Polyglutamine (polyQ) diseases are genetically inherited neurodegenerative disorders. They are caused by mutations that result in polyQ expansions of particular proteins. Mutant proteins form intranuclear aggregates, induce cytotoxicity and cause neuronal cell death. Protein interaction data suggest that polyQ regions modulate interactions between coiled‐coil (CC) domains. In the case of the polyQ disease spinocerebellar ataxia type‐1 (SCA1), interacting proteins with CC domains further enhance aggregation and toxicity of mutant ataxin‐1 (ATXN1). Here, we suggest that CC partners interacting with the polyQ (...) region of a mutant protein, increase its aggregation while partners that interact with a different region reduce the formation of aggregates. Computational analysis of genetic screens revealed that CC‐rich proteins are highly enriched among genes that enhance pathogenicity of polyQ proteins, supporting our hypothesis. We therefore suggest that blocking interactions between mutant polyQ proteins and their CC partners might constitute a promising preventive strategy against neurodegeneration. (shrink)

The force of [Heinrich von] Kleist's story "On the Marionette Theatre" . . . derives from roots deeply sunk into the soil of the past. It is a novel variation on a theme the first author of which may well be Plato. For according to Plato the human mind has been in the dark ever since it lost its place in the community of Truth, in the realm, that is, of the Ideas, the eternal and eternally perfect forms, those now (...) unattainable models which man in his exile is able to see and recognize only as shadows or imperfect copies. And this Platonic parable of the damage suffered by man's soul and consciousness is not unlike the Fall as it is narrated in Genesis. The Fall was the consequence and punishment of man's free will that for the first time had asserted itself against the universal God and rejoiced in a consciousness and pleasure entirely its own—tragically its own; for man had to forsake the indwelling in the supreme Intelligence and thus the harmony between himself and Being as such. The reward for this betrayal was the embarrassment and shame of self-consciousness, the hard labor of maintaining himself in his state of separation, and, soon to follow, the murderous misdeeds of the self-will named Cain. Better to have no mind than a mind thus deprived and impoverished and cruel. Erich Heller, Avalon Foundation Professor in the Humanities at Northwestern University, is the author of The Disinherited Mind: Essays in Modern German Literature and Thought; The Ironic Gentleman: Thomas Mann; The Artist's Journey into the Interior; and Franz Kafka. These books have also appeared in Germany in the author's own translations, and his Dir Wiederkehr der Unschuld [The return of innocence] was recently published there. See also: "Fiction, History, and Empirical Reality" by Murray Krieger in Vol. 1, No. 2; "Psychoanalysis and the Marionette Theater: Interpretation is Not Depreciation" by Margret Schaefer in Vol. 5, No. 1. (shrink)

At the end of his attack on my use of the psychoanalytic model for the interpretation of literature, Heller raises the question concerning what the task of the literary critic is or ought to be. His own "sketch of the Kleistean theme's historical ancestry and its later development," he says, seeks to deepen and enrich the reader's appreciation of Kleist's literary art, the artistry of his phrasing, the persuasiveness of his incidents, the conclusiveness of his examples." By implication he suggests (...) that my method does not have this end—that is, appreciation—for its goal. In this he is partially right. "Appreciation" in Heller's sense is not as directly a goal for me. But does Heller's method of intellectual history and literary relation meet his own criteria of deepening and enriching the reader's appreciation of Kleist? In his capsule treatment of Great Thinkers of the Western World from Plato to Marx, we learn that many writers besides Kleist treated Kleist's theme of man's fall from unconscious grace. What exactly does this tell us about Kleist's treatment of it? How does it deepen the reader's appreciation of Kleist's literary art, the artistry of his phrasing, the persuasiveness of his incidents? It doesn't. It isn't even about Kleist. Although Heller tells us that it is the "thought" and "imagery" which "make for the great distinction of the essay" , his evidence for this consists, in the case of the former, in his tracing the history of the essay's thought and, in the case of the latter, in his statements that Kleist's use of the puppet as the exemplar of the unselfconscious graceful being is "unusual" and "novel" and that his bear story, though it may lack "in immediate plausibility," "gains in making Kleist's point" and is "a memorable exemplar" of the "art of grotesque inventions that are capable of floating for quite a while above and between the comic and the serious before landing with scintillating effect in one domain or the other" . Margret Schaefer is a lecturer in the department of psychiatry at Northwestern University Medical School. She responds here to Erich Heller's "The Dismantling of a Marionette Theater; or, Psychology and the Misinterpretation of Literature" , in which he discussed her article, "Kleist's 'About the Puppet Theater,". (shrink)

I will return to the second point in a different context later; at this moment I will discuss only the issue raised by my pointing up the fact that the essay in question was written by someone in Professor Heller's field. What motivated me to make the statement was not my belief that the use of psychoanalysis in the interpretation of art should be restricted to certified psychoanalysts—indeed, I have always been a staunch advocate of the opposite view. My motive (...) for this, I assumed harmless, and not, of course, irrelevant, indiscretion was that I wanted to show that Professor Heller's critique of psychoanalysis was not broadly based, that his representative example was a piece that happened to have crossed his way, that he was not using the work of an established writer in the field that he was condemning. My statement that your essay is an unacceptable text in a sermon preaching against applied analysis is unrelated to the value of your article. Even if in the future it should turn out that your essay—as far as I know your first contribution to applied psychoanalysis—was the forerunner of a significant oeuvre that would put you into the class of the great contributors of psychoanalytic interpretations of literature, it is at this point not an acceptable text for a sermon against our field. Heinz Kohut, M.D., is Professorial Lecturer in Psychiatry at the University of Chicago, teacher and training analyst at the Chicago Institute for Psychoanalysis, and author of many influential works on the psychology of the self. His works include The Restoration of the Self, The Analysis of the Self: A Systematic Approach to the Psychoanalytic Treatment of Narcissistic Personality Disorders - which has appeared in German, French, and Italian translations - and a collection of his essays, Scientific Empathy and Empathic Science. His "Psychoanalysis and the Interpretation of Literature: A Correspondence with Erich Heller" was published in the Spring 1978 issue of Critical Inquiry. (shrink)

The COVID-19 pandemic revealed numerous weaknesses in pandemic preparedness and response, including underfunding, inadequate surveillance, and inequitable distribution of countermeasures. To overcome these weaknesses for future pandemics, WHO released a zero draft of a pandemic treaty in February, 2023, and subsequently a revised bureau's text in May, 2023. COVID-19 made clear that pandemic prevention, preparedness, and response reflect choices and value judgements. These decisions are therefore not a purely scientific or technical exercise, but are fundamentally grounded in ethics. The latest (...) treaty draft reflects these ethical considerations by including a section entitled Guiding Principles and Approaches. Most of these principles are ethical—they establish core values that undergird the treaty. Unfortunately, the treaty draft's set of principles are numerous, overlapping, and show inadequate coherence and consistency. We propose two improvements to this section of the draft pandemic treaty. First, key guiding ethical principles should be clearer and more precise than they currently are. Second, the link between ethical principles and policy implementation should be clearly established and define boundaries on acceptable interpretation, ensuring that signatories abide by these principles. (shrink)

In this book, one of the most distinguished scholars of German culture collects his essays on a figure who has long been one of his chief preoccupations. Erich Heller's lifelong study of modern European literature necessarily returns again and again to Friedrich Nietzsche. Nietzsche prided himself on having broken with all traditional ways of thinking and feeling, and once even claimed that he would someday be recognized for having ushered in a new millennium. While acknowledging Nietzsche's radicalism, Heller also (...) insists on the continuity of the story in which he does indeed occupy a central place. By considering Nietzsche in relation to Goethe, Rilke, Wittgenstein, Yeats, and others, Heller shows the philosopher's ambivalence toward the tradition he inherited as well as his profound effect on the thought and sensibility of those who followed him. It is hardly an exaggeration to say, as Heller does in his first essay, that Nietzsche is to many modern writers and thinkers--including Mann, Musil, Kafka, Freud, Heidegger, Jaspers, Gide, and Sartre--what St. Thomas Aquinas was to Dante: the categorical interpreter of a world, which they contemplate imaginatively and theoretically without ever much upsetting its Nietzschean structure. Thus it is Nietzsche's thought, so pervasively present in the themes of modernity, that gives coherence and unity to Heller's essays. What emerges from them is that, despite his iconoclastic declarations and unorthodox philosophical practices, Nietzsche deals with the human spirit's persistent concerns. His questions remain urgent, and even the answers, in all their contradictoriness, possess the commanding force of his inquiry. An example is the incompatibility of the famous extremes, the teaching of the U;bermensch and the Eternal Recurrence of All Things. These cancel each other out and yet grow from the same intellectual and spiritual roots, as is shown lucidly and cogently by one of Heller's most forceful essays, "Nietzsche's Terrors: Time and the Inarticulate." In fathoming the depth of this contradiction, Heller at the same time reveals the importance of Nietzsche for those who seek to understand the wellsprings of the epoch's disquiet, turmoil, and creativity. (shrink)

The prospect of consumable meat produced in a laboratory setting without the need to raise and slaughter animals is both realistic and exciting. Not only could such in vitro meat become popular due to potential cost savings, but it also avoids many of the ethical and environmental problems with traditional meat productions. However, as with any new technology, in vitro meat is likely to face some detractors. We examine in detail three potential objections: 1) in vitro meat is disrespectful, either (...) to nature or to animals; 2) it will reduce the number of happy animals in the world; and 3) it will open the door to cannibalism. While each objection has some attraction, we ultimately find that all can be overcome. The upshot is that in vitro meat production is generally permissible and, especially for ethical vegetarians, worth promoting. (shrink)

First published in 1962, this is a book about Marx and Freud - the two intellectual giants of the 20th century.

CHAPTER ONE The Human Scene: INDIVIDUAL, COMMUNITY, COLLECTIVE IN THE COURSE of this study we shall see the evidences of disintegration of the individual in ...

This translation of four of Plato's dialogues brings these classic texts alive for modern readers. Allen introduces and comments on the dialogues in an accessible way, inviting the reader to re-examine the issues Plato continually raises.

A family heirloom. An endangered species. An ancient piece of pottery. A threatened language. These things differ in myriad ways, but they are tied together by a common thread: they are all examples of things that call out to be saved. The world is brimming with things worth saving, and we have limited time and resources. How do we decide what to save? Why do we make these choices? -/- Philosopher Erich Hatala Matthes explores these questions as they surface (...) in radically diverse contexts--from museums to TikTok, and from National Parks to the corner of your attic. Matthes illustrates the deep relationship between the things we might save and our sense of self. If our cares and concerns are a fundamental part of our identity, then what we care for and preserve will play a significant role in shaping and maintaining our understanding of who we are. In a world in which everything that we care about is subject to powerful forces of change--from climate disturbance and armed conflict, to social transformation and the wear and tear of time--the terms on which we confront change will be key to whether and how we can save the things we care about in the ways that really matter to us. Will change be foisted upon us? Or is there a role for us to play in rejecting, influencing, or managing change? As he explores these questions, Matthes tackles related themes such as authenticity, agency, and appropriation: Who exactly should be responsible for saving things, and on whose behalf should such efforts be pursued? These are all essential elements to a fuller understanding of what to save and why. (shrink)

In Man for Himself , Erich Fromm examines the confusion of modern women and men who, because they lack faith in any principle by which life ought to be guided, become the helpless prey forces both within and without. From the broad, interdisciplinary perspective that marks Fromm’s distinguished oeuvre, he shows that psychology cannot divorce itself from the problems of philosophy and ethics, and that human nature cannot be understood without understanding the values and moral conflicts that confront us (...) all. He shows that an ethical system can be based on human nature rather than on revelations or traditions. As Fromm asserts, “If man is to have confidence in values, he must know himself and the capacity of his nature for goodness and productiveness.”. (shrink)

We live in the Information Age. Advances over the past 50 years in computing technology have enabled ever-expanding capacity to generate, store, transfer, process and analyse information about people, societies, products, services, the environment—nearly every aspect of the world. In parallel, concerns over how such data is being used have emerged, focusing especially on issues of privacy and confidentiality. Yet as technological capabilities continue to expand, the debate over ethical uses of data inevitably has evolved as well. Whereas we used (...) to just talk about data, now there is great concern over Big Data. This chapter explores what, exactly, Big Data is; the ethical ramifications of its emergence, particularly for consent and anonymization; and what sorts of policy solutions are being proposed to address these emerging challenges. We will not defend one particular approach, but hope this chapter can be a useful reference for those who are contemplating difficult questions surrounding responsible management of Big Data. (shrink)

This article explores Franz Brentano's opposition to papal infallibility, and sets this in the context of his development as a Catholic scholar. An active participant in the Catholic revival of the nineteenth century, Brentano contributed to the emergence of neoscholasticism through his philosophical rehabilitation of Aristotle. Brentano ultimately left the Church however as the result of intensive scrutiny of his faith occasioned by his analysis of infallibility. This article explores this crisis of faith by analyzing, for the first time, Brentano's (...) position on papal infallibility, and suggesting ways that it informed his philosophical development. (shrink)

During the last 25 years, a large number of publications on the history of analytic philosophy have appeared, significantly more than in the preceding period. As most of these works are by analytically trained authors, it is tempting to speak of a 'historical turn' in analytic philosophy. The present volume constitutes both a contribution to this body of work and a reflection on what is, or might be, achieved in it. The twelve new essays, by an international group of contributors, (...) range from case studies on individual philosophers through discussions of broader themes in the history of analytic philosophy to related methodological reflections. (shrink)

For people to contribute to discourse, they must do more than utter the right sentence at the right time. The basic requirement is that they add to their common ground in an orderly way. To do this, we argue, they try to establish for each utterance the mutual belief that the addressees have understood what the speaker meant well enough for current purposes. This is accomplished by the collective actions of the current contributor and his or her partners, and these (...) result in units of conversation called contributions. We present a model of contributions and show how it accounts for a variety of features of everyday conversations. (shrink)

The predominant view is that a study using health data is observational research and should require individual consent unless it can be shown that gaining consent is impractical. But recent arguments have been made that citizens have an ethical obligation to share their health information for research purposes. In our view, this obligation is sufficient ground to expand the circumstances where secondary use research with identifiable health information is permitted without explicit subject consent. As such, for some studies the Institutional (...) Review Board/Research Ethics Committee review process should not assess the practicality of gaining consent for data use. Instead the review process should focus on assessing the public good of the research, public engagement and transparency. (shrink)

Ethical decision-making frameworks assist in identifying the issues at stake in a particular setting and thinking through, in a methodical manner, the ethical issues that require consideration as well as the values that need to be considered and promoted. Decisions made about the use, sharing, and re-use of big data are complex and laden with values. This paper sets out an Ethics Framework for Big Data in Health and Research developed by a working group convened by the Science, Health and (...) Policy-relevant Ethics in Singapore Initiative. It presents the aim and rationale for this framework supported by the underlying ethical concerns that relate to all health and research contexts. It also describes a set of substantive and procedural values that can be weighed up in addressing these concerns, and a step-by-step process for identifying, considering, and resolving the ethical issues arising from big data uses in health and research. This Framework is subsequently applied in the papers published in this Special Issue. These papers each address one of six domains where big data is currently employed: openness in big data and data repositories, precision medicine and big data, real-world data to generate evidence about healthcare interventions, AI-assisted decision-making in healthcare, public-private partnerships in healthcare and research, and cross-sectoral big data. (shrink)

In this paper, I present an outline of the oppression account of cultural appropriation and argue that it offers the best explanation for the wrongfulness of the varied and complex cases of appropriation to which people often object. I then compare the oppression account with the intimacy account defended by C. Thi Nguyen and Matt Strohl. Though I believe that Nguyen and Strohl’s account offers important insight into an essential dimension of the cultural appropriation debate, I argue that justified objections (...) to cultural appropriation must ultimately be grounded in considerations of oppression as opposed to group intimacy. I present three primary objections to the intimacy account. First, I suggest that in its effort to explain expressive appropriation claims (those that purportedly lack an independent ground), the intimacy account doubles down on the boundary problem. Second, I question whether group intimacy possess the kind of bare normativity that Nguyen and Strohl claim for it. Finally, I argue that these objections give us reason to accept the importance of group intimacy to the cultural appropriation debate, but question the source of its significance as identified by Nguyen and Strohl. (shrink)

An account of non-existing objects called 'classical possibilism', according to which objects that don't actually exist do exist in various other ways, is implemented in a two-dimensional modal logic with non-traditional predication theory. This account is very similar to Priest's, but preserves bivalence and does not endorse dialethism. The power of classical possibilism is illustrated by giving some examples that makes use of a description theory of reference. However, the same effect could also be achieved in a more Millian fashion. (...) It is argued that classical possibilism is ontologically more neutral than is commonly thought, because it allows for the formulation of various forms of reductionism within the object language. (shrink)

Is there something morally wrong with cultural appropriation in the arts? I argue that the little philosophical work on this topic has been overly dismissive of moral objections to cultural appropriation. Nevertheless, I argue that philosophers working on epistemic injustice have developed powerful conceptual tools that can aid in our understanding of objections that have been levied by other scholars and artists. I then consider the relationship between these objections and the harms of cultural essentialism. I argue that focusing on (...) the systematic nature of appropriative harms may allow us to sidestep the problem of essentialism, but not without cost. (shrink)

The future of health research will be characterised by three continuing trends: rising demand for health data; increasing impracticability of obtaining specific consent for secondary research; and decreasing capacity to effectively anonymise data. In this context, governments, clinicians and the research community must demonstrate that they can be responsible stewards of health data. IRBs and RECs sit at heart of this process because in many jurisdictions they have the capacity to grant consent waivers when research is judged to be of (...) particular value. However, several different terms are used to refer to this value, indicating a lack of conceptual clarity regarding the appropriate test for access to health data for research without consent. In this paper we do three things. First we describe the current confusion and instability in terminology relating to public interest in the context of consent waivers. Second we argue for harmonisation of terminology on the grounds of clarity, transparency and consistency. Third we argue that the term ‘public interest’ best reflects the normative work required to justify consent waivers because it is the broadest of the competing terms. ‘Public interest’ contains within its scope positive and negative implications of a study, as well as welfare, justice and rights considerations. In making this argument, we explain the normative basis for consent waivers, and provide a starting place for further discussion about the precise conditions in which a given study can be said to advance the public interest. Ipsos MORI study found that: … the public would be broadly happy with administrative data linking for research projects provided Those projects have social value, broadly defined. Data are de-identified. Data are kept secure. Businesses are not able to access the data for profit. (shrink)

The COVID-19 pandemic has both exposed and created deep rifts in society. It has thrust us into deep ethical thinking to help justify the difficult decisions many will be called upon to make and to protect from decisions that lack ethical underpinnings. This paper aims to highlight ethical issues in six different areas of life highlighting the enormity of the task we are faced with globally. In the context of COVID-19, we consider health inequity, dilemmas in triage and allocation of (...) scarce resources, ethical issues associated with research, ethical considerations relating to tracing apps, and exit strategies such as immunity passports and COVID-19 vaccines. Finally, we consider environmental issues in light of COVID-19. The paper also offers some ethical reflection on these areas as many parts of the world contemplate the recovery phase. (shrink)

A strength of liberal political institutions is their ability to accommodate pluralism, both allowing divergent comprehensive doctrines as well as constructing the common ground necessary for diverse people to live together. A pressing question is how far such pluralism extends. Which comprehensive doctrines are simply beyond the pale and need not be accommodated by a political consensus? Rawls attempted to keep the boundaries of reasonable disagreement quite broad by infamously denying that political liberalism need make reference to the concept of (...) truth, a claim that has been criticized by Joseph Raz, Joshua Cohen, and David Estlund. In this paper, we argue that these criticisms fail due to the fact that political liberalism can remain non-committal on the nature of truth, leaving the concept of truth in the domain of comprehensive doctrines while still avoiding the issues raised by Raz, Cohen, and Estlund. Further substantiating this point is the fact that Rawls would, and should, include parties in the overlapping consensus whose views on truth may be incoherent. Once it is seen that political liberalism allows such incoherence to reasonable parties, it is clear that the inclusion of truth and the requirement of coherence urged by Raz, Cohen, and Estlund requires more of reasonable people than is necessary for a political consensus. (shrink)

In the title essay, Erich Fromm uses the tools of psychoanalysis to examine the development of the dogma of Christ in the context of social history. The remaining essays examine psychological and cultural problems with keen insight and humanistic sympathies.

The book, with its emphasis on the interaction of microstructures with the entire biosphere, ecosystems etc., and on how micro- and macrocosmos mutually create the conditions for their further evolution, provides a comprehensive framework for a deeper understanding of human creativity in a time of transition.

High degrees of uncertainty and a lack of effective therapeutic treatments have characterized the COVID-19 pandemic and the provision of drug products outside research settings has been controversial. International guidelines for providing patients with experimental interventions to treat infectious diseases outside of clinical trials exist but it is unclear if or how they should apply in settings where clinical trials and research are strongly regulated. We propose the Professional Oversight of Emergency-Use Interventions and Monitoring System as an alternative pathway based (...) on guidance developed for the ethical provision of experimental interventions to treat COVID-19 in Singapore. We support our proposal with justifications that establish moral duties for physicians to record outcomes data and for institutions to establish monitoring systems for reporting information on safety and effectiveness to the relevant authorities. Institutions also have a duty to support generation of evidence for what constitutes good clinical practice and so should ensure the unproven intervention is made the subject of research studies that can contribute to generalizable knowledge as soon as practical and that physicians remain committed to supporting learning health systems. We outline key differences between POEIMS and other pathways for the provision of experimental interventions in public health emergencies. (shrink)

We introduce an atomic formula ${\vec{y} \bot_{\vec{x}}\vec{z}}$ intuitively saying that the variables ${\vec{y}}$ are independent from the variables ${\vec{z}}$ if the variables ${\vec{x}}$ are kept constant. We contrast this with dependence logic ${\mathcal{D}}$ based on the atomic formula = ${(\vec{x}, \vec{y})}$ , actually equivalent to ${\vec{y} \bot_{\vec{x}}\vec{y}}$ , saying that the variables ${\vec{y}}$ are totally determined by the variables ${\vec{x}}$ . We show that ${\vec{y} \bot_{\vec{x}}\vec{z}}$ gives rise to a natural logic capable of formalizing basic intuitions about independence and dependence. (...) We show that ${\vec{y} \bot_{\vec{x}}\vec{z}}$ can be used to give partially ordered quantifiers and IF-logic an alternative interpretation without some of the shortcomings related to so called signaling that interpretations using = ${(\vec{x}, \vec{y})}$ have. (shrink)

The first of Erich Neumann's works to be translated into English, this eloquent book draws on a full range of world mythology to show that individual consciousness undergoes the same archetypal stages of development as has human consciousness as a whole. Neumann, one of Jung's most creative students and a renowned practitioner of analytical psychology in his own right, shows how the stages begin and end with the symbol of the Uroboros, or tail-eating serpent. The intermediate stages are projected (...) in the universal myths of the World Creation, Great Mother, Separation of the World Parents, Birth of the Hero, Slaying of the Dragon, Rescue of the Captive, and Transformation and Deification of the Hero. Throughout the sequence the Hero is the evolving ego consciousness. (shrink)