Cells are cognitive entities possessing great computational power. DNA serves as a multivalent information storage medium for these computations at various time scales. Information is stored in sequences, epigenetic modifications, and rapidly changing nucleoprotein complexes. Because DNA must operate through complexes formed with other molecules in the cell, genome functions are inherently interactive and involve two-way communication with various cellular compartments. Both coding sequences and repetitive sequences contribute to the hierarchical systemic organization of the genome. By virtue of nucleoprotein complexes, (...) epigenetic modifications, and natural genetic engineering activities, the genome can serve as a read-write storage system. An interactive informatic conceptualization of the genome allows us to understand the functional importance of DNA that does not code for protein or RNA structure, clarifies the essential multidirectional and systemic nature of genomic information transfer, and emphasizes the need to investigate how cellular computation operates in reproduction and evolution. (shrink)

Bacteria do many things as organized populations. We have recently learned much about the molecular basis of intercellular communication among prokaryotes. Colonies display bacterial capacities for multicellular coordination which can be useful in nature where bacteria predominantly grow as films, chains, mats and colonies. E. coli colonies are organized into differentiated non-clonal populations and undergo complex morphogenesis. Multicellularity regulates many aspects of bacterial physiology, including DNA rearrangement systems. In some bacterial species, colony development involves swarming (active migration of cell groups). (...) Swarm colony development displays precise geometrical controls and periodic phenomena. Motile E. coli cells in semi-solid media form organized patterns due to chemotactic autoaggregation. On poor media, B. subtilis forms branched colonies using group motility and long-range chemical signalling. The significances of bacterial colony patterns thus reside in a deeper understanding of prokaryotic biology and evolution and in experimental systems for studying self-organization and morphogenesis. (shrink)

An appreciation of the life and word of Barbara McClintock, with special emphasis on what made her a unique and visionary scientist. The obituary indicates unappreciated aspects of her work on biological sensing and how organisms restructure their genomes in response to challenges.

The Modern Synthesis was based on Darwin’s gradualist view of evolution and early twentieth Century Mendelian and population genetics. Although early results in microbial and molecular genetics seemed to solidify MS views through the Central Dogma of Molecular Biology, accepting their basic concepts as permanent truths blinded MS proponents to the importance of incompatible discoveries in the second half of the 20th and early 21st Centuries. Discoveries based largely on the DNA record have provided a radically different view of genome (...) complexity and biologically-mediated evolutionary change. (shrink)

Cellular differentiation and multicellular development require the programmed expression of coregulated suites of genetic loci dispersed throughout the genome. How do functionally diverse loci come to share common regulatory motifs? A new paper finds that retrotransposons (RTEs) may play a role in providing common regulation to a group of functions expressed during the development of oocytes and preimplantation embryos. Examining cDNA libraries, Peaston et al.1 find that 13% of all processed transcripts in full-grown mouse oocytes contain RTE sequences, mostly from (...) the MT family of retroviral-like elements. Smaller but still significant percentages of RTE sequences are found in cDNA libraries from 2-cell embryos and blastocysts. A quarter of these RTE sequences are at the 5′ ends of chimeric transcripts that also contain exons from endogenous mouse loci. These chimeric transcripts display restricted expression in oocytes and preimplantation embryos and presumably originate from developmentally regulated LTR promoters. Some, but not all, chimeric transcripts encode novel protein products. BioEssays 27:122–125, 2005. © 2005 Wiley Periodicals, Inc. (shrink)

Fundamental problems in developmental biology, such as the generation of asymmetry, differential transcription, and the execution of positional information, are all exhibited by a prokaryotic system, the Caulobacter cell cycle. Progeny cells resulting from each cell division have different developmental programs with respect to patterns of transcription and the initiation of DNA replication. The binary fission that yields dissimilar progeny results from asymmetry generated in the parent cell. An aspect of this fundamental developmental event is the temporally‐controlled biogenesis of a (...) polar flagellum. Several flagellar promoters require the histone‐like protein, integration host factor (IHF) for transcription activation. IHF introduces bends in DNA resulting in the reorganization of the higher‐order structure of the promoter region. These promoters appear to be transcribed from the chromosome in the swarmer pole of the predivisional cell. The newly replicated chromosomes in the predivisional cell differ in sedimentation coefficient and in the ability to initiate replication in the progeny cell. We hypothesize that the differential higher order structure of the two chromosomes contributes to both replication potential and transcription specificity. (shrink)

These are the abstracts of papers for the conference, History Unveiled Science Unfettered: A Conference in Celebration of James E. McGuire University of Pittsburgh, January 19, 2002.

I respond to Fishkin?s critique of my book The State of Democratic Theory. I reiterate my defense of a competitive model of democracy geared to reducing domination, rather than Fishkin?s deliberative model that deploys structured discussion to enlighten mass preferences. In light of the literatures on framing effects and the value of mutually independent judgments, I question whether the procedures Fishkin recommends would produce outcomes that are better informed rather than differently informed. Recognizing that deliberation might sometimes be helpful in (...) reducing domination, I note that sometimes it will not, and I fault Fishkin for his indiscriminate embrace of exceedingly costly deliberative mechanisms that promise dubious benefits? notably his and Bruce Ackerman?s?Deliberation Day? (shrink)

OBJECTIVE: Pilot study to characterize treatment differences between patients treated in clinical trials and those treated in a clinical setting. Previous studies have shown higher survival rates for participants in trials of cancer therapy. This difference is observed even after rates are adjusted for important covariates such as age and stage of disease. DESIGN: Retrospective chart review. SETTING: Oncology outpatient department in a tertiary care hospital. PATIENTS: Ninety women 18 to 70 years of age with early-stage breast cancer who were (...) diagnosed in 1990. Fifty-one of the women were treated through clinical trials and 39 were treated outside of clinical trials. OUTCOME MEASURES: Number of blood tests, telephone calls, clinic visits and imaging procedures as well as intensity of chemotherapy and use of radiation therapy. The age of the patient and the stage of disease were important covariates. RESULTS: After the analysis was controlled for patient age and stage of disease, patients treated through a clinical trial were more likely to receive standard-dose chemotherapy (p = 0.020, 95% confidence interval 1.20 to 200.73) and more frequent blood tests (p < 0.001, 95% confidence interval 1.02 to 1.13) than other patients treated in the clinic. CONCLUSIONS: Our results provide a plausible mechanism for the observed survival advantage for participants in clinical trials in oncology. Further study is called for. If these results are confirmed, they have important implications for informed consent to participate in clinical trials and for clinical practice. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Kennedy Institute of Ethics Journal 12.1 (2002) 95-102 [Access article in PDF] Bioethics Inside the Beltway Some Initial Reflections on NBAC Eric M. Meslin and Harold T. Shapiro On 3 October 2001, Executive Order 12975 expired, and with it so too did the National Bioethics Advisory Commission (NBAC). Established by President Bill Clinton in 1995, NBAC was the fifth national committee since 1974 created to advise the U.S. (...) government on bioethics policy. In the long political tradition in this country that national bioethics policy advice should use temporary rather than permanent bodies, NBAC followed in the footsteps of the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research (1974-78); the President's Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research (1980-83); the Ethics Advisory Board (1978-80); and the Biomedical Ethics Advisory Committee (1988-89). Arguably, other distinguished panels could lay claim to recognition as a "national bioethics committee" including the Advisory Committee on Human Radiation Experiments (ACHRE) (1994-95); the Fetal Tissue Transplantation Research Panel (1988); the Human Embryo Research Panel (1994); and the National Institutes of Health (NIH) Recombinant DNA Advisory Committee (RAC), which continues to function.These committees and commissions form a kind of a continuum, albeit occasionally interrupted by periods during which no such bodies existed. Each arose from a particular confluence of events and circumstances. NBAC was no different; its history can be traced both to a series of discussions within the White House Office of Science and Technology Policy beginning in 1993 (NBAC 1998a, p. 3), and to a specific recommendation from ACHRE that called for a national committee to address ethical issues in human subjects research (ACHRE 1995, p. 817). Nbac's Impact In his useful comparison of the accomplishments of the National Commission and the President's Commission, Brad Gray concluded that seven lessons were learned, the sixth of which was that "nothing substitutes for having a perceptible impact on either policy or practice" (Gray 1995, p. 304). Assessing NBAC's [End Page 95] impact on "policy or practice" is difficult, particularly given the fact that it so recently completed its work. More time may be needed before a full assessment can be undertaken of the impact of its six reports (and their total of 120 recommendations). Instead, in this essay we offer some reflections on NBAC's initial impact, using some specific examples of how bioethics gets done Inside the Beltway. Eliciting Reaction If immediate reaction by the White House is any measure of impact, then Cloning Human Beings (NBAC 1997) had a significant one. The day after he received this report in a Rose Garden ceremony, President Clinton submitted a bill to Congress that would have extended the moratorium on federal funding to create a child using somatic cell nuclear transfer. This bill never passed, nor has any other bill emerged that has enjoyed the support of the House and the Senate. Five states have enacted legislation to date, but these vary in their permissibility from bans on all forms of cloning to bans similar to the one proposed by NBAC, which recommended a time-limited prohibition only on somatic cell transfer to create a child (reproductive cloning).If the Cloning report elicited speedy action from the White House, this paled in comparison to the reaction that led to and, in turn, was created by Ethical Issues in Human Stem Cell Research (NBAC 1999a). Those who believe that government moves slowly need only be reminded of the events of 8-14 November 1998 (and, as we shall mention below, the further events of 14 July 1999). Some will recall that early in the second week of November 1998, James Thomson and his colleagues published in Nature and John Gearhart and his colleagues published in the Proceedings of the National Academy of Sciences that they had isolated and cultured human primordial stem cells and germ cells respectively. Within days of these remarkable reports, Advanced Cell Technology (ACT) announced via an article written by Nicholas Wade in the... (shrink)

Prominent defenders of the extended cognition thesis have looked to evolutionary theory for support. Roughly, the idea is that natural selection leads one to expect that cognitive strategies should exploit the environment, and exploitation of the right sort results in a cognitive system that extends beyond the head of the organism. I argue that proper appreciation of evolutionary theory should create no such expectation. This leaves open whether cognitive systems might in fact bear a relationship to the environment that leads (...) to their extension. *Received July 2009; revised January 2010. †To contact the author, please write to: Department of Philosophy, 5185 Helen C. White Hall, 600 North Park Street, University of Wisconsin, Madison, WI 53706; e‐mail: [email protected]. (shrink)

Some authors have claimed that ante rem structuralism has problems with structures that have indiscernible places. In response, I argue that there is no requirement that mathematical objects be individuated in a non-trivial way. Metaphysical principles and intuitions to the contrary do not stand up to ordinary mathematical practice, which presupposes an identity relation that, in a sense, cannot be defined. In complex analysis, the two square roots of –1 are indiscernible: anything true of one of them is true of (...) the other. I suggest that ‘i’ functions like a parameter in natural deduction systems. I gave an early version of this paper at a workshop on structuralism in mathematics and science, held in the Autumn of 2006, at Bristol University. Thanks to the organizers, particularly Hannes Leitgeb, James Ladyman, and Øystein Linnebo, to my commentator Richard Pettigrew, and to the audience there. The paper also benefited considerably from a preliminary session at the Arché Research Centre at the University of St Andrews. I am indebted to my colleagues Craige Roberts, for help with the linguistics literature, and Ben Caplan and Gabriel Uzquiano, for help with the metaphysics. Thanks also to Hannes Leitgeb and Jeffrey Ketland for reading an earlier version of the manuscript and making helpful suggestions. I also benefited from conversations with Richard Heck, John Mayberry, Kevin Scharp, and Jason Stanley. CiteULike Connotea Del.icio.us What's this? (shrink)

This comment responds to Shapiro?s State of Democratic Theory. First, it argues that the map of democratic possibilities in the book, dividing forms of democracy into aggregative and deliberative, conflates and obscures important democratic alternatives. Second, I argue that one of the possibilities this map obscures, deliberation with aggregation, avoids the critique Shapiro directs at deliberative democracy. While some of his criticisms are appropriate to other categories, they do not apply to this one. Third, I argue that the (...) empirical work conducted under this category undermines Shapiro?s claims about how democracy can be expected to lead to violations of transitivity in actual practice. Fourth, I argue that there are other lines of defense for deliberative democracy in response to the combination of arguments that Shapiro offers in critique of deliberative democracy. (shrink)

[…] Open the pages of almost any national journal or magazine, and where ten years ago one found only one or another kind of free verse lyric, one now finds well rhymed quatrains, sestinas, villanelles, sonnets, and blank verse dramatic monologues or meditations.1 In a recent issue of the New Criterion, Robert Richman describes this rekindled interest in formal verse among younger poets as a return to the high seriousness, eloquence, and technical fluency that characterized the best achievements of American (...) poetry forty years ago.2 As Mr. Richman numbers me among the younger poets working in form, I ought to be as cheered by these developments as he is. Yet I am anything but cheered. And not because I don’t want to belong to club that would have me as a member, though this may be a part of it; but because I suspect that what Mr. Richman hails as a development may in fact be nothing but a mechanical reaction, and that the new formalists, in rejecting the sins of their experimental fathers may end up merely repeating the sings of their New Critical grandfathers, resuscitating the stodgy, overrefined conventions of the “fifties poem,” conventions which were of course sufficiently narrow and restrictive to provoke rebellion in the first place. Any reform, carried to uncritical extremes by lesser talents who ignore rather than try to assimilate the achievements of their predecessors, will itself require reformation. If James Wright, say, or Robert Bly, produced more than their fair share of imitators, if they even imitate themselves much of the time, they nonetheless have written poems all of us can and ought to learn from. Maybe we have had too much of the “raw” in recent years. But the answer to the raw is not the overcooked. Besides, it’s dangerous to think we have to choose exclusively between free verse and form. The wider the range of styles and forms that we avail ourselves of, the more enriched, more flexible and inclusive our expressive resources will be. It’s as important for those who work in form to be familiar with the experiments and innovatins of the last hundred years as it is for those who work in looser measures to be familiar with traditional verse forms that go back beyond the twentieth century. Alan Shapiro’s most recent book of poems, Happy Hour, was published this year. (shrink)

The majority of psychologists studying memory think that one or another information processing model of memory should explain how human memory works and take computer memory to be its model. They say that: we remember because we store, in our brains, all that we know and know how to do; our minds are the Mind juggling "mental representations" stored in the Memory; recognition is matching an object of perception and its stored "representation", it is knowledge. The purpose of this dissertation (...) is twofold: to demolish IPMM as misleading and useless and to introduce a competing theory of human memory. Some of my theses are: Historically, there have been two theories of memory as related to the brain, these of Aristotle and of William James. In the nineteenth century, the psychology of memory chose 'the wrong theory of evolution' with which it has since stayed. It was Spencer's epistemology that the psychology of memory mistook for a theory of evolution; it was the Darwinian one that the mainstream psychology totally disregarded. IPMM, whose formula is 'memory: computer + the mammalian brain', are only Spencerian, anti-Darwinian versions of Aristotle's theory of memory storage. The most enduring postulate of psychology-memory is storage in the brain, an empirical proposition, has to be given up because it does not have evidence for its support and because there is empirical evidence that the brain which IPMM demand does not exist. Recognition is the only demonstration of cognitive memory common to all mammalian brains, only this demonstration of human memory does not require language. Recognition demonstrates mere familiarity with, not knowledge of, objects, events, sciences, etc; multiple choice tests test mere recognition, not knowledge. The theses pertaining to the theory of memory storage are developed in the first four chapters and are followed by the chapter devoted to William James's Darwinian psychological scheme and my reconstruction of his theory of memory. In the last chapter modifications to James's theory of memory are considered. (shrink)

Donald Green and Ian Shapiro discover a curious gulf between the prestige of rational choice approaches and the dearth of solid empirical findings. But we can understand neither the prestige of rational choice theory nor its pathologies unless we see it as a variant of the equilibrium analysis found in physics, economics, and biology. Only such a global perspective on rational choice theory will reveal its core assumptions and the likely shape of its future in political science. In this (...) light, the growing dominance of rational choice theory in political science is all but inevitable and its pathologies are all but inescapable. (shrink)

First published over thirty years ago, "Classic Philosophical Questions" has presented decades of students with the most compelling classic and contemporary readings on the most enduring and abiding questions in philosophy. The anthology, topically arranged, uses debate and argument as vehicles to teach students the fundamentals of philosophy while also demonstrating that philosophy is a discourse spanning centuries. "James A. Gould" and "Robert J. Mulvaney" continue to provide students with interesting, intriguing essays from major philosophers in a distinctive presentation, (...) often involving a pro/con format, to ensure that both the apparent and subtle points of argument are both meaningful and clear. Features of this new edition: Sections on epistemology and metaphysics introduced earlier in this edition New readings from Martha Nussbaum and Martin Luther King, Jr. Concise, student-friendly introductions to each philosopher and reading Helpful study and reflection questions focus students' reading and improve comprehension. (shrink)

The practice of paying research subjects for participating inclinical trials has yet to receive an adequate moral analysis.Dickert and Grady argue for a wage payment model in whichresearch subjects are paid an hourly wage based on that ofunskilled laborers. If we accept this approach, what follows?Norms for just working conditions emerge from workplacelegislation and political theory. All workers, includingpaid research subjects under Dickert and Grady''s analysis,have a right to at least minimum wage, a standard work week,extra pay for overtime hours, (...) a safe workplace, no faultcompensation for work-related injury, and union organization.If we accept that paid research subjects are wage earners likeany other, then the implications for changes to current practiceare substantial. (shrink)

For years, _Multicultural Education_ has served as an essential resource for education professionals, featuring scholarly articles written by industry leaders and topics, following current trends in education instruction today. The text helps educators understand the concepts, paradigms, and explanations necessary for becoming effective practitioners in the ever-evolving classroom environment, highlighting cultural, raocial and language-focused topics. Each chapter now incorporates new theoretical, conceptual, and research developments within the field, providing an adaptable approach to classroom techniques. With growing classroom diversity, the text (...) also features a chapter that focuses on lesbian, gay, bisexual and transgender issues. Statistical tables, figures and charts have been updated to present the most current information. (shrink)

What is the cognitive significance of talking to ourselves? I criticize two interpretations of this function , and offer a third: I argue that inner speech is a genuine dialogue, not a monologue; that the partners in this dialogue represent the independent interests of experienced meaning and logical articulation; that the former is either silent or capable only of abbreviated speech; that articulation is a logical, not a social demand; and that neither partner is a full-time subordinate of the other. (...) I examine the views of Plato, Arendt, Gadamer, Ryle, Piaget and Vygotsky on the nature of inner speech, and the views of Gazzaniga and Dennett on the role of inner speech in the constitution of human consciousness. (shrink)

A detailed account of certain traits of intellectual character—the epistemic virtues—and of their relation to the responsibility for one's beliefs.

Abstract:This paper is an analysis of Plato's use of the embassy to Achilles in Homer's Iliad book 9 as a literary template for Crito's mission to persuade Socrates to escape from prison in Athens. Plato's purpose is to elevate the nature of a hero by contrasting the impulsive, impetuous, mercurial temper of Achilles with the steady, thoughtful, deliberative, calmly rational argument of Socrates. Plato shows, in a volley fired at the poet, how the philosopher is more meaningfully heroic than the (...) warrior, for where the warrior aims selfishly at securing his own honor, the philosopher aims at political virtue. (shrink)

What is the cognitive significance of talking to ourselves? I criticize two interpretations of this function , and offer a third: I argue that inner speech is a genuine dialogue, not a monologue; that the partners in this dialogue represent the independent interests of experienced meaning and logical articulation; that the former is either silent or capable only of abbreviated speech; that articulation is a logical, not a social demand; and that neither partner is a full-time subordinate of the other. (...) I examine the views of Plato, Arendt, Gadamer, Ryle, Piaget and Vygotsky on the nature of inner speech, and the views of Gazzaniga and Dennett on the role of inner speech in the constitution of human consciousness. (shrink)

Despite Plato's various warnings not to do so, his dialogues have been studied as systematic philosophy since antiquity. In this innovative and controversial reassessment, James Arieti argues that they should be read primarily as works of drama rather than philosophical discourse. Analyses of 18 of the 28 dialogues allow the reader to see them as integrated dramas, with all the ambiguities and uncertainties that literary works contain. As in plays generally, the arguments of particular characters cannot be seen as (...) the opinions of the author, whose views emerge only from examining each work as a whole. This literary reading shows how much of the debate about Plato's meaning has been misplaced. Instead of demonstrating that an argument is fallacious or valid, we need to ask why Plato has the particular character make the argument. Interpreting Plato achieves what no other work on Plato has attempted: to see the philosophical arguments as serving a dramatic purpose. (shrink)

What big questions and large‐scale narratives give coherence to the history of science? From the late 1970s onward, the field has been transformed through a stress on practice and fresh perspectives from gender studies, the sociology of knowledge, and work on a greatly expanded range of practitioners and cultures. Yet these developments, although long overdue and clearly beneficial, have been accompanied by fragmentation and loss of direction. This essay suggests that the narrative frameworks used by historians of science need to (...) come to terms with diversity by understanding science as a form of communication. The centrality of processes of movement, translation, and transmission is already emerging in studies of topics ranging from ethnographic encounters to the history of reading. Not only does this approach offer opportunities for crossing boundaries of nation, period, and discipline that are all too easily taken for granted; it also has the potential for creating a more effective dialogue with other historians and the wider public. (shrink)

What big questions and large‐scale narratives give coherence to the history of science? From the late 1970s onward, the field has been transformed through a stress on practice and fresh perspectives from gender studies, the sociology of knowledge, and work on a greatly expanded range of practitioners and cultures. Yet these developments, although long overdue and clearly beneficial, have been accompanied by fragmentation and loss of direction. This essay suggests that the narrative frameworks used by historians of science need to (...) come to terms with diversity by understanding science as a form of communication. The centrality of processes of movement, translation, and transmission is already emerging in studies of topics ranging from ethnographic encounters to the history of reading. Not only does this approach offer opportunities for crossing boundaries of nation, period, and discipline that are all too easily taken for granted; it also has the potential for creating a more effective dialogue with other historians and the wider public. (shrink)

Since its introduction in 1987, Benjamin Freedman’s principle of clinical equipoise has enjoyed widespread uptake in bioethics discourse. Recent years, however, have witnessed a growing consensus that the principle is fundamentally flawed. One of the most vocal critics has undoubtedly been Franklin Miller. In a 2008 paper, Steven Joffe and Miller build on this critical work, offering a new conception of clinical research ethics based on science, taking what they call a “scientific orientation” toward the ethics of clinical research. Though (...) there is much to recommend Joffe and Miller’s scientifically oriented conception of clinical research ethics, I believe that both the critical and constructive projects suffer from the same basic mistake: inattention to context. The internal norms of science cannot be fully specified, let alone satisfied, independently of contextual (external) factors that only come into view when we are attentive to the particular context of that form of inquiry. (shrink)

(1) Substituting (as Solms does) forebrain for brainstem in the search for a dream “controller” is counterproductive, since a distributed system need have no single controller. (2) Evidence against episodic memory consolidation does not show that REM sleep has no role in other types of memory, contra Vertes & Eastman. (3) A generalization of Revonsuo's “threat simulation” model in reverse is more plausible and is empirically testable. [Hobson et al.; Solms; Revonsuo; Vertes & Eastman].

Competing perspectives on the nature of emotion are illustrated with latent and emergent variable models. Latent variable models draw from classical test theory, assuming that the measured indicators of emotion covary by virtue of some common executive, organizing neural circuit or network in the brain. By contrast, emergent variable models draw from a theory-driven, operational definition tradition, positing that emotions do not cause, but rather are caused by, the measured indicators of emotion, assuming no executive neural circuit or network, and (...) requiring no covariation among indicators. I suggest that the emergent variable model may be more compatible with the extant literature on the nature of emotion, especially in the age of affective neuroscience. (shrink)

As an essential companion to Plato's Apology and Crito, Socrates Against Athens provides valuable historical and cultural context to our understanding of the trial.

This book explores how the Hebraic and classical traditions forming our Western heritage combined from about 300 BCE to 300 CE. James Arieti investigates the principal causes of the merger in the common model of God that developed in the Greek philosophical schools, along with its ethical implications, and the shared portrayal in biblical, rabbinic, and postclassical literature of the compassionate warm character that we recognize as a mentsh.

Thomas S. Kuhn Thomas Samuel Kuhn, although trained as a physicist at Harvard University, became an historian and philosopher of science through the support of Harvard’s president, James Conant. In 1962, Kuhn’s renowned The Structure of Scientific Revolutions helped to inaugurate a revolution—the 1960s historiographic revolution—by providing a new image of science. For … Continue reading Kuhn, Thomas S. →.

Despite their crucial role in the translation of pre-clinical research into new clinical applications, phase 1 trials involving patients continue to prompt ethical debate. At the heart of the controversy is the question of whether risks of administering experimental drugs are therapeutically justified. We suggest that prior attempts to address this question have been muddled, in part because it cannot be answered adequately without first attending to the way labor is divided in managing risk in clinical trials. In what follows, (...) we approach the question of therapeutic justification for phase 1 trials from the viewpoint of five different stakeholders: the drug regulatory authority, the IRB, the clinical investigator, the referring physician, and the patient. Our analysis shows that the question of therapeutic justification actually raises multiple questions corresponding to the roles and responsibilities of the different stakeholders involved. By attending to these contextual differences, we provide more coherent guidance for the ethical negotiation of risk in phase 1 trials involving patients. We close by discussing the implications of our argument for various perennial controversies in phase 1 trial practice. (shrink)

As scholars have observed and analyzed Herodotus's sophistication, the father of history has been recognized as a complex and profound moral historian. How would Herodotus's contemporaries have responded to his recounting of the past? And what enduring lessons does Herodotus have for us? James A. Arieti attempts to discover, as far as possible, Herodotus's purpose in writing, and reveals how in the History of the Persian Wars Herodotus shapes his narrative in order to advise the troubled Greek world of (...) his day. Arieti's reading is an interpretive study, exploring the philosophical, literary, and historical richness of the history--in short, examining why it is a classic. Discourses on the First Book of Herodotus is an important work for historians, classicists, and philosophers. (shrink)