The New RNA-Editing Era - Ethical Considerations.

The characteristics of RNA editing, including the lower risk compared with genome editing, may loosen the ethical barriers that are currently imposed on genetic engineering, thus opening new possibilities for research, therapy, and human enhancement. We should start considering the future ethical and social implications of this new and promising technology.

The genetic structure of SARS-CoV-2 does not rule out a laboratory origin: SARS-COV-2 chimeric structure and furin cleavage site might be the result of genetic manipulation.

Severe acute respiratory syndrome-coronavirus (SARS-CoV)-2's origin is still controversial. Genomic analyses show SARS-CoV-2 likely to be chimeric, most of its sequence closest to bat CoV RaTG13, whereas its receptor binding domain (RBD) is almost identical to that of a pangolin CoV. Chimeric viruses can arise via natural recombination or human intervention. The furin cleavage site in the spike protein of SARS-CoV-2 confers to the virus the ability to cross species and tissue barriers, but was previously unseen in other SARS-like CoVs. Might genetic manipulations have been performed in order to evaluate pangolins as possible intermediate hosts for bat-derived CoVs that were originally unable to bind to human receptors? Both cleavage site and specific RBD could result from site-directed mutagenesis, a procedure that does not leave a trace. Considering the devastating impact of SARS-CoV-2 and importance of preventing future pandemics, researchers have a responsibility to carry out a thorough analysis of all possible SARS-CoV-2 origins.

[Polygenic scores: towards designer babies?] / Scores polygéniques : vers l'embryon à la carte ? - Chroniques génomiques.

A new company is offering extensive genetic analysis of embryos during an in vitro fertilisation procedure, allowing the derivation of polygenic scores for several diseases and embryo choice based on these results. Polygenic scores, if properly implemented, can indeed have substantial predictive value, and the possibility of embryo choice based on these data has become real, raising a number of practical and ethical problems. ‡.

Considerations on genetic engineering: regarding the birth of twins subjected to gene edition.

In this essay, the bioethical implications of the recent genetic manipulation in human embryos with CRISPR-Cas9 to eliminate the CCR5 gene and the birth of a pair of discordant twin girls are analyzed. The experiment was disseminated via social media. The main bioethical flaws identified include the justification of the model, the informed consent process and the lack of disclosure of evident conflicts of interest. The consequences of the experiment on the life of the twins that were born were not properly evaluated, such as the impact on their autonomy, the alleged benefits to be received and the future risks of harm during their lifetime. Having manipulated the germ cell line, the effects on their future offspring were not considered. This type of actions negatively affects the way society conceives science. Genetic engineering should be reserved to the basic experimental context or as clinical research for the correction of known serious diseases of genetic origin under strict regulatory and bioethical supervision and using a gradualist approach in accordance with the advances of gene editing techniques.

En este ensayo se analizan las implicaciones bioéticas de la reciente manipulación genética en embriones humanos con CRISPR-Cas9 para eliminar el gen CCR5 y el nacimiento de dos gemelas discordantes. El experimento se divulgó en medios sociales. Los principales problemas bioéticos identificados son la justificación del modelo, el proceso de consentimiento informado y la falta de declaración de evidentes conflictos de interés. No se evaluaron apropiadamente las consecuencias del experimento sobre la vida de las gemelas nacidas como la afectación a su autonomía, los supuestos beneficios por recibir y los riesgos futuros de daño durante su vida. Habiendo manipulado la línea celular germinal, no se consideraron los efectos sobre su descendencia futura. Este tipo de acciones tiene un impacto negativo en la forma como la sociedad concibe la ciencia. La ingeniería genética debe reservarse al contexto experimental básico o bien como investigación cínica para la corrección de enfermedades conocidas graves de origen genético, bajo estricta supervisión regulatoria y bioética y de manera gradualista de acuerdo con el progreso de las técnicas de edición genética.

Reflexiones sobre la ingeniería genética: a propósito del nacimiento de gemelas sometidas a edición génica / Considerations on genetic engineering: regarding the birth of twins subjected to gene edition

Resumen En este ensayo se analizan las implicaciones bioéticas de la reciente manipulación genética en embriones humanos con CRISPR-Cas9 para eliminar el gen CCR5 y el nacimiento de dos gemelas discordantes. El experimento se divulgó en medios sociales. Los principales problemas bioéticos identificados son la justificación del modelo, el proceso de consentimiento informado y la falta de declaración de evidentes conflictos de interés. No se evaluaron apropiadamente las consecuencias del experimento sobre la vida de las gemelas nacidas como la afectación a su autonomía, los supuestos beneficios por recibir y los riesgos futuros de daño durante su vida. Habiendo manipulado la línea celular germinal, no se consideraron los efectos sobre su descendencia futura. Este tipo de acciones tiene un impacto negativo en la forma como la sociedad concibe la ciencia. La ingeniería genética debe reservarse al contexto experimental básico o bien como investigación cínica para la corrección de enfermedades conocidas graves de origen genético, bajo estricta supervisión regulatoria y bioética y de manera gradualista de acuerdo con el progreso de las técnicas de edición genética.

Abstract In this essay, the bioethical implications of the recent genetic manipulation in human embryos with CRISPR-Cas9 to eliminate the CCR5 gene and the birth of a pair of discordant twin girls are analyzed. The experiment was disseminated via social media. The main bioethical flaws identified include the justification of the model, the informed consent process and the lack of disclosure of evident conflicts of interest. The consequences of the experiment on the life of the twins that were born were not properly evaluated, such as the impact on their autonomy, the alleged benefits to be received and the future risks of harm during their lifetime. Having manipulated the germ cell line, the effects on their future offspring were not considered. This type of actions negatively affects the way society conceives science. Genetic engineering should be reserved to the basic experimental context or as clinical research for the correction of known serious diseases of genetic origin under strict regulatory and bioethical supervision and using a gradualist approach in accordance with the advances of gene editing techniques.

Transhumanism, Moral Perfection, and Those 76 Trombones.

Transhumanism advances an ideology promising a positive human advance through the application of new and as yet unrealized technologies. Underlying the whole is a libertarian ethos married to a very Christian eschatology promising a miraculous transformation that will answer human needs and redress human failings. In this paper, the supposedly scientific basis on which transhumanist promises are built is critiqued as futurist imaginings with little likelihood of actualization. Transhumanists themselves are likened to the affable con man Professor Harold Hill who, in The Music Man, describes as dire social problems whose solution is a youth band he seeks to sell but has no intention of building. Even were some of the transhumanist imaginings to be realized, I argue, the result would be a dystopia in which the few received benefits denied to the many. In advancing imaginary technologies as a solution to human needs, transhumanists and their bioethical fellow travelers handily avoid discussion of or advocacy for the kind of pedestrian social actions that demonstrably could achieve many of their purported goals. So their enthusiasms, I conclude, are not merely fanciful but damaging to the humanist goals they pretend to advance.

The Regulation of Mitochondrial Replacement Techniques Around the World.

Mitochondrial replacement techniques (MRTs, also referred to as mitochondrial replacement therapies) have given hope to many women who wish to have genetically related children but have mitochondrial DNA mutations in their eggs. MRTs have also spurred deep ethical disagreements and led to different regulatory approaches worldwide. In this review, we discuss the current regulation of MRTs across several countries. After discussing the basics of the science, we describe the current law and policy directions in seven countries: the United Kingdom, the United States, Canada, Australia, Germany, Israel, and Singapore. We also discuss the emerging phenomenon of medical tourism (also called medical travel) for MRTs to places like Greece, Spain, Mexico, and Ukraine. We then pull out some key findings regarding similarities and differences in regulatory approaches around the world.

Do we have a right to an unmanipulated genome? The human genome as the common heritage of mankind.

The human genome is commonly regarded as a 'natural' connection between all human beings, as it has been handed down to us by our predecessors. As such, it is believed to represent common heritage of humanity, e.g. a resource of outstanding value that should be the object of special protection and international concern. Some critics argue that germline manipulation would disrupt this natural heritage and that we have a duty to preserve the integrity of the human germline. However, a closer look reveals that the concept of common heritage of humanity does not necessarily imply the impermissibility of germline manipulation. If it is restricted to the prevention of severe diseases, germline manipulation does not represent a threat to the unity and identity of the human species, even though this would create a new form of relationship between human beings, namely that between a designer and a genetically designed person.

Reflexiones ético-teológicas ante la edición genética / Genetic edition and theological ethics

El artículo busca anticipar los desafíos que se vislumbran hacia el futuro una vez que se perfeccione la técnica de la edición genética. En primer lugar, se encuadra la edición genética en el marco de la especificidad de la tecnología moderna. En segundo lugar, se plantea cómo el contraste de lo natural con lo artificial ilumina el problema que significa pretender sustituir lo natural, en el sentido de lo dado, con lo proyectado por la tecnología. Posteriormente, después de constatar el carácter incipiente de la reflexión teológica sobre la técnica, se plantea la convergencia de la idea de creación con un respeto por los equilibrios naturales, propios de la sensibilidad ecológica contemporánea. Se muestra así, que la propuesta cristiana no es la tecnofobia, sino la integración de la técnica -como elemento central de la cultura que desarrolla el ser humano- con la naturaleza y la asunción del carácter limitado de las realidades naturales, incluyendo al mismo ser humano. De este modo, la vulnerabilidad, como realización de esta finitud, es la característica que nos iguala y nos exige el reconocimiento de nuestra dignidad, mucho más que la realización de un ideal de perfección tecnológicamente mediado, aunque fuera accesible para todos

This paper tries to look forward to the incoming ethical challenges related with genetic editing. It begins with contextualizing genetic edition within the specific nature of modern technology. Afterwards it presents the contrast between natural beings and artifacts that sheds light for answering the question about the real possibility of replacing natural beings, as they are, with technologically projected living beings. In the third place, after acknowledging the scarce attention given by contemporary theology to technology, it shows the convergence of the Christian concept of creation with the respect for balance in nature, as most part of the contemporaty ecological sensibility upholds. Building on this common ground it shows that the Christian attitude towards technology is not technofobical but the integration of technology -a central element of contemporary culture- with nature, accepting the limitation of any natural being including mankind. In this way, vulnerability, as a visible consequence of this finitude, is the very attribute of human beings that makes ourselves equal and requieres recongnition of our common dignity, way over the idea of acquiring an ideal perfection through technology, even if it was accesible to all

¿Modificar o no modificar el genoma de nuestra descendencia? Algunos comentarios a raiz de la Declaración del Comité de Bioética de España sobre la edición genómica en humanos / To modify or not to modify the genome of our offspring? Some comments following the Declaration of the Spanish Bioethics Committee on genomic editing in humans / Modificar o no modificar el genoma de la nostra descendència?. Alguns comentaris arran de la Declaració del Comitè de Bioètica d'Espanya sobre l'edició genòmica en humans

La modificación genética de la línea germinal humana presenta grandes problemas de carácter ético y jurídico. El Comité de Bioética de España ha publicado una Declaración ofreciendo una respuesta a estos retos. Este artículo analiza críticamente su postura, subrayando la escasa consistencia de cualquier argumento que pretenda censurar cualquier forma de mejora en la salud humana. Con tal fin, se exponen cuestiones como la relación entre dignidad humana y modificación genética o la inconsistencia de la apelación al argumento de la pendiente resbaladiza en este contexto. Asimismo, se afirma la necesidad de trazar distinciones entre las intervenciones que afectan a bienes absolutos, como la salud, y los que no lo son

Genetic modification of the human germline presents major ethical and legal problems. The Spanish Bioethics Committee has published a Declaration offering a response to these challenges. This article critically analyzes its position, underlining the scarce consistency of any argument that attempts to censor any form of improvement in human health. To this end, questions such as the relationship between human dignity and genetic modification or the inconsistency of the appeal to the argument of the slippery slope in this context are raised. At the same time, this paper highlights the need to draw distinctions between interventions that affect absolute goods, such as health, and those that are not

La modificació genètica de la línia germinal humana presenta enormes problemes de caràcter ètic i jurídic. El Comitè de Bioètica d'Espanya ha publicat una Declaració oferint una resposta a aquests reptes. Aquest article analitza críticament la seva postura, subratllant l'escassa consistència de qualsevol argument que pretengui censurar qualsevol forma de millora en la salut humana. Amb tal fi, s'exposen qüestions com la relació entre dignitat humana i modificació genètica o la inconsistència de l'apel·lació a l'argument del pendent relliscós en aquest context. Així mateix, s'afirma la necessitat de traçar distincions entre les intervencions que afecten béns absoluts, com la salut, i els que no ho són

[Bioethics theories, the protection of life and natural law]. / Teorías bioéticas, protección de la vida y ley natural.

Principlist Bioethics by Beauchamp and Childress has reached a prominent status in contemporary Bioethics. Nevertheless, it includes some important theoretical problems: some lacks when defining some concepts, a tendency to ethical relativism, etc. Among the ethical alternative approaches from which such problems can be solved, we think that the most appropiate is the Natural Law theory. It offers a reasoned reflection on the concept of good and on human basic goods and their relation with moral general principles. From such goods, this ethical theory supports the existence of actions that are always maleficent acts, that is, intrinsically and universally evil acts. The article applies the Natural Law theory to issues related to the protection of human life (abortion, euthanasia, self-defense and genetic manipulation)..

Controlling CRISPR Through Law: Legal Regimes as Precautionary Principles.

Since its advent in 2012, CRISPR has spawned a cottage industry of bioethics literature. One principal criticism of the technology is its virtually instant widespread adoption prior to deliberative bodies conducting a meaningful ethical review of its harms and benefits-a violation, to some, of bioethics' "precautionary principle." This view poorly considers, however, the role that the law can play-and does, in fact, play-in policing the introduction of ethically problematic uses of the technology. This Perspective recounts these legal regimes, including regulatory agencies and premarket approval, tort law and deterrence, patents and ethical licenses, funding agencies and review boards, as well as local politics. Identifying these legal regimes and connecting them to the precautionary principle should be instructive for bioethicists and policy makers who wish to conduct ethical reviews of new applications of CRISPR prior to their introduction.

Heritable Genome Editing: Who Speaks for "Future" Children?

Approximately 80% of rare and often incurable and serious conditions affect newborns and children, and roughly half of all rare diseases are considered to have an onset in childhood. Somatic gene therapies are already in clinical trials for spinal muscular atrophy, beta thalassemia, and macular degeneration. If proven to be safe and effective, could heritable genome editing be seen as a form of preventive personalized medicine and as fostering the right to health of the child? The latest calls for global moratoria on clinical applications of heritable genome editing are troubling in that they may create an illusion of control over rogue science and stifle the necessary international debate surrounding an ethically responsible translational path forward. Children are people with distinct rights and interests. An arbitrary moratorium neither fosters their best interests or health nor respects their right to benefit from the advancements of science.

Heritable Genome Editing and the Downsides of a Global Moratorium.

In 2018, Dr. He Jiankui reported that he had edited human embryos and transferred them to a woman, causing her to give birth to twin girls with modified genomes. An international group of scientists and ethicists responded by proposing a global moratorium on heritable genome editing (HGE). In this article, I oppose this proposal on several grounds. A global moratorium might encourage participating nations to ban HGE or postpone access to it indefinitely. It might also deter or delay basic research that could lead to safe and effective HGE. Lastly, a global moratorium might induce participating nations to adopt or maintain laws and regulations that stigmatize children born with modified genomes. As an alternative, I argue that nations should regulate HGE for safety and efficacy only and without distinguishing between therapeutic and enhancing modifications.

The Use and Misuse of Brave New World in the CRISPR Debate.

When writing about CRISPR and similar technologies, many bioethicists use science-fiction references to help readers picture the ramifications of germline gene editing. By a large margin, the most frequently referenced novel in this debate is Aldous Huxley's 1932 dystopia Brave New World. Despite its iconic status and effectiveness at communicating specific ethical issues, Brave New World provides relatively poor examples of interventions such as gene therapy or enhancement. In addition, the eugenic tropes that Huxley promotes in much of his work make Brave New World an uncomfortable choice for authors who oppose the use of CRISPR for illiberal purposes. Ethicists should consider bringing a wider variety of fiction references into the discourse on genome editing, especially stories that can complement Brave New World with insights about the ethical issues left undeveloped in Huxley's novel.

Estimating Demand for Germline Genome Editing: An In Vitro Fertilization Clinic Perspective.

Germline genome editing (GGE) holds the potential to mitigate or even eliminate human heritable genetic disease, but also carries genuine risks if not appropriately regulated and performed. It also raises fears in some quarters of apocalyptic scenarios of designer babies that could radically change human reproduction. Clinical need and the availability of alternatives are key considerations in the ensuing ethical debate. Writing from the perspective of a fertility clinic, we offer a realistic projection of the demand for GGE. We lay out a framework proposing that GGE, hereditary genetic disorders, and in vitro fertilization are fundamentally entwined concepts. We note that the need for GGE to cure heritable genetic disease is typically grossly overestimated, mainly due to the underappreciated role of preimplantation genetic testing. However, we might still find applications for GGE in the correction of chromosomal abnormalities in early embryos, but techniques for that purpose do not yet exist.

The Daunting Economics of Therapeutic Genome Editing.

There is no shortage of enthusiasm for the clinical potential of CRISPR-based genome editing: many life-changing cures appear to be just around the corner. However, as mature genetic therapies reach the market, it seems that million-dollar price tags are the new normal. Several factors contribute to the extreme pricing of next-generation medicines, including the need to recoup development costs, the undeniable value of these powerful therapies, and the inherent technical challenges of manufacture and delivery. CRISPR technology has been hailed as a great leveler and a democratizing force in biomedicine. But for this principle to hold true in clinical contexts, therapeutic genome editing must avoid several pitfalls that could substantially limit access to its transformative potential, especially in the developing world.