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The development of CRISPR technology has catapulted the issue of germline editing to the forefront of a debate between the goals of medical advancement and promotion of human diversity. The US National Academy of Sciences and the National Academy of Medicine recommended in a joint report that germline editing should be tightly regulated and pursued only for "serious diseases." A follow-up statement from an international summit on human genome editing emphasized a more general point that "the risks [are] too great to permit clinical trials of germline editing at this time." Here we review their recommendations in the context of genetic deafness, a condition that historically has been viewed by the medical community as a pathology. Deafness does not meet the standard of "serious disease" for experiments with human germline editing, but there is a real concern that scientists may soon begin to do germline editing with deaf individuals because, as we will discuss, they are in many ways ideal subjects for a clinical study of CRISPR, though their condition is neither fatal nor debilitating. In light of this, we worry about the potential for medical overreach and expediency. Drawing from examples of living deaf communities around the world, we propose an expansive view of human diversity that recognizes the value of genetic, linguistic, and cultural diversity to the future health of humankind.

This article considers the existential and eugenic risks of gene editing with CRISPR-Cas9. It brings forward epistemological and phenomenological questions concerning what CRISPR technology suggests about the limits of being human. By illuminating the paradoxical relationship between our "then self" and "now self," it considers the fragility of our individual and collective future-making endeavors. To do this, the article offers an overview of the existential dilemmas facing modern subjects, a history of eugenics and the ideology of health, a meditation on the limits of human knowledge, and an explication of the cultural work of metaphor. It argues for the benefits of human variation for individuals and communities and concludes by calling for an attitude of humility and restraint to guide the development and implementation of humane technologies rather than genetic manipulation technologies that aim to control future outcomes through present actions.

Germline genome editing has garnered dire predictions about its societal effects, but experience with other reproductive technologies should caution us about making extravagant claims. Amniocentesis was predicted to result in increased stigmatization of people born with Down syndrome, but in fact people with these conditions have been increasingly integrated into schools and workplaces. Artificial insemination by donor was predicted to result in women choosing to "optimize" their children, but in fact most women eschewed the offerings of the so-called "genius sperm bank," and when choosing among donors, have tended to look for those who most resemble their husbands and partners. IVF was predicted to cause parents to view children as commodities, but no such change has been evidenced. Preimplantation genetic diagnosis was predicted to become widespread and used for an ever-increasing range of conditions, including those unrelated to serious disease or shortened life span, but this has not happened either. Critics of germline genome editing have argued that even if it were safe and effective, it would inevitably be abused by prospective parents who wish to improve upon what is already predicted to be a healthy outcome, and that this practice would become sufficiently widespread among those able to afford it that we would be creating a new genetic caste system. Before developing policy around such predictions, it is important to learn from the past.

The raging controversy about whether heritable genome editing should be permitted is shaped and structured by the prevailing and countervailing narratives in circulation. In recent years, considerable shortcomings have come to characterize this discourse; it is now time to identify and correct a number of serious misunderstandings and distortions that have taken hold. This essay begins by briefly evaluating reactions to the November 2018 announcement that gene-edited babies had been born; it asserts that widespread agreement about the researcher's recklessness and dire ethical violations concealed deep fault lines among participants in the heritable genome editing debate. It goes on to consider several key omissions and misrepresentations that distort public understanding and undermine genuine debate. It suggests that the conversation must be refocused away from technical, medical, and scientific considerations toward matters of societal meanings, values, context, and consequences. It concludes with criteria for a broadly inclusive and meaningful decision-making process about whether heritable genome editing has any place in the shared and just future to which we aspire.

Human germline genetic modification has long been a controversial topic. Until recently it remained largely a hypothetical debate: whether one accepted or opposed the idea in principle, it was not only too risky but impractical to execute in reality. With the advent of genome editing technologies, however, heritable modifications to the human genome became a much more concrete possibility; nonetheless, the consensus has to date remained that human heritable genome editing is not yet safe enough for clinical application. The announcement of the birth of two genome-edited babies in late 2018, therefore, was condemned almost universally as premature, irresponsible, and dangerous. But what does responsibility require, and from whom? How should risk and precaution be balanced in assessing heritable genome editing, and against what alternatives? This paper reexamines commonly held assumptions about risk and responsibility with respect to human genome editing and argues that the precautionary approach that has so far been favored is not well justified, that the risks of heritable versus somatic genome editing should be reassessed, and that a fuller account of responsibility-scientific, social, and global-is required for the ethical governance of genome editing.

The ability to make direct genetic changes to the DNA of future children poses profound challenges for governance. Over the last several years, efforts to establish frameworks of ethical deliberation and governance for human genome editing have focused largely on technical criteria for proceeding with research and rules and mechanisms for regulating it. Less attention has been given to the question of who decides, and on the basis of what authority. The power to decide is exercised not only in giving answers to ethical questions or suppling policy advice, but in designating what questions should (and should not) be asked in the first place. The ways problems are framed and terms of collective debate are set is a crucial element of governance. This essay examines how certain framings that have dominated in influential arenas of deliberation about human germline genome editing underwrite (false) imperatives of governance. These imperatives have shaped not only ethical deliberation and governance agendas, but the trajectory of science itself. The essay focuses in particular upon the case of He Jiankui, arguing that his project is not an aberration, but, rather, an expression of ideas about science, ethics, and progress that are widely shared within the scientific community.

In the current agon between those promoting and opposing the development of human reproductive applications of genome editing techniques, the bone of contention is often whether the prospective reproductive technologies answer an "unmet medical need." Proponents often point to highly unusual cases of inherited genetic conditions as exhibiting that need. This essay argues that we ought to admit that the opponents are correct: human reproductive genome editing cannot be justified on medical grounds. Taking a deliberately provocative line, the essay suggests how inscribing such practices within a conventional model of biomedical research fails to take proper account of the interrelated interests in play, including those of the wider society and its future members. It also obscures important questions about how the public significance and value of human genome editing are produced through the dynamic encounter between science, technology, and social morality. This has certain discomfiting implications that will require both courage and humility to confront and-finally, perhaps-to embrace.

Ensuring experimental outcomes are of the highest clinical caliber is crucial prior to the introduction of germline genome editing. However, if we are to police scientific progress using probability or the potential to go wrong, then we must account for the specious standards of human reproduction. With 15% of clinically recognized pregnancies estimated to end in spontaneous miscarriage within the first trimester, and 25% of all pregnancies ending in miscarriage, human reproduction has a high failure rate. These figures, coupled with the percentage of all births with congenital defects and the number of these who will die in the first year of life, paint two scenarios: one, that evolutionary checkpoints are cruel but critical, and two, that for the seemingly inevitable 3%, or 8 million babies born annually with congenital disorders, perhaps more must be done for prevention, when methods exist for prediction. Unifying progress in three coevolving technologies-assisted reproduction, genome editing, and genome sequencing-could produce revolutionary clinical changes in the harsh global statistics of hereditary disease. A historical perspective on the rocky foundations upon which IVF was built suggests that lessons should be learned from the misalignment of research and clinical practice due to funding and research restrictions. At present, it seems likely that history will repeat itself, and that progress in research will be hampered by hypocritical hesitation.

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.

Today's debate about the use of gene-editing technologies to alter human DNA brings together two longstanding lines of inquiry in bioethics: the ethics of human enhancement, and the ethics of heritable genetic modification. This article traces that lineage by identifying key distinctions and ethics questions in these preexisting lines of inquiry that are also employed in four recent policy and ethics statements on human gene editing. These distinctions and ethics questions can be helpful heuristics for organizing discussion, learning from existing analysis, and highlighting what is at stake with new gene-editing technologies. Yet scientists, policymakers, and others new to the ethics of emerging technologies should also be aware of both the limitations of these distinctions and past challenges in adequately addressing the ethics questions they raise. In particular, the treatment-enhancement distinction and the somatic-germline distinction are not as clear-cut as they might initially appear. More importantly, they cannot be used to definitively differentiate right from wrong uses of the technologies in question.