What we know about effective public engagement on CRISPR and beyond.

Advances in gene editing technologies for human, plant, and animal applications have led to calls from bench and social scientists, as well as a wide variety of societal stakeholders, for broad public engagement in the decision-making about these new technologies. Unfortunately, there is limited understanding among the groups calling for public engagement on CRISPR and other emerging technologies about 1) the goals of this engagement, 2) the modes of engagement and what we know from systematic social scientific evaluations about their effectiveness, and 3) how to connect the products of these engagement exercises to societal decision or policy making. Addressing all three areas, we systematize common goals, principles, and modalities of public engagement. We evaluate empirically the likely successes of various modalities. Finally, we outline three pathways forward that deserve close attention from the scientific community as we navigate the world of Life 2.0.

Budgets versus Bans: How U.S. Law Restricts Germline Gene Editing.

In late 2019, He Jiankui, the Chinese scientist who created the world's first gene-edited babies, and two embryologists were sentenced to prison and fined. Thirteen months earlier, when the world first learned about the experiment, He and his colleagues drew swift and nearly uniform international condemnation for prematurely moving to human trials, for the risks they took with the children's health, and for He's secrecy. The organizing committee for the second genome editing summit said the experiment failed to conform with international norms." In the United States, the legal picture is complex. No doubt the specific experiment He performed would have run afoul of long-standing research regulations due to its problems with informed consent and ethical review. But other laws also affect this kind of work, in particular, a budget rider that for the past four years has been included in federal appropriations legislation.

Focusing on Human Rights: a framework for CRISPR germline genome editing ethics and regulation.

The late 2018 announcement of the claimed births of CRISPR-edited babies has stimulated widespread condemnation and calls by some leading scientists for a moratorium on any further germline genome editing (GGE) for reproductive purposes. Concurrently, national and international bodies are calling for the development of robust guidelines and regulations that will identify permissible conditions under which such GGE efforts might eventually proceed. Crucially, these conditions go beyond rigorous safety standards to address some of the social and ethical concerns that arise with germline interventions. As these bodies convene to navigate this unique terrain, we suggest an important standard for generating ethically robust guidelines. Our approach builds from concerns about social exclusion and social justice with a focus on fundamental human rights. We believe that a deontological or rights-based approach, rather than a utilitarian approach, is needed to ensure that this socially disruptive technology minimizes further marginalization of people with disabilities and does not create a new form of social injustice. In pursuit of a deontological framework, we propose the implementation of an objective assessment tool: the Human Rights Impact Assessment (HRIA). Use of the HRIA establishes necessary constraints on applications of GGE in order to safeguard the most vulnerable members of society.

Does human genome editing reinforce or violate human dignity?

Germline genome editing is often disapproved of at the international policy level because of its possible threats to human dignity. However, from a critical perspective the relationship between this emerging technology and human dignity is relatively understudied. We explore the main principles that are referred to when 'human dignity' is invoked in this context; namely, the link with eugenics, the idea of a common genetic heritage, the principle of equal birth and broader equality and justice concerns. Yet the concept is also used in favour of germline genome editing as it might improve the overall well-being of future generations. We conclude that dignity concerns do not justify a complete ban on safe heritable genome editing but should inform the implementation of side constraints to ensure that the value judgements about human traits that are inherent in this practice do not result in a diminished basic respect for those people affected by them.

Why Include the Public in Genome Editing Governance Deliberation?

With the birth of genetically engineered twins in November 2018, international debate about human genome editing governance has moved from an emphasis on mutual engagement among multiple stakeholders to a self-regulatory model enacted through high-level expert groups with little or no public input. This article reconstructs this paradigm shift and suggests that inclusive public deliberation should still have a role in public decision making about genome editing.

Meeting report of the OECD conference on "Genome Editing: Applications in Agriculture-Implications for Health, Environment and Regulation".

The "OECD Conference on Genome Editing: Applications in Agriculture-Implications for Health, Environment and Regulation" was held on the 28-29 June 2018 at the OECD headquarter and conference centre in Paris, France. It brought together policy makers, academia, innovators and other stakeholders involved in the topic, in order to take stock of the current technical developments and implementations of genome editing, as well as their applications in various areas of agriculture and the implications they give rise to (More information on the "OECD Conference on Genome Editing: Applications in Agriculture-Implications for Health, Environment and Regulation" can be found on the OECD Genome Editing hub: http://www.oecd.org/environment/genome-editing-agriculture/ ; the hub also contains the detailed conference programme, the biographies of all conference speakers, the detailed conference abstracts, and the presentations of the two-day conference). The conference aimed to provide a clearer understanding of the regulatory considerations raised by products of genome editing, pointing towards a coherent policy approach to facilitate innovations involving genome editing.

The clinical application of gene editing: ethical and social issues.

Gene-editing techniques have progressed rapidly in the past 5 years. There are already ongoing human somatic gene-editing clinical trials for multiple diseases. And there has been one purported scenario of human germline gene editing in late 2018. In this paper, we will review the current state of the technology, discuss the ethical and social issues that surround the various forms of gene editing, as well as review emerging stakeholder data from professionals, the 'general public' and individuals and families dealing with genetic diseases potentially treatable by gene editing.

Policy Considerations Regarding Genome Editing.

The international Organisation for Economic and Co-operative Development (OECD) conference on genome editing (June 2018) provided a timely platform for scientists, risk assessors, policy-makers, and regulators to discuss the applications and implications of this technology in various agriculture areas and the related policy considerations; in addition questions related to appropriate safety assessments and the regulation of genome-edited products were debated.

Should human germ line editing be allowed? Some suggestions on the basis of the existing regulatory framework.

The application of genetic editing techniques for the prevention or cure of disease is a highly promising tool for the future of humanity. However, its implementation contains a number of ethical and legal challenges that should not be underestimated. On this basis, some sectors have already asked for a veto on any intervention that modifies the human germ line, while supporting somatic line editing. In this paper, I will support that this suggestion makes no sense at all, because the somatic/germ line disjunctive has no moral relevance and, therefore, it should not play any role in legal terms. I will provide a number of reasons to hold this assumption, such as the non-sacred nature of the germ line, the difference between germ line and human genome modification, or the moral importance of the presence of a will to create modified descendants. While doing so, I will provide some examples of the different approaches to germ line editing adopted by different regulations so as to demonstrate that, contrary to what is sometimes stated, a general ban on this practice is not the rule, but the exception. Additionally, I will show how alternative options which currently exist, such as a selective ban based on criteria different to the germ line/somatic line distinction, match better with the need to conciliate research needs and legitimate ethical concerns. Finally, I will introduce some further suggestions to this same purpose.

The contribution of transgenic and genome-edited animals to agricultural and industrial applications.

For centuries, animal breeders have intentionally selected the parents of the next generation based on their concept of the 'ideal' animal. The dramatic differences seen in the appearance and productivity of different breeds show the power of such selection on DNA sequence variations. Unfortunately, the global furore over the use of modern biotechnologies to introduce desired genetic variations into animal breeding programmes, and the regulatory uncertainty associated with these recombinant DNA techniques, has effectively precluded the use of these technologies in food animal breeding programmes. Ironically, many of these early transgenic animal applications targeted traits that favoured sustainability, such as disease resistance and decreased environmental impact. As a consequence, transgenic animals have had little opportunity to affect global agriculture, and only a handful of pharmaceutical applications have been successfully commercialised. New developments in genome editing hold considerable promise for targeting traits that improve both animal health and welfare, and frequently involve no introduction of DNA sequences from other species. Nonetheless, future global regulation and public acceptance of such methods remain uncertain. Proposals to regulate genome-edited animals based solely on the process used to influence DNA sequence variations (i.e. intentional genome editing) and any potential attendant risks, with no counterbalancing consideration of the ensuing benefits or risks associated with conventional selection programmes, will potentially forestall the use of genome editing in animal breeding programmes. No activity can survive a risk-only evaluation, and there are considerable opportunity costs associated with preventing breeders' access to safe technologies in order to achieve genetic improvements in livestock populations.

Pendant des siècles, les éleveurs ont exercé une sélection des reproducteurs au sein de leurs troupeaux afin de donner naissance à de nouvelles générations d'animaux correspondant à leur conception de l'animal d'élevage « idéal ¼. Les différences d'aspect et de productivité constatées entre les différentes races démontrent l'importance des effets de cette sélection sur les mutations des séquences d'ADN. Malheureusement, l'indignation planétaire suscitée par le recours aux biotechnologies modernes pour introduire des traits d'amélioration génétique chez les animaux d'élevage et les incertitudes sur la réglementation applicable aux techniques de l'ADN recombiné ont eu pour effet d'exclure l'utilisation de ces technologies dans les programmes d'élevage d'animaux destinés à la consommation humaine. L'ironie de la chose est que la plupart des premières applications recourant aux animaux transgéniques visaient à introduire des traits favorisant un élevage durable, par exemple des traits induisant une résistance contre certaines maladies ou permettant de diminuer l'impact environnemental des élevages. En conséquence, les conditions n'étaient guère réunies pour que les animaux transgéniques contribuent à transformer l'agriculture mondiale et seules quelques rares applications pharmaceutiques, ont pu être mises au point et commercialisées avec succès. Les récents développements de l'édition génomique ouvrent des voies extrêmement prometteuses pour cibler des traits permettant d'améliorer la santé et le bien-être des animaux, très souvent sans qu'il soit nécessaire d'introduire des séquences d'ADN provenant d'autres espèces. Néanmoins, des incertitudes subsistent sur l'évolution de la réglementation mondiale en la matière et sur l'acceptation sociale de ces méthodes à l'avenir. On peut donc s'attendre à ce que l'utilisation de l'édition génomique dans les programmes de sélection animale sera devancée par des propositions visant à la réglementer ; ces propositions ne prendront en compte que le processus induisant une modification ciblée de séquences d'ADN et les risques potentiels qui lui sont associés, sans les contrebalancer par un examen des bénéfices apportés ni des risques inhérents aux programmes de sélection classiques. Aucune activité ne peut survivre à une évaluation basée exclusivement sur les risques ; par ailleurs, les coûts d'opportunité induits par le fait d'empêcher les éleveurs d'accéder à des technologies sûres pour améliorer le patrimoine génétique des populations d'animaux d'élevage sont considérables.

Durante siglos, los criadores de animales han seleccionado intencionadamente a los progenitores de la siguiente generación en función de su concepción de animal «idóneo¼. Las espectaculares diferencias de aspecto externo y productividad que se observan entre las distintas razas ponen de manifiesto el poder de esta selección ejercida sobre las variaciones de secuencias de ADN. Lamentablemente, el clamor mundial contra el empleo de las modernas biotecnologías para introducir las variaciones genéticas deseadas en los programas de producción animal, sumado a las incertidumbres reglamentarias existentes en torno a esas técnicas de ADN recombinante, han obstaculizado el uso eficaz de estas tecnologías en programas de cría selectiva de animales destinados a la producción alimentaria. Irónicamente, muchas de esas primeras aplicaciones de animales transgénicos tenían que ver con rasgos que favorecían la sostenibilidad, como la resistencia a enfermedades o la reducción del impacto ambiental. Como consecuencia, apenas ha habido ocasión de que los animales transgénicos influyan en la agricultura mundial y solo se han comercializado con éxito un puñado de aplicaciones farmacéuticas. Las últimas novedades surgidas en la edición genómica parecen bastante prometedoras para actuar sobre rasgos que mejoren tanto la salud como el bienestar de los animales, a menudo sin que ello requiera la introducción de secuencias de ADN de otras especies. Sin embargo, sigue reinando la incertidumbre acerca del grado de aceptación pública y la futura reglamentación de tales métodos a escala mundial. Lo más probable es que las propuestas de reglamentar la cuestión de los animales obtenidos por edición genómica atendiendo únicamente al proceso empleado para obtener variantes de secuencias de ADN (esto es, la edición genómica deliberada) y a los eventuales riesgos conexos (sin tener en cuenta, en contrapartida, los consiguientes beneficios o riesgos asociados a los programas de selección convencionales) desemboquen en la imposibilidad de aplicar la edición genómica a programas de cría selectiva de animales. No hay actividad alguna que pueda superar el filtro de una evaluación basada únicamente en el riesgo, y el hecho de impedir que los criadores accedan a tecnologías seguras para lograr la mejora genética de sus poblaciones de ganado entraña importantes costos de oportunidad.