The rejection of a “characterless” moral self is central to some of Bernard Williams’ most important contributions to philosophy. By the time of _Truth and Truthfulness_, he works instead with a model of the self constituted and stabilized out of more primitive materials through deliberation and in concert with others that takes inspiration from Diderot. Although this view of the self raises some difficult questions, it serves as a useful starting point for thinking about the process of developing an authentic (...) moral point of view in the context of contemporary living. In what follows, I begin to fill out and extend this picture of the self and its related notion of authenticity by exploring some of the “technologies of the self” at play in Rachel Cusk’s recent work (primarily, the Outline trilogy, _Coventry_, _Second Place_, and “The Stuntman”) that ask us to rethink the possibility and importance of stability; seek a way of constituting oneself and one’s values outside the confining structures of traditional narrative (focusing instead on a framework that might be provided by the visual arts); and give a different role to the sort of internalized other Williams sees as being at work in the mechanisms of shame. (shrink)

In recent years, much public attention has been devoted to the existence of pay discrepancies between men and women at the upper end of the income scale. For example, there has been considerable discussion of the ‘Hollywood gender pay gap’. We can refer to such discrepancies as cases of millionaire inequality. These cases generate conflicting intuitions. On the one hand, the unequal remuneration involved looks like a troubling case of gender injustice. On the other, it’s natural to feel uneasy when (...) confronted with the suggestion that multi-millionaires are somehow being paid inadequately. In this paper, we consider two arguments for rectifying millionaire inequality, clarifying their appeal but also identifying the obstacles that each will have to surmount in order to succeed. (shrink)

By definition, pain is a sensory and emotional experience that is felt in a particular part of the body. The precise relationship between somatic events at the site where pain is experienced, and central processing giving rise to the mental experience of pain remains the subject of debate, but there is little disagreement in scholarly circles that both aspects of pain are critical to its experience. Recent experimental work, however, suggests a public view that is at odds with this conceptualisation. (...) By demonstrating that the public does not necessarily endorse central tenets of the “mental” view of pain (subjectivity, privacy, and incorrigibility), experimental philosophers have argued that the public holds a more “body-centric” view than most clinicians and scholars. Such a discrepancy would have important implications for how the public interacts with pain science and clinical care. In response, we tested the hypothesis that the public is capable of a more “mind-centric” view of pain. Using a series of vignettes, we demonstrate that in situations which highlight mental aspects of pain the public can, and does, recognize pain as a mental phenomenon. We also demonstrate that the public view is subject to context effects, by showing that the public’s view is modified when situations emphasizing mental and somatic aspects of pain are presented together. (shrink)

Co-authored letter to the APA to take a lead role in the recognition of teaching in the classroom, based on the participation in an interdisciplinary Conference on the Role of Advocacy in the Classroom back in 1995. At the time of this writing, the late Myles Brand was the President of Indiana University and a member of the IU Department of Philosophy.

Purpose This paper aims to formalize long-term trajectories of human civilization as a scientific and ethical field of study. The long-term trajectory of human civilization can be defined as the path that human civilization takes during the entire future time period in which human civilization could continue to exist. -/- Design/methodology/approach This paper focuses on four types of trajectories: status quo trajectories, in which human civilization persists in a state broadly similar to its current state into the distant future; catastrophe (...) trajectories, in which one or more events cause significant harm to human civilization; technological transformation trajectories, in which radical technological breakthroughs put human civilization on a fundamentally different course; and astronomical trajectories, in which human civilization expands beyond its home planet and into the accessible portions of the cosmos. -/- Findings Status quo trajectories appear unlikely to persist into the distant future, especially in light of long-term astronomical processes. Several catastrophe, technological transformation and astronomical trajectories appear possible. -/- Originality/value Some current actions may be able to affect the long-term trajectory. Whether these actions should be pursued depends on a mix of empirical and ethical factors. For some ethical frameworks, these actions may be especially important to pursue. (shrink)

The COVID-19 has had a significant impact on people's lives and business operations around the world. Additionally, it has an effect on the purchasing habits of the Filipino youth. The researchers employed a qualitative research technique in this study to determine changes in the purchasing behavior of Filipino youth, specifically young adults aged 18-25 in Metro Manila. Our findings indicate that young Filipinos have become significantly interested in digital commerce in the country, a trend that has been growing consistently since (...) the pandemic started. Since the pandemic began, they have valued the effeciency and convenience of making purchases thru online platforms. As a result, many individuals chose to support local businesses by downloading apps or visiting websites that enable them to purchase online. According to the findings of the study, many of the respondents said that they prioritized buying necessities over wants. Because money was tight due to the lockdowns, which caused the majority of Filipinos to lose their jobs or stop working, Filipinos were careful with their expenditures throughout the pandemic. We the researchers concluded based on the responses we got thru our online interviews, that the pandemic indeed impacted the buying behavior of the Filipino youth. (shrink)

Schopenhauer’s pessimistic philosophy is a depressing read. He writes many pages about how suffering is the norm, and any happiness we feel is merely a temporary alleviation of suffering. Even so, his account of suffering rings true to many readers. What are we to do with our lives if Schopenhauer is right, and we are doomed to suffer? In this paper, I use William James’ pragmatic method to find practical implications of Schopenhauer’s pessimism. I provide a model for how (...) we are to live our lives in a suffering world, a model that provides means to reduce suffering. (shrink)

Burton Dreben taught a generation of scholars the value of closely attending to the recent philosophical past. But the few papers he authored do little to capture his philosophical voice. In this article, I turn instead to an unpublished transcript of Dreben in conversation with his contemporaries. In addition to yielding insights into a transitional period in W.V. Quine’s and Donald Davidson’s thought, I argue that this document showcases Dreben in his element, revealing the way that he shaped the views (...) of key analytic philosophers. More broadly, I argue that by writing conversationalists like Dreben into our histories we can capture the collaborative nature of philosophy. (shrink)

Given W.V. Quine’s and Donald Davidson’s extensive agreement about much of the philosophy of language and mind, and the obvious methodological parallels between Quine’s radical translation and Davidson’s radical interpretation, many—including Quine and Davidson—are puzzled by their occasional disagreements. I argue for the importance of attending to these disagreements, not just because doing so deepens our understanding of these influential thinkers, but because they are in fact the shadows thrown from two distinct conceptions of philosophical inquiry: Quine’s “naturalism” and what (...) I call Davidson’s “humanism.” The clash between Quine and Davidson thus provides valuable insight into the history of analytic naturalism and its malcontents. (shrink)

This paper examines the tensions at play in three important documents involved in the ‘war on terror’: the “Application of Treaties” White House Legal Counsel Memo of 2001, the “National Security Strategy” document of 2002, and the 2004 Supreme Court decision Hamdi v. Rumsfeld. Reading these documents, it becomes clear that there is an overarching misunderstanding and confusion of the traditionally separate concepts of ‘criminal’ and ‘enemy’ in the struggle against globalized terrorism.

An underexplored aspect of moral experience is the experience of apprehending other people as mattering, grasping the significance of whether their interests are set back or enhanced. I refer to these as value-apprehensional experiences. I argue, partly on the basis of data regarding moral cognition in psychopaths, that experiencing other people's value is one way that we attain adequate systematic comprehension of morality, understanding that others' welfare is the point behind rules against harming them. I then turn to a positive (...) account of what capacities we should expect to facilitate value-apprehensional experiences. I suggest we should look to the capacity to care emotionally about others: roughly, to feel emotions congruent with someone else's well-being, for her sake. I argue that this 'emotional caring' is better suited to explain value-apprehensional experience than other constructs, including empathy. The broader hypothesis this raises is that emotional caring enables and improves our value-apprehensional abilities. To the extent that is true, I argue, we should consider caring people to have more trustworthy moral intuitions than others, especially if they are not just competent, but skilled at caring about others. Emotions are, of course, biased in various ways, so I suggest attention-refocusing strategies for mitigating these biases. These are epitomized by an unaffiliated caring perspective, one removed from affiliation with any of a morally relevant situation's protagonists, but informed through emotional caring about the the interests of each. Finally, I turn to special value-apprehensional experiences that we have in intense, reciprocal relationships of caring with individuals who are special to us. I argue that, if we accept that general v-a experiences reveal people's moral significance, we have even more reason to think that special v-a experiences reveal the special moral significance not only of the parties in the relationship, but of their participation in the relationship, for both their sakes. That is, there are moral reasons to devote caring attention to special others, even if we could otherwise do objectively more good. Emotional cares reveal not only values within everyone but reasons to devote ourselves to the individuals we care about. (shrink)

Tento článek se zastává skepticko-realistického tzv. novo- humovského, výkladu Humovy teorie kauzality navzdory kritice ze strany Zuzany Parusnikové. Autor však v souladu se svou vývojovou interpretací hájí tzv. „nového Huma" pouze pro pozdní tvorbu tohoto skot- ského filosofa.

Rather than to focus upon a particular ‘right to life’, we should consider what rights there are pertaining to our lives and to our living. There are different sorts. There are, for instance, rights that constitute absences of particular duties and rights that correspond to the duties of other agents or agencies. There are also natural and non-natural rights and duties. Different people in different contexts can have different moral duties and different moral rights including rights to life. The question (...) of the moral rights there are to and pertaining to life is considered with reference to James Griffin’s account of human rights. Also considered is the question of who or what can be a bearer of them. (shrink)

Forgiveness theorists focus a good deal on explicating the content of what they take to be a shared folk concept of forgiveness. Our empirical research, however, suggests that there is a range of concepts of forgiveness present in the population, and therefore that we should be folk conceptual pluralists about forgiveness. We suggest two possible responses on the part of forgiveness theorists: (1) to deny folk conceptual pluralism by arguing that forgiveness is a functional concept and (2) to accept folk (...) conceptual pluralism and focus on a revisionary conceptual ethics project. (shrink)

My essay begins by providing a broad vision of how William James’s psychology and philosophy were a two-pronged attempt to revive the self whose foundations had collapsed after the Civil War. Next, I explain how this revival was all too successful insofar as James inadvertently resurrected the imperial self, so that he was forced to adjust and develop his philosophy of religion in keeping with his anti-imperialism. James’s mature philosophy of religion therefore articulates a vision of the (...) radically ethical saint religiously bound to a decidedly pluralistic universe. I evaluate James’s philosophy of religion by comparing it to Enrique Dussel’s psychological portrait of the imperialist ego, Dussel’s attempt to religiously bind this ego, and the more radical philosophy that results. I suggest that Dussel’s philosophy of liberation: 1) better theorizes the religious contraction of the self as a necessary part of ethical and political life and 2) offers a more concrete and radically democratic philosophy. My overarching aim is to show how Dussel’s liberation philosophy can help critically develop James’s pragmatist claim that religion might provide a force for widely and positively transforming our ethical and political lives. (shrink)

In this brief, we argue that there is a diversity of ways in which humans (Homo sapiens) are ‘persons’ and there are no non-arbitrary conceptions of ‘personhood’ that can include all humans and exclude all nonhuman animals. To do so we describe and assess the four most prominent conceptions of ‘personhood’ that can be found in the rulings concerning Kiko and Tommy, with particular focus on the most recent decision, Nonhuman Rights Project, Inc v Lavery.

Can new technology enhance purpose-driven, democratic dialogue in groups, governments, and societies? Online Deliberation: Design, Research, and Practice is the first book that attempts to sample the full range of work on online deliberation, forging new connections between academic research, technology designers, and practitioners. Since some of the most exciting innovations have occurred outside of traditional institutions, and those involved have often worked in relative isolation from each other, work in this growing field has often failed to reflect the full (...) set of perspectives on online deliberation. This volume is aimed at those working at the crossroads of information/communication technology and social science, and documents early findings in, and perspectives on, this new field by many of its pioneers. -/- CONTENTS: -/- Introduction: The Blossoming Field of Online Deliberation (Todd Davies, pp. 1-19) -/- Part I - Prospects for Online Civic Engagement -/- Chapter 1: Virtual Public Consultation: Prospects for Internet Deliberative Democracy (James S. Fishkin, pp. 23-35) -/- Chapter 2: Citizens Deliberating Online: Theory and Some Evidence (Vincent Price, pp. 37-58) -/- Chapter 3: Can Online Deliberation Improve Politics? Scientific Foundations for Success (Arthur Lupia, pp. 59-69) -/- Chapter 4: Deliberative Democracy, Online Discussion, and Project PICOLA (Public Informed Citizen Online Assembly) (Robert Cavalier with Miso Kim and Zachary Sam Zaiss, pp. 71-79) -/- Part II - Online Dialogue in the Wild -/- Chapter 5: Friends, Foes, and Fringe: Norms and Structure in Political Discussion Networks (John Kelly, Danyel Fisher, and Marc Smith, pp. 83-93) -/- Chapter 6: Searching the Net for Differences of Opinion (Warren Sack, John Kelly, and Michael Dale, pp. 95-104) -/- Chapter 7: Happy Accidents: Deliberation and Online Exposure to Opposing Views (Azi Lev-On and Bernard Manin, pp. 105-122) -/- Chapter 8: Rethinking Local Conversations on the Web (Sameer Ahuja, Manuel Pérez-Quiñones, and Andrea Kavanaugh, pp. 123-129) -/- Part III - Online Public Consultation -/- Chapter 9: Deliberation in E-Rulemaking? The Problem of Mass Participation (David Schlosberg, Steve Zavestoski, and Stuart Shulman, pp. 133-148) -/- Chapter 10: Turning GOLD into EPG: Lessons from Low-Tech Democratic Experimentalism for Electronic Rulemaking and Other Ventures in Cyberdemocracy (Peter M. Shane, pp. 149-162) -/- Chapter 11: Baudrillard and the Virtual Cow: Simulation Games and Citizen Participation (Hélène Michel and Dominique Kreziak, pp. 163-166) -/- Chapter 12: Using Web-Based Group Support Systems to Enhance Procedural Fairness in Administrative Decision Making in South Africa (Hossana Twinomurinzi and Jackie Phahlamohlaka, pp. 167-169) -/- Chapter 13: Citizen Participation Is Critical: An Example from Sweden (Tomas Ohlin, pp. 171-173) -/- Part IV - Online Deliberation in Organizations -/- Chapter 14: Online Deliberation in the Government of Canada: Organizing the Back Office (Elisabeth Richard, pp. 177-191) -/- Chapter 15: Political Action and Organization Building: An Internet-Based Engagement Model (Mark Cooper, pp. 193-202) -/- Chapter 16: Wiki Collaboration Within Political Parties: Benefits and Challenges (Kate Raynes-Goldie and David Fono, pp. 203-205) -/- Chapter 17: Debian’s Democracy (Gunnar Ristroph, pp. 207-211) -/- Chapter 18: Software Support for Face-to-Face Parliamentary Procedure (Dana Dahlstrom and Bayle Shanks, pp. 213-220) -/- Part V - Online Facilitation -/- Chapter 19: Deliberation on the Net: Lessons from a Field Experiment (June Woong Rhee and Eun-mee Kim, pp. 223-232) -/- Chapter 20: The Role of the Moderator: Problems and Possibilities for Government-Run Online Discussion Forums (Scott Wright, pp. 233-242) -/- Chapter 21: Silencing the Clatter: Removing Anonymity from a Corporate Online Community (Gilly Leshed, pp. 243-251) -/- Chapter 22: Facilitation and Inclusive Deliberation (Matthias Trénel, pp. 253-257) -/- Chapter 23: Rethinking the ‘Informed’ Participant: Precautions and Recommendations for the Design of Online Deliberation (Kevin S. Ramsey and Matthew W. Wilson, pp. 259-267) -/- Chapter 24: PerlNomic: Rule Making and Enforcement in Digital Shared Spaces (Mark E. Phair and Adam Bliss, pp. 269-271) -/- Part VI - Design of Deliberation Tools -/- Chapter 25: An Online Environment for Democratic Deliberation: Motivations, Principles, and Design (Todd Davies, Brendan O’Connor, Alex Cochran, Jonathan J. Effrat, Andrew Parker, Benjamin Newman, and Aaron Tam, pp. 275-292) -/- Chapter 26: Online Civic Deliberation with E-Liberate (Douglas Schuler, pp. 293-302) -/- Chapter 27: Parliament: A Module for Parliamentary Procedure Software (Bayle Shanks and Dana Dahlstrom, pp. 303-307) -/- Chapter 28: Decision Structure: A New Approach to Three Problems in Deliberation (Raymond J. Pingree, pp. 309-316) -/- Chapter 29: Design Requirements of Argument Mapping Software for Teaching Deliberation (Matthew W. Easterday, Jordan S. Kanarek, and Maralee Harrell, pp. 317-323) -/- Chapter 30: Email-Embedded Voting with eVote/Clerk (Marilyn Davis, pp. 325-327) -/- Epilogue: Understanding Diversity in the Field of Online Deliberation (Seeta Peña Gangadharan, pp. 329-358). -/- For individual chapter downloads, go to odbook.stanford.edu. (shrink)

DESENVOLVIMENTO EMBRIONÁRIO E DIFERENCIAÇÃO SEXUAL -/- E. I. C. da Silva Departamento de Agropecuária – IFPE Campus Belo Jardim Departamento de Zootecnia – UFRPE sede -/- 1.1 INTRODUÇÃO O sexo foi definido como a soma das diferenças morfológicas, fisiológicas e psicológicas que distinguem o macho da fêmea permitindo a reprodução sexual e assegurando a continuidade das espécies. Os processos de diferenciação sexual são realizados durante o desenvolvimento embrionário, onde ocorre a proliferação, diferenciação e maturação das células germinativas e primordiais, precursoras (...) de ovócitos e espermatozoides em fêmeas e machos, respectivamente. Assim, os embriões machos e fêmeas iniciam o seu desenvolvimento de forma semelhante, de modo que em ambos os sexos se estabelecem em estruturas idênticas a partir das quais se formarão os órgãos reprodutores correspondentes a cada sexo. O conhecimento da origem e do desenvolvimento do aparelho genital é indispensável para entender sua função e as alterações que produzem infertilidade ou esterilidade. 1.2 DETERMINAÇÃO DO SEXO CROMOSSÔMICO Nos mamíferos, o sexo cromossômico é determinado no momento da fertilização, quando um óvulo, que contém um cromossomo X, é fecundado por um espermatozoide portador de um cromossomo X ou um cromossomo Y. No primeiro caso, o complemento cromossômico seria XX, o que originaria uma fêmea (sexo homogamético), e no segundo daria como resultado um macho com a fórmula cromossômica XY (sexo heterogâmico). 1.3 A GÔNADA INDIFERENCIADA A primeira manifestação das gônadas se aprecia no embrião em forma de um par de eminências longitudinais chamadas cristas ou dobras gonodais, situadas em ambos os lados da linha média entre os mesonefros (rins em desenvolvimento) e do mesentério dorsal. Nos embriões dos mamíferos, as células germinativas primordiais (CGP) manifestam-se em estágios precoces do desenvolvimento, podendo ser detectadas pela primeira vez na metade da gastrulação. As CGP são células grandes, de citoplasma claro e núcleo grande e redondo, localizadas na parede do saco vitelino, perto do alantoide. Essas células possuem grande capacidade de proliferação e vão migrar desde o endoderma do intestino e o epitélio do saco vitelino, através do mesentério, até as cristas gonodais. Isso ocorre por volta do 26° dia da gestação no bovino. Sua migração realiza-se graças aos movimentos de translocação passiva e deslocamento ameboide ativo. Desconhece-se o mecanismo pelo qual estas células são dirigidas para as cristas gonodais, porém foram estudadas algumas moléculas que se expressam durante sua migração e que poderiam desempenhar um papel importante na diferenciação deste tipo celular. A fosfatase alcalina é uma enzima que tem sido usada como marcador de CGP para determinar a sua origem e migração. Num estudo recente, foi inserido um marcador fluorescente que se exprime unicamente nas células germinativas primordiais de embriões transgênicos, e utilizando este marcador e a fosfatase alcalina determinou-se a origem e o padrão de migração destas células. O primeiro sinal de diferenciação das células germinativas primordiais é a expressão de fosfatase alcalina, e esta apareceu pela primeira vez na parte mais posterior da linha primitiva. No sétimo dia de desenvolvimento no embrião do camundongo, o endoderma visceral (AF+) é substituído pelo endoderma definitivo (AF-) originado na parte anterior da linha primitiva. O fator de transcrição Oct-4 é expresso nas CGP de ambos os sexos, pelo que acredita-se estar envolvido na mantença a totipotêncialidade das células. O receptor tirosina quinase, cujo ligante é o fator de Steel, é outra das moléculas que expressam as CGP. Tem sido demonstrado que este receptor possui um papel muito importante na sobrevivência deste tipo celular. Existem outros fatores que promovem a sobrevivência e/ou proliferação de CGP in vitro. Em experiências realizadas com o fator de transformação beta I (TGFβ-I), observou-se que este tem um efeito negativo sobre a proliferação das CGP. Outra atividade que tem sido postulada a este fator é o de um agente quimioatraente que possivelmente possa direcionar a migração destas células para a gônada. a) Um formado pelas células germinativas primordiais (precursoras dos gametas masculinos ou femininos), rodeadas de células somáticas das quais posteriormente se derivarão as células de Sertoli no macho e as células da granulosa na fêmea. b) O tecido que formará o estroma da gônada: tecido conjuntivo, vasos sanguíneos e as células intersticiais com atividade esteroidogênica (células de Leydig no testículo e a teca interna do ovário). As células somáticas do primórdio gonodal originam-se do mesoderma. Inicialmente são de três tipos: mesenquimáticas, mesoteliais e endoteliais. As células mesenquimáticas e mesoteliais iniciam grande atividade proliferativa ao chegar as CGP. Observa-se então uma condensação de células de origem mesotelial e mesenquimatoso que forma um agregado compacto denominado "blastema gonodal". A partir deste primórdio embrionário, diferenciam-se dois tecidos gonodais: os cordões sexuais e o estroma. Os cordões sexuais são arranjos epiteliais que se encontram delimitados por uma folha basal, e dentro deles encontramos as CGP. Por sua vez, no estroma encontram-se células do tipo mesenquimático e vasos sanguíneos. Neste momento, as gônadas são indiferenciadas e bipotencialmente sexuais, sendo impossível diferenciar, morfologicamente, uma gônada masculina de uma feminina, mas no caso dos machos genéticos já existe uma diferenciação da gônada a nível molecular. Nesta fase já se encontram presentes as estruturas das quais se desenvolvem os dutos mesonéfricos ou de Wolff precursores do aparelho genital masculino e os dutos paramesonéfricos ou de Müller que darão origem ao aparelho reprodutor feminino. Há uma série de fatores envolvidos no desenvolvimento precoce da gônada, entre os quais o fator esteroidogênico I (SFI: Steroidogenic fator l), que é um membro da subfamília de receptores nucleares, receptores órfãos. Este fator de transcrição tem um local de ligação ao DNA composto por dois dedos-de-Zinc. O SFI foi identificado como um ativador de genes envolvidos na biossíntese de esteroides em diferentes células. O SFI está presente durante o desenvolvimento embrionário em regiões associadas com funções endócrinas como gônadas, adrenais, pituitárias e hipotálamos. Os animais homozigotos para o gene SFI defeituoso, necessitam de gônadas e adrenais e têm a função gonadotrófica alterada. Os ratos sem SFI carecem de gonadotrofos e têm um desenvolvimento anormal do núcleo ventro-medial do hipotálamo; em particular as gônadas deixam de se desenvolver entre os dias 11 a 15 e degeneram-se por apoptose. No entanto, a crista genital forma-se e é colonizada pelas células germinativas, o que indica que estas continuam a receber o sinal adequado para a sua migração. Portanto, o SFI não está envolvido no desenvolvimento precoce da gônada e do sistema urogenital, mas parece estar envolvido na manutenção do crescimento das células somáticas presentes na gônada indiferenciada. O gene associado ao tumor de Wilms (WTI: Wilm's tumor Associated) está envolvido no desenvolvimento da gônada e do rim. Durante o desenvolvimento embrionário, WTI se expressa em todo o mesoderma intermediário e posteriormente na gônada indiferenciada, bem como no rim em formação. WTI regula o sinal indutivo do mesênquima para o epitélio celômico dos mesonefros. Se este for o caso, então WTI é responsável pelo crescimento da crista genital ao dirigir a entrada do epitélio celômico. Dado que estas células darão origem às células de Sertoli, a carência de WTI pode causar o desenvolvimento de embriões XY como fêmeas simplesmente porque não se formam as células de Sertoli. Em geral, todos os genes importantes na diferenciação do mesoderma intermediário e do sistema urogenital intervêm no desenvolvimento da gônada precoce. 1.4 DIFERENCIAÇÃO GONODAL O desenvolvimento das gônadas e ductos genitais descritos até o momento, é o mesmo para ambos os sexos. Igualmente, os genes descritos, que estão envolvidos no desenvolvimento das gônadas, ductos genitais e migração das células germinativas, afetam igualmente os embriões com genótipo XX ou XY. A gônada primitiva consiste anatomicamente de uma medula (interna) e uma crosta (externa), e de acordo com o local onde ocorre a colonização das células germinativas, diferenciara em testículo ou um ovário, respectivamente. Nos mamíferos, a primeira manifestação estrutural de diferenciação sexual é detectada na gônada dos machos, onde as células germinativas estão localizadas na medula. A diferenciação do testículo inicia-se quando os cordões sexuais se separam do epitélio celômico como consequência dos arranjos produzidos por uma invasão do mesênquima e vasos sanguíneos que provoca a compactação dos cordões, agora denominados cordões testiculares. As células que rodeiam os cordões se achatam e formam as células mioides, que são responsáveis pela formação das membranas basais. As células do epitélio interno, ou seja, as células de Sertoli, têm duas funções principais: o suporte das CGP e a síntese da hormona antimulleriana, responsável pela regressão dos ductos de Müller e secretada durante o período de diferenciação sexual. As células do estroma que rodeiam os cordões testiculares diferenciam-se para formar vários tipos de células: células mioides, fibroblastos, endotélio e células de Leydig, que são as mais importantes pela sua atividade endócrina. Posteriormente, os cordões testiculares dão origem aos túbulos seminíferos, que contêm o epitélio que produzirá os espermatozoides ao chegar à puberdade. Na fêmea, durante os estágios iniciais de diferenciação gonodal, não se observam mudanças em relação à gônada indiferenciada, só pode-se observar um certo crescimento devido à proliferação de células somáticas e germinativas. As células germinativas iniciam um período de proliferação, que termina com o início da meiose. Iniciada a meiose, dá-se o processo de foliculogênese; neste momento os cordões epiteliais se fragmentam, de tal maneira que cada ovócito fica rodeado de células epiteliais cobertas por uma folha basal fina (figura 1). Para que a gônada primitiva se desenvolva em testículo é indispensável a presença do cromossoma Y, independentemente do número de cromossomas X que contenha o genoma de um indivíduo. O gene determinante do testículo encontra-se localizado no cromossoma Y, denominado sry em ratos e SRY em humanos. O gene sry se expressa durante o desenvolvimento embrionário na crista genital de embriões de camundongos. A expressão é detectável no dia 10,5, pouco depois do aparecimento das cristas genitais, atinge o seu máximo durante o dia 11,5 e mantém-se até pouco depois de ocorrerem os primeiros sinais morfológicos de diferenciação testicular no dia 12,5. Este padrão de expressão é compatível com a teoria de que sry atua induzindo a ativação dos genes (figura 2) que conduzem ao desenvolvimento testicular, sem que exista a necessidade da expressão contínua de sry para manter a diferenciação do testículo após o dia 12,5. Como mencionado anteriormente, a gônada primitiva é composta por vários tipos de células. No entanto, as células germinativas primordiais não são o local de expressão do sry, já que os embriões que necessitam de células germinativas mantêm a expressão de sry e desenvolvem o sexo gonodal normalmente. As células somáticas na gônada em desenvolvimento incluem também as células de suporte. Sabe-se que é nestas células que o sry é expresso para que se diferenciem em células de Sertoli, e a expressão transitória de sry indica que deve ativar a outros genes para a manutenção das células de Sertoli. Uma vez diferenciadas as células de Sertoli, elas se encarregarão da diferenciação do resto das células na gônada. -/- Figura 1: Representação da diferenciação dos órgãos genitais internos. Adaptado de BRONSON, 1989. Figura 2: Cascada de genes envolvidos na diferenciação sexual, adaptado de KOOPMAN, 1999. O fator sry é necessário para a diferenciação do testículo. Embora não se conheçam os genes que provavelmente regulam esse gene, estudos realizados em camundongos demonstram que este gene parece coordenar-se com certos genes autossômicos. Entre estes genes autossômicos, o sox9, que é produzido pelas células de Sertoli uma vez que são estimuladas por sry, de modo que sox9 é um dos genes relacionados estruturalmente com sry. O Sox9 funciona como um fator de transcrição, mas não se sabe se a proteína tem qualquer outra função estrutural; este gene exprime-se abundantemente nos condrócitos e está relacionado com defeitos do aparelho ósseo chamados displasia campomélica. Curiosamente, os pacientes XY com esta condição sofrem frequentemente de reversão do sexo. O Sox9 é um dos poucos genes, além do SRY, do qual as mutações demonstraram interferir com a determinação sexual masculina. No entanto, apenas 75% dos pacientes com anomalias esqueléticas de tipo displasia campomélica têm reversão sexual e não foram encontrados casos de reversão sexual devido a um defeito de Sox9 que não seja acompanhado de defeitos esqueléticos. Isso indica que o Sox9 é apenas um membro da rede de genes que são ativados para determinar a diferenciação sexual, enquanto a rota que rege a condrogênese é mais sensível a perturbações deste. O momento em que se detecta a expressão do gene Sox9 (11dpc em ratos) coincide com a máxima expressão de sry, o que poderia indicar a possibilidade de que sry regule positivamente a Sox9. De fato, na região do promotor de Sox9 há um local de união ao que potencialmente se pode unir o sry. A expressão de Sox9 durante a diferenciação sexual sugere um papel abaixo de sry na diferenciação das células de Sertoli. O cromossoma X também é importante na diferenciação gonodal. O gene DAX-I foi isolado do lócus DSS (Dosage sensitive sex reversal) do cromossoma X. DAX-I é parte da cascata de determinação sexual, mas não é necessário para a formação do testículo. DAX-I é um membro dos receptores nucleares conhecidos como receptores órfãos. Este gene demonstrou ser um poderoso repressor da transcrição de SFI e de vários genes. Os padrões de expressão de DAX-I são complementares daqueles de SFI, ambos expressos nas cristas genitais. Em resumo, dada a evidência exposta, desenvolveu-se a hipótese de que DAX-I é um antagonista de sry; esse antagonismo é dependente dos níveis relativos de DAX-I e sry e de um limiar que varia de espécie para espécie. A DAX-I foi classificada como o gene antitestículo. Na fêmea (cariótipo XX) é importante que ocorra a inativação de um dos cromossomas sexuais X para que se mantenha o equilíbrio genético ao igualar o conteúdo de DNA dos cromossomas. Esse cromossoma inativado constitui o chamado corpúsculo de Barr. No entanto, para que a meiose se realize, é necessário dos dois cromossomas X ativos nos ovócitos para assegurar a diferenciação ovárica e a fertilidade. 1.5 DIFERENCIAÇÃO DOS DUCTOS SEXUAIS O embrião possui, além das gônadas indiferenciadas, dois sistemas de ductos: os de potencialidade masculina denominam-se ductos de Wolff ou mesonéfricos, e os de potencialidade feminina se chamam ductos de Müller ou paramesonéfricos (figura 1). Se a diferenciação gonodal levou à formação de um testículo, a partir do ducto mesonéfrico ou de Wolff se desenvolverão os ductos eferentes, o epidídimo, os ductos deferentes e as vesículas seminais. As hormonas importantes no desenvolvimento do aparelho genital masculino são a testosterona, produzida pelas células de Leydig, e sua forma 5α reduzida, a 5α di-hidrotestosterona. Acredita-se que a testosterona é responsável pela virilização dos ductos de Wolff, e a di-hidrotestosterona dos órgãos genitais externos. No macho, os canais de Müller atrofiam-se devido à ação de uma hormona fetal de origem testicular denominada hormona inibidora das estruturas de Müller (HIM) ou hormona antimulleriana. Este processo começa assim que os cordões espermáticos se formam e se diferenciam as células de Sertoli. A existência de HIM foi proposta baseada em estudos realizados em bezerras freemartin, devido à existência de uma hormona responsável pela atresia dos ductos de Müller que na fêmea dá origem ao útero e aos ovidutos. Essa hormona provoca a involução do aparelho genital do bovino nas gestações gemelares nas quais os produtos de diferente sexo têm comunicação sanguínea por ter ocorrido a anastomose dos vasos de ambas as placentas (figura 3). A HIM é uma glicoproteína pertencente à subfamília de TGFβ, é expressa pelas células que darão origem às células de Sertoli e é um dos primeiros marcadores de diferenciação nestas células. A HIM é secretada na vida adulta pelas células de Sertoli no testículo e por células da granulosa no ovário. No rato a HIM é expressa-se no 12° dia em um teste padrão que segue muito de perto o aumento na expressão de sry. No macho, esta secreção de HIM continua durante a vida fetal e adulta, contudo os níveis de HIM declinam na puberdade devido a um aumento na secreção de testosterona. Vários fatores intervêm na regulação do gene de HIM, incluindo os acima descritos SFI e Sox9. O gene HIM contém segmentos de DNA que são conservados em várias espécies de vertebrados. Existe um nexo de ligação para SFI, que ativa a transcrição de HIM. A mutação no local de ligação de SFI resulta em reversão do sexo em indivíduos XY incluindo genitais femininos normais, presença de um útero formado enfatizando a importância de SFI na determinação sexual e na expressão de HIM. Embora SFI seja um bom candidato como regulador de HIM, é expresso em outras células, como as de Leydig e adrenais, que não expressam HIM. Em contrapartida, Sox9 é expresso unicamente nas células de Sertoli que são as produtoras de HIM. O gene HIM também tem um nexo de ligação para Sox9. Além disso, Sox9 pode atuar sinergicamente com SFI para promover a secreção de HIM. Ao contrário destes dois fatores de transcrição, DAX-I antagoniza a ação de Sox9 e provavelmente SFI sobre o promotor de HIM. Assim, para que as células de Sertoli secretem HIM, a transcrição de DAX-I deve diminuir. Figura 3: Representação da diferenciação dos órgãos genitais externos. Adaptado de BRONSON, 1989. Os ductos de Wolff tornam-se o sistema de ejaculação do macho. A porção mais próxima dos testículos dá origem ao epidídimo, a parte central ao ducto deferente e a porção mais distal às vesículas seminais. A próstata e a parte membranosa da uretra do macho desenvolvem-se a partir da porção pélvica do seio urogenital. A virilização e diferenciação dos ductos de Wolff dependem da produção de testosterona pelo testículo. Quanto aos órgãos genitais externos do macho, o tubérculo genital é ampliado e as dobras uretrais se fundem para formar a uretra peniana. A fusão das dobras uretrais aproxima os tubérculos genitais para formar o escroto (figura 4). Figura 4: Diferenciação do aparelho genital da fêmea e do macho. Adaptado de KOOPMAN, 1989. A diferenciação dos órgãos genitais da fêmea ocorre de forma passiva, já que a ausência de testículos e por isso da hormona inibidora dos ductos de Müller (HIM), assim como dos andrógenos virilizantes, favorece o desenvolvimento dos ductos de Müller, enquanto os de Wolff sofrem atrofia. A porção cefálica dos ductos de Müller dá origem aos ovidutos, que na sua terminação caudal se fundem com o útero. O contato dos ductos de Müller com o seio urogenital induz uma intensa proliferação celular que resulta na formação da área uterovaginal localizado entre o seio urogenital e os ductos de Müller. As células do prato uterovaginal proliferam e aumentam a distância entre as duas estruturas criando o espaço que formará a vagina quando o prato é canalizado e forma um lúmen. Em contraste com o que ocorre no macho, na fêmea a maior parte do seio urogenital se mantém exposta na superfície da abertura onde desembocam a vagina e a uretra. O tubérculo urogenital da fêmea tem um crescimento limitado e forma o clitóris. A sequência de passos da diferenciação sexual do aparelho genital é resumida na tabela 1. Tabela 1: Destino em desenvolvimento dos rudimentos sexuais dos fetos macho e fêmea dos mamíferos -/- Rudimento sexual Macho Fêmea Gônada Testículo Ovário Ductos de Müller (Paramesonéfricos) Vestígios Útero, parte da vagina, ovidutos Ductos de Wolff (Mesonéfricos) Ductos eferentes deferentes, epidídimo, vesículas seminais Vestígios Seio urogenital Uretra, próstata, glândulas bulbouretrais Parte da vagina, uretra, vestíbulo, glândulas vestibulares Tubérculo genital Pênis Clitóris Pregas vestibulares Escroto Lábios vulvares Fonte: HAFEZ, 2004. 1.6 DIFERENCIAÇÃO SEXUAL DO HIPOTÁLAMO Os processos de diferenciação sexual não se limitam apenas às células somáticas do organismo do feto, mas incluem também os centros nervosos superiores do cérebro. Assim, da mesma maneira que a gônada e os ductos sexuais se desenvolvem para o tipo feminino ou masculino, propôs-se que o cérebro pode ser "masculinizado" ou permanecer "Feminizado". A diferenciação do hipotálamo vai depender do ambiente esteroidal do neonato e ocorre na fase perinatal. Estes eventos serão de grande transcendência na vida reprodutiva do indivíduo. Tanto a fêmea como o macho nascem com a capacidade de secreção de gonadotropinas de acordo com um padrão cíclico; contudo, no macho, a exposição do hipotálamo à ação dos andrógenos testiculares durante os primeiros dias da vida extrauterina provoca a masculinização, com o qual o hipotálamo do macho é programado para que a secreção de gonadotropinas se realize a um ritmo relativamente constante por parte da hipófise (secreção tônica). Na fêmea, tanto a secreção tônica como a cíclica se conservam. No entanto, observou-se que a injeção de testosterona ou o transplante de testículo na rata fêmea durante os primeiros dias de vida, suprime a sua futura atividade estral (secreção cíclica). Por outro lado, se os ovários forem transplantados para o rato macho normal castrado na idade adulta, o animal não desenvolve qualquer atividade cíclica, mas se os machos transplantados forem castrados ao nascer, o ovário é capaz de efetuar mudanças cíclicas e ovulações. Isto foi demonstrado em roedores, mas não em animais domésticos ou na espécie humana. Portanto, o padrão de secreção de gonadotropinas, seja cíclico ou tônico, não depende da hipófise, mas do hipotálamo e sua correta diferenciação. 1.7 CONCLUSÕES A maioria dos conhecimentos no campo da biologia do desenvolvimento e, muito especificamente, dos processos de diferenciação sexual têm sido originados de estudos relacionados com desordens congênitas, que na sua maioria devem-se a defeitos de genes específicos. A análise detalhada destas desordens permitiu entender alguns mecanismos endócrinos, moleculares e genéticos envolvidos na diferenciação sexual. A identificação do gene sry como determinante do testículo foi uma contribuição crucial e abriu as portas à compreensão dos mecanismos moleculares e celulares relacionados com o desenvolvimento do testículo. Se este gene não estiver presente, é criado um programa genético alternativo para levar a cabo a diferenciação gonodal para o ovário. Finalmente, devemos ter presente que é necessária uma correlação entre mudanças morfológicas e expressão de genes durante o desenvolvimento para entender os mecanismos relacionados com a diferenciação. -/- Apoio -/- Realização -/- REFERÊNCIAS BIBLIOGRÁFICAS ANDERSON, Robert et al. The onset of germ cell migration in the mouse embryo. Mechanisms of development, v. 91, n. 1-2, p. 61-68, 2000. AUSTIN, Colin Russell; SHORT, R. V. Reproduction in Mammals: Volume 1, Germ Cells and Fertilization. Londres: Cambridge University Press, 1972. BRONSON, Franklin H. Mammalian reproductive biology. Chicago: University of Chicago Press, 1989. BUEHR, Mia. The primordial germ cells of mammals: some current perspectives. Experimental cell research, v. 232, n. 2, p. 194-207, 1997. BYSKOV, Anne G. Differentiation of mammalian embryonic gonad. Physiological reviews, v. 66, n. 1, p. 71-117, 1986. CAPEL, Blanche et al. Migration of mesonephric cells into the mammalian gonad depends on Sry. Mechanisms of development, v. 84, n. 1-2, p. 127-131, 1999. CAPEL, Blanche. The battle of the sexes. Mechanisms of development, v. 92, n. 1, p. 89-103, 2000. DERIVAUX, Jules; BARNABÉ, Renato Campanarut. Reprodução dos animais domésticos. Zaragoza: Acribia, 1980. DOMENICE, Sorahia et al. Aspectos moleculares da determinação e diferenciação sexual. Arquivos Brasileiros de Endocrinologia & Metabologia, v. 46, n. 4, p. 433-443, 2002. DONAHOE, Patricia K. et al. Mullerian inhibiting substance activity in bovine fetal, newborn and prepubertal testes. Biology of reproduction, v. 16, n. 2, p. 238-243, 1977. HAFEZ, Elsayed Saad Eldin; HAFEZ, B. Reprodução animal. São Paulo: Manole, 2004. HANLEY, Neil A. et al. Steroidogenic factor 1 (SF-1) is essential for ovarian development and function. Molecular and cellular endocrinology, v. 163, n. 1-2, p. 27-32, 2000. HIORT, Olaf; PAUL-MARTIN, H. The molecular basis of male sexual differentiation. European journal of endocrinology, v. 142, n. 2, p. 101-110, 2000. HOLY, Lubos; MARTÍNEZ JÚSTIZ, G. Colab. Biología de la reproducción bovina. Havana: Revolucionária, 1975. JOSSO, Nathalie et al. The role of anti-Müllerian hormone in gonadal development. Molecular and cellular endocrinology, v. 145, n. 1-2, p. 3-7, 1998. JOST, Alfred et al. Studies on sex differentiation in mammals. In: Proceedings of the 1972 Laurentian Hormone Conference. Londres: Academic Press, 1973. p. 1-41. KNOBIL, Ernst. Knobil and Neill's physiology of reproduction. EUA: Gulf Professional Publishing, 2006. KOFMAN ALFARO, S.; MERCHANT LARIOS, H.; PEREZ PALACIOS, G. Diferenciacion sexual. I. Bases biologicas del dimorfismo sexual. Rev. invest. clín, p. 349-59, 1982. KOOPMAN, Peter. Sry and Sox9: mammalian testis-determining genes. Cellular and Molecular Life Sciences CMLS, v. 55, n. 6-7, p. 839-856, 1999. MCDONALD, L. E. Veterinary endocrinology. Lea & Febiger, Philadelphia, Pa, 1969. MEIZEL, S.; JOHNSON, M. H. Development in mammals. MH Johnson, Ed, v. 3, p. 1-64, 1978. MELLO, Maricilda Palandi de; ASSUMPÇÃO, Juliana de G.; HACKEL, Christine. Genes envolvidos na determinação e diferenciação do sexo. Arquivos Brasileiros de Endocrinologia & Metabologia, v. 49, n. 1, p. 14-25, 2005. -/- REFERÊNCIAS BIBLIOGRÁFICAS MERCHANT-LARIOS, H. Ovarian differentiation. The Vertebrate Ovary, p. 47-81, 1978. MIES FILHO, Antonio. Reprodução dos animais. Porto Alegre: Sulina, 1987. NEF, Serge; PARADA, Luis F. Hormones in male sexual development. Genes & Development, v. 14, n. 24, p. 3075-3086, 2000. PARKER, Keith L.; SCHEDL, Andreas; SCHIMMER, Bernard P. Gene interactions in gonadal development. Annual review of physiology, v. 61, n. 1, p. 417-433, 1999. SWAIN, Amanda; LOVELL-BADGE, Robin. Mammalian sex determination: a molecular drama. Genes & development, v. 13, n. 7, p. 755-767, 1999. WILHELM, Dagmar; PALMER, Stephen; KOOPMAN, Peter. Sex determination and gonadal development in mammals. Physiological reviews, v. 87, n. 1, p. 1-28, 2007. WILSON, Jean D.; GRIFFIN, James E.; GEORGE, Fredrick W. Sexual differentiation: early hormone synthesis and action. Biology of reproduction, v. 22, n. 1, p. 9-17, 1980. -/- Emanuel Isaque Cordeiro da Silva Belo Jardim, 07 de Maio de 2020. (shrink)

The practice of medicine frequently involves the unconsented restriction of liberty. The reasons for unilateral liberty restrictions are typically that being confined, strapped down, or sedated are necessary to prevent the person from harming themselves or others. In this paper, we target the ethics of chemical restraints, which are medications that are used to intentionally restrict the mental states associated with the unwanted behaviors, and are typically not specifically indicated for the condition for which the patient is being treated. Specifically, (...) we aim to identify the conditions under which chemical restraints are ethically permissible. It is wrong to assume that what is morally true of physical restraints is also true of chemical restraints. Our aim is thus to identify the conditions under which chemical restraints are permissible while distinguishing these conditions from those of the application of physical restraints. (shrink)

Some theorists argue that moral bioenhancement ought to be compulsory. I take this argument one step further, arguing that if moral bioenhancement ought to be compulsory, then its administration ought to be covert rather than overt. This is to say that it is morally preferable for compulsory moral bioenhancement to be administered without the recipients knowing that they are receiving the enhancement. My argument for this is that if moral bioenhancement ought to be compulsory, then its administration is a matter (...) of public health, and for this reason should be governed by public health ethics. I argue that the covert administration of a compulsory moral bioenhancement program better conforms to public health ethics than does an overt compulsory program. In particular, a covert compulsory program promotes values such as liberty, utility, equality, and autonomy better than an overt program does. Thus, a covert compulsory moral bioenhancement program is morally preferable to an overt moral bioenhancement program. (shrink)

As the science and technology of the brain and mind develop, so do the ways in which brains and minds may be surveilled and manipulated. Some cognitive libertarians worry that these developments undermine cognitive liberty, or “freedom of thought.” I argue that protecting an individual’s cognitive liberty undermines others’ ability to use their own cognitive liberty. Given that the threatening devices and processes are not relevantly different from ordinary and frequent intrusions upon one’s brain and mind, strong protections of cognitive (...) liberty may proscribe neurotechnological intrusions, but also ordinary intrusions. Thus, the cognitive libertarian position “hog-ties” others’ use of their own liberties. This problem for the cognitive libertarian is the same problem that ordinary libertarianism faces in protecting individual rights to property and person. But the libertarian strategies for resolving the problem don’t work for the cognitive libertarian. I conclude that the right to mental privacy is weaker than what cognitive libertarians want it to be. (shrink)

Epistemic burdens – the nature and extent of our ignorance (that and how) with respect to various courses of action – serve to determine our incentive structures. Courses of action that seem to bear impossibly heavy epistemic burdens are typically not counted as options in an actor’s menu, while courses of action that seem to bear comparatively heavy epistemic burdens are systematically discounted in an actor’s menu relative to options that appear less epistemically burdensome. That ignorance serves to determine what (...) counts as an option means that epistemic considerations are logically prior to moral, prudential, and economic considerations: in order to have moral, prudential, or economic obligations, one must have options, and epistemic burdens serve to determine our options. One cannot have obligations without doing some epistemic work. We defend this claim on introspective grounds. We also consider how epistemic burdens distort surrogate decision-making. The unique epistemology of surrogate cases makes the priority of the epistemic readily apparent. We then argue that anyone who accepts a principle similar to ought implies can is committed to the logical priority of the epistemic. We also consider and reject several possible counterarguments. -/- . (shrink)

It has recently been argued that a person’s moral judgments (about both their own and others’ actions) are constrained by the nature and extent of their relevant ignorance and, thus, that such judgments are determined in the first instance by the person’s epistemic circumstances. It has been argued, in other words, that the epistemic is logically prior to other normative (e.g., ethical, prudential, pecuniary) considerations in human decision-making, that these other normative considerations figure in decision-making only after (logically and temporally) (...) relevant ignorance has constrained the decision-maker’s menu of options. If this is right, then a person’s moral judgments in some set of circumstances should vary with their knowledge and ignorance of these circumstances. In this study, we test the hypothesis of the logical priority of the epistemic. We describe two experiments in which subjects’ knowledge and ignorance of relevant consequences were manipulated. In the second experiment, we also compared the effect of ignorance on moral judgments with that of personal force, a factor previously shown to influence moral judgments. We found broad empirical support for the armchair arguments that epistemic considerations are logically prior to normative considerations. (shrink)

Despite the lack of evidence for their effectiveness, the use of physical restraints for patients is widespread. The best ethical justification for restraining patients is that it prevents them from harming themselves. We argue that even if the empirical evidence supported their effectiveness in achieving this aim, their use would nevertheless be unethical, so long as well known exceptions to informed consent fail to apply. Specifically, we argue that ethically justifiable restraint use demands certain necessary and sufficient conditions. These conditions (...) are that the physician obtain informed consent for their application, that their application be medically appropriate, and that restraints be the least liberty-restricting way of achieving the intended benefit. It is a further question whether their application is ever medically appropriate, given the dearth of evidence for their effectiveness. (shrink)

What is W. V. O. Quine’s relationship to classical pragmatism? Although he resists the comparison to William James in particular, commentators have seen an affinity between his “web of belief” model of theory confirmation and James’s claim that our beliefs form a “stock” that faces new experience as a corporate body. I argue that the similarity is only superficial. James thinks our web of beliefs should be responsive not just to perceptual but also to emotional experiences in (...) some cases; Quine denies this. I motivate James’s controversial view by appealing to an episode in the history of medicine when a researcher self-experimented by swallowing a vial of bacteria that at the time had not been studied in much detail. The researcher’s commitment to his own as-yet untested hypothesis was based in part on emotional considerations. Finally, I argue that Quine’s insistence that emotions can never be relevant to adjusting our web of belief reflects a tacit holdover of one of logical positivism’s crucially anti-pragmatist commitments—that philosophy of science should focus exclusively on the context of justification, not the context of discovery. James’s emphasis on discovery as a (perhaps the) crucial locus for epistemological inquiry is characteristic of pragmatism in general. Since Quinean epistemology is always an epistemology of justification, he is not happily viewed as a member of the pragmatist tradition. (shrink)

Hubert Dreyfus has argued that cases of absorbed bodily coping show that there is no room for self-awareness in flow experiences of experts. In this paper, I argue against Dreyfus’ maxim of vanishing self-awareness by suggesting that awareness of agency is present in expert bodily action. First, I discuss the phenomenon of absorbed bodily coping by discussing flow experiences involved in expert bodily action: merging into the flow; immersion in the flow; emergence out of flow. I argue against the claim (...) that flow experience does not involve an awareness of agency for each of these features, while conceding that fluent agency does not involve self-awareness in the thetic sense. I challenge the assumption that the awareness of fluent agency must be understood in terms of a thetic awareness of agency. Instead, I develop an Anscombean account of the awareness of fluent agency in terms of the phenomenal character of knowing one’s aims. I respond to the challenge that if an Anscombean account of the awareness of agency is to succeed, then agents must be able to answer Anscombean questions. I consider the objection that awareness of agency is not a form of self-awareness by outlining an account of self-awareness as self-synthesis that is distinct from self-perception and self-ascription, but which makes room for self-awareness in expert bodily action. (shrink)

In biomedical ethics, there is widespread acceptance of moral realism, the view that moral claims express a proposition and that at least some of these propositions are true. Biomedical ethics is also in the business of attributing moral obligations, such as “S should do X.” The problem, as we argue, is that against the background of moral realism, most of these attributions are erroneous or inaccurate. The typical obligation attribution issued by a biomedical ethicist fails to truly capture the person's (...) actual obligations. We offer a novel argument for rife error in obligation attribution. The argument starts with the idea of an epistemic burden. Epistemic burdens are all of those epistemic obstacles one must surmount in order to achieve some aim. Epistemic burdens shape decision-making such that given two otherwise equal options, a person will choose the option that has the lesser of epistemic burdens. Epistemic burdens determine one's potential obligations and, conversely, their non-obligations. The problem for biomedical ethics is that ethicists have little to no access to others' epistemic burdens. Given this lack of access and the fact that epistemic burdens determine potential obligations, biomedical ethicists often can only attribute accurate obligations out of luck. This suggests that the practice of attributing obligations in biomedical ethics is rife with error. To resolve this widespread error, we argue that this practice should be abolished from the discourse of biomedical ethics. (shrink)

There is recent empirical evidence that personal identity is constituted by one’s moral traits. If true, this poses a problem for those who advocate for moral enhancement, or the manipulation of a person’s moral traits through pharmaceutical or other biological means. Specifically, if moral enhancement manipulates a person’s moral traits, and those moral traits constitute personal identity, then it is possible that moral enhancement could alter a person’s identity. I go a step further and argue that under the right conditions, (...) moral enhancement can constitute murder. I then argue that these conditions are not remote. (shrink)

In a recent issue of Bioethics, I argued that compulsory moral bioenhancement should be administered covertly. Alexander Zambrano has criticized this argument on two fronts. First, contrary to my claim, Zambrano claims that the prevention of ultimate harm by covert moral bioenhancement fails to meet conditions for permissible liberty‐restricting public health interventions. Second, contrary to my claim, Zambrano claims that covert moral bioenhancement undermines autonomy to a greater degree than does overt moral bioenhancement. In this paper, I rebut both of (...) these arguments, then finish by noting important avenues of research that Zambrano’s arguments motivate. (shrink)

It is plausible that current generations owe something to future generations. One possibility is that we have a duty to not harm them. Another possibility is that we have a duty to protect them. In either case, however, to satisfy the duties to future generations from environmental or political degradation, we need to engage in widespread collective action. But, as we are, we have a limited ability to do so, in part because we lack the self-discipline necessary for successful collective (...) action. Given that having an obligation hinges on being able to satisfy it, the apparent duty to future generations is at odds with our apparent inability to satisfy it. Thus, we either need to rethink our duties to future generations or rethink the nature of our abilities. I argue in this chapter that we should rethink the nature of our abilities. Specifically, we should enhance our self-discipline, which is distinct from enhancements of motivation, judgment, or emotion. Even the most intelligent, motivated, and empathetic actor is likely to slip up, which encourages others to withdraw their cooperation. Without the necessary self-discipline to sustain our public cooperative behavior, collective action is likely to fail, leaving us with one alternative: to abandon our duties to future generations. (shrink)

Moral bioenhancement is the potential practice of manipulating individuals’ moral behaviors by biological means in order to help resolve pressing moral issues such as climate change and terrorism. This practice has obvious ethical implications, and these implications have been and continue to be discussed in the bioethics literature. What have not been discussed are the epistemological implications of moral bioenhancement. This article details some of these implications of engaging in moral bioenhancement. The argument begins by making the distinction between moral (...) bioenhancement that manipulates the contents of mental states and that which manipulates other, non-representational states. Either way, I argue, the enhanced moral psychology will fail to conform to epistemic norms, and the only way to resolve this failure and allow the moral bioenhancement to be effective in addressing the targeted moral issues is to make the moral bioenhancement covert. (shrink)

It has recently been argued that a person’s moral judgments (about both their own and others’ actions) are constrained by the nature and extent of their relevant ignorance and, thus, that such judgments are determined in the first instance by the person’s epistemic circumstances. It has been argued, in other words, that the epistemic is logically prior to other normative (e.g., ethical, prudential, pecuniary) considerations in human decision-making, that these other normative considerations figure in decision-making only after (logically and temporally) (...) relevant ignorance has constrained the decision-maker’s menu of options. If this is right, then a person’s moral judgments in some set of circumstances should vary with their knowledge and ignorance of these circumstances. In this study, we test the hypothesis of the logical priority of the epistemic. We describe two experiments in which subjects’ knowledge and ignorance of relevant consequences were manipulated. In the second experiment, we also compared the effect of ignorance on moral judgments with that of personal force, a factor previously shown to influence moral judgments. We found broad empirical support for the armchair arguments that epistemic considerations are logically prior to normative considerations. (shrink)

As the federal government distributed remdesivir to some of the states COVID-19 hit hardest, policymakers scrambled to develop criteria to allocate the drug to their hospitals. Our state, Michigan, was among those states to receive an initial quantity of the drug from the U.S. government. The disparities in burden of disease in Michigan are striking. Detroit has a death rate more than three times the state average. Our recommendation to the state was that it should prioritize the communities that bear (...) a disproportionate burden of suffering in the allocation of the new potential treatment. This recommendation is justified not only for new drugs with uncertain effects, but also for drugs of certain benefit or vaccines. For states with significant health disparities, such as Michigan, this allocation priority may help to repair them. In fact, any other allocation strategy may make them worse. (shrink)

Most current dental ethics curricula use a deontological approach to biomedical and dental ethics that emphasizes adherence to duties and principles as properties that determine whether an act is ethical. But the actual ethical orientation of students is typically unknown. The purpose of the current study was to determine the ethical orientation of dental students in resolving clinical ethical dilemmas. First-year students from one school were invited to participate in an electronic survey that included eight vignettes featuring ethical conflicts common (...) to the health care setting. The Multidimensional Ethics Scale was used to evaluate the students’ ethical judgments of these conflicts. Students rated each vignette along 13 ethically relevant items using a 7-point scale. Nine of the thirteen items were analyzed because they represent the dominant ethical theories, including deontology. One hundred sixteen dental students successfully completed the survey. Of the analyzed items, those associated with deontology had comparatively weak associations with whether students judged the action to be ethical and whether students judged themselves likely to perform the action. Whether an action was judged to be caring had the strongest association with whether the action was judged to be ethical and whether students judged themselves likely to perform the action. These results suggest that adherence to duties or principles has weaker association with students’ ethical judgments and behavior compared to caring, which was found to be more influential in their ethical judgments and behavior. Current dental school curricula with a primary focus on deontology may no. (shrink)

Default positions, predetermined starting points that aid in complex decision-making, are common in clinical medicine. In this article, we identify and critically examine common default positions in clinical ethics practice. Whether default positions ought to be held is an important normative question, but here we are primarily interested in the descriptive, rather than normative, properties of default positions. We argue that default positions in clinical ethics function to protect and promote important values in medicine—respect for persons, utility, and justice. Further, (...) default positions in clinical ethics may also guard against harm. Where default positions exist, there are epistemic burdens to overturn them. The person wishing to reject the default position, rather than the person endorsing it, bears this burden. The person who bears the burden of meeting the epistemic requirements must provide evidence proportional to the degree of harm the default position protects against. Default positions that protect against significant harm impose significant epistemic requirements to overturn. This asymmetry not only makes medical decision-making more economical but also serves to promote and protect certain values. The identification and analysis of common and recognizable default positions can help to identify other default positions and the conditions under which their associated epistemic requirements are met. The article concludes with considerations of potential problems with the use of default positions in clinical ethics. (shrink)

We aim to establish the following claim: other factors held constant, the relative weights of the epistemic burdens of competing treatment options serve to determine the options that patient surrogates pursue. Simply put, surrogates confront an incentive, ceteris paribus, to pursue treatment options with respect to which their knowledge is most adequate to the requirements of the case. Regardless of what the patient would choose, options that require more knowledge than the surrogate possesses (or is likely to learn) will either (...) be neglected altogether or deeply discounted in the surrogate’s incentive structure. We establish this claim by arguing that the relation between epistemic burdens and incentives in decision-making is a general feature of surrogate decision-making. After establishing the claim, we draw out some of the implications for surrogate decision-making in medicine and offer philosophical and psychological explanations of the phenomenon. (shrink)

Brummett and Salter propose a useful and timely taxonomy of clinical ethics expertise (2019). As the field becomes further “professionalized” this taxonomy is important, and the core of it is right. It needs some refinement around the edges, however. In their conclusion, Brummett and Salter rightly point out that there is a significant difference between the ethicist whose recommendations are procedure- and process-heavy, consensus-driven, and dialogical and the authoritarian ethicist whose recommendations flow from “private moral views” (Brummett and Salter, 2019). (...) This admission doesn’t go far enough. Brummett and Salter’s taxonomy fails to capture the notion that offering recommendations whose normative force is moral is different in kind from recommendations whose normative force is non-moral, such as those recommendations that are free of moral content or justified by convention. The difference is in kind, not scale. I argue further that clinical ethics expertise, if possible, consists at least in offering recommendations whose normative force is moral. These two claims imply that the taxonomy fails to cut clinical ethics expertise at the joints: the ethicist who offers justified non-moral normative recommendations is a different kind of ethicist from the one who offers justified moral normative recommendations, yet both are categorized as clinical ethics experts. I finish by offering a refinement of the taxonomy that more precisely categorizes clinical ethicists. (shrink)

We thank all the thoughtful authors for their insightful comments. In this response, we try to address some of themes that emerged from the commentaries. We leave aside some of those comments that...

Humans are morally deficient in a variety of ways. Some of these deficiencies threaten the continued existence of our species. For example, we appear to be incapable of responding to climate change in ways that are likely to prevent the consequent suffering. Some people are morally better than others, but we could all be better. The price of not becoming morally better is that when those events that threaten us occur, we will suffer from them. If we can prevent this (...) suffering from occurring, then we ought to do so. That we ought to make ourselves morally better in order to prevent very bad things from happening justifies, according to some, the development and administration of moral enhancement. I address in this paper the idea that moral enhancement could give rise to moral transhumans, or moral post-persons. Contrary to recent arguments that we shouldn’t engender moral post-persons, I argue that we should. Roughly, the reasons for this conclusion are that we can expect moral post-persons to resemble the morally best of us, our moral exemplars. Since moral exemplars promote their interests by promoting the interests of others (or they promote others’ interests at the expense of their own) we can expect moral post-persons to pursue our interests. Since we should also pursue our own interests, we should bring about moral post-persons. (shrink)

Various thinkers are concerned that the Orthodox view of Ancestral Sin does not avoid the age-old Augustinian concern of Pelagianism. After all, the doctrine of Ancestral Sin maintains that fallen human beings do not necessarily or inevitably commit actual sins. In contemporary literature, this claim could be articulated as a denial of the ‘inevitability thesis.’ A denial of the inevitability thesis, so contemporary thinkers maintain, seems to imply both that human beings can place themselves in right relation to God as (...) well as the Pelagian denial that all require Christ's work to attain this right relation to God. This article demonstrates that the Ancestral Sin, along with a denial of the inevitability thesis, is neither Pelagian nor Semi-Pelagian. I show that the doctrine of Ancestral Sin denies (Semi-) Pelagianism in various ways. I show that, for Ancestral Sin to entail (Semi-) Pelagianism, one must commit to several assumptions, each of which is plausibly deniable and none of which Orthodox thinkers affirm. (shrink)

PURPOSE: The conventional wisdom in dental and medical education is that dental and medical students experience "ethical erosion" over the duration of dental and medical school. There is some evidence for this claim, but in the case of dental education this evidence consists entirely of survey research, which doesn't measure behavior. The purpose of this study was to measure the altruistic behavior of dental students, in order to fill the significant gap in knowledge of how students are disposed to behave, (...) rather than how they are disposed to think. -/- METHODS: To test the altruistic behavior of dental students, we conducted a field experiment using the Ultimatum Game, which is a game commonly used in economics to observe social behavior. Students from each of the four years of dental school played the game in standardized conditions with real money. -/- RESULTS: Students exhibited greater levels of altruism than the general population typically does. Students' altruism peaked in year four. Students' altruism was associated with the socioeconomic status of responder. -/- CONCLUSION: The results suggest that that dental students are more altruistic than the population average and that altruism increases during their education. Thus, if a decreasing ability to behave altruistically is observed during dental school, it is not likely due to a general disposition of students, but rather some factor specific to the educational environment in which the decrease is observed. (shrink)

Augustine’s privation theory of evil maintains that something is evil in virtue of a privation, a lack of something which ought to be present in a particular nature. While it is not evil for a human to lack wings, it is indeed evil for a human to lack rationality according to the end of a rational nature. Much of the literature on the privation theory focuses on whether it can successfully defend against counterexamples of positive evils, such as pain. This (...) focus of the discussion is not surprising, given that the privation theory is a theory about the nature of evil. But it is also a theory that protects venerable theological concerns, namely, that God is the good creator of everything, and that everything is good. It is the purpose of this article to further this discussion on both fronts. I argue that the counterexample of pain still defeats the privation theory despite the most recent defense. What is more, I suggest, this is not theologically disastrous. The individual who rejects the privation theory is not obligated to reject the theological theses which motivate it. To show how a rejection of the privation theory is a live option, I offer an alternative view of evil that also maintains these theological theses and encompasses both privative and positive evils. (shrink)

Objective: Evidence suggests people experience an oral size illusion and commonly perceive oral size inaccurately; however, the nature of the illusion remains unclear. The objectives of the present study were to confirm the presence of an oral size illusion, determine the magnitude (amount) and direction (underestimation or overestimation) of the illusion, and determine whether immediately prior crossmodal perceptual experiences affected the magnitude and direction. Design: Participants (N = 27) orally assessed 9 sizes of stainless steel spheres (1/16 in to 1/2 (...) in) categorized as small, medium, or big, and matched them with digital and visual reference sets. Each participant completed 20 matching tasks in 3 assessments. For control assessments, 6 oral spheres were matched with reference sets of same-sized spheres. For primer-control assessments, similar to control, 6 matching tasks were preceded by cross-modal experiences of the same-sized sphere. For experimental assessments, 8 matching tasks were preceded by a cross-modal experience of a differently sized sphere. Results: For control assessments, small and medium spheres were consistently underestimated, and big spheres were consistently overestimated. For experimental assessments, magnitude and direction of the oral size illusion varied according to the size of the sphere used in the cross-modal experience. Conclusion: Results seemed to confirm an oral size illusion, but direction of the illusion depended on the size of the object. Immediately prior cross-modal experiences influenced magnitude and direction of the illusion, suggesting that aspects of oral perceptual experience are dependent upon factors outside of oral perceptual anatomy and the properties of the oral stimulus. (shrink)

Berger (forthcoming) states that moral intimacy is important in applying the best interests standard. But what he calls moral intimacy requires that someone has overcome epistemic burdens needed to represent the patient. We argue elsewhere that good surrogate decision-making is first and foremost a matter of overcoming epistemic burdens, or those obstacles that stand in the way of a surrogate decision-maker knowing what a patient wants and how to satisfy those preferences. Berger’s notion of moral intimacy depends on epistemic intimacy: (...) the fact that a surrogate's epistemic burdens with respect to the best interests of the incapacitated patient have been adequately surmounted, plus some other feature. Thus, where a particular patient-surrogate relationship fails to be morally intimate, what is lacking is either epistemic intimacy or this second feature. Furthermore, Berger uses the notion of moral intimacy as an explanans for the application of the best interests standard. We argue that the notions of epistemic intimacy and epistemic burdens not only help to explain the notion of moral intimacy, but also better explain the application of the best interests standard. Given the role of epistemic burdens and the epistemic intimacy that overcoming them enables, bioethicists and physicians should consider a surrogate’s epistemic standing relative to the patient’s best interests before pronouncing on the former’s ethical probity. (shrink)

Among psychiatric conditions, delusions have received significant attention in the philosophical literature. This is partly due to the fact that many delusions are bizarre, and their contents interesting in and of themselves. But the disproportionate attention is also due to the notion that by studying what happens when perception, cognition, and belief go wrong, we can better understand what happens when these go right. In this paper, I attend to delusions for the second reason—by evaluating the epistemology of delusions, we (...) can better understand the epistemology of ordinary belief. More specifically, given recent advancements in our understanding of how delusions are formed, the epistemology of delusions motivates a proper functionalist account of the justification of belief. Proper functionalist accounts of the justification of belief hold that whether a belief is justified is partly determined by whether the system that produces the belief is functioning properly. Whatever pathology is responsible for delusion formation, restoring it to its proper function resolves the epistemic condition, an effect which motivates proper functionalism. (shrink)

We critically engage two traditional views of scientific data and outline a novel philosophical view that we call the pragmatic-representational view of data. On the PR view, data are representations that are the product of a process of inquiry, and they should be evaluated in terms of their adequacy or fitness for particular purposes. Some important implications of the PR view for data assessment, related to misrepresentation, context-sensitivity, and complementary use, are highlighted. The PR view provides insight into the common (...) but little-discussed practices of iteratively reusing and repurposing data, which result in many datasets’ having a phylogeny—an origin and complex evolutionary history—that is relevant to their evaluation and future use. We relate these insights to the open-data and data-rescue movements, and highlight several future avenues of research that build on the PR view of data. (shrink)

The Monad’s components are as follows: 1: Monism as the state of eternal undifferentiation 2: Dualism as the state of infinite differentiations -/- MONAD = ET = INF ET Ψ INF.

The collapse of society is inevitable, even if it is in the distant future. When it collapses, it is likely to do so within the lifetimes of some people. These people will have matured in pre-collapse society, experience collapse, and then live the remainder of their lives in the post-collapse world. I argue that this group of people—the transitional generation—will be the worst off from societal collapse, far worse than subsequent generations. As the transitional generation, they will suffer disparately. This (...) intergenerational disparity in suffering is inequitable. Given that other disparities in suffering are worthy of remediation, this intergenerational disparity in suffering is worthy of remediation. However, the only way to do so is to target the mental states of the members of the transitional generation. (shrink)