This open peer commentary critiques Cwik's approach to categorizing germline gene editing interventions. The authors argue that Cwik's framework, which prioritizes technical categories and dimensions to map the "ethical terrain," is fundamentally flawed by putting the technical aspects before ethical considerations. They identify four key problems with his approach: it is arbitrary in its categorizations, relies on dynamic membership that changes with scientific knowledge, requires extensive technical expertise that many bioethicists lack, and most importantly, approaches the analysis "back-to-front" (...) by starting with technical rather than ethical distinctions. The authors argue that ethical assessment should begin with examining the goals and justifications of an intervention, rather than its technical specifications. They use the example of mitochondrial replacement therapy to illustrate how classification should proceed from ethical considerations to technical ones, not vice versa. The commentary concludes that while Cwik offers a complex framework, it is both incorrectly structured and impractical to use consistently. (shrink)

The application of genetic editing techniques for the prevention or cure of disease is a highly promising tool for the future of humanity. However, its implementation contains a number of ethical and legal challenges that should not be underestimated. On this basis, some sectors have already asked for a veto on any intervention that modifies the human germ line, while supporting somatic line editing. In this paper, I will support that this suggestion makes no sense (...) at all, because the somatic/germ line disjunctive has no moral relevance and, therefore, it should not play any role in legal terms. I will provide a number of reasons to hold this assumption, such as the non‐sacred nature of the germ line, the difference between germ line and human genome modification, or the moral importance of the presence of a will to create modified descendants. While doing so, I will provide some examples of the different approaches to germ line editing adopted by different regulations so as to demonstrate that, contrary to what is sometimes stated, a general ban on this practice is not the rule, but the exception. Additionally, I will show how alternative options which currently exist, such as a selective ban based on criteria different to the germ line/somatic line distinction, match better with the need to conciliate research needs and legitimate ethical concerns. Finally, I will introduce some further suggestions to this same purpose. (shrink)

Reproductive biotechnologies can separate concepts of parenthood into genetic, gestational and social dimensions, often leading to a fragmentation of heteronormative kinship models and posing a challenge to historical methods of establishing legal and/or moral parenthood. Using fictional cases, this article will demonstrate that the issues surrounding the intersection of current and emerging reproductive biotechnologies with definitions of parenthood are already leading to confusion regarding social and legal family ties for offspring, which is only expected to increase as new technologies develop. (...) Rather than opposing these new technologies to reassert traditional concepts of the family, however, this article will explore the opportunities that these technologies represent for re‐imagining various culturally cherished values of family‐making in a way that is inclusive of diverse genders, sexualities and cultures. It will consider IVF, gametogenesis, mitochondrial donation, surrogacy, artificial gestation, CRISPR‐Cas9 gene editing, foster care and adoption as some of many possible pathways to parenthood, including for members of the LGBTIAUQ+ community. (shrink)

In 2015, a flourish of “alarums and excursions” by the scientific community propelled CRISPR/Cas9 and other new gene-editing techniques into public attention. At issue were two kinds of potential gene-editing experiments in humans: those making inheritable germ-line modifications and those designed to enhance human traits beyond what is necessary for health and healing. The scientific consensus seemed to be that while research to develop safe and effective human gene editing should continue, society's (...) moral uncertainties about these two kinds of experiments needed to be better resolved before clinical trials of either type should be attempted. In the United States, the National Academies of Science, Engineering and Medicine convened the Committee on Human Gene Editing: Scientific, Medical and Ethical Considerations to pursue that resolution. The committee's 2017 consensus report has been widely interpreted as “opening the door” to inheritable human genetic modification and holding a line against enhancement interventions. But on a close reading it does neither. There are two reasons for this eccentric conclusion, both of which depend upon the strength of the committee's commitment to engaging diverse public voices in the gene-editing policy-making process. (shrink)

Recently, Chinese researchers published the results of their research using a gene-editing technology on abnormal human zygotes. The research team believes this research has prospective clinical application, viz., for gene therapy for?-thalassemia, a white blood cell disorder, and plan to persist with further studies, despite technical problems in this experiment. The research has elicited international criticism from both scientific and bioethics domains, because it innovates beyond the current global consensus against human germ line modification. This (...) paper comments on some ethical issues presented by the research report and concludes that, under present circumstances, the Chinese research team did not meet a standard of scientific responsibility.Bangladesh Journal of Bioethics 2015 Vol.6 (1):22-26. (shrink)

Objetivo del presente artículo es poner de relieve las contradicciones de la relación entre bioética y bioderecho que, lejos de ser un problema meramente teórico, tiene un impacto real en las reglamentaciones de las innovaciones en el campo de la biomedicina. Con el ánimo de demostrar esa fuerte conexión de la cuestión aparentemente teórica con la praxis, el ensayo, dotado de una metodología inductiva, moverá sus primeros pasos a partir de las técnicas de edición genética germinal. En la primera parte (...) del trabajo se aclararán matices científicos de dichas técnicas y se presentarán los primeros avances de la reglamentación jurídica que tienen su origen en el Consejo de Europa. Finalmente, a través de los límites y contradicciones de la reglamentación supuestamente biojurídica de la edición genética germinal se pondrá en evidencia la asimetría que domina en la relación entre bioética y bioderecho. ---The goal of this article is to stand out contradictions in the relationship among bioethics and biolaw that, far from being merely a theoretical quandary, has a real impact in the regulations of innovations in the biomedical field. Aiming to show that strong connection between the apparently theoretical question with the praxis, the essay, with an inductive methodology, goes straight showing the first steps of regulation of the germ-line gene editing. In the first part of the article, after a summary about the scientific highlights of germ-line gene editing, we undertake an investigation on the juridical regulation of germline-gene editing, based on the Council of Europe’s provisions. Finally, showing the limitations and contradictions of these supposedly biojuridical regulations, we highlight the dominant asymmetry in the relationship among bioethics and biolaw. (shrink)

Somatic cell gene therapy has yielded promising results. If germ cell gene therapy can be developed, the promise is even greater: hundreds of genetic diseases might be virtually eliminated. But some claim the procedure is morally unacceptable. We thoroughly and sympathetically examine several possible reasons for this claim but find them inadequate. There is no moral reason, then, not to develop and employ germ-line gene therapy. Taking the offensive, we argue next that medicine has (...) a prima facie moral obligation to do so. (shrink)

Germ-line gene therapy, like many other medical technologies, raises questions of special concern to Christians. It not only raises questions about medical effects, actual or possible, of genetic interventions that would be inherited from one generation to another but also, more importantly, raises anthropological questions and so questions about parental attitudes. These are questions about the dignity and value of human life, about inter-human relations and about the God-human relationship.1 For this reason the paper starts with an (...) exploration of the implications of Christian anthropology, viewed from a Roman Catholic perspective. A set of conditions will be specified in the light of which germ-line gene therapy’s compatibility with Christian attitudes, a Christian understanding of the human being, and the meaning of human life can be assessed. (shrink)

Although the ability to perform gene therapy in human germ-line cells is still hypothetical, the rate of progress in molecular and cell biology suggests that it will only be a matter of time before reliable clinical techniques will be within reach. Three sets of arguments are commonly advanced against developing those techniques, respectively pointing to the clinical risks, social dangers and better alternatives. In this paper we analyze those arguments from the perspective of the client-centered ethos that (...) traditionally governs practice in medical genetics. This perspective clarifies the merits of these arguments for geneticists, and suggests useful new directions for the professional discussion of germ-line gene therapy. It suggests, for example, that the much discussed prospect of germ-line therapy in human pre-embryos may always be more problematic for medical genetics than adult germ-line interventions, even though the latter faces greater technical difficulties. (shrink)

Contributors to the debate surrounding the ethics of germ line gene manipulation have by and large concentrated their efforts on discussions of the potential risks that are associated with the use of this technology. Many international advisory committees have ruled out the acceptability of germ line gene manipulation at least for the time being. The purpose of this work is to generate much needed discussion on the many other ethical issues concerning the implementation of (...) not only germ line gene manipulation but also other related biotechnologies. In this paper I systematically investigate and analyse the most salient issues put forward by proponents and opponents alike. I argue that if germ line manipulation proves to be a safe and effective procedure, then the principle of beneficence imposes on the medical profession a moral duty to pursue the technology. (shrink)

The classification of techniques used in mitochondrial donation, including their role as purported germ-line gene therapies, is far from clear. These techniques exhibit characteristics typical of a variety of classifications that have been used in both scientific and bioethics scholarship. This raises two connected questions, which we address in this paper: how should we classify mitochondrial donation techniques?; and what ethical implications surround such a classification? First, we outline how methods of genetic intervention, such as germ- (...) class='Hi'>line gene therapy, are typically defined or classified. We then consider whether techniques of mitochondrial donation fit into these, whether they might do so with some refinement of these categories, or whether they require some other approach to classification. To answer the second question, we discuss the relationship between classification and several key ethical issues arising from mitochondrial donation. We conclude that the properties characteristic of mitochondrial inheritance mean that most mitochondrial donation techniques belong to a new sub-class of genetic modification, which we call ‘conditionally inheritable genomic modification’. (shrink)

Gene editing tools are ‘revolutionizing’ microbiological research. Much of the public debate focuses on the possibility of human germ line applications. The use of genome editing to alter non-human animals, however, will have more immediate impacts on our daily lives. Genome edited animals are used for basic biological and biomedical research and could soon play a role in the livestock industry and ecosystem management. Genome editing thus provides an occasion to rethink societal narratives about (...) the relationships between humans and other animals. Even though the technique can be easily incorporated as an example into a conventional storyline about the development of the modern life sciences as striving for control over nature, it can also help to highlight the anthropocentric biases expressed in these narratives and demonstrate the continuities between humans and other animals. (shrink)

Recombinant DNA technology will soon allow physicians an opportunity to carry out both somatic cell- and Germ-Line gene therapy. While somatic cell gene therapy raises no new ethical problems, gene therapy of gametes, fertilized eggs or early embryos does raise several novel concerns. The first issue discussed here relates to making a distinction between negative and positive eugenics; the second issue deals with the evolutionary consequences of lost genetic diversity. In distinguishing between positive and negative (...) eugenics, the concept of malady is applied as a definitional criterion for identifying genetic disorders that could qualify for Germ-Line therapy. Because gene replacement techniques are currently unavailable for humans, and because even if they were possible the number of people involved would be quite small, the loss of diversity concern seems moot. Finally, we dissuss the issue of iatrogenic disorders associated with gene therapy and discuss several ‘real world considerations.’. (shrink)

With pre-implantation genetic diagnosis (PGD), genetic testing and selective transfer of embryos is possible. In the future, germ-line gene therapy (GLGT) applied to embryos before implantation, in order to introduce missing genes or replace mutant ones, may be possible. The objective of this dissertation is to analyse moral aspects of these technologies, as described by eighteen British, Italian and Swedish gynaecologists and geneticists. The objective is systematised into three parts: research interviews and qualitative analysis, philosophical analysis, and (...) elaboration of a framework that supports the combination of analytic methods. PGD was described as positive since it enabled some couples at risk for a genetic disease to have a child without the disease. PGD was described as in different senses ‘better’ than methods for prenatal diagnosis and selective termination of pregnancy. It was also described as positive since it provided couples at risk with one more option, even if it did not result in the birth of a healthy child. However, interviewees were concerned about the difficulty of defining and evaluating genetic disease. They were also concerned about patients’ choices, and about exaggerated use or misuse. Whereas PGD gave rise to ambivalence in terms of how to understand, describe and evaluate it, GLGT was often described as unrealistic or undesirable. The results of the qualitative analysis are used in a philosophical analysis of the concepts of choice, autonomous choice, ambivalence, trust and ambivalence in trust relations. A set of distinct characteristics of each concept are elaborated. The results of the philosophical analysis are used in the discussion of the results of the qualitative analysis. The study shows that the technologies imply both ‘new’ ways to perform ‘old’ medical practices and ‘new’ practices. Old moral questions are reformulated. New moral questions are added. Against the background of this, the concept of genetic identity is discussed. Key words: empirical ethics, pre-implantation genetic diagnosis, germ-line gene therapy, qualitative research, philosophical analysis, medical progress, genetic disease, choice, autonomous choice, ambivalence, trust, genetic identity. (shrink)

This paper attempts to debunk the slippery-slope argument against human germ-line gene therapy by showing that the downside of the slope – genetic enhancement – need not be as unethical or unjust as some people have supposed. It argues that if genetic enhancement is governed by proper regulations and is accompanied by adequate education, then it need not violate recognized principles of morality or social justice. Keywords: germ-line therapy, slippery slope argument, future generations, social justice (...) CiteULike Connotea Del.icio.us What's this? (shrink)

With the arrival of new methods of genome editing, especially CRISPR/cas 9, new perspectives on germline interventions have arisen. Supporters of germ line genome editing claim that the procedure could be used as a means of disease prevention. As a possible life-saving therapy, it provides benefits that outweigh its risks. Opponents of GGE claim that the medical and societal risks, especially the use of GGE for genetic enhancement, are too high. In our paper, we analyze the (...) risks and benefits of GGE. We show that the medical risk on an individual level might be reduced by further research in the near future so that they may be outweighed by the benefits. We also show that the societal risks of the procedure, i.e. genetic enhancement, are manageable by establishing a regulative framework before the GGE is implemented. Since the effects of modifying genes for the genepool of a given population are extremely difficult to model, the medical risks on the population level might be too high. (shrink)

In this paper I deal with ethical factors surrounding germline gene therapy. Such implications include intergenerational responsibility, human dignity, moral status of embryos and so on. I will explore the relevance of the above mentioned issues to discuss the ethical implication of human germline gene therapy (HGLT). We will see that most of arguments claimed by bioethicists do not provide valid reason to oppose HGLT. I will propose an alternative view, based on personal identity issues, to discuss the (...) ethics of human inheritable gene modification. (shrink)

Recently it has been argued that some instances of germ‐line gene therapy will change the identity of the person who receives the benefit of therapy, and that in these instances there is no good moral reason to conduct germ‐line gene therapy. Against this we argue that even if gene therapy should have an effect on the identity of the resulting person, this would not diminish the urgency of the therapy. Not only would impersonal (...) moral reasons speak in favour of such radical gene therapy, there would also be person‐affecting reasons to perform it. (shrink)

This issue of the Hastings Center Report features a couple of interesting takes on the governance challenges of emerging technologies. In an essay on the National Academies of Science, Engineering, and Medicine report published this February on human germ-line gene editing, Eric Juengst, a philosopher at the University of North Carolina, argues that the NASEM committee did not manage to rethink the rules. Juengst reaches what he calls an “eccentric conclusion”: “The committee's 2017 consensus report has (...) been widely interpreted as ‘opening the door’ to inheritable human genetic modification and holding a line against enhancement interventions. But on a close reading it does neither.” In the column Policy and Politics, Sarah Chan, a chancellor's fellow at the University of Edinburgh, discusses the emerging science of “organoids,” “embryoids,” and “synthetic human entities with embryo-like features” and calls for a sustained effort to rethink the rules for embryo research. (shrink)

Sexually reproducing metazoans establish a cell lineage during development that is ultimately dedicated to gamete production. Work in a variety of animals suggests that a group of conserved molecular determinants act in this germ line maintenance and function. The most universal of these genes are Vasa and Vasa‐like DEAD‐box RNA helicase genes. However, recent evidence indicates that Vasa genes also function in other cell types, distinct from the germ line. Here we evaluate our current understanding of (...) Vasa function and its regulation during development, addressing Vasa's emerging role in multipotent cells. We also explore the evolutionary diversification of the N‐terminal domain of this gene and how this impacts the association of Vasa with nuage‐like perinuclear structures. (shrink)

This dissertation evaluates the ethical challenges posed by the prospect of human germ line gene transfer . It argues that GLGT presents a new, unprecedented and complex ethical challenge. While GLGT has not yet been attempted with human beings, it has the potential not only to introduce changes into human nature that are radical and different, but also to substantially affect attitudes about human dignity and human rights. This dissertation focuses on the principled ethical arguments and the (...) frameworks, both rational and theological, which must frame the practice of GLGT in order for it to be used in a constructive manner. Additionally it assesses which applications of GLGT are ethically acceptable, taking into account the different goals that GLGT will serve, the means by which it is practiced and the research that is required to make it possible. ;Chapter One reviews the history of genetics and genetic science, locating GLGT in the context of the rapid development in genetic science and biotechnology. Chapter Two examines the history of the debates about genetic engineering and GLGT, with particular focus on the political, regulatory, and theological analyses of the 1970s--1980s. Chapter Three explores the theoretical frameworks utilized by proponents and opponents of GLGT. Utilizing categories provided by Kurt Bayertz, principled arguments are delineated and analyzed based on whether they represent a substantialist or a subjectivist approach to human nature and identity. The shortcomings of each framework taken individually, and the impasse reached by the two sides of the debate evidence the need for an expanded ethical framework. The expanded ethical framework is comprised of an enhanced critical approach that draws on the critical thought of Gerald McKenny and Michel Foucault and of an enhanced appreciation for human embodiment that draws on Pope John Paul II's theology of the body. Chapter Four applies the principles identified in Chapter Three in the course of examining: the possible goals for applications of GLGT technology; the ethics of the means by which germ line changes could be introduced; and whether and how GLGT can be regulated. (shrink)

On April 3, 2015, a group of prominent biologists and ethicists called for a worldwide moratorium on human genetic engineering in which the genetic modifications would be passed on to future generations. Describing themselves as “interested stakeholders,” the group held a retreat in Napa, California, in January to “initiate an informed discussion” of CRISPR/Cas9 genome engineering technology, which could enable high-precision insertion, deletion, and recoding of genes in human eggs, sperm, and embryos. The group declared that the advent of a (...) technology that makes human germ-line genetic engineering plausible makes a corollary discussion of its ethical implications urgent. Echoing this sentiment, the National Academy of Sciences and the National Academy of Medicine have announced plans to convene an international summit in fall 2015 to assess the implications of CRISPR/Cas9. Yet the notion that the advent of this particular technology is the warrant for initiating a public discussion is remarkable, and so too is the idea that the experts who have brought it into being and are putting it to use are best positioned to define the terms of the debate. The relevant ethical questions are by no means specific, let alone subsidiary, to the CRISPR/Cas9 technology. They are longstanding questions about what features of human life ought not be taken as objects of manipulation and control. They are questions about our responsibilities to our children and our children's children, where the mark of our actions will be inscribed upon their bodies and their lives. (shrink)

:Any space program involving long-term human missions will have to cope with serious risks to human health and life. Because currently available countermeasures are insufficient in the long term, there is a need for new, more radical solutions. One possibility is a program of human enhancement for future deep space mission astronauts. This paper discusses the challenges for long-term human missions of a space environment, opening the possibility of serious consideration of human enhancement and a fully automated space exploration, based (...) on highly advanced AI. The author argues that for such projects, there are strong reasons to consider human enhancement, including gene editing of germ line and somatic cells, as a moral duty. (shrink)

This essay presents a hypothesis which contends that the development of organismic complexity in the eukaryotes depended extensively on propagation via flagellated and ciliated gametes. Organisms utilizing flagellate and ciliate gametes to propagate their germ line have contributed most of the organismic complexity found in the higher animals. The genes of the flagellum and the flagellar assembly system (intraflagellar transport) have played a disproportionately important role in the construction of complex tissues and organs. The hypothesis also proposes that (...) competition between large numbers of haploid flagellated male gametes rigorously conserved the functionality of a key set of flagellar genes for more than 700 million years. This in turn has insured that a large set (>600) of highly functional cytoskeletal and signal pathway genes is always present in the lineage of organisms with flagellated or ciliated gametes to act as a dependable resource, or “toolkit,” for organ elaboration. Also see the video abstract here: https://youtu.be/lC5nC-WOcm8. (shrink)

Germ-line genetic interventions, like all medicine, can present opportunities to remove suffering, save and prolong human life, and support the conditions for successful human performance. Like all medicine, these interventions also present risks that reflect fallen humans’ age-old egocentric ambition to secure their health and improve their quality of life by relying exclusively on their own power, wisdom, and technical means. Moreover, man has always been tempted to overstep Divine prohibitions and to disregard his own calling to become (...) deified by grace. Wherever man succumbs to such tendencies, this inescapably leads to a disruption of the vital relationship between man and God. The legitimacy of the intervention itself depends on the theological status of the genome. Orthodox theology recognizes that the human genome, just as everything else that is created, must be understood in terms of its relationship to God. This consideration, however, does not mean that it can be idolized or is therefore untouchable. Interventions and alterations can be accepted within the constraints set by God, as formulated in the theology of creative logoi of beings in the teaching of the Fathers of the Church, and thus in view of man’s divine vocation. The Christian acceptability or inacceptability of human germ-line gene therapy depends directly on the extent to which it accords with an Orthodox spiritual life, or else hinders such a life. In this sense, this intervention can be examined in the same way as the application of all medical knowledge. When this is used to relieve pain and is motivated by selfless love for one’s neighbor, then it can be considered God’s gift to humankind. When, however, it becomes an absolute and attempts to usurp the presence of God in human life, then use becomes abuse and modern man faces yet another form of idolatry, even though more refined than earlier forms. (shrink)

: The current difference in attitude toward germ-line enhancement in humans and nonhumans is unjustified. Society should be more cautious in modifying the genes of nonhumans and more bold in thinking about modifying our own genome. I identify four classes of arguments pertaining to germ-line enhancement: safety arguments, justice arguments, trust arguments, and naturalness arguments. The first three types are compelling, but do not distinguish between human and nonhuman cases. The final class of argument would justify (...) a distinction between human and nonhuman germ-line enhancement; however, this type of argument fails and, therefore, the discrepancy in attitude toward human and nonhuman germ-line enhancement is unjustified. (shrink)

Enhancements of the human germ-line introduce further inequalities in the competition for scarce goods, such as income and desirable social positions. Social inequalities, in turn, amplify the range of genetic inequalities that access to germ-line enhancements may produce. From an egalitarian point of view, inequalities can be arranged to the benefit of the worst-off group (for instance, through general taxation), but the possibility of an indefinite growth of social and genetic inequality raises legitimate concerns. It is (...) argued that inequalities produced by markets of germ-line enhancements are just if it they are embedded in a framework of social institutions that satisfies two conditions: (i) Rawls’ Difference Principle, which states that inequalities of income and wealth should benefit the worst-off group; (ii) the lexically prior 'principle of rough equality', which states that citizens’ initial life-chances should be similar enough, so that extreme inequalities in income, wealth and power are not produced or accumulated through institutions justified by the Difference Principle. The principle of rough equality replaces the Rawlsian principles of the Fair Value of the Political Liberties and Fair Equality of Opportunity in a post-genomic society and expresses a concern with background political equality, which is argued to be a condition of the freedom and equality of citizens that should not be traded off with material benefits. Extreme inequalities are defined in terms of political equality. (shrink)

August Weismann proposed that genetic changes in somatic cells cannot pass to germ cells and hence to next generations. Nevertheless, evidence is accumulating that some environmental effects can promote heritable changes in the DNA of germ cells, which implies that some somatic influence on germ line is possible. This influence is mostly detrimental and related to the presence of oxidative stress, which induces mutations and epigenetic changes. This effect should be stronger in males due to the (...) particular characteristics of sperm. Here, we propose the hypothesis that females are able to avoid males with oxidatively damaged DNA in the germ line by using oxidative‐dependent (pre‐ and post‐mating) signals. This new hypothesis may shed light on unsolved questions in evolutionary biology, such as the benefits of polyandry, the lek paradox, or the role of sexual selection on the evolution of aging. BioEssays 30:1212–1219, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

Newman objects to human germ-line editingGerm-line editing on both philosophical and practical grounds. While the philosophical grounds are compelling, I argue that they are not sufficiently strong to exclude all germ-line editingGerm-line editing to eliminate genetic diseasesGenetic disease. However, the practical reasons he offers preclude germ-line editing except in very limited circumstances. I argue that my requirement of gene specificityGene specificity in Cut-and-Paste Genetics can address his concerns. Meanwhile (...) Baxter argues that my criteria are so restrictive that they would exclude all presently plausible candidate genes from being edited in the human germ-line editingGerm-line editing. I agree that this may be the case but that it is an acceptable policy situation because it behooves us to be very careful when editing of the human germ-line is at stake. (shrink)

Technical, ethical, and social questions of germ-line gene interventions have been widely discussed in the literature. The majority of these discussions focus on planned interventions executed on the nuclear DNA (nDNA). However, human cells also contain another set of genes that is the mitochondrial DNA (mtDNA). As the characteristics of the mtDNA grossly differ from those of nDNA, so do the social, ethical, psychological, and safety considerations of possible interventions on this part of the genetic substance.

The emergence of CRISPR/Cas9 technology has revolutionized gene editing and made both gene therapy and eugenic control of future human evolution plausible. This accessible book puts these developments in their historical and scientific contexts and analyzes the policy and ethical challenges they raise. It presents the case for altering the human germ-line to eliminate a large number of genetic diseases controlled by a single or few genes, while pointing out that gene therapy is likely (...) to ineffective for diseases with more complex causation. In parallel it explores the possibility of genetic enhancement in a similarly subscribed set of cases. But it also argues that, in general, genetic enhancement is ethically problematic and should be approached with caution. Given the success of CRISPR/Cas9 gene editing, and the explosion of related techniques, in practice it would be virtually impossible to ban germ-line editing for the future. A more useful goal is to regulate it with oversight that represents all stakeholders. That, in turn, requires an informed public discussion of these issues which this book aims to foster. (shrink)

In 1982, the President's Commission produced its report on human gene therapy. One of that report's recommendations was to expand the Recombinant DNA Advisory Committee to the National Institutes of Health to include a subcommittee on human gene therapy. In 1984, the Human Gene Therapy Subcommittee was established, and in 1989 it produced a document—“Points to Consider for Protocols for the Transfer of Recombinant DNA into Human Subjects”—that stated the RAC's position on what sorts of protocols it (...) would approve.In assessing the impact of the President's Commission report, Alexander Capron wrote,[t]he line [the report] drew between somatic cell and germ-line therapies has shaped subsequent discussions and policy formulation. Its conclusion … that somatic cell therapy resembles medical treatment is the basic premise of the RAC subcommittee's “Points to Consider,” while the Commission's view that ethical as well as technical barriers preclude present attempts to alter germ cells continues to be generally accepted by scientists and nonscientists alike. (shrink)

Sex chromosomes are advantageous to mammals, allowing them to adopt a genetic rather than environmental sex determination system. However, sex chromosome evolution also carries a burden, because it results in an imbalance in gene dosage between females (XX) and males (XY). This imbalance is resolved by X dosage compensation, which comprises both X chromosome inactivation and X chromosome upregulation. X dosage compensation has been well characterized in the soma, but not in the germ line. Germ cells (...) face a special challenge, because genome wide reprogramming erases epigenetic marks responsible for maintaining the X dosage compensated state. Here we explain how evolution has influenced the gene content and germ line specialization of the mammalian sex chromosomes. We discuss new research uncovering unusual X dosage compensation states in germ cells, which we postulate influence sexual dimorphisms in germ line development and cause infertility in individuals with sex chromosome aneuploidy. (shrink)

This Open Access book is about the risks and the ethics of human germline gene editing, i.e., the possibility to make heritable changes to the DNA of early human embryos or germ cells. Is there something particularly morally problematic about editing the human germline? Is there something unique about germline editing, and, if so, does this suggest that we ought not to edit the human germline, or only in particular circumstances or for particular purposes? What (...) would be a wise and responsible approach to editing the human germline from a moral perspective? The book has three broad aims. First, to present an inclusive map over the current scholarly debate on the ethics of human germline gene editing. Second, to provide a philosophical and critical guide to the various ideas and arguments in this debate. Third, to apply an ethics of risk perspective and defend a morally cautious position on human germline gene editing. (shrink)

The revolutionary potential of the CRISPR-Cas9 gene editing technique has created a resurgence in enthusiasm and concern in genetic research perhaps not seen since the mapping of the human genome at the turn of the century. Some such concerns and anxieties revolve around crossing lines between somatic and germline interventions as well as treatment and enhancement applications. Underpinning these concerns, there are familiar concepts of safety, unintended consequences and damage to genetic identity and the creation of designer children (...) through pursuing human enhancement and eugenics. In the policy realm, these morally laden distinctions and anxieties are emerging as the basis for making important and applied measures to respond to the fast-evolving scientific developments. This paper argues that the dominant normative framing for such responses is insufficient for this task. This paper illustrates this insufficiency as arising from a continued reliance on misleading genetic essentialist assumptions that generate groundless speculation and over-reactionary normative responses. This phenomenon is explicit with regard to prospective human genetic enhancements. While many normative theorists and state-of-the-art reports continue to gesture toward the influence of environmental and social influences on a person and their traits and capacities, this recognition does not extend to the substance of the arguments themselves which tend to revert to the debunked genetic determinist framework. Given the above, this paper argues that there is a pressing need for a more central role for sociological input into particular aspects of this “enhancement myth” in order to give added weight, detail and substance to these environmental influences and influence from social structures. (shrink)

The emergence of CRISPR/Cas9 technology has revolutionized gene editing and made both gene therapy and eugenic control of future human evolution plausible. This accessible book puts these developments in their historical and scientific contexts and analyzes the policy and ethical challenges they raise. It presents the case for altering the human germ-line to eliminate a large number of genetic diseases controlled by a single or few genes, while pointing out that gene therapy is likely (...) to ineffective for diseases with more complex causation. In parallel it explores the possibility of genetic enhancement in a similarly subscribed set of cases. But it also argues that, in general, genetic enhancement is ethically problematic and should be approached with caution. Given the success of CRISPR/Cas9 gene editing, and the explosion of related techniques, in practice it would be virtually impossible to ban germ-line editing for the future. A more useful goal is to regulate it with oversight that represents all stakeholders. That, in turn, requires an informed public discussion of these issues which this book aims to foster. (shrink)

The February 1997 announcement of the birth of Dolly, the sheep cloned from a mammary cell of an adult ewe, has drawn attention to the growing ability to select, alter, or otherwise manipulate the genome of offspring. Prior to Dolly, ethical discussion of genes in reproduction had focused on negative selection: carrier screening, prenatal diagnosis, and abortion or embryo discard. After Dolly, ethical debate will have to consider the direct or positive use of genetic selection or alteration technology.The principal use (...) of genetic selection techniques in human reproduction likely will be to treat or prevent disease in offspring. In the future, however, such techniques might also be used to enhance or even diminish expected characteristics of progeny. Techniques to accomplish these goals are likely to include: selection of the nuclear genome, as occurs in somatic cell cloning; chromosomal transplants; or direct insertion or deletion of specific genes. (shrink)

Literature on maternal exposures and the risk of epigenetic changes or diseases in the offspring is growing. Paternal contributions are often not considered. However, some animal and epidemiologic studies on various contaminants, nutrition, and lifestyle‐related conditions suggest a paternal influence on the offspring's future health. The phenotypic outcomes may have been attributed to DNA damage or mutations, but increasing evidence shows that the inheritance of environmentally induced functional changes of the genome, and related disorders, are (also) driven by epigenetic components. (...) In this essay we suggest the existence of epigenetic windows of susceptibility to environmental insults during sperm development. Changes in DNA methylation, histone modification, and non‐coding RNAs are viable mechanistic candidates for a non‐genetic transfer of paternal environmental information, from maturing germ cell to zygote. Inclusion of paternal factors in future research will ultimately improve the understanding of transgenerational epigenetic plasticity and health‐related effects in future generations. (shrink)

Despite widespread agreement that it would be ethical to use somatic cell gene therapy to correct serious diseases, there is still uneasiness on the part of the public about this procedure. The basis for this concern lies less with the procedure's clinical risks than with fear that genetic engineering could lead to changes in human nature. Legitimate concerns about the potential for misuse of gene transfer technology justify drawing a moral line that includes corrective germline therapy but (...) excludes enhancement interventions in both somatic and germline contexts. Keywords: somatic cell, germ line, genetic diseases, genetic engineering, humanness, enhancement, eugenics CiteULike Connotea Del.icio.us What's this? (shrink)

Plant reproduction is vital for species survival, and is also central to the production of food for human consumption. Seeds result from the successful fertilization of male and female gametes, but our understanding of the development, differentiation of gamete lineages and fertilization processes in higher plants is limited. Germ cells in animals diverge from somatic cells early in embryo development, whereas plants have distinct vegetative and reproductive phases in which gametes are formed from somatic cells after the plant has (...) made the transition to flowering and the formation of the reproductive organs. Recently, novel insights into the molecular mechanisms underlying male germ‐line initiation and male gamete development in plants have been obtained. Transcriptional repression of male germ‐line genes in non‐male germ‐line cells have been identified as a key mechanism for spatial and temporal control of male germ‐line development. This review focuses on molecular events controlling male germ‐line development especially, on the nature and regulation of gene expression programs operating in male gametes of flowering plants. BioEssays 29:1124–1132, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

To discern the ethical issues involved incurrent gene therapy research, to explore theproblems inherent in possible future genetherapies, and to encourage debate within thescientific community about ethical questionsrelevant to both, we surveyed American Societyof Human Genetics scientists who engage inhuman genetics research. This study of theopinions of U.S. scientific experts about theethical issues discussed in the literature ongene therapy contributes systematic data on theattitudes of those working in the field as wellas elaborative comments. Our survey finds thatrespondents are highly (...) supportive of thepotential use of somatic cell gene therapy tocure serious diseases in adults and children aswell as prospective offspring. A clearmajority, however, believe that using suchgenetic techniques for enhancement purposes isunacceptable. Delineating the line betweendisease/disorder and improvement/enhancementposes a problem not easily resolved and oneconducive to the growth of slippery-slopeapprehensions. The majority of respondents alsoadvocate germ-line therapy, in theory at least,and under similar restrictions, but theyrecognize the roadblock that the existence ofunanticipated negative consequences currentlypresents. Another complex matter involvestrying to determine appropriate reasons forchoosing target diseases for research, forwhich the dichotomy between rare single-geneand common multifactorial diseases reveals anongoing dilemma. (shrink)

types of application of genetic engineering for the insertion of genes into humans. The scientific requirements and the ethical issues associated with each type are discussed. Somatic cell gene therapy is technically the simplest and ethically the least controversial. The first clinical trials will probably be undertaken within the next year. Germ line gene therapy will require major advances in our present knowledge and it raises ethical issues that are now being debated. In order to provide (...) guidelines for determining when germ line gene therapy would be ethical, the author presents three criteria which should be satisfied prior to the time that a clinical protocol is attempted in humans. Enhancement genetic engineering presents significant, and troubling, ethical concerns. Except where this type of therapy can be justified on the grounds of preventive medicine, enhancement engineering should not be performed. The fourth type, eugenic genetic engineering, is impossible at present and will probably remain so for the foreseeable future, despite the widespread media attention it has received. Keywords: genetic engineering, somatic cells, germ cells, enhancement, eugenics, humanhood CiteULike Connotea Del.icio.us What's this? (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Human Gene TherapyMary Carrington Coutts (bio)On September 14, 1990, researchers at the U.S. National Institutes of Health (NIH) performed the first approved gene therapy procedure on a four-year-old girl named Ashanti DeSilva. Born with a rare genetic disease, severe combined immune deficiency (SCID), Ashanti lacked a healthy immune system and was extremely vulnerable to infection. Children with SCID usually develop overwhelming infections and rarely survive to adulthood; (...) even a common childhood illness like chicken pox is life-threatening. Ashanti led a cloistered existence, avoiding contact with people outside her family, remaining in the sterile environment of her home, and battling frequent illnesses with massive amounts of antibiotics.In Ashanti's gene therapy procedure, her own white blood cells were genetically modified and then infused back into her bloodstream. Laboratory tests show that the therapy has strengthened Ashanti's immune system. She no longer has recurrent colds, has been allowed to attend school, and has been immunized against whooping cough. This gene therapy procedure is not a cure, however. The genetically-treated white blood cells only survive for a few months and must then be replaced, but Ashanti's future is much brighter because of the new therapy (VI, Thompson [The First] 1993).Although this simplified description of Ashanti's gene therapy procedure sounds like a happy ending, it is little more than an optimistic chapter in a long story. The road to the first approved gene therapy procedure was rocky and fraught with controversy. The biology of human gene therapy is very complex, and there are still many techniques that need to be developed and diseases that need to be understood more fully before gene therapy is well established. The public policy debate surrounding the possible use of genetically engineered material in human subjects is equally complex. Major participants in the debate come from the fields of biology, government, law, medicine, philosophy, politics, and religion, each bringing different views to the discussion.In studying the ethics of gene therapy, one should draw a distinction between [End Page 63] therapy on somatic (non-reproductive) cells and germ (reproductive) cells. Only the germ cells carry the genes that will be passed on to the next generation. Reactions to gene therapy have varied widely. Some commentators on gene therapy object to any form of genetic manipulation, no matter how well-intentioned (VI, Rifkin 1983). Another reaction is to allow the use of somatic-cell therapy, but not to approve the use of germ-line therapy, which could have unforeseeable effects on future generations. A different stance is that, with proper regulation and safeguards, germ-line gene therapy is a logical extension of the progress made to date and that it is an ethically acceptable procedure.TechniquesTo date, 43 research protocols have been approved for somatic-cell gene therapy in the United States. The techniques employed in each protocol vary, but in general a virus is used as a "vector" to insert the desired gene into the DNA of the patient's cells, in order to compensate for a defective gene. For Ashanti's gene therapy, this technique involved obtaining white blood cells and introducing properly functioning genes into as many of the cells as possible. The normal genes were delivered through the use of a specially-engineered virus.Although similar techniques are used in germ-line gene therapy, the procedure is more difficult. There are two basic ways to perform germ-line gene therapy: (1) to treat a preimplantation embryo that carries a serious genetic defect before its implantation in the mother, which necessitates the use of in vitro fertilization techniques; or (2) to treat the germ cells (sperm or egg cells) of afflicted adults so that the genetic defects would not be passed on to their offspring, which requires the technical expertise to delete the defective gene and insert a properly functioning replacement. Because of the complexity of the procedures involved and the attendant ethical controversy, germ-line therapy is not currently performed.Candidate Diseases for Gene TherapyAt present, gene therapy is likely to be most successful in treating diseases that are caused by single-gene defects and has been approved for treating diseases such... (shrink)