrino states that we propose that fiduciary duties be abolished. Quite the contrary, our position is that fiduciary obligations are essential to the maintenance of trust—which we believe to be an efficient as well as an ethical element of the patient-provider relationship. If fiduciary duties are undercut, as we pointed out they are by the Oregon Medicaid legislation, then some other method of promoting trust must be established, and, as we point out in the article, it is difficult to identify what that method could be.Maxwell J. MehlmanandSusan R. MasseyThe Law Medicine CenterArter & HaddenCase Western Reserve UniversityCleveland, OHSchool of LawCleveland, OHReport of the Human Embryo Research PanelMadam: In the December 1994 issue of the Kennedy Institute of Ethics Journal, I reported on the controversy surrounding the work of the NIH Human Embryo Research Panel and the conclusions reached in its report, which was formally presented to NIH Director Harold Varmus on September 27, 1994. At that time, the report was to be reviewed by the Advisory Committee to the Director (ACD) until its next meeting in early December. I am writing to update your readers on the fate of the Panel's report.On the morning of December 2, 1994, following a previous afternoon of animated discussion, the ACD unanimously accepted the Report of the Human Embryo Research Panel. Panel members and members of the NIH staff who were present and had worked for nearly a year on the Report were gratified by this vote of confidence and by the strong support of NIH Director Harold Varmus.We had little time to enjoy this success. Within a matter of hours, the White House issued a press release in which President Clinton thanked the committee for its work and then, in a remark overruling one of the key recommendations in our report, stated: "I do not believe that federal funds should be used to support the creation of human embryos for research purposes, and I have directed that NIH not allocate any resources for such research." [End Page 83]As a Panel member and active participant in that day's events, my initial response was one of shock. I was particularly distressed that the President and his advisors chose a moment so late in the process to make their views known. Why had we worked for months, I asked, without a word of concern from the White House? Although Panel members were guided primarily by our perceptions of the ethical and scientific issues involved, some were close to the political realities of Washington and would have introduced these concerns into the Panel's deliberations.Within a matter of days, my own sense of outrage had diminished. First of all, it was clear that whatever the personal sources of the President's objections to the Panel's recommendations, this high level political intervention was inevitable. Less than a month before, on November 8, with the election of a majority House and Senate, the political environment for embryo research had changed dramatically. The previous June, 32 congressmen, most of them members of a minority Republican party, had signed a letter protesting the Panel's work. Now, one of the signers of that letter, Newt Gingrich, was destined to be Speaker of the House.Second, it became clear that the damage was not total. The President has forbidden NIH to support work involving the deliberate creation of embryos for research. Without exception, members of the Panel had come to the conclusion that some development of "research embryos" must be permitted to reduce the risks of new assisted reproductive technologies, to enhance scientific knowledge, and to develop new therapies for a range of serious diseases. All these... (shrink)

In this paper I defend Max Weber's concept of political legitimacy as a standard for the moral evaluation of states. On this view, a state is legitimate when its subjects regard it as having a valid claim to exercise power and authority. Weber’s analysis of legitimacy is often assumed to be merely descriptive, but I argue that Weberian legitimacy has moral significance because it indicates that political stability has been secured on the basis of civic alignment. Stability on this basis (...) enables all the goods of peaceful cooperation with minimal state violence and intimidation, thereby guarding against alienation and tyranny. Furthermore, I argue, since Weberian legitimacy is empirically measurable in terms that avoid controversial value judgments, its adoption would bridge a longstanding divide between philosophers and social scientists. (shrink)

PurposeAdvance directives have been criticized for failing to help physicians make decisions consistent with patients’ wishes. This pilot study sought to determine if an interactive, computer-based decision aid that generates an advance directive can help physicians accurately translate patients’ wishes into treatment decisions.MethodsWe recruited 19 patient-participants who had each previously created an advance directive using a computer-based decision aid, and 14 physicians who had no prior knowledge of the patient-participants. For each advance directive, three physicians were randomly assigned to review (...) the advance directive and make five to six treatment decisions for each of six (potentially) end-of-life clinical scenarios.From the three individual physicians’ responses, a “consensus physician response” was generated for each treatment decision (total decisions = 32). This consensus response was shared with the patient whose advance directive had been reviewed, and she/he was then asked to indicate how well the physician translated his/her wishes into clinical decisions.ResultsPatient-participants agreed with the consensus physician responses 84 percent (508/608) of the time, including 82 percent agreement on whether to provide mechanical ventilation, and 75 percent on decisions about cardiopulmonary resuscitation (CPR).Across the six vignettes, patient-participants’ rating of how well physicians translated their advance directive into medical decisions was 8.4 (range = 6.5-10, where 1 = extremely poorly, and 10 = extremely well). Physicians’ overall rating of their confidence at accurately translating patients’ wishes into clinical decisions was 7.8 (range = 6.1-9.3, 1 = not at all confident, 10 = extremely confident).ConclusionFor simulated cases, a computer-based decision aid for advance care planning can help physicians more confidently make end-of-life decisions that patients will endorse. (shrink)

The law requires that plaintiffs in fraud cases be 'justified' in relying on a misrepresentation. I deploy the accumulated intuitions of the law to defend externalist accounts of epistemic justification and knowledge against Laurence BonJour's counterexamples involving clairvoyance. I suggest that the law can offer a well-developed model for adding a no-defeater condition to either justification or knowledge but without requiring that subjects possess positive reasons to believe in the reliability of an epistemic source.

Abstract In the contemporary literature on self-knowledge discussion is framed by and large by two competing models of self-knowledge: the observational (or perceptual) model and the constitutive model. On the observational model self-knowledge is the result of ?cognitively viewing? one's mental states. Constitutive theories of self-knowledge, on the other hand, hold that self-knowledge is constitutive of intentional states. That is, self-ascription is a necessary condition for being in a particular mental state. Akeel Bilgrami is a defender of the constitutive model. (...) I argue that the constitutive model gives rise to a regress problem. This paper will focus on that problem as well as its application to Bilgrami's version of the constitutive model. (shrink)

This collection of original essays, by some of the best known contemporary criminal law theorists, tackles a range of issues about the criminal law's 'special part' - the part of the criminal law that defines specific offences. One of its aims is to show the importance, for theory as well as for practice, of focusing on the special part as well as on the general part which usually receives much more theoretical attention. Some of the issues covered concern the proper (...) scope of the criminal law, for example how far should it include offences of possession, or endangerment? If it should punish only wrongful conduct, how can it justly include so-called 'mala prohibita', which are often said to involve conduct that is not wrongful prior to its legal prohibition? Other issues concern the ways in which crimes should be classified. Can we make plausible sense, for instance, of the orthodox distinction between crimes of basic and general intent? Should domestic violence be defined as a distinct offence, distinguished from other kinds of personal violence? Also examined are the ways in which specific offences should be defined, to what extent those definitions should identify distinctive types of wrongs, and the light that such definitional questions throw on the grounds and structures of criminal liability. Such issues are discussed in relation not only to such crimes as murder, rape, theft and other property offences, but also in relation to offences such as bribery, endangerment and possession that have not traditionally been subjects for in depth theoretical analysis. (shrink)

25 leading contemporary theorists of criminal law tackle a range of foundational issues about the proper aims and structure of the criminal law in a liberal democracy. The challenges facing criminal law are many. There are crises of over-criminalization and over-imprisonment; penal policy has become so politicized that it is difficult to find any clear consensus on what aims the criminal law can properly serve; governments seeking to protect their citizens in the face of a range of perceived threats have (...) pushed the outer limits of criminal law and blurred its boundaries. To think clearly about the future of criminal law, and its role in a liberal society, foundational questions about its proper scope, structure, and operations must be re-examined. What kinds of conduct should be criminalized? What are the principles of criminal responsibility? How should offences and defences be defined? The criminal process and the criminal trial need to be studied closely, and the purposes and modes of punishment should be scrutinized. Such a re-examination must draw on the resources of various disciplines-notably law, political and moral philosophy, criminology and history; it must examine both the inner logic of criminal law and its place in a larger legal and political structure; it must attend to the growing field of international criminal law, it must consider how the criminal law can respond to the challenges of a changing world.Topics covered in this volume include the question of criminalization and the proper scope of the criminal law; the grounds of criminal responsibility; the ways in which offences and defences should be defined; the criminal process and its values; criminal punishment; the relationship between international criminal law and domestic criminal law. Together, the essays provide a picture of the exciting state of criminal law theory today, and the basis for further research and debate in the coming years. (shrink)

The focus of this study was to analyze the content, distribution, and comparative genome relationships of 996 chromosome bin-mapped expressed sequence tags accounting for 2266 restriction fragments on the homoeologous group 3 chromosomes of hexaploid wheat. Of these loci, 634, 884, and 748 were mapped on chromosomes 3A, 3B, and 3D, respectively. The individual chromosome bin maps revealed bins with a high density of mapped ESTs in the distal region and bins of low density in the proximal region of the (...) chromosome arms, with the exception of 3DS and 3DL. These distributions were more localized on the higher-resolution group 3 consensus map with intermediate regions of high-mapped-EST density on both chromosome arms. Gene ontology classification of mapped ESTs was not significantly different for homoeologous group 3 chromosomes compared to the other groups. A combined analysis of the individual bin maps using 537 of the mapped ESTs revealed rearrangements between the group 3 chromosomes. Approximately 232 of the consensus mapped ESTs matched sequences on rice chromosome 1 and revealed large- and small-scale differences in gene order. Of the group 3 mapped EST unigenes ∼21 and 32% matched the Arabidopsis coding regions and proteins, respectively, but no chromosome-level gene order conservation was detected. (shrink)

European Journal of Philosophy, EarlyView.

Many biologists appeal to the so-called Krogh principle when justifying their choice of experimental organisms. The principle states that “for a large number of problems there will be some animal of choice, or a few such animals, on which it can be most conveniently studied”. Despite its popularity, the principle is often critiqued for implying unwarranted generalizations from optimal models. We argue that the Krogh principle should be interpreted in relation to the historical and scientific contexts in which it has (...) been developed and used. We interpret the Krogh Principle as a heuristic, i.e., as a recommendation to approach biological problems through organisms where a specific trait or physiological mechanism is expected to be most distinctively displayed or most experimentally accessible. We designate these organisms “Krogh organisms.” We clarify the differences between uses of model organisms and non-standard Krogh organisms. Among these is the use of Krogh organisms as “negative models” in biomedical research, where organisms are chosen for their dissimilarity to human physiology. Importantly, the representational scope of Krogh organisms and the generalizability of their characteristics are not fixed or assumed but explored through experimental studies. Research on Krogh organisms is steeped in the comparative method characteristic of zoology and comparative physiology, in which studies of biological variation produce insights into general physiological constraints. Accordingly, we conclude that the Krogh principle exemplifies the advantages of studying biological variation as a strategy to produce generalizable insights. (shrink)

If stem cell-based therapies are developed, we will likely confront a difficult problem of justice: for biological reasons alone, the new therapies might benefit only a limited range of patients. In fact, they might benefit primarily white Americans, thereby exacerbating long-standing differences in health and health care.

Two years ago in two articles in a thematic issue of this journal the three of us engaged in a critique of principlism. In a subsequent issue, B. Andrew Lustig defended aspects of principlism we had criticized and argued against our own account of morality. Our reply to Lustig's critique is also in two parts, corresponding with his own. Our first part shows how Lustig's criticisms are seriously misdirected. Our second and philosophically more important part picks up on Lustig's challenge (...) to us to show that our account of morality is more adequate than principlism. In particular we show that recognition of morality as public and systematic enables us to provide a far better description of morality than does principlism. This explains why we adopt the label “Dartmouth Descriptivism.”. (shrink)

In Belief and the Will, van Fraassen employed a diachronic Dutch Book argument to support a counterintuitive principle called Reflection. There and subsequently van Fraassen has put forth Reflection as a linchpin for his views in epistemology and the philosophy of science, and for the voluntarism (first-person reports of subjective probability are undertakings of commitments) that he espouses as an alternative to descriptivism (first-person reports of subjective probability are merely self-descriptions). Christensen and others have attacked Reflection, taking it to have (...) unpalatable consequences. We prescind from the question of the cogency of diachronic Dutch Book arguments, and focus on Reflection's proper interpretation. We argue that Reflection is not as counterintuitive as it appears — that once interpreted properly the status of the counterexamples given by Christensen and others is left open. We show also that descriptivism can make sense of Reflection, while voluntarism is not especially well suited to do so. (shrink)

:In this essay I defend an alternative account of why markets are legitimate. I argue that markets have a raison d’être—a potential to be valuable that, if fulfilled, would justify their existence. I characterize this potential in terms of the goods that are promoted by the legal protection of economic agency: resource discretion, contribution esteem, wealth, diffusion of power, and freedom of association. I argue that market institutions deliver these goods without requiring the participants to have shared ends, or shared (...) deliberation about joint ends—indeed, this feature is the source of the market’s distinctive contribution to well-being. I suggest that when markets lack legitimacy, this is because they fail to fulfill their raison d’être, or fail to be recognized as doing so. Thus, the contours of legal protection must be drawn so that these goods are realized together in a recognizable way, without sacrificing one good for the sake of others. Finally, I argue that this account is appealing because it allows regulators to consider a plurality of goods, and because it makes room for the essential role of rhetoric in securing market legitimacy. (shrink)

Although ethics is an essential component of undergraduate medical education, research suggests current medical ethics curricula face considerable challenges in improving students’ ethical reasoning. This paper discusses these challenges and introduces a promising new mode of graduate and professional ethics instruction for overcoming them. We begin by describing common ethics curricula, focusing in particular on established problems with current approaches. Next, we describe a novel method of ethics education and assessment for medical students that we have devised, the Medical Ethics (...) Bowl. Finally, we suggest pedagogical advantages to MEBs when compared to other ethics curricula. (shrink)

Extensive literatures exist on the epistemology of testimony, memory, and perception, but for the most part these literatures do not systematically consider the extent of the analogies between the three epistemic sources. A number of the same problems reappear in all three literatures, however. Dealing simultaneously with all three sources and making a careful accounting of the analogies and disanalogies between them should therefore avoid unnecessary duplication of effort. Other than limits on the scope of which memorially- and testimonially-based beliefs (...) should be included in the Parity Thesis, I argue that most of the disanalogies that different philosophers have proffered between the sources do not mark distinctions among the universes of possible testimonially-, memorially-, and perceptually-based beliefs regarding the explanation of those beliefs' epistemic status. I first criticize the suggestion that perception is a generative epistemic source, while testimony and memory are not; I propose and defend counterexamples in which testimony and memory produce new beliefs. Next, I criticize a variety of distinctions that have been drawn between testimony and perception, taken chiefly from the reductionist-antireductionist literature on testimony. I criticize the suggestion that the conceptualization of content and the transparency of experience affect the epistemologies of testimony and perception in different ways. Regarding memory and testimony, I advocate modeling testimony on the legal relationship of a principal and an agent, arguing that law's apparatus used to analyze such situations suggests that using others' epistemic services in testimony will supply the same epistemic benefits and burdens as if we had performed those epistemic tasks personally and then relied only on memory. I apply this analysis to the transmission of defeaters in testimony. I argue that memory does feature the epistemic equivalent of a perceptual image and that both perceptually- and memorially-based beliefs can concern either the past or the present. Finally, I construct a set of six transformations that turn individual possible instances of perceptually-, memorially-, or testimonially-based beliefs into individual possible instances of the other two types of beliefs without changing the structure of those beliefs' epistemologies. (shrink)

Advanced Cell Technology's Ethics Advisory Board has been called window dressing for a corporate marketing plan. But the scientists and managers have paid attention, and the lawyers have gone along.

This paper focuses on historic anthropological photographs, meant to depict Indigenous individuals as generic models of colonial stereotypes, and examines their later reclamation as portraits. Applying an intention-based account of portraiture, we discuss the historical context and contemporary examples of the utilisation of these images in order to address several questions. What happens when the depicted persons in colonial imagery are treated and presented as sitters, rather than model specimens? Does this change the nature of the image? If a photograph (...) was not originally intended as a portrait, can it come to function as such at a later stage? Regardless of whether they fulfill all the requirements necessary for portraiture, these colonial photographs represent a vital resource for the reclamation of Indigenous cultural heritage. As such, this paper serves as an introductory discussion into the complex issues surrounding the recategorisation, repatriation, and restitution of colonial photographic archives. (shrink)

The objectives of this study were to develop a high-density chromosome bin map of homoeologous group 7 in hexaploid wheat, to identify gene distribution in these chromosomes, and to perform comparative studies of wheat with rice and barley. We mapped 2148 loci from 919 EST clones onto group 7 chromosomes of wheat. In the majority of cases the numbers of loci were significantly lower in the centromeric regions and tended to increase in the distal regions. The level of duplicated loci (...) in this group was 24% with most of these loci being localized toward the distal regions. One hundred nineteen EST probes that hybridized to three fragments and mapped to the three group 7 chromosomes were designated landmark probes and were used to construct a consensus homoeologous group 7 map. An additional 49 probes that mapped to 7AS, 7DS, and the ancestral translocated segment involving 7BS also were designated landmarks. Landmark probe orders and comparative maps of wheat, rice, and barley were produced on the basis of corresponding rice BAC/PAC and genetic markers that mapped on chromosomes 6 and 8 of rice. Identification of landmark ESTs and development of consensus maps may provide a framework of conserved coding regions predating the evolution of wheat genomes. (shrink)

Recent writers in the libertarian tradition have suggested a natural affinity between hermeneutics and libertarian politics. This case is not persuasive. We look at two different ways the link has been attempted. In one, markets themselves are seen as constituting a hermeneutic conversation of sorts. A second approach uses hermeneutics to underpin the traditional liberal confinement of the state to setting the rules of the game—to matters of the right as opposed to the good. But the conception of the self (...) that emerges from hermeneutic thought leads to a communitarian rather than a liberal politics. (shrink)