Auditing the Editor: A Review of Key Translational Issues in Epigenetic Editing

Currently, most advances in site-specific epigenetic editing for human use are concentrated in basic research, yet, there is considerable interest to translate this technology beyond the bench. This review highlights recent developments with epigenetic editing technology in comparison with the canonical CRISPR-Cas genome editing, as well as the epistemic and ethical considerations with preemptive translation of epigenetic editing into clinical or commercial use in humans. Key considerations in safety, equity, and access to epigenetic editing are highlighted, with a spotlight on the ethical, legal, and social issues of this technology in the context of global health equity

Revolutionizing the Biological Landscape: the Power of Genome Editing

In recent decades, the advent of genome editing has brought about profound transformations in biology, allowing for precise modifications to the genetic material of living organisms beyond traditional genetic manipulation methods. This summary explores the vast potential, diverse applications, and ethical considerations associated with genome editing. Led by CRISPR-Cas9, this technology revolutionizes genetic engineering by providing unparalleled accuracy and versatility. Scientists can now manipulate genes with unprecedented precision, impacting various fields such as agriculture and medicine. Genome editing facilitates the creation of genetically modified organisms with desirable traits, from enhancing crop disease resistance to pioneering human therapies. Moreover, it sheds light on gene function, offering crucial biological insights. Despite its transformative potential, ethical concerns accompany genome editing, especially in terms of editing the germ line and its implications for future generations. This necessitates ongoing discussions to address unintended consequences, highlighting the importance of responsible use. Ultimately, genome editing represents a revolutionary advancement with the potential to transform agriculture, medicine, and our understanding of life. Moving forward, inclusive dialogues involving scientists, ethicists, policymakers, and the public are essential to ensure the responsible application of genome editing for the benefit of humanity and the environment

Promissory Ethical Regimes: Publics and Public Goods in Genome Editing for Human Health

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

Governance of heritable human gene editing world-wide and beyond

To date, the controversy surrounding the unknown risks and consequences of heritable genome editing has grown, with such work raising biosafety and ethical concerns for future gener- ations. However, the current guideline of global governance is limited. In the context of the new framework for the governance of human genome editing developed by the World Health Orga- nization (WHO) committee, this paper presents further analysis by highlighting predicaments of governance on germline engineering that merit the most attention: (1) building a scientific culture informed by a broader set of values and considerations in the internal scientific community at large, such as codes of ethics, and education, in addition to awareness-raising measures; and (2) reflecting on and institutionalizing policies in grassroots practice according to local conditions in external governance, such as the experimentalist governance, which is a multi-layered model of governance that establishes an open-ended framework from the top and offers stakeholders the freedom of discussion. The key to achieving these goals is more democratic deliberation between the public and the inclusive engagement of the global scientific community, which has been extensively used in the Biological and Toxin Weapons Convention (BTWC). On a global scale, we believe that practicing heritable human genome editing in accordance with the WHO and BTWC appears to be a good choice

Rewriting Human History and Empowering Indigenous Communities with Genome Editing Tools.

Appropriate empirical-based evidence and detailed theoretical considerations should be used for evolutionary explanations of phenotypic variation observed in the field of human population genetics (especially Indigenous populations). Investigators within the population genetics community frequently overlook the importance of these criteria when associating observed phenotypic variation with evolutionary explanations. A functional investigation of population-specific variation using cutting-edge genome editing tools has the potential to empower the population genetics community by holding "just-so" evolutionary explanations accountable. Here, we detail currently available precision genome editing tools and methods, with a particular emphasis on base editing, that can be applied to functionally investigate population-specific point mutations. We use the recent identification of thrifty mutations in the CREBRF gene as an example of the current dire need for an alliance between the fields of population genetics and genome editing

Cellular xenotransplantation of animal cells into people: benefits and risk

The main benefit of xenotransplantation is its potential to overcome the worldwide organ shortage experienced in allotransplantation. Allogeneic transplantation is the only successful therapy for several life-threatening diseases, with cell, tissue or organ donation only partially meeting the demand and many patients dying while waiting for treatment. With supply falling short of demand, it is foreseen that the use of porcine material may at some stage overcome the existing gap between organ availability and clinical need. Recently, pig islet cells have been utilised in clinical trials, with safety being demonstrated. Indeed, pig-derived cells present several advantages: i) porcine cells have a stable function and differentiation pattern and are not tumorigenic; ii) pig cells have been shown to meet the physiological needs in large animal models; iii) the source of pig cells can be scaled up to meet demands in a highly standardised manner, and with respect to animal welfare regulations; iv) ‘designated-pathogen-free’ (DPF) pig lines can be produced, which could result in a higher safety profile than allotransplantation itself; v) the risk of zoonosis, which was raised years ago as the major hurdle, has been recently circumvented and is actually viewed as a controlled risk; and vi) immune risks are being circumvented via the use of genetically modified donor animals and encapsulation of porcine cells, particularly for the treatment of diabetes. Overall, the benefit appears to outweigh potential risks with respect to cellular xenotransplantation and this is discussed further in this review

An Afrocentric approach to CRISPR-Cas9: analysing the use of genetic technologies in human reproduction through the lens of human rights and African values.

Doctoral Degree. University of KwaZulu-Natal, Durban.In the wake of the advent of genome editing technology CRISPR-Cas9, there has been global debate about the potential use of this technology on human gametes or embryos to create individuals with genetically modified genomes. This is a process commonly referred to as germline genome editing (GGE). Given that several countries, including South Africa (SA), have no regulation speaking to GGE, many proposals have been put forward regarding how this technology ought to be regulated in a way that attends to the ethical issues raised by the prospect of modifying the genomes of future generations. Within this global discourse, however, there are several material gaps. Most notably, the proposals have primarily been framed through a Eurocentric paradigm that omits material contextual considerations relevant to SA and the African continent. Furthermore, the proposals tend to be based on value judgements on ethical issues — such as the moral significance of the human genome — rooted in the Western philosophical tradition. This thesis endeavours to respond to these gaps by providing a novel theoretical approach to the regulation of GGE in South Africa, termed an ‘Afrocentric approach’. This approach entails responding to the legal, ethical and human rights issues related to GGE that is rooted in an African philosophical perspective on these issues, and that is sensitive to the realities of the South African context. This thesis concludes that SA ought to be open to the prospect of parents modifying the genomes of future offspring but must also place reasonable and evidence-based constraints on GGE. This thesis finds that there is a tenable argument that prospective parents have a ‘right to CRISPR’, but this right may be limited. Such limitations must be rationally related to the goals of (1) protecting public interests, or (2) promoting the best interests of the prospective child