Two genetic technologies capable of making heritable changes to the human genome have revived interest in, and in some quarters a very familiar panic concerning, so-called germline interventions. These technologies are: most recently the use of CRISPR/Cas9 to edit genes in non-viable IVF zygotes and Mitochondrial Replacement Therapy the use of which was approved in principle in a landmark vote earlier this year by the United Kingdom Parliament. The possibility of using either of these techniques in humans has encountered (...) the most violent hostility and suspicion. However it is important to be aware that much of this hostility dates back to the fears associated with In Vitro Fertilization and other reproductive technologies and by cloning; fears which were baseless at the time concerning both IVF and cloning the use of both of which have proved to be highly beneficial to humanity and which have been effectively regulated and controlled. This paper argues that CRISPR should by pursued through res.. (shrink)

Manipulation of the human germline is sometimes criticised as a severe intervention into human nature. In order to assess the tenability of this claim, different uses of the term “human nature” and distinct scientific and clinical contexts must be differentiated. The first live birth of an edited human child will probably take the form of an unproven intervention and not a clinical trial. As an unproven intervention, germline manipulation must be regarded as a severe intervention into (...) the nature of a prospective newborn. Nevertheless, once the technique of germline manipulation can be regarded as a safe therapeutic option, and if its use is restricted to the prevention of severe genetic diseases, it can no longer be regarded as a particularly severe intervention into human nature. However, such a use would make human nature the object of technoscience and the edited human beings would have to be regarded as biofacts, i. e., a form of incarnated and living technological design. This introduces a new quality into the notion of “human nature”, which can be regarded as ethically acceptable, as long as the intervention is restricted to the prevention of severe genetic diseases. (shrink)

Until recently, scientific consensus held firm that genetically manipulated embryos created through methods including Mitochondrial Replacement Therapy or human germline genome editing should not be used to initiate a pregnancy. In countries that have relevant laws pertaining to heritable human germline modifications, the vast majority prohibit or restrict this practice. In the last several years, scholars have observed a transformation of scientific and policy restrictions with insistent calls for creating a regulatory pathway. Multiple stakeholders highlight the role of (...) social consensus and public engagement for governance of heritable human germline modifications. However, in the drive to gain public acceptance and lift restrictions, some proponents provide distorted or misleading narratives designed to influence public perception and incrementally shift the consensus. This article describes eight discrete strategies that proponents employ to influence framing, sway public opinion, and revise policymaking of human germline modifications in a manner that undermines honest engagement. (shrink)

As advances in genomics and in vitro fertilization unite to bring us such technologies as germline manipulation and in‐depth embryo diagnosis, must there be a battle over their use? Policymakers might, after all, acknowledge the arrival of these technologies, accept that people differ in their attitudes toward them, realize that society will adjust as it has to past advances such as the birth‐control pill, and support efforts to minimize risks and maximize benefits. Unfortunately, that scenario is unlikely.

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)

It has recently been argued that reproductive genetic manipulation technologies like mitochondrial replacement and germline CRISPR modifications cannot be said to save anyone’s life because, counterfactually, no one would suffer more or die sooner absent the intervention. The present article argues that, on the contrary, reproductive genetic manipulations may be life-saving (and, from this, have therapeutic value) under an appropriate population health perspective. As such, popular reports of reproductive genetic manipulations potentially saving lives or preventing disease are not (...) necessarily mistaken, though such terminology still requires further empirical validation. (shrink)

In the wake of the advent of genome editing technology CRISPR-Cas9 (clustered regularly interspaced palindromic repeat (CRISPR)-associated protein 9), there has been a global debate around the implications of manipulating the human genome. While CRISPR-based germline gene editing is new, the debate about the ethics of gene editing is not – for several decades now, scholars have debated the ethics of making heritable changes to the human genome. The arguments that have been raised both for and against the use (...) of genetic technologies in human reproduction reiterate much of the arguments made in the pre-CRISPR debate. As such, it is instructive for South Africa to reflect on these arguments now, in considering our position on the regulation of the use of this novel biotechnology. There are two dominant schools of thought in this area, bioliberalism and bioconservatism. Bioconservatives raise concerns about the risks of genetic manipulation, and argue that it ought to be limited or prohibited to avert these risks to human health and human nature. Bioliberal scholars are more open to the prospect of genetic manipulation, because of its potential utility. In this article, I conclude that in liberal democracies such as our own, bioliberal arguments ought to be seriously considered when formulating policy on human genome editing because of the extent to which they resonate with our Constitutional values and human rights. I further suggest that there is a need for an enquiry into the relevance of African perspectives on the ethical questions that arise concerning germline genome editing. (shrink)

The human genome is commonly regarded as a ‘natural’ connection between all human beings, as it has been handed down to us by our predecessors. As such, it is believed to represent common heritage of humanity, e.g. a resource of outstanding value that should be the object of special protection and international concern. Some critics argue that germline manipulation would disrupt this natural heritage and that we have a duty to preserve the integrity of the human germline. (...) However, a closer look reveals that the concept of common heritage of humanity does not necessarily imply the impermissibility of germline manipulation. If it is restricted to the prevention of severe diseases, germline manipulation does not represent a threat to the unity and identity of the human species, even though this would create a new form of relationship between human beings, namely that between a designer and a genetically designed person. (shrink)

In this paper, I will present the empirical version of the slippery slope argument (SSA) in the field of genome editing. According to the SSA, if we adopt germline manipulation of embryos we will eventually end up performing or allowing something morally reprehensible, such as new coercive eugenics. I will investigate the actual possibility of sliding towards eugenics: thus, I will examine enhancement and eugenics both in the classical and liberal versions, through the lens of SSA. In the (...) first part, I will discuss the classical eugenics from a historical perspective and conclude that classical eugenics is morally deplorable; but by currently accepting genome editing I argue that it is not possible to ‘slip’ into classical eugenics. Then, I will analyze liberal eugenics: I will consider Habermas’ and Sandel’s objections to liberal eugenics and genetic human enhancement. Subsequently, I will reply to these arguments affirming that, although it is not possible to refuse any form of genetic enhancement, liberal eugenics would not consider the principles of justice, non-maleficence, and non-instrumentalization; hence, it should be considered not morally acceptable. In addition, I will support the thesis according to which the possibility of relapsing into liberal eugenics is more likely than relapsing into classical eugenics. Then, I will present a strategy that, while avoiding falling into the undesirable scenarios related to SSA, still accepts some application of germline genome editing of embryos and gametes. In such a way, I will show that even if we accept the plausibility of a certain slip into an undesirable scenario, SSA does not offer conclusive reasons to forbid any use of germline genome editing technique in both therapeutic and enhancement fields. (shrink)

Mitochondrial replacement techniques, known in the popular media as 'three-parent' or 'three-person' IVFs, have the potential to enable women with mitochondrial diseases to have children who are genetically related to them but without such diseases. In the debate regarding whether MRTs should be made available, an issue that has garnered considerable attention is whether MRTs affect the characteristics of an existing individual or whether they result in the creation of a new individual, given that MRTs involve the genetic manipulation (...) of the germline. In other words, do MRTs affect the qualitative identity or the numerical identity of the resulting child? For instance, a group of panelists on behalf of the UK Human Fertilisation and Embryology Authority has claimed that MRTs affect only the qualitative identity of the resulting child, while the Working Group of the Nuffield Council on Bioethics has argued that MRTs would create a numerically distinct individual. In this article, I shall argue that MRTs do create a new and numerically distinct individual. Since my explanation is different from the NCOB's explanation, I shall also offer reasons why my explanation is preferable to the NCOB's explanation. (shrink)

Tendencies and efforts have shifted from genome description, DNA mapping, and DNA sequencing to active and profound re-programming, repairing life on genetic and molecular levels in some parts of contemporary life science research. Mirroring and materializing this atmosphere, various life engineering technologies have been used and established in many areas of life sciences in the last decades. A contemporary progressive example of one such technology is DNA editing. Novel developments related to reproductive technologies, particularly embryo editing, prenatal human life engineering, (...) and germline engineering need to be analyzed against the broader social and structural background. The crucial analytical scope for this paper is a specific field: the life-editing technologies used in reproductive medicine and performed experimentally on viable human embryos, particularly CRISPR/cas9 technology. This text argues that germline editing technologies, as a representative part of contemporary biomedicine, are merging ideas of treatment and enhancement to avoid future risks. Using this specific life manipulation of embryos and gametes, the text analyzes these processes within the concept of power over life—biopower and the specific governing rationality that imagines, classifies, and governs contemporary societies. The text specifically focuses on the potential to create, define, and manage future risks and uncertainties related to prenatal life. (shrink)

:Since the advent of recombinant DNA technology, expectations about the potential for altering genes and controlling our biology at the fundamental level have been sky high. These expectations have gone largely unfulfilled. But though the dream of being able to control our biology is still far off, gene editing research has made enormous strides toward potential clinical use. This paper argues that when it comes to determining permissible uses of gene editing in one important medical context—germline intervention in reproductive (...) medicine—issues about enhancement and eugenics are, for the foreseeable future, a red herring. Current translational goals for gene editing research involve a different kind of editing than would be required to achieve manipulation of complex traits such as intelligence, and there are more pressing questions that need attention if clinical use of gene editing in reproductive medicine ever becomes a possibility. (shrink)

Understanding how complex sexual reproduction arose, and why sexual organisms have been more successful than otherwise similar asexual organisms, is a longstanding problem in evolutionary biology. Within this problem, the potential role of endosymbionts or intracellular pathogens in mediating primitive genetic transfers is a continuing theme. In recent years, several remarkable activities of mitochondria have been observed in the germline cells of complex eukaryotes, and it has been found that bacterial endosymbionts related to mitochondria are capable of manipulating diverse (...) aspects of metazoan gametogenesis. An attempt is made here to rationalize these observations with an endosymbiotic model for the evolutionary origins of sex. It is hypothesized that the contemporary life cycle of germline cells has descended from the life cycle of the endosymbiotic ancestor of the mitochondrion. Through an actin‐based motility that drove it from one cell to another, the rickettsial ancestor of mitochondria may have functioned as a primitive transducing particle, the evolutionary progenitor of sperm. BioEssays 26:558–566, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

In February 2016, the Institute of Medicine released a report, commissioned by the United States Food and Drug Administration, on the ethical and social‐policy implications of so‐called three‐parent in vitro fertilization. The IOM endorses commencement of clinical trials on three‐parent IVF, subject to some initial limitations. Also called mitochondrial replacement or transfer, three‐parent IVF is an intervention comprising two distinct procedures in which the genetic materials of three people—the DNA of the father and mother and the mitochondrial DNA of an (...) egg donor—can be used to create a child. Three‐parent IVF would enable a woman with mitochondrial disease to have a genetically related child without transmitting the disease to the child. The possibility for three‐parent children has prompted criticism from many corners. Critics have pointed to ethical issues including safety concerns and risks to children, genetic and germline engineering concerns, the potential exploitation of the third‐parent egg donor, donor anonymity and privacy, and objections to creating babies with three parents, which undermines natural and traditional conceptions of procreation. Additionally, developing the technology would involve experimenting on, manipulating, and disposing of embryos. Although the IOM report considers the ethical concerns about the value of the three‐parent IVF technology, the IOM failed to give due attention to an important objection to the development of this technology: three‐parent IVF lacks the social value necessary to make investment of public resources in it ethical.Unlike the other concerns, this objection is not based on conservativism about new reproductive technologies or default favoritism of the status quo. I argue that the technology does not meet a plausible social value standard to render public research investment into its development ethical. Proponents of three‐parent IVF make inaccurate and exaggerated claims that it will eradicate mitochondrial disease and save lives. Were these claims true, proponents would have a strong case for the social value of the technology. But three‐parent IVF alone will not eradicate mitochondrial disease, and it will not save lives. Rather, it can create healthy lives. As I discuss, the moral distinction is crucial. Most importantly, investment in three‐parent IVF comes at the opportunity cost of researching treatment for mitochondrial disease that would benefit actual, living disease sufferers. (shrink)

Development of the nematode Caenorhabditis elegans has been described completely on a cell‐by‐cell basis. In an invariant pattern five somatic founder cells and the primordial germ cell are generated within the first hour after the onset of cleavage. Using a laser microbeam for manipulation of individual blastomers several aspects of early embryogenesis have been investigated, including the expression of cellular polarity, the localization of lineage‐specific cleavage potential, the necessity for early cell–cell interaction, and the control of differential cell‐cycle timing. (...) The experiments demonstrate the central importance of a correct partitioning of cytoplasmic components during early embryogenesis and suggest a stepwise, binary segregation mechanism associated with the unequal cleavages in the germline. (shrink)

CRISPR keeps me up at night. I marvel at its potential to cure insidious genetic diseases and scourges like malaria. I shudder at the ways it might be misused to create biological weapons. What frightens me most, though, is what I can't predict: how will we use CRISPR? How will it change evolution? How will it redefine the very nature of our existence?CRISPR is an ingenious cut-and-paste system that homes in on a particular DNA gene sequence and then, using Cas9 (...) enzymes, snips it out. That sequence is then replaced with a new one that rewrites or repairs the original. Two different cells—somatic, from the body, and germline, from gametes—can be manipulated... (shrink)

In an article in this journal, Katherine Drabiak argues that green lighting genome editing of human embryos is contrary to “fundamental human rights law.” According to the author, genome editing of human embryos violates what we should recognize as a fundamental human right to inherit a genome without deliberate manipulation. In this reply article, we assess Drabiak's legal analysis and show methodological and substantive flaws. Methodologically, her analysis omits the key international legal instruments that form the so‐called International Bill (...) of Rights and thus fails to provide a full and accurate account of the fundamental international human rights standards. Substantively, Drabiak invokes, as a basis for prohibiting gene editing of human embryos, a legal standard (the rights and integrity of the future child) that is unknown to international law. Contrary to Drabiak's account, genome editing of human embryos is not prohibited under international law. Indeed, the right to health and the right to benefit from scientific progress may be interpreted as the basis of a legal duty to provide equality of access to germline gene editing, once determined it is beneficial and safe to use. (shrink)

The United Kingdom is the first and so far only country to pass explicit legislation allowing for the licensed use of the new reproductive technology known as mitochondrial replacement therapy. The techniques used in this technology may prevent the transmission of mitochondrial DNA diseases, but they are controversial because they involve the manipulation of oocytes or embryos and the transfer of genetic material. Some commentators have even suggested that MRT constitutes germline genome modification. All eyes were on the (...) United Kingdom as the most likely location for the first MRT birth, so it was a shock when, on September 27, 2016, an announcement went out that the first baby to result from use of the intervention had already been born. In New York City, United States-based scientist John Zhang used maternal spindle transfer to generate five embryos for a woman carrying oocytes with deleterious mutations of the mitochondrial DNA. Zhang then shipped the only euploid embryo to Mexico, where it was transferred to the mother's uterus. Zhang's team's travel across international borders to carry out experimental procedures represents a form of scientific tourism that has not been properly ethically explored; it can, however, have seriously detrimental effects for developing countries. (shrink)

In his book The future of human nature, Jürgen Habermas argues against a scenario of liberal eugenics, in which parents are free to prenatally manipulate their children’s genetic constitution via germline interventions. In this paper, I draw attention to the fact that his species‐ethical line of argument is pervaded by a substantial ambiguity between an argument from actual intervention (AAI) and an argument from mere controllability (AMC). Whereas the first argument focuses on threats for the autonomy and equality of (...) prenatally modified persons, the second argument takes all human beings, whether they have been modified or not, into account. Hence, when invoking Habermas in these debates, bioethicists need to consider carefully which argument they are referring to. (shrink)

In this paper I explore the heuristic limits ofhuman genetics, in particular the claim that itis possible to manipulate human germcells in a pre-ordinate way (Gordon, 1999). I arguethat this claim is unrealistic based ongenetic reductionism and a wrong concept ofgenetic diseases.

It is becoming increasingly clear that most, if not all, animals and plants are associated with a diverse array of resident gut microbiota. This symbiosis is regulated by host-microbiome interactions which influence the development, homeostasis, adaptation and evolution of the host. Recent evidence indicated that these interactions can also affect the host germline and have a potential of supporting transgenerational effects, including inheritance of acquired characteristics. Taken together, the influence of gut bacteria on the host soma and germline (...) could potentially give rise to emergent phenotypes, which may be partially inherited by three distinguishable modes of transgenerational influence of gut bacteria: 1) “soma-to-soma” 2) “soma-to-germline” and 3) “soma-germline-soma”. Here, we discuss these possibilities in light of evidence supporting bacterial-mediated modes of transgenerational inheritance. All animals are consortiums of hosts and microbiota. Their interactions influence many aspects of the adaptation and evolution of the Holobiont. The host germline can also be affected which can give rise to new modes of transgenerational influence of gut bacteria: 1) “soma-to-soma” 2) “soma-to-germline,” and 3) “soma-germline-soma.”. (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)

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)

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)

Cancers often express hundreds of genes otherwise specific to germ cells, the germline/cancer (GC) genes. Here, we present and discuss the hypothesis that activation of a “germline program” promotes cancer cell malignancy. We do so by proposing four hallmark processes of the germline: meiosis, epigenetic plasticity, migration, and metabolic plasticity. Together, these hallmarks enable replicative immortality of germ cells as well as cancer cells. Especially meiotic genes are frequently expressed in cancer, implying that genes unique to meiosis (...) may play a role in oncogenesis. Because GC genes are not expressed in healthy somatic tissues, they form an appealing source of specific treatment targets with limited side effects besides infertility. Although it is still unclear why germ cell specific genes are so abundantly expressed in cancer, from our hypothesis it follows that the germline's reproductive program is intrinsic to cancer development. (shrink)

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)

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)

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)

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)

Writers have debated whether germline genome‐editing is person‐affecting or identity‐affecting. The difference is thought to be ethically relevant to whether we should choose genome‐editing or choose preimplantation genetic diagnosis and embryo selection, when seeking to prevent or produce bad conditions (e.g., cystic fibrosis, or deafness) in the individuals who will grow from the embryo edited or selected. We consider the very recent views of three prominent bioethicists and philosophers who have grappled with this issue. We claim that both sides (...) are right, but that the sense in which genome‐editing is person‐affecting is less important, morally, when the aim is to have healthy children. Since this is the predominant objective of engaging in embryo selection and genome‐editing, and since there are certain risks, at least for now, with genome‐editing, it remains better, morally, to engage in embryo selection than genome‐editing. (shrink)

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.

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)

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)

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)

In this paper I critically assess Derk Pereboom’s book, Free Will, Agency, and Meaning in Life. In it, I resist Pereboom’s manipulation argument for incompatibilism and his indictment of desert-based accounts of moral responsibility.

Egg or sperm? The mechanism of sexual fate decision in germ cells has been a long‐standing issue in biology. A recent analysis identified foxl3 as a gene that determines the sexual fate decision of germ cells in the teleost fish, medaka. foxl3/Foxl3 acts in female germline stem cells to repress commitment into male fate (spermatogenesis), indicating that the presence of mitotic germ cells in the female is critical for continuous sexual fate decision of germ cells in medaka gonads. Interestingly, (...) foxl3 is found in most vertebrate genomes except for mammals. This provides the interesting possibility that the sexual fate of germ cells in mammals is determined in a different way compared to foxl3‐possessing vertebrates. Considering the fact that germline stem cells are the cells where foxl3 begins to express and sexual fate decision initiates and mammalian ovary does not have typical germline stem cells, the mechanism in mammals may have been co‐evolved with germline stem cell loss in mammalian ovary. (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...

A great deal of scholarly attention has been paid to coercion. Less attention has been paid to what might be a more pervasive form of influence: manipulation. The essays in this volume address this relative imbalance by focusing on manipulation, examining its nature, moral status, and its significance in personal and social life.

We use recent interventionist theories of causation to develop a compatibilist account of causal sourcehood, which provides a response to Manipulation Arguments for the incompatibility of free will and determinism. Our account explains the difference between manipulation and determinism, against the claim of Manipulation Arguments that there is no relevant difference. Interventionism allows us to see that causal determinism does not mean that variables outside of the agent causally explain her actions better than variables within the agent, (...) whereas the causal source of a manipulated agent’s actions instead lies outside of the agent in the intentions of the manipulator. As a result, determined agents can have free will and be morally responsible in a way that manipulated agents cannot, contrary to what Manipulation Arguments conclude. In this way, our account demonstrates not only how Manipulation Arguments fail but also how compatibilism can be strengthened by means of a plausible account of causal sourcehood. (shrink)

Carl Craver’s mutual manipulability criterion aims to pick out all and only those components of a mechanism that are constitutively relevant with respect to a given phenomenon. In devising his criterion, Craver has made heavy use of the notion of an ideal intervention, which is a tool for illuminating causal concepts in causal models. The problem is that typical mechanistic models contain non-causal relations in addition to causal ones, which is why the standard concept of an ideal intervention is not (...) appropriate in that context. In this paper, I first show how top-down interventions in mechanistic models violate the conditions for ideal interventions. Drawing from recent developments in the causal exclusion literature, I then argue for extended interventionism better suited for the purposes of the new mechanist. Finally, I show why adopting such an extended account leads to the surprising consequence that an important subset of mechanistic interlevel relations comes out as causal. (shrink)

Nudges involve designing social “choice contexts” to promote what “experts” regard as beneficial for individuals and the society, by making the “right” choices easier. The most common form of nudge...

Evolutionary processes such as natural selection and random drift are commonly regarded as causes of population-level change. We respond to a recent challenge that drift and selection are best understood as statistical trends, not causes. Our reply appeals to manipulation as a strategy for uncovering causal relationships: if you can systematically manipulate variable A to bring about a change in variable B, then A is a cause of B. We argue that selection and drift can be systematically manipulated to (...) produce different kinds of population-level change. They should therefore be regarded as causes. (shrink)