Human Genome Editing Research Articles

The platforming of human embryo editing: prospecting “disease free” futures

In November 2018, a scientific scandal broke when news emerged that the world’s first gene edited babies had been born in China on the eve of the 2nd International Summit on Human Genome Editing in Hong Kong. He Jiankui had recruited a total of seven couples who were in need of fertility treatment to participate in an effort to clinically apply human embryo editing with the promise that, if successful, their future children would be protected from HIV. While He Jiankui has since been jailed for illegal medical practice and much has been written about his unethical and flawed “experiment,” in this article we suggest that the Hong Kong summit nevertheless marked the moment when human embryo editing came to be platformed. Human embryo editing brings together a complete set of new reproductive and genetic technologies into a total bio-reproductive platform shaped by socio-technical “disease free” imaginaries.

Public and Stakeholder Engagement in Developing Human Heritable Genome Editing Policies: What Does it Mean and What Should it Mean?

As scientific research pushes the boundaries of knowledge, new discoveries and technologies often raise ethical and social questions. Public responses vary from surprise, to unrealistic optimism about imminent new treatments, confusion, and absolute opposition. Regardless of the intent, the use of a precise gene editing tool on human embryos, such as CRISPR-Cas9, is an example of such a controversial emerging technology. Substantive disagreement about the appropriate research pathways and permissible clinical applications is to be expected. Many ethical concerns, especially related to genetic manipulation of human embryos, are rooted in deeply held moral, religious, or ideological beliefs that science alone cannot address. Today, more scientists and scientific societies as well as policy makers are calling for public and stakeholder engagement in developing guidelines and policies governing scientific practice. We conducted a critical interpretive review of the literature on public and stakeholder engagement in science policy development regarding emerging technologies to determine the ideals that should guide engagement efforts of entities developing recommendations or guidelines on policy for such technologies. We identify and describe five ideals. To illustrate possible applications of these ideals, we review the engagement efforts described in three reports on heritable human genome editing and assess those efforts in light of these ideals. Finally, we recommend possible avenues for engagement that would advance those goals.

Germline genome editing: Moratorium, hard law, or an informed adaptive consensus?

With the development of practical means of human germline genome editing (HGGE) in recent years, there have been calls for stricter regulation and oversight over HGGE interventions with potential for heritable changes in the germline. An international moratorium has been advocated. We examine the practicality of such a proposal, as well as of a regulation through the “traditional” mechanisms of international and municipal laws. We argue that these mechanisms are unlikely to achieve their intended objectives and that the better approach is to engage the international community of stakeholders, researchers, scientists, clinicians, and other workers directly involved in the field in working toward the development of an “informed adaptive consensus”. We offer suggestions as to how this may be achieved and how existing indirect levers of regulation may be harnessed toward this end.

Germline genome modification through novel political, ethical, and social lenses.

Much has been written about gene modifying technologies (GMTs), with a particularly strong focus on human germline genome editing (HGGE) sparked by its unprecedented clinical research application in 2018, shocking the scientific community. This paper applies political, ethical, and social lenses to aspects of HGGE to uncover previously underexplored considerations that are important to reflect on in global discussions. By exploring 4 areas—(1) just distribution of HGGE benefits through a realist lens; (2) HGGE through a national interest lens; (3) “broad societal consensus” through a structural injustice lens; and (4) HGGE through a scientific trustworthiness lens—a broader perspective is offered, which ultimately aims to enrich further debates and inform well-considered solutions for developments in this field. The application of these lenses also brings to light the fact that all discussions about scientific developments involve a conscious or unconscious application of a lens that shapes the direction of our thinking.

Human Germline Genome Editing: Curse or Blessing?

"Technological developments in genome editing raise high expectations for clinical applications, also for germline genome editing (GGE). Clinical (reproductive) GGE is currently categorically prohibited in many countries, in line with relevant European regulations. What are the arguments behind this prohibitive legislation - and are they convincing? If a technique could help to avoid serious genetic disorders in future children in a safe and effective way, would this be a reason to reconsider a categorical prohibition? Taking account of both deontological and (different types of) consequentialist ethical arguments, it is argued that: - both basic and preclinical research regarding GGE can be morally justified on conditions; - while clinical GGE would be totally premature, it might become a responsible intervention in the future, both as an add-on to and an alternative for preimplantation genetic testing (PGT) for genetic conditions, but only after adequate pre-clinical research suggesting that GGE is sufficiently safe and effective; - the categorical prohibition of clinical GGE needs critical discussion, also at a European level; - a strict regulation of clinical GGE is warranted given the relevant safety and societal concerns about unsound applications.

A virtual deliberative public engagement study on heritable genome editing among South Africans: Study protocol.

This article outlines the protocol for a prospective study for virtual deliberative public engagement on heritable genome editing in humans. The study intends to create a platform for a diverse group of 25–30 South Africans to engage with a facilitator and each other on 15 policy questions regarding heritable genome editing, with a focus on: a) the prevention of heritable genetic conditions; b) editing for immunity; and c) editing for enhancement. The aim is to understand the views on these issues so as to inform further research and policy, and to analyse the process and effect of deliberation on opinion. Participants will be expected to study the provided resource materials and pass the entrance exam—aligning with the protocols of the Harvard Personal Genome Project. In this way, the commitment, openness and basic knowledge of the candidates will be tested to ascertain whether they are suitable participants for the deliberative engagement.

Shifting Perceptions of CRISPR

Shifting Perceptions of CRISPR

The Moral Clause in Patent Law and Threats Posed by Human Germl ine Genome Editing

This article examines whether the lack of closure of moral clauses in patent laws, particularly in dealing with the issue of human germline genome editing, causes such clauses to fail to function as a moratorium in countries like Mexico. The hypothesis posed here is that a general, open, moral clause in intellectual property legislation, specifically in patent law, is ineffective when confronted with a foreseeable but strong innovation that alters an area of applied biology such as human germline genome editing. Using the deductive method, this research aims to determine whether countries like Mexico need to provide more specific guidance in their legislation on technological innovations like human germline modification in order to foster an atmosphere of legal certainty. A comparative analysis of the closed morals clause in the European Patent Convention and the open morals clause in Mexico’s intellectual property law confirms this hypothesis. Specifically, the lack of closure of a morals clause in patent law, when confronted with novel and complex technological advances, will likely fail to function as a moratorium.

Promissory ethical regimes: publics and public goods in genome editing for human health

Abstract This paper analyses promissory discourse for genome editing and human health in the UK, attending to the articulation of public goods and their beneficiary publics. Focusing on promissory reasoning about an emerging technology field as anticipatory and ethical considerations as integral to such debates, the notion of ethical regime as a mode of governance is applied to the concept of promissory regime. By analyzing key documents and interviews with opinion leaders—thus focusing on the discursive dimension—an enabling promissory ethical regime for genome editing and its contestation are identified. This regime posits scientific knowledge production now, and improved treatment or prevention of hereditary diseases later, as key goods of genome editing for human health and as a sociotechnical project worthy of support. Specific publics are created as beneficiaries. These publics and goods play out as ethical rationales for the promissory governance of the emerging field of human genome editing.

First Positive Clinical Data for In Vivo Genome Editing in Humans Opens "New Era of Medicine".

First Positive Clinical Data for In Vivo Genome Editing in Humans Opens "New Era of Medicine".

The DNA-Dialogue: A Broad Societal Dialogue About Human Germline Genome Editing in the Netherlands.

For years, calls for public involvement in the debate concerning the acceptability of human germline genome editing (HGGE) have been made. A multidisciplinary consortium of 11 organizations in the Netherlands organized a broad societal dialogue to inquire about the views of Dutch society toward HGGE. The project aimed to reach a wide and diverse audience and to stimulate a collective process of deliberative opinion forming and reflection. To that end, several instruments and formats were developed and employed. We present the results of 27 moderated dialogues organized between October 2019 and October 2020. Overall, participants of the dialogues were capable of assessing and discussing the subject of HGGE in a nuanced way. Analysis of these dialogues shows that in general, participants had no fundamental and absolute objections toward HGGE technology. However, they only deemed HGGE to be acceptable when it is used to prevent serious heritable diseases and under strict conditions, without affecting important (societal) values. There was a small group of participants who found HGGE fundamentally unacceptable because it would cross natural, socio-ethical, or religious boundaries.

Governing Heritable Human Genome Editing: A Textual History and a Proposal for the Future.

Heritable human genome editing (HHGE) has become a topic of intense public interest, especially since 2015. In the early 1980s, a related topic—human genetic engineering—was the subject of sustained public discussion. There was particular concern about germline genetic intervention. During the 1980s debate, an advisory committee to the Director of the National Institutes of Health (NIH)—the Recombinant DNA Advisory Committee (RAC)—agreed to provide initial public review of proposals for deliberate introduction of DNA into human beings. In 1984 and 1985, the RAC developed guidelines for research involving DNA transfer into patients. The committee also commented on the possibility of deliberately altering the human germline. We track the textual changes over time in the RAC's response to the possibility of germline genetic intervention in humans. In 2019, the NIH RAC was abolished. New techniques for genome editing, including CRISPR-based techniques, make both somatic and germline alterations much more feasible. These novel capabilities have again raised questions about oversight. We propose the creation of a new structure for the public oversight of proposals to perform HHGE. In parallel with a technical review by a regulatory agency, such proposals should also be publicly evaluated by a presidentially appointed Bioethics Advisory Commission.

Toward anticipatory governance of human genome editing: a critical review of scholarly governance discourse

ABSTRACT The rapid development of human genome editing (HGE) techniques evokes an urgent need for forward-looking deliberation regarding the aims, processes, and governance of research. The framework of anticipatory governance (AG) may serve this need. This article reviews scholarly discourse about HGE through an AG lens, aiming to identify gaps in discussion and practice and suggest how AG efforts may fill them. Discourse on HGE has insufficiently reckoned with the institutional and systemic contexts, inputs, and implications of HGE work, to the detriment of its ability to prepare for a variety of possible futures and pursue socially desirable ones. More broadly framed and inclusive efforts in foresight and public engagement, focused not only upon the in-principle permissibility of HGE activities but upon the contexts of such work, may permit improved identification of public values relevant to HGE and of actions by which researchers, funders, policymakers, and publics may promote them.

Heritable human genome editing: our moral responsibilities towards future generations

The uncharted territory of genome editing technology, which can be described as the Copernican revolution of our age, presents the challenge of the trade-offs between the benefits to people now and the known unknowns concerning future dangers and risks. It is for this reason that critics of human germline modification argue that it is unethical to harvest benefits in the immediate future while causing a whirlwind in the far-distant future! The current generation has, therefore, to make sensible decisions about the research and clinical application of human gene editing technologies to prevent far-reaching deleterious impact on an indefinite number of generations yet to come. Certainly, techniques of heritable human genome editing could increase vulnerability, discrimination and division among and between generations without the guidance of social justice which is inseparable from solidarity. Since the descendants of edited human embryos may be exposed to unknown, possibly negative long-term effects, without consenting to having these risks imposed on them, the thorny issues of harm, safety and precaution are crucial to address the knowledge-gaps and uncertainties implied the clinical application of human genome editing. Thus, the intergenerational moral consciousness and conscientiousness on the benefits and risks of human genome editing have to remain vigilant and alert!

WHO issues human genome–editing recommendations

The World Health Organization has issued the first global recommendations and a governance framework for safe, effective, and ethical use of human genome editing for public health. The guidance comes after 2 years of work by an expert advisory committee the WHO created after news broke in 2018 that babies had been born from embryos whose genes had been changed using CRISPR technology. The recommendations cover international collaboration; human genome–editing registries; intellectual property; education and empowerment; and illegal, unethical, or unsafe research. For example, in addition to existing clinical trial registries, the recommendations say the WHO should work with the international scientific community to develop a registry for basic and preclinical research and to “develop an assessment mechanism to identify clinical trials using human genome editing technologies that may be of concern.” In a statement announcing the release of the recommendations , WHO chief scientist Soumya Swaminathan says, “As global

WHO issues human genome–editing recommendations

WHO issues human genome–editing recommendations

Right to Health in the International Legal System of Human Rights at the Universal and Regional Levels

INTRODUCTION.The individual's right to health is a set of natural and positive legal frameworks that govern a person’s life activity, individual and family wellbeing, enforcement of health guarantees by the statesparticipants of universal and regional treaties of the field under question. The formation of this right stems from biological characteristics of each person, socio-economic conditions, environment, access to health and sanitation services, national health-care system progress, existence of vulnerable groups of population. Goals of the UN Sustainable Development Agenda 2030 (UN General Assembly resolution 70/1) include such essential aspects of the right to health as ending poverty and hunger in all its forms everywhere; promote food security and healthy lifestyle; the well-being of all individuals at any age; ensure availability and sustainable management of water and sanitation for all; protection and restoration of water-related ecosystems; enhancement of the States capacity to prevent and reduce national and global health risks. According to the position of the World Health Organization (WHO) the right to health imposes on the States a legal obligation to ensure timely access to adequate levels of high-quality health care, clean and safe drinking water, sanitation, adequate nutrition, shelter, health-related information and education, gender equality. As a result, the considerable amount of attention is paid to the analysis of the content of general and specific international instruments at the universal level and the international legal specificities of enshrining and maintaining an individual's right to health. The text also places the emphasis on its normative framing in the law of the Council of Europe and the European Union, reflecting the decisions and rulings of the European Court of Human Rights (ECHR).MATERIALS AND METHODS. The legal framework of the study is based on universal international treaties of the UN system, regional regulations of the Council of Europe and the EU, legal position of the UN specialized agencies, the International Committee of the Red Cross (ICRC) and the ECHR. The scientific works of domestic and foreign authors related to the study of the right to health are used as a theoretical foundation. The research uses general scientific and special cognitive techniques wherein legal analysis and synthesis, systemic, formal-legal, comparative-legal, historical-legal and dialectical methods are applied.RESEARCH RESULTS. The research indicates that the modern international legal concept of the right to health is being developed at the universal and regional level. Furthermore, specific international legal guarantees for the protection of this right are emerging for special groups such as women and children, refugees, stateless persons and migrant workers, protected persons, the wounded and the sick – all persons affected by international armed conflicts. There is a certain trend in Council of Europe and EU law towards an extended interpretation of the human right to health responding to new challenges to the realization that right, concerning bioethics, human genome editing, and the effects of nuclear testing and environmental pollution.DISCUSSION AND CONCLUSIONS.Following a review of the content and implementation of the right to health in the universal and regional international legal systems for the human rights and freedoms protection, the authors suggest its incorporation in a group of personal rights, social benefits provided by the state, and simultaneously in a collective right to development pertaining to the population as a whole. The universal international legal institutions establishing special rights for vulnerable groups will continue to be applied by member states in the context of a situational response to the global needs of families, women and children, international migration, armed conflicts, environmental conditions, and bioethical issues. The authors encourage the complement of the European system of human rights protection with an additional protocol to the Council of Europe Convention for the Protection of Human Rights and Fundamental Freedoms of 1950, involving the right to health security.

Screening Platforms for Genetic Epilepsies-Zebrafish, iPSC-Derived Neurons, and Organoids.

Recent advances in molecular and cellular engineering, such as human cell reprogramming, genome editing, and patient-specific organoids, have provided unprecedented opportunities for investigating human disorders in both animals and human-based models at an improved pace and precision. This progress will inevitably lead to the development of innovative drug-screening platforms and new patient-specific therapeutics. In this review, we discuss recent advances that have been made using zebrafish and human-induced pluripotent stem cell (iPSC)-derived neurons and organoids for modeling genetic epilepsies. We also provide our prospective on how these models can potentially be combined to build new screening platforms for antiseizure and antiepileptogenic drug discovery that harness the robustness and tractability of zebrafish models as well as the patient-specific genetics and biology of iPSC-derived neurons and organoids.

Right to health in european legal system: the content and guarantees

This article reviews the content and the implementation of the right to health in the regional international legal systems for the human rights and freedoms protection. Therefore, the study is based on the analysis of universal international treaties of the UN system, regional regulations of the Council of Europe, the European Union (EU), and the European Court of Human Rights (EctHR), using general scientific and special cognitive techniques wherein legal analysis and synthesis, systemic, formal-legal, comparative-legal, historical-legal and dialectical methods are applied. The research indicates that the modern international legal concept of the right to health is being developed at the regional level. There is a certain trend in Council of Europe and EU law towards an extended interpretation of the human right to health responding to new challenges to the realization of that right, concerning bioethics, human genome editing, and the effects of nuclear testing and environmental pollution. The author encourages the complement of the European system of human rights protection with an additional protocol to the Council of Europe Convention for the Protection of Human Rights and Fundamental Freedoms of 1950, involving the right to health security.

Thinking the unthinkable: how did human germline genome editing become ethically acceptable?

Two major reports in the UK and USA have recently sanctioned as ethically acceptable genome editing of future generations for the treatment of serious rare inherited conditions. This marks an important turning point in the application of recombinant DNA techniques to humans. The central question this paper addresses is how did it became possible for human genetic engineering (HGE) of future generations to move from an illegitimate idea associated with eugenics in the 1980s to a concrete proposal sanctioned by scientists and bioethicists in 2020? The paper uses the concept of a regime of normativity to understand the co-evolution and mutual shaping of technology, imaginaries, norms and governance processes in debates about HGE in the USA and UK. It will be argued that interlinked discursive, institutional, political and technological changes have made proposals for the use of genome editing in the genetic engineering of future generations both “thinkable” and legitimate.