Following the Second Summit on Human Gene Editing in Hong Kong in 2018, where the birth of two girls with germline genome editing was revealed, the need for a responsible pathway to the clinical application of human germline genome editing has been repeatedly emphasised. This paper aims to contribute to the ongoing discussion on research ethics issues in germline genome editing by exploring key issues related to the initial applications of CRISPR in reproductive medicine. Following an overview of the current (...) discussion on bringing germline genome editing into clinical practice, we outline the specific challenges associated with such interventions and the features that distinguish them from conventional clinical testing of new medical treatments. We then review proposed ethical requirements for initial heritable genome editing, such as the absence of reasonable alternatives, the existence of sufficient and reliable preclinical data, appropriate informed consent, requirements related to safety, and long-term follow-up. (shrink)

The successes of the human genome project and genomics research programs portend great potential to improve upon health and enhance life. As scientific advancements continue, bioethicists and policy makers deliberate over the social and ethical implications of genetic and genomic technologies and information (ggT/I). The application of ggT/I to human reproduction raises conceptual and moral questions about being human and the links between offspring, parents, and society. Given ggT/I’s ability to significantly affect the biological constitution of humans and future human (...) generations thinking through such issues is fundamental to ethical and policy analysis. By means of a systematic literature review and accompanying content analysis, this paper highlights the dominant ethical concerns raised within recent bioethics discourse over the use of ggT/I for human reproduction. Based on these findings it aso offers a framework through which, and demarcates where, religious perspectives can add value to genethics debates and policy deliberation. (shrink)

Human germline gene editing is often debated in hypothetical terms: if it were safe and efficient, on what further conditions would it then be ethically acceptable? This paper takes another course. The key question is: how can scientists reduce uncertainty about safety and efficiency to a level that may justify initiation of first-time clinical trials? The only way to proceed is by well-designed preclinical studies. However, what kinds of investigation should preclinical studies include and what specific conditions should they satisfy (...) in order to be considered well-designed? It is argued that multispecies and multigenerational animal studies are needed as well as human embryo editing without implantation. In order to be possible to translate to first-time clinical trials, animal studies need to satisfy strict conditions of validity. Moreover, embryo studies intended for translation to first-time clinical trials need to correspond to the animal studies in experimental design. Only in this way can uncertainty about risk for harm and prospect of benefit in first-time clinical trials be reduced to a modest level. If uncertainty is not reduced to such a level, first-time clinical trials in germline gene editing should not be initiated. (shrink)

Human germline gene editing is often debated in hypothetical terms: if it were safe and efficient, on what further conditions would it then be ethically acceptable? This paper takes another course. The key question is: how can scientists reduce uncertainty about safety and efficiency to a level that may justify initiation of first-time clinical trials? The only way to proceed is by well-designed preclinical studies. However, what kinds of investigation should preclinical studies include and what specific conditions should they satisfy (...) in order to be considered well-designed? It is argued that multispecies and multigenerational animal studies are needed as well as human embryo editing without implantation. In order to be possible to translate to first-time clinical trials, animal studies need to satisfy strict conditions of validity. Moreover, embryo studies intended for translation to first-time clinical trials need to correspond to the animal studies in experimental design. Only in this way can uncertainty about risk for harm and prospect of benefit in first-time clinical trials be reduced to a modest level. If uncertainty is not reduced to such a level, first-time clinical trials in germline gene editing should not be initiated. (shrink)

A dissociated area of medical research warrants bioethical consideration: a proposed transplantation of a donor’s entire body, except head, to a patient with a fatal degenerative disease. The seeming improbability of such an operation can only underscore the need for thorough bioethical assessment: Not assessing a case of such potential ethical import, by showing neglect instead of facing the issue, can only compound the ethical predicament, perhaps eroding public trust in ethical medicine. This article discusses the historical background of full-body (...) transplantation, documents the seriousness of its current pursuit, and builds an argument for why prima facie this type of transplant is bioethically distinct. Certainly, this examination can only be preliminary, indicating what should be a wide and vigorous discussion among practitioners and ethicists. It concludes with practical suggestions for how the medical and bioethics community may proceed with ethical assessment. (shrink)

The ethical issues associated with germline gene modification and embryo research are some of the most contentious in current international science policy debates. In this paper, we argue that new genetic techniques, such as CRISPR, demonstrate that there is an urgent need for China to develop its own regulatory and ethical framework governing new developments in genetic and embryo research. While China has in place a regulatory framework, it needs to be strengthened to include better compliance oversight and explicit criteria (...) for how different types of research should be reviewed by regulatory authorities. We also document a variety of opinions about the new technologies among the public, scholars, and policy makers. China needs to develop its own regulations in coordination with other countries; but it is unlikely that an international consensus will be achieved in this area, given the existing differences in regulations between countries. We should aim at harmonization, not necessarily complete consensus, and the perspective from China is vital when international norms are developed and harmonized. Chinese policy makers and researchers need to be aware of the international discussions, at the same time as the international community is aware of, and accommodates, Chinese positions on important policy options. (shrink)

Abstract:There is a role for regulatory oversight over new genetic technologies. Research must ensure the rights of human subjects, and all medical products and techniques should be ensured to be safe and effective. In the United States, these forms of regulation are largely the purview of the National Institutes of Health and the Food and Drug Administration. Some have argued, however, that human genetic therapies require new regulatory agencies empowered to enforce cultural norms, protect against hypothetical social harms, or ensure (...) that the human genome remains unchanged. Focusing on the United States, this essay will briefly review these arguments and argue that the current limited regulatory role over human gene therapies is sufficient to protect public health, bodily autonomy, and reproductive freedom. (shrink)

In light of the development of “CRISPR” technology, new promising advances in therapeutic and preventive approaches have become a reality. However, with it came many ethical challenges. The most recent worldwide condemnation of the first use of CRISPR to genetically modify a human embryo is the latest example of ethically questionable use of this new and emerging field. Monotheistic religions are very conservative about such changes to the human genome and can be considered an interference with God’s creation. Moreover, these (...) changes could cause perpetual changes to future generations. The Muslim scholars establish their decisions by addressing five foundations of Islamic law i.e. “maqāṣid al sharı̄`a”; the purposes of the law. These are dın̄, nafs, nasl, `aql and māl. To achieve this, the five principles should all be met before approval of an experiment like the Chinese embryo modifications; Qaṣd which is achieved in this case as it aims to protect the embryo from HIV. Yaqın̄ and Ḍarar were not satisfied as they require strong scientific certainty of the procedures, and evidence of safety. Ḍarūra by which the alternatives being compared; in this case more established and proven safe alternatives to protect the HIV transmission from the father are available, so this principle is not met. The final principle is `Urf, by which the social context of using any contemporary technology should be taken in consideration, and clearly this was not achieved. Collectively, germline changes are rejected from an Islamic perspective until the five principles are fulfilled. In the Chinese Twins gene editing case, there was clearly no justification or support for it according to the Muslim Jurisprudence laws. These laws and approaches can serve as an ethical checklist for such controversial research, especially in early stages of the research. (shrink)

This article traces the rapid progression of policy pertaining to human genome germline modifications using genome editing. It provides an overview of how one fertility physician implemented and advertised experimental techniques as part of his fertility clinic services, examines US law and policy, and assesses the impact of rhetoric influencing global policy and interpretation of the law. This article provides an in-depth examination of the medical rationale driving the acceptance of genome editing human embryos in two contexts: to cure disease (...) and treat infertility. It describes complexities in genomics and outlines risks currently associated with genome editing, asserting the available evidence fails to demonstrate genome editing constitutes a curative therapy. (shrink)

Design of clinical trials for germline gene editing stretches current accepted standards for human subjects research. Among the challenges involved is a set of issues concerningintergenerational monitoring—long-term follow-up study of subjects and their descendants. Because changes made at the germline would be heritable, germline gene editing could have adverse effects on individuals’ health that can be passed on to future generations. Determining whether germline gene editing is safe and effective for clinical use thus may require intergenerational monitoring. The aim of (...) this paper is to identify and argue for the significance of a set of ethical issues raised by intergenerational monitoring in future clinical trials of germline gene editing. Though long-term, multigenerational follow-up study of this kind is not without precedent, intergenerational monitoring in this context raises unique ethical challenges, challenges that go beyond existing protocols and standards for human subjects research. These challenges will need to be addressed if clinical trials of germline gene editing are ever pursued. (shrink)

Targeted modifications of the human epigenome, epigenome editing (EE), are around the corner. For EE, techniques similar to genome editing (GE) techniques are used. While in GE the genetic information is changed by directly modifying DNA, intervening in the epigenome requires modifying the configuration of DNA, for example, how it is folded. This does not come with alterations in the base sequence (‘genetic code’). To date, there is almost no ethical debate about EE, whereas the discussions about GE are voluminous. (...) Our article introduces EE into bioethics by translating knowledge from science to ethics and by comparing the risks of EE with those of GE. We, first (I), make the case that a broader ethical debate on EE is due, provide scientific background on EE, compile potential use-cases and recap previous debates. We then (II) compare EE and GE and suggest that the severity of risks of novel gene technologies depends on three factors: (i) the choice of an ex vivo versus an in vivo editing approach, (ii) the time of intervention and intervention windows and (iii) the targeted diseases. Moreover, we show why germline EE is not effective and reject the position of strong epigenetic determinism. We conclude that EE is not always ethically preferable to GE in terms of risks, and end with suggestions for next steps in the current ethical debate on EE by briefly introducing ethical challenges of new areas of preventive applications of EE (III). (shrink)