Does human genome editing reinforce or violate human dignity?

Germline genome editing is often disapproved of at the international policy level because of its possible threats to human dignity. However, from a critical perspective the relationship between this emerging technology and human dignity is relatively understudied. We explore the main principles that are referred to when ‘human dignity' is invoked in this context; namely, the link with eugenics, the idea of a common genetic heritage, the principle of equal birth and broader equality and justice concerns. Yet the concept is also used in favour of germline genome editing as it might improve the overall well-being of future generations. We conclude that dignity concerns do not justify a complete ban on safe heritable genome editing but should inform the implementation of side constraints to ensure that the value judgements about human traits that are inherent in this practice do not result in a diminished basic respect for those people affected by them.     

Is the precautionary principle unscientific?

The precautionary principle holds that we should not allow scientific uncertainty to prevent us from taking precautionary measures in response to potential threats that are irreversible and potentially disastrous. Critics of the principle claim that it deters progress and development, is excessively risk-aversive and is unscientific. This paper argues that the principle can be scientific provided that (1) the threats addressed by the principle are plausible threats, and (2) the precautionary measures adopted are reasonable. The paper also argues that one may use epistemic criteria, such as consistency, coherence and explanatory power, to determine whether a threat is plausible, and that one may use practical considerations, such as effectiveness, proportionality, cost-effectiveness, realism and consistency, to determine whether a response to a threat is reasonable.     

Underpinning the precautionary principle with evidence: A spatial concept for guiding wind power development in endangered species’ habitats

The precautionary principle is an essential guideline in decision making, particularly for regulating novel developments with unknown or insufficiently proven environmental impact. However, due to the inherent component of uncertainty it has been widely criticized for being “unscientific”, i.e. hindering progress without sufficient evidence. The consequential postulation, that precautionary measures are only justified if the addressed threats are plausible and the measures reasonable, calls for methods to guide action in the face of uncertainty. Using the example of species conservation versus wind-farm construction, an expanding development with hypothesized – but unexplored – effects on our model species the capercaillie (Tetrao urogallus), we present an approach that aims at compensating the lack of knowledge about the threat itself by making best use of the available knowledge about the object at risk. By systematically combining information drawn from population monitoring and spatial modelling with population ecological thresholds, we identified areas of different functionality and importance to metapopulation persistence and connectivity. We integrated this information into a spatial concept defining four area-categories with different implications for wind power development. Highest priority was assigned to areas covering the spatial and functional requirements of a minimum viable population, i.e. sites where the plausibility for threat is highest, the uncertainty as regards importance for the population is lowest, and thus the justification for precautionary measures is strongest. This gradated approach may also enhance public acceptance, as it attempts to avoid either error-minimization bias (i.e. being too restrictive or permissive) the precautionary principle is frequently criticized for.     

Policy on Synthetic Biology: Deliberation,Probability, and the Precautionary Paradox

Synthetic biology is a cutting‐edge area of research that holds the promise of unprecedented health benefits. However, in tandem with these large prospective benefits, synthetic biology projects entail a risk of catastrophic consequences whose severity may exceed that of most ordinary human undertakings. This is due to the peculiar nature of synthetic biology as a ‘threshold technology’ which opens doors to opportunities and applications that are essentially unpredictable. Fears about these potentially unstoppable consequences have led to declarations from civil society groups calling for the use of a precautionary principle to regulate the field. Moreover, the principle is prevalent in law and international agreements. Despite widespread political recognition of a need for caution, the precautionary principle has been extensively criticized as a guide for regulatory policy. We examine a central objection to the principle: that its application entails crippling inaction and incoherence, since whatever action one takes there is always a chance that some highly improbable cataclysm will occur. In response to this difficulty, which we call the ‘precautionary paradox,’ we outline a deliberative means for arriving at threshold of probability below which potential dangers can be disregarded. In addition, we describe a Bayesian mechanism with which to assign probabilities to harmful outcomes. We argue that these steps resolve the paradox. The rehabilitated PP can thus provide a viable policy option to confront the uncharted waters of synthetic biology research.     

Germline Modification and Engineering in Avian Species

Production of genome-edited animals using germline-competent cells and genetic modification tools has provided opportunities for investigation of biological mechanisms in various organisms. The recently reported programmed genome editing technology that can induce gene modification at a target locus in an efficient and precise manner facilitates establishment of animal models. In this regard, the demand for genome-edited avian species, which are some of the most suitable model animals due to their unique embryonic development, has also increased. Furthermore, germline chimera production through long-term culture of chicken primordial germ cells (PGCs) has facilitated research on production of genome-edited chickens. Thus, use of avian germline modification is promising for development of novel avian models for research of disease control and various biological mechanisms. Here, we discuss recent progress in genome modification technology in avian species and its applications and future strategies.     

CRISPR Ethics: Moral Considerations for Applications of a Powerful Tool

With the emergence of CRISPR technology, targeted editing of a wide variety of genomes is no longer an abstract hypothetical, but occurs regularly. As application areas of CRISPR are exceeding beyond research and biomedical therapies, new and existing ethical concerns abound throughout the global community about the appropriate scope of the systems' use. Here we review fundamental ethical issues including the following: 1) the extent to which CRISPR use should be permitted; 2) access to CRISPR applications; 3) whether a regulatory framework(s) for clinical research involving human subjects might accommodate all types of human genome editing, including editing of the germline; and 4) whether international regulations governing inappropriate CRISPR utilization should be crafted and publicized. We conclude that moral decision making should evolve as the science of genomic engineering advances and hold that it would be reasonable for national and supranational legislatures to consider evidence-based regulation of certain CRISPR applications for the betterment of human health and progress.     

Environmental protection: applying the precautionary principle and proactive regulation to biotechnology

Biotechnology is a broad field encompassing diverse disciplines from agriculture to zoology. Advances in research are occurring at a rapid pace, and applications that have broad implications socially, economically, ecologically and politically are emerging. Along with notable benefits, environmental consequences that affect core quality-of-life issues for present and future generations are materializing. The precautionary principle should be applied to biotechnology research, activities and products, and a strengthened, enforceable and proactive regulatory framework is needed. The environmental impacts of agriculture, aquaculture, genetically modified organisms (GMOs) and even pharmaceuticals are raising public concerns and demonstrate the need for guidance from a variety of social, economic and scientific disciplines to insure the benefits of biotechnology are enjoyed without unacceptable and irreversible environmental costs.     

Using the therapy and enhancement distinction in law and policy

In a first major study, the UK’s Royal Society found that 76% of people in the UK are in favour of therapeutic germline genomic editing to correct genetic diseases in human embryos, but found there was little appetite for germline genomic editing for non-therapeutic purposes. Assuming the UK and other governments acted on these findings, can lawmakers and policymakers coherently regulate the use of biomedical innovations by permitting their use for therapeutic purposes but prohibiting their use for enhancement purposes? This paper examines the very common claim in the enhancement literature that the therapy v enhancement distinction does little meaningful work in helping us think through the ethical issues, a claim that has significant implications for these lawmakers and policymakers who may wish to regulate genomic editing techniques to reflect the findings of this important study. The focus of this paper is on germline genomic editing as one of the main themes in this special issue.     

From Eden to a hell of uniformity? directed evolution in humans

For the first time during evolution of life on this planet, a species has acquired the ability to direct its own genetic destiny. Following 200,000 years of evolution, modern man now has the technologies not only to eradicate genetic disease but also to prolong life and enhance desired physical and mental traits. These technologies include preimplantation diagnosis, cloning, and gene therapy in the germline on native chromosomes or by adding artificial ones. At first glance, we should all be in favor of eliminating genetic diseases and enhancing genetic traits. Evolutionary considerations, however, uncover hidden dangers and suggest caution against the total embracement of such actions. The first major concern is that the genome will never be a completely reliable crystal ball for predicting human phenotypes. This is especially true for predictions concerning the performance of alleles in future generations whose populations might be subjected to different environmental and social challenges. The second, and perhaps more important, concern is that the end result of germline intervention and genetic enhancement will likely lead to the impoverishment of gene variants in the human population and deprive us of one of our most valued assets for survival in the future, our genetic diversity.     

基因组编辑技术在精准医学中的应用

基因组编辑技术的飞速发展,尤其是近年来CRISPR/Cas9基因组编辑体系的出现,使得研究人员能高效地在细胞系和动物模型中对基因组进行精确编辑。基于基因组编辑技术的各种实验研究平台被相继开发,包括通过在细胞系中引入疾病相关突变位点建立疾病模型,通过高通量筛选寻找导致肿瘤耐药性的突变基因,通过体内原位靶向致病基因并修改突变进行基因治疗等。这些基因组编辑技术研究平台极大推动了精准医学研究领域的发展。本文对基因组编辑技术在精准医学领域的基础研究、转化应用、目前存在的问题以及未来发展的方向进行了讨论。     

Great minds think different: Preserving cognitive diversity in an age of gene editing

It is likely that gene editing technologies will become viable in the current century. As scientists uncover the genetic contribution to personality traits and cognitive styles, parents will face hard choices. Some of these choices will involve trade-offs from the standpoint of the individual's welfare, while others will involve trade-offs between what is best for each and what is good for all. Although we think we should generally defer to the informed choices of parents about what kinds of children to create, we argue that decisions to manipulate polygenic psychological traits will be much more ethically complicated than choosing Mendelian traits like blood type. We end by defending the principle of regulatory parsimony, which holds that when legislation is necessary to prevent serious harms, we should aim for simple rules that apply to all, rather than micro-managing parental choices that shape the traits of their children. While we focus on embryo selection and gene editing, our arguments apply to all powerful technologies which influence the development of children.     

Consumer acceptance of food crops developed by genome editing

One of the major problems regarding consumer acceptance of genetically modified organisms (GMOs) is the possibility that their transgenes could have adverse effects on the environment and/or human health. Genome editing, represented by the CRISPR/Cas9 system, can efficiently achieve transgene-free gene modifications and is anticipated to generate a wide spectrum of plants. However, the public attitude against GMOs suggests that people will initially be unlikely to accept these plants. We herein explored the bottlenecks of consumer acceptance of transgene-free food crops developed by genome editing and made some recommendations. People should not pursue a zero-risk bias regarding such crops. Developers are encouraged to produce cultivars with a trait that would satisfy consumer needs. Moreover, they should carefully investigate off-target mutations in resultant plants and initially refrain from agricultural use of multiplex genome editing for better risk–benefit communication. The government must consider their regulatory status and establish appropriate regulations if necessary. The government also should foster communication between the public and developers. If people are informed of the benefits of genome editing-mediated plant breeding and trust in the relevant regulations, and if careful risk–benefit communication and sincere considerations for the right to know approach are guaranteed, then such transgene-free crops could gradually be integrated into society.     

Global Climate Change and the Precautionary Principle

The precautionary principle is promoted as a common sense approach that avoids unreasonable delays in taking action. A weak form of the precautionary principle, that action should not wait until all uncertainties are resolved, is indeed common sense and consistent with even the most elementary application of the methods of decision making under uncertainty to the climate change problem. The standard tools of decision analysis imply conclusions consistent with a weak precau tionary principle of taking some action before all the evidence is in. Decision theory also reveals what the basis is for stronger recommendations from the precautionary principle, to the effect that action should be based on the most pessimistic possible interpretation of the future. This conclusion is only possible if prior beliefs are so pessimistic and so strong that they would outweigh any possible new scientific evidence.     

Frameworks for risk communication and disease management: the case of Lyme disease and countryside users

Management of zoonotic disease is necessary if countryside users are to gain benefit rather than suffer harm from their activities, and to avoid disproportionate reaction to novel threats. We introduce a conceptual framework based on the pressure-state-response model with five broad responses to disease incidence. Influencing public behaviour is one response and requires risk communication based on an integration of knowledge about the disease with an understanding of how publics respond to precautionary advice. A second framework emphasizes how risk communication involves more than information provision and should address dimensions including points-of-intervention over time, place and audience. The frameworks are developed by reference to tick-borne Lyme borreliosis (also known as Lyme disease), for which informed precautionary behaviour is particularly relevant. Interventions to influence behaviour can be directed by knowledge of spatial and temporal variation of tick abundance, what constitutes risky behaviour, how people respond to information of varying content, and an understanding of the social practices related to countryside use. The frameworks clarify the response options and help identify who is responsible for risk communication. These aspects are not consistently understood, and may result in an underestimation of the role of land-based organizations in facilitating appropriate precautionary behaviour.     

Ethical Issues of Using CRISPR Technologies for Research on Military Enhancement

This paper presents an overview of the key ethical questions of performing gene editing research on military service members. The recent technological advance in gene editing capabilities provided by CRISPR/Cas9 and their path towards first-in-human trials has reinvigorated the debate on human enhancement for non-medical purposes. Human performance optimization has long been a priority of military research in order to close the gap between the advancement of warfare and the limitations of human actors. In spite of this focus on temporary performance improvement, biomedical enhancement is an extension of these endeavours and the ethical issues of such research should be considered. In this paper, we explore possible applications of CRISPR to military human gene editing research and how it could be specifically applied towards protection of service members against biological or chemical weapons. We analyse three normative areas including risk–benefit analysis, informed consent, and inequality of access as it relates to CRISPR applications for military research to help inform and provide considerations for military institutional review boards and policymakers.     

Biosafety in Populus spp. and other forest trees: from non-native species to taxa derived from traditional breeding and genetic engineering

Forest trees are fundamental components of our environment, mainly due to their long lifetime and important role in forest ecology. In the past, some non-native tree species and taxa from traditional breeding have induced severe environmental impacts such as biological invasion, changes in the ‘gene pool’, and spread of diseases in forestry. Genetically modified trees obtained in different research groups worldwide are particularly confronted with increased concerns regarding biosafety issues. In the light of current biosafety research worldwide, various threats facing forests and natural tree populations are evaluated in this review: biological invasions, horizontal gene transfer, vertical gene transfer and effects on other organisms. Results available from groups working in biosafety research and risk avoidance using forest trees, with emphasis on transgenic trees, are reviewed. Independent biosafety research as well as the establishment of biosafety research programs for forest trees financed by national and international authorities is now more important than ever before. Biosafety problems detected in the past clearly show the importance of a prior case-by-case evaluation of non-native species, new taxa and also genetically modified trees according to the precautionary principle before their release to avoid risks to the environment and human health.     

Between a rock and a hard place: Farmers’ perspectives on gene editing in livestock agriculture in Bavaria

Farmers’ opinions and concerns are rarely considered in public debates about the use of gene‐editing technologies to modify farm animals. Subject Categories: Synthetic Biology & Biotechnology, S&S: Economics & Business

CRISPR‐Cas9, a new method for precisely modifying DNA, has received significant public attention in recent years. Heralded as a breakthrough technology to genetically modify organisms with hitherto unknown ease, precision and at low cost, CRISPR‐Cas9 has reignited controversies in science and society about the kind of genetic modifications that can and should be achieved in animals, plants and humans. Historically, such public debates have been particularly heated in two areas: human germline modification and agricultural applications. This article focuses on the latter and explores how small‐ and medium‐scale farmers evaluate the possibility and the potential benefits of gene editing livestock. This article importantly adds their voices to the discussion – voices that are surprisingly often unheard or ignored in public debates about using genetic technologies in agriculture.

… CRISPR‐Cas9 has reignited controversies in science and society about the kind of genetic modifications that can and should be achieved in animals, plants and humans.

     

Renewal ecology: conservation for the Anthropocene

The global scale and rapidity of environmental change is challenging ecologists to reimagine their theoretical principles and management practices. Increasingly, historical ecological conditions are inadequate targets for restoration ecology, geographically circumscribed nature reserves are incapable of protecting all biodiversity, and the precautionary principle applied to management interventions no longer ensures avoidance of ecological harm. In addition, human responses to global environmental changes, such as migration, building of protective infrastructures, and land use change, are having their own negative environmental impacts. We use examples from wildlands, urban, and degraded environments, as well as marine and freshwater ecosystems, to show that human adaptation responses to rapid ecological change can be explicitly designed to benefit biodiversity. This approach, which we call “renewal ecology,” is based on acceptance that environmental change will have transformative effects on coupled human and natural systems and recognizes the need to harmonize biodiversity with human infrastructure, for the benefit of both.     

Clinical significance of germline copy number variation in susceptibility of human diseases

Germline copy number variation (CNV) is considered to be an important form of human genetic polymorphisms. Previous studies have identified amounts of CNVs in human genome by advanced technologies, such as comparative genomic hybridization, single nucleotide genotyping, and high-throughput sequencing. CNV is speculated to be derived from multiple mechanisms, such as nonallelic homologous recombination (NAHR) and nonhomologous end-joining (NHEJ). CNVs cover a much larger genome scale than single nucleotide polymorphisms (SNPs), and may alter gene expression levels by means of gene dosage, gene fusion, gene disruption, and long-range regulation effects, thus affecting individual phenotypes and playing crucial roles in human pathogenesis. The number of studies linking CNVs with common complex diseases has increased dramatically in recent years. Here, we provide a comprehensive review of the current understanding of germline CNVs, and summarize the association of germline CNVs with the susceptibility to a wide variety of human diseases that were identified in recent years. We also propose potential issues that should be addressed in future studies.