Summary: Edward Lanphier and colleagues contend that human germline editing is an unethical technology because it could have unpredictable effects on future generations. In our view, such misgivings do not justify their proposed moratorium.

BackgroundClustered Regularly Interspaced Short Palindromic Repeats-associated technology may allow for efficient and highly targeted gene editing in single-cell embryos. This possibility brings human germline editing into the focus of ethical and legal debates again.Main bodyAgainst this background, we explore essential ethical and legal questions of interventions into the human germline by means of CRISPR-Cas: How should issues of risk and uncertainty be handled? What responsibilities arise regarding future generations? Under which conditions can germline editing (...) measures be therapeutically legitimized? For this purpose, we refer to a scenario anticipating potential further development in CRISPR-Cas technology implying improved accuracy and exclusion of germline transmission to future generations. We show that, if certain concepts regarding germline editing are clarified, under such conditions a categorical prohibition of one-generation germline editing of single-cell embryos appears not to be ethically or legally justifiable.ConclusionThese findings are important prerequisites for the international debate on the ethical and legal justification of germline interventions in the human embryo as well as for the harmonization of international legal standards. (shrink)

The development of the genome editing system called CRISPR–Cas9 has opened a huge debate on the possibility of modifying the human germline. But the types of changes that could and/or ought to be made have not been discussed. To cast some light on this debate, I will describe the story of the CRISPR–Cas9 system. Then, I will briefly review the projects for modification of the human species that were discussed by biologists throughout the twentieth century. Lastly, I will (...) show that for plenty of reasons, both scientific and societal, germline modification is no longer a priority for our societies. (shrink)

Potential applications of genome editing in assisted reproductive technology (ART) raise a vast array of strong opinions, emotional reactions and divergent perceptions. Acknowledging the need for caution and respecting such reactions, we observe that at least some are based on either a misunderstanding of the science or misconceptions about the content and flexibility of the existing legal frameworks. Combining medical, legal and ethical expertise, we present and discuss regulatory responses at the national, European and international levels. The discussion has (...) an EU starting point and is meant as a contribution to the general international regulatory debate. Overall, this paper concludes that gene editing technologies should not be regulated autonomously. Rather, potential uses should be regulated under general, existing frameworks and where applicable by reference to sufficiently equivalent technologies and techniques already subject to specific regulation. To be clear, we do not argue for the hasty introduction of gene editing as a reproductive treatment option in the immediate future. We call for caution with regard to overreaching moratoria and prohibitions that will also affect basic research. We recommend flexible regulations that allow for further responsible research into the potential development of the technology. We call for an open and inclusive debate and argue that scientific communication should claim a more prominent role to counter the danger of widespread misinformation. A high level of transparency and accuracy should guide scientific communication while simultaneously global‐scale responsibility and governance should be fostered by promoting cross‐disciplinary thinking and multi‐level stakeholder involvement in legal and regulatory processes. (shrink)

Scheinerman (2023) proposes a Citizen’s Jury on human germline genome editing (HGGE) to promote more inclusive public engagement, agenda setting and governance. She argues these juries should work...

Potential applications of genome editing in assisted reproductive technology (ART) raise a vast array of strong opinions, emotional reactions and divergent perceptions. Acknowledging the need for caution and respecting such reactions, we observe that at least some are based on either a misunderstanding of the science or misconceptions about the content and flexibility of the existing legal frameworks. Combining medical, legal and ethical expertise, we present and discuss regulatory responses at the national, European and international levels. The discussion has (...) an EU starting point and is meant as a contribution to the general international regulatory debate. Overall, this paper concludes that gene editing technologies should not be regulated autonomously. Rather, potential uses should be regulated under general, existing frameworks and where applicable by reference to sufficiently equivalent technologies and techniques already subject to specific regulation. To be clear, we do not argue for the hasty introduction of gene editing as a reproductive treatment option in the immediate future. We call for caution with regard to overreaching moratoria and prohibitions that will also affect basic research. We recommend flexible regulations that allow for further responsible research into the potential development of the technology. We call for an open and inclusive debate and argue that scientific communication should claim a more prominent role to counter the danger of widespread misinformation. A high level of transparency and accuracy should guide scientific communication while simultaneously global‐scale responsibility and governance should be fostered by promoting cross‐disciplinary thinking and multi‐level stakeholder involvement in legal and regulatory processes. (shrink)

Innovative healthcare technologies may raise ethical concerns which prevent their implementation for fear of unexpected or undesirable outcomes, even before they are introduced into usual clinical practice. Essential to innovation is therefore to analyze benefits and drawbacks from a multidisciplinary point of view (i.e., biomedical, social, financial). Value-based healthcare is currently the most comprehensive theoretical framework to evaluate the benefits of healthcare technologies on patients and society in the longer term. Technically, “the systematic evaluation of properties, effects and/or impacts of (...) health technologies” must be performed by validated procedures of Health Technology Assessment (HTA), supported by early HTA procedures to retrieve preliminary evidence and expert opinions. The aim of this study is to perform an early HTA of germline editing technologies in order to estimate their impact on patients and society, in light of the recent, controversial debate which followed the germline gene editing of human embryos. (shrink)

With recent reports that a Chinese scientist used CRISPR-Cas9 to heritably edit the genomes of human embryos (i.e., germline editing) brought to term, discussions regarding the ethics of the technology are urgently needed. Although certain applications of germline editing have been endorsed by both the National Academy of Sciences (US) and the Nuffield Council (UK), this paper explores the ethical concerns related even to such therapeutic uses of the technology. Additionally, this paper questions whether the technology (...) could ever feasibly be contained to the therapeutic realm. Consequently, this paper necessarily considers the ethical concerns related to enhancement uses of the technology even if only therapeutic applications are initially considered. In light of the concomitant risks, this paper assesses the technology’s countervailing benefits to conclude they do not prevail given that similar outcomes can largely be achieved with existing technologies. Consequently, this paper recommends an international ban on germline editing. (shrink)

Germline editing has a promising potential to prevent not only much human suffering, but also animal suffering. There are thus special reasons why a virtuous person would support the advancement of such research. Nevertheless, genome editing research is often pursued in a vicious manner, demonstrating not only a lack of moral virtue, but also a deficiency of intellectual virtue. In this chapter, three germline editing studies that were recently conducted on animals will be evaluated through (...) a virtue ethics framework. It will be shown that these studies, like most other kinds of animal research, is rife with not only moral failings, such as a lack of compassion for laboratory animals, but also intellectual failing, such as a failure to calculate the right means to the end of human health. It will conclude by suggesting some systematic changes that must be made in the animal research community before animal germline research can be characterized as truly virtuous. (shrink)

The reported birth of genetically modified twins in late 2018 has given new fuel to debates about the ethics of germline genome editing (GGE). There is a broad consensus among stakeholders that clinical uses of GGE should be temporarily banned as the technology is not yet deemed safe for use in humans. However, the idea of a complete ban is dismissed by many based on the expectation that more research will eventually allow scientists to make the technology safe (...) without having to put humans at risk first. In this article, I will analyse this assumption and argue that it is undermined by recent developments in the postgenomic life sciences. In particular, I will argue that in a postgenomic view of germline editing a complete ban on specific uses of the technology is warranted, because the research needed to assess the safety of these interventions would not be morally defensible. (shrink)

Two years ago, the US National Academy of Sciences and the National Academy of Medicine released a report drafted by an international committee regarding the use of gene editing in humans. Once a tedious and expensive process, gene editing has now become more accessible and cheaper using the new CRISPR technology, making the issue of its use more urgent and pressing. The committee cites general support for somatic nonheritable gene editing to correct for a serious disease already (...) present in a human being, but more controversial is germline gene editing for heritable conditions. Performing gene editing that affects an individual's descendants is at present tightly controlled in the US, but around the... (shrink)

The surprise announcement in November 2018 that a Chinese researcher had implanted and brought to term two gene-edited embryos, resulting in the birth of twin girls, had the effect of galvanizing a debate that goes back decades. Should we make heritable changes in our children's DNA? Until recently, this was hypothetical only, and the easy response was to say it is too uncertain and too unnecessary to be tolerated. Suddenly, however, the possibility that there might be real uses for mitochondrial (...) DNA replacement or for germline editing has led to a more nuanced debate, ranging from calls to double-down on prohibiting this technology to discussions of how to permit it for a... (shrink)

In 2015 scientists called for a partial ban on genome editing in human germline cells. This call was a response to the rapid development of the CRISPR–Cas9 system, a molecular tool that allows researchers to modify genomic DNA in living organisms with high precision and ease of use. Importantly, the ban was meant to be a trust-building exercise that promises a ‘prudent’ way forward. The goal of this paper is to analyse whether the ban can deliver on this (...) promise. To do so the focus will be put on the precedent on which the current ban is modelled, namely the Asilomar ban on recombinant DNA technology. The analysis of this case will show (a) that the Asilomar ban was successful because of a specific two-step containment strategy it employed and (b) that this two-step approach is also key to making the current ban work. It will be argued, however, that the Asilomar strategy cannot be transferred to human genome editing and that the current ban therefore fails to deliver on its promise. The paper will close with a reflection on the reasons for this failure and on what can be learned from it about the regulation of novel molecular tools. (shrink)

The prospect of using genome technologies to modify the human germline has raised profound moral disagreement but also emphasizes the need for wide-ranging discussion and a well-informed policy response. The Hinxton Group brought together scientists, ethicists, policymakers, and journal editors for an international, interdisciplinary meeting on this subject. This consensus statement formulated by the group calls for support of genome editing research and the development of a scientific roadmap for safety and efficacy; recognizes the ethical challenges involved in (...) clinical reproductive applications of genome editing but, importantly, rejects the idea that human reproductive germline modification is necessarily morally unacceptable; and highlights the importance of meaningful engagement in discussions of genome editing and the development of regulation and oversight mechanisms to govern future uses of such technologies. (shrink)

Volume 20, Issue 8, August 2020, Page 44-46.

CRISPR is widely considered to be a disruptive technology. However, when it comes to the most controversial topic, germline genome editing (GGE), there is no consensus on whether this technology has any substantial advantages over existing procedures such as embryo selection after in vitro fertilization (IVF) and preimplantation genetic diagnosis (PGD). Answering this question, however, is crucial for evaluating whether the pursuit of further research and development on GGE is justified. This paper explores the question from both a (...) clinical and a moral viewpoint, namely whether GGE has any advantages over existing technologies of selective reproduction and whether GGE could complement or even replace them. In a first step, I review an argument of extended applicability. The paper confirms that there are some scenarios in which only germline intervention allows couples to have (biologically related) healthy offspring, because selection will not avoid disease. In a second step, I examine possible moral arguments in favour of genetic modification, namely that GGE could save some embryos and that GGE would provide certain benefits for a future person that PGD does not. Both arguments for GGE have limitations. With regard to the extended applicability of GGE, however, a weak case in favour of GGE should still be made. (shrink)

The precautionary principle aims to influence decision‐making in contexts where some activity poses uncertain but potentially grave threats. This perfectly describes the controversy surrounding germline gene editing. This article considers whether the precautionary principle should influence how we weigh the risks and benefits of human germline interventions, focusing especially on the possible threats to the health of future generations. We distinguish between several existing forms of the precautionary principle, assess their plausibility and consider their implications for the (...) ethics of germline modification. We also offer a novel form of the precautionary principle: the sufficientarian precautionary principle. Some plausible versions of the precautionary principle recommend placing somewhat greater weight on avoiding threats to future generations than on achieving short‐term benefits. However, no plausible versions of the precautionary principle entail that we should outright reject the use germline gene editing in human reproduction and some, such as the sufficientarian version, might endorse its use. (shrink)

Interventions in the human germline have been regarded as a red line in genetic engineering up to now. However, with the recent progress in genome editing techniques, first and foremost CRISPR-based methods, the tide seems to be turning. The therapeutic benefits in particular are brought forward as an argument in favor of germline genome editing. According to this view, the main benefit of GGE is disease prevention. The procedure could be used to prevent monogenetic conditions for (...) which no treatment is available so far. This leads many commentators to the view that the benefits of GGE outweigh the risks. In this article, I examine the status and ethical implications of GGE as a means of disease prevention. I intend to show that the notion of GGE as disease prevention is only true for one specific application. Instead of being preventive treatments, most applications of GGE are advanced techniques of assisted reproduction. As such, they can be thought of as wish-fulfilling medicine, that is the use of medical techniques for non-medically indicated purposes. Thus, it is necessary to reconsider the risk-benefit analysis of GGE for most of its applications. (shrink)

Human germline gene editing constitutes an extremely promising technology; at the same time, however, it raises remarkable ethical, legal, and social issues. Although many of these issues have been largely explored by the academic literature, there are gender issues embedded in the process that have not received the attention they deserve. This paper examines ways in which this new tool necessarily affects males and females differently—both in rewards and perils. The authors conclude that there is an urgent need (...) to include these gender issues in the current debate, before giving a green light to this new technology. (shrink)

Ever since the publication of Derek Parfit’s Reasons and Persons, bioethicists have tended to distinguish between two different ways in which reproductive technologies may have implications for the...

Germline gene editing has many applications or uses. This article focuses on specific applications. Specifically, the article draws on a moral norm arising from the thinking about the value of communal relationships in the Afro-communitarian _ubuntu_ philosophy to interrogate key issues that specific applications of germline gene editing – for xeno-transplantation, agriculture and wildlife – raise. The article contends that the application of germline gene editing in these areas is justified to the extent that (...) they foster the capacity to relate with others and to be communed with by others. The article grants that our today’s decisions about germline gene editing will likely affect future humans, but will attempt to justify how this may be ethically permissible. (shrink)

This paper describes maslahah, a fundamental concept in Islam and its application in deliberating permissibility of human germline gene editing from an Islamic perspective. This paper refers to He Jiankui’s research that led to the birth of the world’s first gene edited babies, who were edited to be protected from HIV. The objective, procedure, and output of the research were assessed against the conditions of maslahah. It can be concluded that the experiment did not meet the conditions; it (...) is inconsistent with the objectives of shariah and some fundamental Islamic teachings that it did not preserve greater benefit, hence it could be considered impermissible. (shrink)

Volume 20, Issue 8, August 2020, Page 36-38.

Volume 19, Issue 7, July 2019, Page 45-47.

Sperm, eggs and embryos are made up of more than genes, and there are indications that changes to non‐genetic structures in these elements of the germline can also be inherited. It is, therefore, a mistake to treat phrases like ‘germline inheritance’ and ‘genetic inheritance’ as simple synonyms, and bioethical discussion should expand its focus beyond alterations to the genome when considering the ethics of germline modification. Moreover, additional research on non‐genetic inheritance draws attention to a variety of (...) means whereby differences can be inherited in offspring generations that do not rely on differences in germline structures. Research on these diverse forms of inheritance challenges the notion that there is some special form of ethical concern that falls on germline interventions in general, and on interventions to the nuclear genome within the germline in particular. (shrink)

Germline Gene Editing has enormous potential both as a research tool and a therapeutic intervention. While other types of gene editing are relatively uncontroversial, GGE has been strongly resisted. In this article, we analyse the ethical arguments for and against pursuing GGE by allowing and funding its development. We argue there is a strong case for pursuing GGE for the prevention of disease. We then examine objections that have been raised against pursuing GGE and argue that these (...) fail. We conclude that the moral case in favour of pursuing GGE is stronger than the case against. This suggests that pursuing GGE is morally permissible and indeed morally desirable. (shrink)

Volume 20, Issue 8, August 2020, Page 46-49.

Many people find the manipulation of the human germline—editing the DNA of sperm or egg cells such that these genetic changes are passed to the resulting offspring—to be morally impermissible. In this paper, I argue for the claim that editing the human germline is morally permissible. My argument starts with the claim that outcome uncertainty regarding the effects of germline editing shows that the duty to not harm cannot ground the prohibition of germline (...) editing. Instead, if germline editing is wrong, it is wrong because it violates a duty to protect. However, we also have an epistemic duty to gather evidence regarding the effects of editing the human germline which overrides any moral duty to protect future generations. Thus, we have a duty to gather evidence regarding the effects of editing the human germline, which is to say that we have a duty to edit the human germline. (shrink)

The year 2018 was the 40th anniversary of the birth of Louise Joy Brown, marking four decades of clinical in vitro fertilization and embryo transfer. Though this milestone, reached first by Steptoe and Edwards in the United Kingdom, is well acknowledged through Nobel accolade, the achievement was not entirely celebrated at the time. Global contention was not just moral, but political and legislative. In the United States, the achievement led in 1978 to the freezing of federal funds by the National (...) Institute of Health for research on human embryos and oocytes.A report published on May 4, 1979, by the Ethics Advisory Board of the Department of Health... (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)

Human germline genome editing is increasingly being seen as acceptable provided certain conditions are satisfied. Accordingly, genetic modifications would take place on eggs or sperm (or their prec...

Gene-editing technologies, such as CRISPR/Cas9, are internationally ethically fraught. In the United States, policy surrounding gene-editing has yet to be implemented, while the science continues to speed ahead. However, it is not enough that policy be implemented: in order for policy to establish limits for the technology such that benefits are possible while threats are kept at bay, such policy must be ethical. In turn, the ethics of gene-editing is a culturally determined field of inquiry. This piece (...) presents a proposal for a study whose goal is to arrive at ethical policy recommendations for policymakers. To achieve this goal, this study proposes, what needs to be done is, first, to understand the full history and foundation of gene-editing by conducting a thorough legal, bioethical, and policy review for precedent assisted reproductive technologies and genetic reproductive technologies. Following this effort, an empirical study must be conducted involving careful surveys of key stakeholder groups on their knowledge and opinions of gene-editing. Such stakeholder groups must include bioethicists, medical geneticists, and lay persons, including those in the disability community. (shrink)

CRISPR germline editing therapies hold unprecedented potential to eradicate hereditary disorders. However, the prospect of altering the human germline has sparked a debate over the safety, efficacy, and morality of CGETs, triggering a funding moratorium by the NIH. There is an urgent need for practical paths for the evaluation of these capabilities. We propose a model regulatory framework for CGET research, clinical development, and distribution. Our model takes advantage of existing legal and regulatory institutions but adds elevated (...) scrutiny at each stage of CGET development to accommodate the unique technical and ethical challenges posed by germline editing. (shrink)

Bioethics, Volume 35, Issue 7, Page 688-695, September 2021.

There are good theoretical rationales for considering germline gene editing (GGE) as a recommended and perhaps even necessary procedure for future long-term human space missions. This paper examines the arguments for applying GGE in a hypothetical future scenario where future parents living on Earth make decisions about applying GGE to their future children with the goal of allowing them to participate in space missions. The paper presents an ethical rationale for GGE. The paper also recognizes an area of (...) potential moral controversy that is not so much related to the application of GGE itself, but to the risk of different perceptions of well-being by parents and children that may result in the need for genetically modified children to leave Earth against their will. (shrink)

Assisted reproductive technologies have greatly increased our control over reproductive choices, leading some bioethicists to argue that we face unprecedented moral obligations towards progeny. Several models attempting to balance the principle of procreative autonomy with these obligations have been proposed. The least demanding is the minimal threshold model (MTM), according to which every reproductive choice is permissible, except creating children whose lives will not be worth living. Hence, as long as the future child is likely to have a life worth (...) living, prospective parents may be allowed to use preimplantation genetic diagnosis (PGD) to select embryos with genetic diseases or disabilities. Assuming a consequentialist person‐affecting view of morality, this paper investigates whether the MTM is an appropriate tool to guide procreative decisions given the continuous development of reproductive genetic technologies. In particular, I consider germline genome editing (GGE) and I argue that its application in human reproduction, unlike PGD, should be conceived as person‐affecting towards future progeny. I claim that even if we assume the plausibility of the MTM within PGD, we are committed to accepting that a greater moral obligation towards progeny should guide procreative decisions if GGE were available. In this case, the MTM should no longer be considered an appropriate instrument to guide procreative choices. Finally, I investigate when we face this greater moral obligation, concluding that it applies only when prospective parents have already engaged in the in vitro fertilization process. (shrink)

The recent development of CRISPR/Cas9 technology has rekindled the ethical debate concerning human germline modification that has begun decades ago. This inexpensive technology shows tremendous promise in disease prevention strategies, while raising complex ethical concerns about safety and efficacy of the technology, human dignity, tampering with God’s creation, and human genetic enhancement. Germline gene editing may result in heritable changes in the human genome, therefore the question of whether it should be allowed requires deep and careful discussion (...) from various perspectives. This paper explores Islamic perspectives on the concerns raised and highlights the ethical principles in Islam that should be taken into consideration when assessing the permissibility of CRISPR/ Cas9-mediated human germline gene editing. As argued in this paper, human germline gene editing would be considered lawful for medical purpose under certain conditions. It should not be applied on humans until the safety and efficacy issues are resolved. Robust ethical guidelines and strict regulations are necessary to preserve human dignity and to prevent premature and misuse of the technology. Maqasid al-shariah’s principles of preservation of human life, lineage, and dignity and ‘preventing harm takes precedence over securing benefit’ are among the guiding principles in assessing the permissibility of CRISPR/Cas9-mediated human germline editing from an Islamic perspective. Further discussions are important to address the controversies as well as to explore the related ethical principles. (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)

When the use of CRIsPR-Cas9 to edit DNA was first reported in 2012, it was quickly heralded by scientists, policymakers, and journalists as a transformative technology. CRISPR-Cas9 provides the means to change DNA in ways that either were not generally possible using previous genetic technologies or that were orders of magnitude more laborious or inefficient to undertake. CRISPR's possible applications were readily apparent and seemingly endless, from supercharging laboratory research to modifying insects that transmit disease to eliminating genetic conditions. By (...) 2015, Wired magazine was calling the discovery "The Genesis Engine."Against a backdrop of disappointing results from gene transfer... (shrink)