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)

Episodic memory is memory for past events. It’s characteristically associated with an experience of ‘mentally replaying’ one’s experiences in the mind’s eye. This biological phenomenon has inspired the development of several ‘experience replay’ algorithms in AI. In this chapter, I ask whether experience replay algorithms might shed light on a puzzle about episodic memory’s function: what does episodic memory contribute to the cognitive systems in which it is found? I argue that experience replay algorithms can serve as idealized models of (...) episodic memory for the purposes of addressing this question. Taking the DQN algorithm as a case study, I suggest that these algorithms provide some support for mnemonic accounts, on which episodic memory’s function lies in the storage, encoding and retrieval of information. By extending and adapting experience replay algorithms, we might gain further insight into episodic memory’s operations and contributions to cognition. (shrink)

Many recent AI systems take inspiration from biological episodic memory. Here, we ask how these ‘episodic-inspired’ AI systems might inform our understanding of biological episodic memory. We discuss work showing that these systems implement some key features of episodic memory whilst differing in important respects, and appear to enjoy behavioural advantages in the domains of strategic decision-making, fast learning, navigation, exploration and acting over temporal distance. We propose that these systems could be used to evaluate competing theories of episodic memory’s (...) operations and function. However, further work is needed to validate them as models of episodic memory and isolate the contributions of their memory systems to their behaviour. More immediately, we propose that these systems have a role to play in directing episodic memory research by highlighting novel or neglected hypotheses as pursuit-worthy. In this vein, we propose that the evidence reviewed here highlights two pursuit-worthy hypotheses about episodic memory’s function: that it plays a role in planning that is independent of future-oriented simulation, and that it is adaptive in virtue of its contributions to fast learning in novel, sparse-reward environments. (shrink)

Where does the mind begin and end? Most philosophers and cognitive scientists take the view that the mind is bounded by the skull or skin of the individual. Robert Wilson, in this provocative and challenging 2004 book, provides the foundations for the view that the mind extends beyond the boundary of the individual. The approach adopted offers a unique blend of traditional philosophical analysis, cognitive science, and the history of psychology and the human sciences. The companion volume, Genes and (...) the Agents of Life, explores the theme in the biological sciences. Written with verve and clarity, this ambitious book will appeal to a broad swathe of professionals and students in philosophy, psychology, cognitive science, and the history of the behavioural and human sciences. You can download the table of contents here. (shrink)

1. The Situation in Cognition 2. Situated Cognition: A Potted Recent History 3. Extensions in Biology, Computation, and Cognition 4. Articulating the Idea of Cognitive Extension 5. Are Some Resources Intrinsically Non-Cognitive? 6. Is Cognition Extended or Only Embedded? 7. Letting Nature Take Its Course.

David Sloan Wilson has recently revived the idea of a group mind as an application of group selectionist thinking to cognition. Central to my discussion of this idea is the distinction between the claim that groups have a psychology and what I call the social manifestation thesis-a thesis about the psychology of individuals. Contemporary work on this topic has confused these two theses. My discussion also points to research questions and issues that Wilson's work raises, as well as (...) their connection to externalist conceptions of the mind familiar since the work of Putnam and Burge. (shrink)

Essentialism is widely regarded as a mistaken view of biological kinds, such as species. After recounting why (sections 2-3), we provide a brief survey of the chief responses to the “death of essentialism” in the philosophy of biology (section 4). We then develop one of these responses, the claim that biological kinds are homeostatic property clusters (sections 5-6) illustrating this view with several novel examples (section 7). Although this view was first expressed 20 years ago, and has received recent discussion (...) and critique, it remains underdeveloped and is often misrepresented by its critics (section 8). (shrink)

In the latter half of the twentieth century, philosophers of science have argued (implicitly and explicitly) that epistemically rational individuals might compose epistemically irrational groups and that, conversely, epistemically rational groups might be composed of epistemically irrational individuals. We call the conjunction of these two claims the Independence Thesis, as they together imply that methodological prescriptions for scientific communities and those for individual scientists might be logically independent of one another. We develop a formal model of scientific inquiry, define four (...) criteria for individual and group epistemic rationality, and then prove that the four definitions diverge, in the sense that individuals will be judged rational when groups are not and vice versa. We conclude by explaining implications of the inconsistency thesis for (i) descriptive history and sociology of science and (ii) normative prescriptions for scientific communities. (shrink)

Jim Joyce argues for two amendments to probabilism. The first is the doctrine that credences are rational, or not, in virtue of their accuracy or “closeness to the truth” (1998). The second is a shift from a numerically precise model of belief to an imprecise model represented by a set of probability functions (2010). We argue that both amendments cannot be satisfied simultaneously. To do so, we employ a (slightly-generalized) impossibility theorem of Seidenfeld, Schervish, and Kadane (2012), who show that (...) there is no strictly proper scoring rule for imprecise probabilities. -/- The question then is what should give way. Joyce, who is well aware of this no-go result, thinks that a quantifiability constraint on epistemic accuracy should be relaxed to accommodate imprecision. We argue instead that another Joycean assumption — called strict immodesty— should be rejected, and we prove a representation theorem that characterizes all “mildly” immodest measures of inaccuracy. (shrink)

Comparative cognitive science often involves asking questions like ‘Do nonhumans have C?’ where C is a capacity we take humans to have. These questions frequently generate unproductive disagreements, in which one party affirms and the other denies that nonhumans have the relevant capacity on the basis of the same evidence. I argue that these questions can be productively understood as questions about natural kinds: do nonhuman capacities fall into the same natural kinds as our own? Understanding such questions in this (...) way has several advantages: it preserves the intuition that these are substantive empirical questions worth asking; it helps us to understand why they so frequently give rise to disagreements of the kind described; and it provides clues about how to diagnose and resolve them. (shrink)

Uptake is typically understood as the hearer’s recognition of the speaker’s communicative intention. According to one theory of uptake, the hearer’s role is merely as a ratifier. The speaker, by expressing a particular communicative intention, predetermines what kind of illocutionary act she might perform. Her hearer can then render this act a success or a failure. Thus the hearer has no power over which act could be performed, but she does have some power over whether it is performed. Call this (...) the ratification theory of uptake. Several philosophers have recently endorsed an alternative theory of uptake, according to which the hearer can determine the nature of the act the speaker performs. According to this theory, if the hearer regards an utterance as illocutionary act y, then it is act y, even if the speaker intended to perform act x. Call this the constitution theory of uptake. The purported advantage of this theory is that it identifies a common but underanalysed way in which speakers can be silenced. I argue that despite its initial intuitive pull, the constitution theory of uptake should be rejected. It is incompatible with ordinary intuitions about speech, it entails a conceptual impossibility, and it has unsavoury political implications, entailing that marginalised speakers barely qualify as agents. (shrink)

While memory is conceptualized predominantly as an individual capacity in the cognitive and biological sciences, the social sciences have most commonly construed memory as a collective phenomenon. Collective memory has been put to diverse uses, ranging from accounts of nationalism in history and political science to views of ritualization and commemoration in anthropology and sociology. These appeals to collective memory share the idea that memory ‘‘goes beyond the individual’’ but often run together quite different claims in spelling out that idea. (...) This paper reviews a sampling of recent work on collective memory in the light of emerging externalist views within the cognitive sciences, and through some reflection on broader traditions of thought in the biological and social sciences that have appealed to the idea that groups have minds. The paper concludes with some thoughts about the relationship between these kinds of cognitive metaphors in the social sciences and our notion of agency. (shrink)

Introduction in chapter viii of book ii of An Essay Concerning Human Understanding, John Locke provides various putative lists of primary qualities. Insofar as they have considered the variation across Locke's lists at all, commentators have usually been content simply either to consider a self-consciously abbreviated list (e.g., "Size, Shape, etc.") or a composite list as the list of Lockean primary qualities, truncating such a composite list only by omitting supposedly co-referential terms. Doing the latter with minimal judgment about what (...) terms are co-referential gives us the following list of eleven qualities (in the order in which they appear in this chapter of the Essay): solidity, extension, figure, mobility, motion or rest, number, bulk, texture, motion, size, and situation. Perhaps surprisingly given the attention to the primary/secondary distinction since Locke, Locke's primary qualities themselves have received little more than passing mention in the bulk of the subsequent literature. In particular, no discussion both offers an interpretation of Locke's conception of primary qualities and makes sense of Locke's various lists as lists of primary qualities. A central motivation for this paper is the idea that these two tasks are not independent. (shrink)

Who is recognised as a philosopher and what counts as philosophy influence both the content of a philosophical education and academic philosophy’s continuing demographic skew. The “philosophical who” and the “philosophical what” themselves are a partial function of matters that have been passed over in collective silence, even if that now feels to some like a silence belonging to the distant past. This paper discusses some philosophical silences regarding race, gender, and disability in the context of reflection on philosophical education (...) and on philosophical practice in the public sphere. It focuses on Charles Mills’ writings on race, Susan Babbitt’s on race and gender, and on more collaboratively-generated work on eugenics and disability. (shrink)

In this paper I offer a philosophical analysis of the act of ‘liking’ a post on social media. First, I consider what it means to ‘like’ something. I argue that ‘liking’ is best understood as a phatic gesture; it signals uptake and anoints the poster’s positive face. Next, I consider how best to theorise the power that comes with amassing many ‘likes’. I suggest that ‘like’ tallies alongside posts institute and record a form of digital social capital. Finally, I consider (...) whether ‘likes’ have ultimately improved online discourse. I argue that while the ‘liking’ function itself is relatively innocuous, public ‘like’ tallies introduce a corrosive motivation to online communication. By making the prospect of increased social capital perpetually salient to us, they encourage us to prioritise high levels of engagement over meaningful engagement. (shrink)

This paper introduces and defends a new principle for when a structural equation model is apt for analyzing actual causation. Any such analysis in terms of these models has two components: a recipe for reading claims of actual causation off an apt model, and an articulation of what makes a model apt. The primary focus in the literature has been on the first component. But the problem of structural isomorphs has made the second especially pressing (Hall 2007; Hitchcock 2007a). Those (...) with realist sympathies have reason to resist the standard response to this problem, which introduces a normative parameter into the metaphysics (Hall 2007; Halpern and Hitchcock 2010, 2015; Halpern 2016a; Menzies 2017; Gallow 2021). However, the only alternative solution in the literature leaves central questions unanswered (Blanchard and Schaffer 2017). I propose an independently motivated aptness requirement, Evident Mediation, that provides the missing details and resolves the structural isomorph problem without need for a normative parameter. (shrink)

Eugenic thinking involves distinguishing between sorts or kinds of people in terms of the perceived desirable or undesirable traits that those people are likely to transmit to future generations. While eugenics itself is often thought of as an ideology that generated a social movement of global influence from roughly 1900 to 1945, eugenic thinking both pre-dates this period and continues to inform a range of contemporary debates and social policies, including those concerning prenatal screening, transhumanism, population control, and disability. Various (...) sciences, including the then-nascent sciences of psychology and psychiatry, played important roles in early twentieth-century eugenics, and their legacy is reflected in contemporary eugenic thinking and policies. Understanding the history of eugenics and the role of these early sciences of cognition in that history is useful in reflecting further on ongoing forms of eugenic thinking to which the contemporary cognitive sciences are relevant. (shrink)

This paper examines the standard view of realization operative incontemporary philosophy of mind, and proposes an alternative, generalperspective on realization. The standard view can be expressed, insummary form, as the conjunction of two theses, the sufficiency thesis andthe constitutivity thesis. Physicalists of both reductionist and anti-reductionist persuasions share a conception of realization wherebyrealizations are determinative of the properties they realize and physically constitutive of the individuals with those properties. Centralto the alternative view that I explore here is the idea that (...) the requisite,metaphysically robust notion of realization is ineliminably context-sensitive. I shall argue that the sufficiency and constitutivity theses aretypically not jointly satisfied by any one candidate realizer, and that goingcontext-sensitive in one's metaphysics is preferable to the standard view.The context-sensitive views developed here are implicit in a range ofcommon views in both the philosophy of mind and the philosophy of biology,even if they have not been explicitly articulated, and even though theyundermine other views that are commonly endorsed. (shrink)

This volume of twelve specially commissioned essays about species draws on the perspectives of prominent researchers from anthropology , botany, developmental psychology , the philosophy of biology and science, protozoology, and zoology . The concept of species has played a focal role in both evolutionary biology and the philosophy of biology , and the last decade has seen something of a publication boom on the topic (e.g., Otte and Endler 1989; Ereshefsky 1992b; Paterson 1994; lambert and Spence 1995; Claridge, Dawah, (...) and Wilson 1997; Wheeler and Meier 1999; Howard and Berlocher 1998). (shrink)

Christian B. Miller has noted a “realism challenge” for virtue ethicists to provide an account of how the character gap between virtuous agents and non-virtuous agents can be bridged. This is precisely one of Han Feizi’s key criticisms against Confucian virtue ethics, as Eric L. Hutton argues, which also cuts across the Aristotelian one: appealing to virtuous agents as ethical models provides the wrong kind of guidance for the development of virtues. Hutton, however, without going into detail, notes that the (...) notion of rituals in the Confucian tradition may be able to sidestep Han Feizi’s criticism. In this essay, I wish to explore not only how the notion of rituals, alongside its corollaries in Xunzi’s Confucian program for ethical cultivation, indeed addresses Han Feizi’s criticism, but also observe that Aristotle’s tragic poetry plays functionally equivalent roles in his own understanding of ethical upbringing. I will begin by considering Han Feizi’s critique of ethical cultivation in virtue ethics as such and how it poses a specific problem for the acquisition of the ‘constitutive reasoning’ shared by Aristotle and Xunzi. I will then briefly note that this problem trades on the synthetic structure of human nature found in both Aristotle and Xunzi (the rational/irrational parts of the soul and the heartmind/five faculties), which grounds the way they understand ethical action and agency. Finally, I will suggest how both Aristotle and Xunzi understand the role of the arts in their extensive programme of ethical cultivation, allowing them to respond to Han Feizi’s attack as too narrow a construal of their respective ethical projects. It is hoped that, through this, we may gain a better sense of how more recent virtue ethicists may similarly draw on aesthetic resources for ethical development. (shrink)

Distinctions in fundamentality between different levels of description are central to the viability of contemporary decoherence-based Everettian quantum mechanics (EQM). This approach to quantum theory characteristically combines a determinate fundamental reality (one universal wave function) with an indeterminate emergent reality (multiple decoherent worlds). In this chapter I explore how the Everettian appeal to fundamentality and emergence can be understood within existing metaphysical frameworks, identify grounding and concept fundamentality as promising theoretical tools, and use them to characterize a system of explanatory (...) levels (with associated laws of nature) for EQM. This Everettian level structure encompasses and extends the ‘classical’ levels structure. The ‘classical’ levels of physics, chemistry, biology, etc. are recovered, but they are emergent in character and potentially variable across Everett worlds. EQM invokes an additional fundamental level, not present in the classical levels picture, and a novel potential role for self-location in interlevel metaphysics. When given a modal realist interpretation, EQM also makes trouble for supervenience-based approaches to levels. (shrink)

We evaluate the asymptotic performance of boundedly-rational strategies in multi-armed bandit problems, where performance is measured in terms of the tendency (in the limit) to play optimal actions in either (i) isolation or (ii) networks of other learners. We show that, for many strategies commonly employed in economics, psychology, and machine learning, performance in isolation and performance in networks are essentially unrelated. Our results suggest that the appropriateness of various, common boundedly-rational strategies depends crucially upon the social context (if any) (...) in which such strategies are to be employed. (shrink)

We introduce two notions–the shadows and the shallows of explanation–in opening up explanation to broader, interdisciplinary investigation. The shadows of explanation refer to past philosophical efforts to provide either a conceptual analysis of explanation or in some other way to pinpoint the essence of explanation. The shallows of explanation refer to the phenomenon of having surprisingly limited everyday, individual cognitive abilities when it comes to explanation. Explanations are ubiquitous, but they typically are not accompanied by the depth that we might, (...) prima facie, expect. We explain the existence of the shadows and shallows of explanation in terms of there being a theoretical abyss between explanation and richer, theoretical structures that are often attributed to people. We offer an account of the shallows, in particular, both in terms of shorn-down, internal, mental machinery, and in terms of an enriched, public symbolic environment, relative to the currently dominant ways of thinking about cognition and the world. (shrink)

The Eugenic Mind Project is a wide-ranging, philosophical book that explores and critiques both past and present eugenic thinking, drawing on the author’s intimate knowledge of eugenics in North America and his previous work on the cognitive, biological, and social sciences, the fragile sciences. Informed by the perspectives of Canadian eugenics survivors in the province of Alberta, The Eugenic Mind Project recounts the history of eugenics and the thinking that drove it, and critically engages contemporary manifestations of eugenic thought, newgenics. (...) An accessible, original work of scholarship adopting what the author calls a standpoint eugenics, this book focuses on the roots of eugenic thinking past and present. It will provoke and enrich discussions about human nature and human diversity, the social uses of biotechnology, and social policy governing future generations. You can download the preface and acknowledgements here. (shrink)

This paper offers an overview of "the species problem", arguing for a view of species as homeostatic property cluster kinds, positioning the resulting form of realism about species as an alternative to the claim that species are individuals and pluralistic views of species. It draws on taxonomic practice in the neurosciences, especially of neural crest cells and retinal ganglion cells, to motivate both the rejection of the species-as-individuals thesis and species pluralism.

It is widely accepted that there is a visual field, but the analogous notion of an auditory field is rejected by many philosophers on the grounds that the metaphysics or phenomenology of audition lack the necessary spatial or phenomenological structure. In this paper, I argue that many of the common objections to the existence of an auditory field are misguided and that, contrary to a tradition of philosophical scepticism about the spatiality of auditory experience, it is as richly spatial as (...) visual experience—and in some ways even more so. By carefully considering the spatiality and boundedness of audition, along with how sounds or their sources are experienced as occurring within the surrounding acoustic environment, we can gain a better understanding of (i) our auditory experience of space and (ii) the conditions for the existence of spatial sensory fields in general in a way that does not privilege vision over the other senses. (shrink)

Epistemic decision theory (EDT) employs the mathematical tools of rational choice theory to justify epistemic norms, including probabilism, conditionalization, and the Principal Principle, among others. Practitioners of EDT endorse two theses: (1) epistemic value is distinct from subjective preference, and (2) belief and epistemic value can be numerically quantified. We argue the first thesis, which we call epistemic puritanism, undermines the second.

The ontological turn (OT) is a loose cluster of theoretical approaches within cultural anthropology that advocates a synthetic, overarching way forward for ethnographically oriented cultural anthropology. We argue that in order to contribute substantively to ethnobiology the OT needs to distance itself from a long-standing tradition of thinking within ethnography that assumes some kind of fundamental divide between the natural and the social sciences. This distancing seems especially unlikely in light of the meta-anthropological nature of the OT as primarily a (...) perspective on ethnographic methodology. Instead, we advocate for naturalistic theoretical alternatives for thinking about human sociality, where philosophical innovation develops in concert with ongoing empirical work across the biological, cognitive, and social sciences. We illustrate this perspective by drawing on two naturalistic accounts likely to prove more fruitful for ethnobiological practice, namely, trans-genera models of sociality and progenerative views of kinship. (shrink)

In On the Plurality of Worlds (Lewis 1986), David Lewis imposes a condition on realist theories of modality which he calls ‘plenitude’. Lewis apparently assigns this condition considerable importance, and uses it to motivate his Humean principle of recombination, but he never says exactly what plenitude amounts to. This chapter first sets aside some obvious ways of reconstructing the plenitude criterion which do not fit with the textual evidence. An objection to modal realism due to John Divers and Joseph Melia (...) (Divers and Melia 2002) is diagnosed as equivocating between an overly-demanding plenitude constraint and a weaker constraint which fails to establish their conclusion. An alternative deflationary interpretation of the plenitude condition has it following from an application of standard theoretical virtues to a modal realist’s total theory; Lewis’ correspondence provides new evidence in support of this interpretation. The deflationary plenitude criterion also has broader application, beyond Lewisian modal realism. (shrink)

A dynamical system is called chaotic if small changes to its initial conditions can create large changes in its behavior. By analogy, we call a dynamical system structurally chaotic if small changes to the equations describing the evolution of the system produce large changes in its behavior. Although there are many definitions of “chaos,” there are few mathematically precise candidate definitions of “structural chaos.” I propose a definition, and I explain two new theorems that show that a set of models (...) is structurally chaotic if it contains a chaotic function. I conclude by discussing the relationship between structural chaos and structural stability. (shrink)

The conceptualisation of kinship and its study remain contested within anthropology. This paper draws on recent cognitive science, developmental cognitive psychology, and the philosophy of science to offer a novel argument for a view of kinship as progeneratively or reproductively constrained. I shall argue that kinship involves a form of extended cognition that incorporates progenerative facts, going on to show how the resulting articulation of kinship’s progenerative nature can be readily expressed by an influential conception of kinds, the homeostatic property (...) cluster view. Identifying the distinctive role that our extended cognitive access to progenerative facts plays in kinship delivers an integrative, progenerativist view that avoids standard performativist criticisms of progenerativism as being ethnocentric, epistemically naïve, and reductive. (shrink)

Philosophers of biology and biologists themselves for the most part assume that the concept of kin is progenerative: what makes two individuals kin is a direct or indirect function of reproduction. Derivatively, kinship might likewise be presumed to be progenerative in nature. Yet a prominent view of kinship in contemporary cultural anthropology is a kind of constructivism or performativism that rejects such progenerativist views. This paper critically examines an influential line of thinking used to critique progenerativism and support performativism that (...) cites cross-cultural diversity in what I will call kinmaking. I challenge several key assumptions made in moving from this appeal to ethnography to conclusions about kinship and progeneration, arguing that closer scrutiny of both the ethnographic record and inferences that draw on it in fact support progenerative views of both kinship and kinmaking. (shrink)

This paper provides a general introduction to the use of causal models in the metaphysics of causation, specifically structural equation models and directed acyclic graphs. It reviews the formal framework, lays out a method of interpretation capable of representing different underlying metaphysical relations, and describes the use of these models in analyzing causation.

This paper is a critique of some ideas about narrow content owing to Horgan and Tienson and Brian Loar.

Eugenics does not feel so distant from where I stand. This essay explains why.

Speech act theorists tend to hold that the illocutionary force of an utterance is determined by one interlocutor alone: either the speaker or the hearer. Yet experience tells us that the force of our utterances is not determined unilaterally. Rather, communication often feels collaborative. In this paper, I develop and defend a collaborative theory of illocutionary force, according to which the illocutionary force of an utterance is determined by an agreement reached by the speaker and the hearer. This theory, which (...) builds upon linguistic and sociological work on adjacency pairs and conversational interaction, can accommodate the complexity of speaker intentions (which may be disjunctive, indeterminate, and/or inconsistent over time), and renders speech act theory more compatible with theories of common ground. (shrink)

Dominant views of personal identity in philosophy take some kind of psychological continuity or connectedness over time to be criterial for the identity of a person over time. Such views assign psychological states, particularly those necessary for narrative memory of some kind, special importance in thinking about the nature of persons. The extended mind thesis, which has generated much recent discussion in the philosophy of mind and cognitive science, holds that a person’s psychological states can physically extend beyond that person’s (...) body. Since “person” is a term of both metaphysical and moral significance, and discussions of both extended minds and personal identity have often focused on memory, this article explores the relevance of extended cognition for the identity of persons with special attention to neuroethics and memory. (shrink)

This paper addresses the question of what constitutes an apt interpreted model for the purpose of analyzing causation. I first collect universally adopted aptness principles into a basic account, flagging open questions and choice points along the way. I then explore various additional aptness principles that have been proposed in the literature but have not been widely adopted, the motivations behind their proposals, and the concerns with each that stand in the way of universal adoption. I conclude that the remaining (...) work of articulating aptness for a SEM analysis of causation is tied up with issues to do with modality, ontology, and mereology. Continuing this work is therefore likely to shed light on the relationship between these areas and causation more generally. (shrink)

This paper considers ten questions that those puzzled by or skeptical of extended cognition have posed. Discussion of these questions ranges across substantive, methodological, and dialectical issues in the ongoing debate over extended cognition, such as whether the issue between proponents and opponents of extended cognition is merely semantic or a matter of convention; whether extended cognition should be treated in the same way as extended biology; and whether conscious mental states pose a special problem for the extended mind thesis. (...) Lethocerus, the giant water bug, will be a recurrent reference point for much of the discussion. (shrink)

The impressive variation amongst biological individuals generates many complexities in addressing the simple-sounding question what is a biological individual? A distinction between evolutionary and physiological individuals is useful in thinking about biological individuals, as is attention to the kinds of groups, such as superorganisms and species, that have sometimes been thought of as biological individuals. More fully understanding the conceptual space that biological individuals occupy also involves considering a range of other concepts, such as life, reproduction, and agency. There has (...) been a focus in some recent discussions by both philosophers and biologists on how evolutionary individuals are created and regulated, as well as continuing work on the evolution of individuality. (shrink)

This paper explores the relationship between eugenics, disability, and dehumanization, with a focus on forms of eugenics beyond Nazi eugenics.

The pandemic significantly raised the stakes for the translation of bioethics insights into policy. The novelty, range and sheer quantity of the ethical problems that needed to be addressed urgently within public policy were unprecedented and required high‐bandwidth two‐way transfer of insights between academic bioethics and policy. Countries such as the United Kingdom, which do not have a National Ethics Committee, faced particular challenges in how to facilitate this. This paper takes as a case study the brief career of the (...) Ethics Advisory Board (EAB) for the NHS Covid‐19 App, which shows both the difficulty and the political complexity of policy‐relevant bioethics in a pandemic and how this was exacerbated by the transience and informality of the structures through which ethics advice was delivered. It analyses how and why, after EAB's demise, the Westminster government increasingly sought to either take its ethics advice in private or to evade ethical scrutiny of its policies altogether. In reflecting on EAB, and these later ethics advice contexts, the article provides a novel framework for analysing ethics advice within democracies, defining four idealised stances: the pure ethicist, the advocate, the ethics arbiter and the critical friend. (shrink)

These comments are part of a book symposium on Karen Bennett's book, _Making Things Up_.

It is common to assume that the problem of induction arises only because of small sample sizes or unreliable data. In this paper, I argue that the piecemeal collection of data can also lead to underdetermination of theories by evidence, even if arbitrarily large amounts of completely reliable experimental and observational data are collected. Specifically, I focus on the construction of causal theories from the results of many studies (perhaps hundreds), including randomized controlled trials and observational studies, where the studies (...) focus on overlapping, but not identical, sets of variables. Two theorems reveal that, for any collection of variables V, there exist fundamentally different causal theories over V that cannot be distinguished unless all variables are simultaneously measured. Underdetermination can result from piecemeal measurement, regardless of the quantity and quality of the data. Moreover, I generalize these results to show that, a priori, it is impossible to choose a series of small (in terms of number of variables) observational studies that will be most informative with respect to the causal theory describing the variables under investigation. This final result suggests that scientific institutions may need to play a larger role in coordinating differing research programs during inquiry. (shrink)

This paper begins by saying enough about eugenics to explain why disability is central to eugenics (section 2), then elaborates on why cognitive disability has played and continues to play a special role in eugenics and in thinking about moral status (section 3) before identifying three reasons why eugenics remains a live issue in contemporary bioethics (section 4). After a reminder of the connections between Nazi eugenics, medicine, and bioethics (section 5), it returns to take up two more specific clusters (...) of issues at the intersection of eugenics, disability, and bioethics. These concern questions of life, death, and reproductive value (section 6) and the value of standpoint theory and epistemology for understanding some of the tensions between bioethics and disability in light of a shared eugenic past (section 7). (shrink)

Nous éprouvons une fière réjouissance d’avoir assisté à l’événement « De la musique avant toute chose ! » et c’est l’enthousiasme que cette rencontre aura produit qui nous aura poussé à approfondir la réflexion entamée ce jour-là. À tel point que la pluralité et la rigueur des vues exposées par les différentes interventions philosophiques, et encore l’exaltante performance musicale, aurons rendu compte de l’ampleur et de la richesse que revêt la question musicale. D’une part, nous avons compris lors de cet (...) événement à quel point la musique est omniprésente en notre monde et que nous devrions en éliminer sa diffusion superflue. D’autre part, nous avons vu toute la somptuosité de cette forme d’art dans ses multiples manifestations et rapports culturels. Enfin, nous avons appris en quoi la musique nous émeut tant selon les commentaires de différents philosophes traditionnels à travers l’histoire. Or, il n’en demeure pas moins que nous sommes restés dans une impasse : il nous a semblé ardu, voir inextricable, de discerner ce qui nous permettrait de conclure sur ce qui définit ce qu’est une grande musique, de conclure sur ce qui fait la grandeur de cette musique qui nous passionne tant. Pourtant, nous avions l’opportunité « avant toute chose » de faire l’expérience de cette même beauté, de vivre cette grandeur musicale. Aurions-nous dû, afin de trouver une réponse à nos questions, nous tourner vers cette expérience même que nous vivions, réfléchir à ce que nous avions vécu, essayer de comprendre le phénomène immédiatement vécu ? C’est cette question qui nous intéresse. (shrink)

A Guide to Good Reasoning has been described by reviewers as “far superior to any other critical reasoning text.” It shows with both wit and philosophical care how students can become good at everyday reasoning. It starts with attitude—with alertness to judgmental heuristics and with the cultivation of intellectual virtues. From there it develops a system for skillfully clarifying and evaluating arguments, according to four standards—whether the premises fit the world, whether the conclusion fits the premises, whether the argument fits (...) the conversation, and whether it is possible to tell. (shrink)

This is the first complete English translation and publication of Donoso’s carta de 24 de octubre, 1851, a letter encapsulating many of his views on revolution and decision. This remarkable letter, sent as a diplomatic missive while he was serving the Spanish crown in Paris, describes how Napoleon III––stuck between the 1848 constitution’s prohibition against his election and his impending coup that will crown him emperor––must gain the support of the liberal bourgeoise middle class if he is to maintain his (...) rule over France. The letter is also of great importance to Donoso and Schmitt scholars because it contains the first and only time Donoso uses the complete term “las clases discutidoras,” which, through Schmitt’s injudicious and repeated misspellings as “una clasa discutidora” has become famous for its characterization of the liberal bourgeoisie as the “discussing” or “disputing” class that is incapable of action at the precise historical moment when a decision is most direly needed to save the constitution from inner or outer existential threats. (shrink)

This Discussion Piece is a response to Mark Windsor's Discussion Piece (2023) 'Photographic Registers are Latent Images', which is a response to my article, (2021) 'Invisible Images and Indeterminacy: Why we need a Multi-stage Account of Photography' JAAC 79(2) 161-174.. -/- I argue that a photosensitive surface does not produce invisible pictorial features when it is exposed to light, and conclude, contra Windsor, that a photographic register is not a latent image. I argue that Windsor does not succeed in defending (...) a single-stage account of photography and I reconfirm that a multi-stage account is correct. (shrink)

In this article, I reconsider bio-essentialism in the study of kinship, centering on David Schneider’s influential critique that concluded that kinship was “a non-subject” (1972:51). Schneider’s critique is often taken to have shown the limitations of and problems with past views of kinship based on biology, genealogy, and reproduction, a critique that subsequently led those reworking kinship as relatedness in the new kinship studies to view their enterprise as divorced from such bio-essentialist studies. Beginning with an alternative narrative connecting kinship (...) past and present and concluding by introducing a novel way of thinking about kinship, I have three constituent aims in this research article: (1) to reconceptualize the relationship between kinship past and kinship present; (2) to reevaluate Schneider’s critique of bio-essentialism and what this implies for the contemporary study of kinship; and (3) subsequently to redirect theoretical discussion of what kinship is. This concluding discussion introduces a general view, the homeostatic property cluster (HPC) view of kinds, into anthropology, providing a theoretical framework that facilitates realization of the often-touted desideratum of the integration of biological and social features of kinship. [bio-essentialism, kinship studies, homeostatic property cluster kinds, Schneider, genealogy]. (shrink)