Ethical issues of synthetic biology: a personalist perspective

The main objective of this thesis is to assess the bioethical issues raised by Synthetic Biology from a specific bioethical approach, personalism, specifically ontological personalism, a philosophy that shows the objective value of the person on the basis of its ontological structure. The person, as a being endowed with reason, freedom and awareness, has a special value which is above that of other beings.El objetivo principal de este trabajo es evaluar las cuestiones bioéticas planteadas por la Biología Sintética desde un enfoque bioético específico, el personalismo, específicamente el personalismo ontológico, una filosofía que muestra el valor objetivo de la persona sobre la base de su estructura ontológica.Ciencias ExperimentalesPrograma Oficial de Doctorado en Bioétic

Propuesta ética en la prevención de enfermedades hereditarias asociadas al ADN mitocondrial

Máster Oficial en BioéticaA día de hoy, las enfermedades debidas a alteraciones en el ADNmt no tienen cura. No obstante, existe una variedad de técnicas, más o menos desarrolladas, que podrían evitar la transmisión madre-hijo de estas enfermedades hereditarias. Sin embargo, estas técnicas requieren de la manipulación y destrucción de numerosos embriones y vulneran la unidad procreación-sexualidad. En este trabajo se revisan las distintas técnicas disponibles para posteriormente desarrollar una valoración ética de las mismas. Así, se definieron como moralmente inaceptables el diagnóstico genético preimplantacional (PGD), la transferencia nuclear (NT) y la pronuclear transfer (PNT). La transferencia citoplasmática (CT) y la aggregated chromosomes transfer (ACT), por su parte, no son éticamente ilícitas en sí mismas, pero sí lo es su aplicación práctica tal y como se desarrollaría actualmente. En cuanto al diagnóstico prenatal (PND), puede darse un doble uso del mismo, bueno o malo, pero su aplicabilidad es limitada. Finalmente, la germinal vesicle transfer o injection (GVT/I) y la maternal spindle transfer (MST) no presentan problemas éticos por sí mismas y su aplicación en este campo podría ser lícita siempre y cuando se le asociara una técnica de reproducción asistida moralmente aceptable, como pueden ser la transferencia intratubárica de gametos (GIFT) o la low tubal oocyte transfer (LTOT).Medicin

Guidelines for the ethical assessment of interventions on the human body in view of the emergence of nbic technologies for enhancement

El reciente desarrollo de las tecnologías emergentes NBIC ha propiciado la aparición de nuevas técnicas que permiten modificar aspectos genéticos, morfológicos y fisiológicos del ser humano para mejorar sus capacidades. Ante esta circunstancia, se reabre el eterno debate: ¿es todo lo técnicamente posible éticamente aceptable? Para responder a esta pregunta, se hace necesaria una reflexión ética para valorar el alcance de las técnicas de mejoramiento y orientarlas al servicio del progreso humano y del bien común. Muchos autores han comenzado ya esta reflexión y optan por la evaluación caso por caso. Sin embargo, se considera que hay un gran déficit de concreción en la definición de los criterios que permitirían un análisis ético de cada técnica para determinar la licitud de su aplicación. Como respuesta a esta necesidad, se propone una guía práctica de valoración ética ya no solo de las técnicas de mejoramiento humano, sino, en general, de cualquier intervención sobre nuestro cuerpo. Esta guía se basa en los cuatro principios de la bioética personalista propuestos por Sgreccia: principio de defensa de la vida humana física, de totalidad o terapéutico, de libertad y responsabilidad, y de sociabilidad y subsidiariedad. Estos principios son el hilo conductor de unos cuestionarios que sirven como apoyo en el discernimiento sobre la licitud de una técnica, en virtud del bien global de la persona en su estructura tridimensional: cuerpo, psique y espíritu, y del respeto a su dignidad inalienable.The recent development of NBIC technologies has led to the emergence of new techniques that allow the modification of genetic, morphological, and physiological aspects of the human being to improve their capacities. In light of this situation, the eternal debate continues: is everything technically possible ethically acceptable? To answer this question, an ethical reflection is needed to assess the scope of enhancement techniques and to direct them to the service of human progress and the common good. Many authors have already begun this reflection, opting for a case-by-case evaluation. However, there is a great lack of specificity in the definition of the criteria that would allow an ethical analysis of each technique, in order to determine the licitness of its application. In response to this need, a practical guide for the ethical assessment of not only human enhancement techniques, but of any intervention on the human body is proposed. This guide is based on the four principles of personalist bioethics proposed by Sgreccia: the principle of defense of physical human life, the principle of totality or the therapeutic principle, the principle of freedom and responsibility, and the principle of sociability and subsidiarity. These principles are the common thread of some questionnaires that serve as support in discerning the licitness of a technique, by virtue of the overall good of the person in their three-dimensional structure: body, mind and spirit, and the respect for their inalienable dignity.Medicin

Crispr-cas9. The greatest advancement in genetic edition techniques requires an ethical reflection.

La adaptación del sistema CRISPR como herramienta de edición genética ha supuesto una revolución en numerosos campos de aplicación, pues esta técnica resulta considerablemente más rápida, fácil de realizar y eficaz que las técnicas predecesoras. Sin embargo, algunas de estas aplicaciones suscitan objetivas cuestiones éticas que deben ser abordadas. En este trabajo discutimos, en base a los datos más recientes, las distintas cuestiones relacionadas con las aplicaciones de CRISPR sobre la línea germinal, su introducción en ensayos clínicos, la edición genética de animales y plantas para consumo humano y el novedoso gene drive.The adaptation of the CRISPR system as a genetic editing tool has led to a revolution in many fields of application, as this technique is considerably faster, easier to perform and more efficient than predecessor techniques. However, some of these applications raise objective ethical issues that must be addressed. In this paper we discuss, based on the most recent data, the different issues related to CRISPR applications on the germ line, its introduction in clinical trials, the genetic edition of animals and plants for human consumption and the novel gene drive.Medicin

Towards an ethically acceptable proposal in the prevention of mitochondrial DNA-associated diseases

Le malattie dovute alle alterazioni del DNA mitocondriale (mtDNA) sono attualmente incurabili. C’è tuttavia un certo numero di metodi a vari livelli di sviluppo che potrebbe evitare la trasmissione madre-figlio di questi disturbi ereditari. Tra questi metodi ci sono due tecniche che sono attualmente attirando l’attenzione di ricercatori, decisori e pazienti: il trasferimento pronucleare (PNT) e il trasferimento del fuso materno (MST). Questi metodi comportano l’uso di mitocondri sani da un donatore. PNT ha luogo in uno zigote, mentre nell’MST, le cellule uovo sono manipolate. Questi metodi sono molto promettenti, in quanto sembrano essere efficaci e sicuri, e infatti, potranno presto essere utilizzati nella pratica clinica nel Regno Unito, dove sono già state elaborate alcune misure legislative. Tuttavia, queste tecniche, come sono concepite oggi, sollevano diverse questioni etiche. In questo articolo, proponiamo una possibile soluzione per superare questi problemi, dando alle famiglie colpite la possibilità di concepire bambini sani. Noi crediamo che, allo stadio attuale di sviluppo, ci sono due tecniche, la MST e il Trasferimento di Vescicola Germinale o l’Iniezione di Vescicola Germinale (GVT o GVI), che combinati con una tecnica di riproduzione, come il trasferimento nelle tube di Falloppio di gameti (GIFT) o il trasferimento della cellula uovo nella parte prossimale della tuba di Falloppio (LTOT), potrebbe essere ampiamente accettati. Al contrario, il PNT senza fornire alcun beneficio in termini di efficacia o sicurezza, comporta ulteriori gravi difficoltà da un punto di vista etico. A nostro parere, la ricerca e la legislazione devono seguire questa linea, dal momento che numerose questioni etiche verrebbero superate senza compromettere efficacia e sicurezza.Diseases due to alterations in mitochondrial DNA (mtDNA) are currently incurable. However, there are a number of methods in various stages of development that could avoid mother-child transmission of these hereditary disorders. Among them are two techniques that are currently attracting the attention of researchers, policymakers and patients: pronuclear transfer (PNT) and maternal spindle transfer (MST). These methods involve use of healthy mitochondrial from a donor. PNT takes place in a zygote, whereas in MST egg are manipulated. These methods are highly promising, since they seem to be effective and safe, and in fact, they could soon be used in clinical practice in the UK, where legislative steps have already been taken. Nevertheless, these techniques, as they are conceived today, pose several ethical issues. In this paper, we propose a possible solution to overcome these issues, while giving affected families the possibility of conceiving healthy children. We believe that, at the current stage of development, there are two techniques, MST and Germinal Vesicle Transfer or Germinal Vesicle Injection (GVT or GVI), which combined with a reproduction technique such as gamete intra-fallopian transfer (GIFT) or low tubal oocyte transfer (LTOT), could be widely accepted. In contrast, the PNT without providing any benefit to these in terms of efficacy or safety, entails more serious ethical difficulties. In our opinion, research and legislation must be conducted in this line, since several ethical issues would be overcome without compromising effectivity and safety.Medicin

SP1 and NFY Regulate the Expression of PNPT1, a Gene Encoding a Mitochondrial Protein Involved in Cancer

The Polyribonucleotide nucleotidyltransferase 1 gene (PNPT1) encodes polynucleotide phosphorylase (PNPase), a 30-50 exoribonuclease involved in mitochondrial RNA degradation and surveillance and RNA import into the mitochondrion. Here, we have characterized the PNPT1 promoter by in silico analysis, luciferase reporter assays, electrophoretic mobility shift assays (EMSA), chromatin immunoprecipitation (ChIP), siRNA-based mRNA silencing and RT-qPCR.We show that the Specificity protein 1 (SP1) transcription factor and Nuclear transcription factor Y (NFY) bind the PNPT1 promoter, and have a relevant role regulating the promoter activity, PNPT1 expression, and mitochondrial activity. We also found in Kaplan–Meier survival curves that a high expression of either PNPase, SP1 or NFY subunit A (NFYA) is associated with a poor prognosis in liver cancer. In summary, our results show the relevance of SP1 and NFY in PNPT1 expression, and point to SP1/NFY and PNPase as possible targets in anti-cancer therapy.Medicin

Quimeras humano-animales. Una revisión sistemática de los problemas éticos que plantean y sus posibles soluciones

Las investigaciones con quimeras humano-animales han evolucionado gradualmente hasta día de hoy, en que se plantean grandes proyectos relacionados con el intento de solucionar patologías que nos ayuden a los seres humanos a paliar enfermedades. Sin embargo, se debe de tener en cuenta, que muchos de estos avances científicos llevan implícito un dilema ético importante en muchos casos, y más si se involucra a personas en dichos experimentos. En la presente revisión sistemática se buscó identificar estos problemas éticos relacionados con las quimeras, así como posibles soluciones a los mismos propuestas en la literatura, incluyendo medios técnicos para la realización de quimeras menos humanizadas. Se realizó una búsqueda bibliográfica sistemática en las bases de datos Pubmed, Embase y Medes con fecha 4 de enero de 2022. Se seleccionan los artículos que cumplían estrictamente con los objetivos seleccionados para la realización del trabajo. Un total de 21 artículos componen nuestra muestra, de los cuales se extraen problemas éticos relacionados con las quimeras, posibles soluciones y medios técnicos para evitar la obtención de quimeras demasiado humanizadas. Las cuestiones identificadas en los artículos seleccionados son problemas relacionados con el bienestar animal, adquisición de rasgos humanos de las quimeras, preocupaciones médicas derivadas de la experimentación como pueden ser las zoonosis, el origen de las células pluripontenciales para la realización de quimeras, la creación de gametos humanos por parte de dichas quimeras, el quimerismo neurológico y el estatus moral de las quimeras. En el trabajo se aportan soluciones para estos problemas, tales como la utilización de genes suicidas en las células humanas que se activarían si estas se diferencian en células neuronales o el uso de la edición genética mediante el mecanismo CRISPR/Cas9 para incapacitar a estas células para que no se diferencien en células neuronales. La única cuestión que permanece elusiva a la propuesta de soluciones es la relativa al potencial estatus moral de las quimeras. Ciertamente es una cuestión compleja dada la variedad de propuestas sobre el concepto de estatus moral disponibles en la literatura. Es necesario por tanto aterrizar estas propuestas en la reflexión respecto a las quimeras humano-animales para iniciar una discusión que pueda arrojar luz sobre esta cuestión.Human-animal chimera research has gradually evolved to the present day, in which large projects related to the attempt to solve pathologies that help us human beings to alleviate diseases. However, it must be considered that many of these advances in science imply an important ethical dilemma in many cases, and even more so if we involve people in said experiments. In the present systematic review we sought to identify these ethical problems related to chimeras, as well as possible solutions to them proposed in the literature, including technical means for the realization of less humanized chimeras. A bibliographic search was carried out in the Pubmed, Embase and Medes databases on January 4th, 2022. The articles that strictly comply with the objectives selected for the completion of the work will be selected. A total of 21 articles makes up our sample, from which ethical problems related to chimeras, possible solutions and technical means to avoid obtaining too humanized chimeras will be extracted. The issues identified in the articles are problems related to animal welfare, acquisition of human traits from chimeras, medical concerns derived from experimentation such as zoonoses, the origin of pluripotential cells for chimera production, the creation of human gametes by said chimeras, neurological chimerism and the moral status of chimeras. This paper provides solutions for these problems, such as the use of suicide genes in human cells that would be activated if they differentiate into neuronal cells or the use of gene editing through the CRISPR/Cas9 mechanism to incapacitate these cells so that they do not differentiate into neuronal cells. The only question that remains elusive to the proposal of solutions is the one related to the potential moral status of chimeras. It is certainly a complex issue given the variety of proposals on the concept of moral status available in literature. It is therefore necessary to bring these proposals closer to reflection on human-animal chimeras in order to initiate a discussion that can shed light on this issue.MedicinaInstituto de Ciencias de la Vid

Biosafety and biosecurity in Synthetic Biology: A review

Synthetic Biology is a growing field which holds great promise in several areas of application. However, it also poses serious risks for human health and the environment that must be anticipated in order to develop effective prevention and management measures. Here, the current situation on biosafety and biosecurity in this scientific field is reviewed. Biosafety concerns mainly relate to the damaging effects for workers and the environment that could result from accidental interactions with dangerous biological agents. On the other hand, biosecurity risks refer to the potential misuses of Synthetic Biology, such as bioterrorism, biowarfare or bioattacks that could derive from the genetic engineering of organisms. In this paper, the specific challenges posed by Synthetic Biology are discussed, and perspectives in the development of measures to guide the safe advance of this discipline are presentedLucía Gómez-Tatay is in receipt of a Escuela de Doctorado of Universidad Católica de Valencia San Vicente Mártir (EDUCV) doctoral fellowship (EDUCV-PRE-2015-002).Biotecnologí

The Conception of Synthetic Entities from a Personalist Perspective

Synthetic biology opens up the possibility of producing new entities not found in nature, whose classification as organisms or machines has been debated. In this paper we are focusing on the delimitation of the moral value of synthetic products, in order to establish the ethically right way to behave towards them. In order to do so, we use personalism as our ethical framework. First, we examine how we can distinguish between organisms and machines. Next, we discuss whether the products of synthetic biology can be considered organisms at all and assess what their moral value is and how should we behave towards them. Finally, we discuss the hypothetical case of synthetic humans.Medicin

Is it possible to avoid the transmission of mitocondrial diseases?. Ethical and medical asessment

El 24 de febrero de 2015 se aprobó por el Parlamento Británico el uso de la transferencia mitocondrial (TM), para prevenir la transmisión de enfermedades mitocondriales (TEM). El uso de la TM para prevenir la TEM plantea indudables problemas éticos, de los que no es el menor la posibilidad de modificar la línea germinal y, desde un punto de vista social, la producción de niños vinculados genéticamente a tres personas, la madre con las mitocondrias alteradas, la donante de las mitocondrias sanas y el varón utilizado para fecundar el óvulo sano producido. Para evitar esta circunstancia recientemente se han propuesto dos nuevas técnicas, la CRISPR/Cas9 y la TALENs, que evitan el uso de la transferencia mitocondrial, minimizando algunos de los problemas que esta técnica conlleva. Ambas técnicas consisten en reparar el ADN mitocondrial, mediante la sustitución de determinados fragmentos por otros de las características que se deseen (CRISPR/Cas9) o su supresión (TALENs). Se pretende aplicar estas técnicas en la corrección directa de las anomalías genéticas de las mitocondrias humanas alteradas. También se pueden utilizar para tratar problemas de infertilidad de causa mitocondrial. Este trabajo es una aproximación al estado actual de la investigación en este campo, analizando tanto los avances tecnológicos y biomédicos más recientes como las consecuencias bioéticas que de ellos pueden derivarse.On February 24, 2015 the use of mitochondrial transfer (MT) to prevent transmission of mitochondrial diseases (MDT) was passed by the British Parliament. The use of MT to prevent MDT raises undoubted ethical problems, which is not the least the possibility of modifying the germ line and from a social point of view, the production of children genetically related to three people, the mother with altered mitochondria, the donor of healthy mitochondria and the male used to fertilize the healthy egg produced. Recently, two new techniques have been proposed, the CRISPR/ Cas9 and TALENs, that exempt mitochondrial transfer process, minimizing some of the problems that this entails. Both techniques consist in repairing the anomalous fragments of mitochondrial DNA, by replacing them by others with the desired features (CRISPR / Cas9) or deletion of specific fragments (TALENs). These techniques are intended to apply to the direct correction of the altered genetic abnormalities of human mitochondria. They can also be used to treat infertility problems with a mitochondrial cause. This paper is an approach to the current state of research in this field, analyzing both the latest technological and biomedical advances as bioethical consequences that may result from them.Medicin