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)

Current advances in assisted reproductive technologies aim to promote the health and well-being of future children. They offer the possibility to select embryos with the greatest potential of being born healthy (eg, preimplantation genetic testing) and may someday correct faulty genes responsible for heritable diseases in the embryo (eg, human germline genome modification (HGGM)). Most laws and policy statements surrounding HGGM refer to the notion of ‘serious’ as a core criterion in determining what genetic diseases should be targeted (...) by these technologies. Yet, this notion remains vague and poorly defined, rendering its application challenging and decision making subjective and arbitrary. By way of background, we begin by briefly presenting two conceptual approaches to ‘health’ and ‘disease’: objectivism (ie, based on biological facts) and constructivism (ie, based on human values). The basic challenge under both is sorting out whether and to what extent social and environmental factors have a role in helping to define what qualifies as a ‘serious’ disease beyond the medical criteria. We then focus on how a human rights framework (eg, right to science and right to the highest attainable health) could integrate the concepts of objectivism and constructivism so as to provide guidance for a more actionable consideration of ‘serious’. Ultimately, it could be argued that a human rights framework, by way of its legally binding nature and its globally accepted norms and values, provides a more universal foundation for discussions of the ethical, legal and social implications of emerging or disruptive technologies. (shrink)

With progress in genetic research advancing as it is, a host of novel theoretical and practical challenges are thereby being raised. From a bioethical perspective, it is easy to get the feeling that, because of this rapid progress, many fundamental concepts that should be in place arent yet in place. This lack may be felt especially in relation to human gene modification. with the Human Genome Projects potential to yield innumerable applications, one of the things that should be in (...) place is a set of fundamental conceptual guidelines demarcating the kinds of genetic modifications that should count as ethically acceptable and legally permissible. In this paper, my goal is to articulate such guidelines, specifically for the set of all possible human germline modifications. (shrink)

Genome editing holds the promise of revolutionizing many fields in which human interventions have hitherto proved to be insufficient to meet major global challenges, like nutrition and environmental protection. However, it is controversial how far this method might also be applied to the human germline with a view to preventing the transmission of serious genetic diseases to offspring. While there is a near-consensus that genome editing, at the present stage of science, should not be applied clinically, it is unclear (...) whether this also extends to clinically oriented research. It is argued that among the arguments against interventions in the human germline there is only one that is sufficiently strong to be practically relevant: The argument that it is doubtful whether the challenge of off-target effects with potentially fatal health consequences can be met. Since nearly all objectives of human germline genome editing can be attained by PGD, there are good grounds for directing clinically oriented research toward the improvement of this alternative method, which has been proven to be without substantial risks and which involves no ethical problems over and above those involved in genome editing. (shrink)

Explains how and why laws against human germline modification will do more harm than good.

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)

Should we use human germline genome modification only when serious diseases are involved? This belief is the underlying factor in the article written by Kleiderman, Ravitsky and Knoppers to which I now respond. In my opinion, the answer to this question should be negative. In this paper, I attempt to show that there are no good reasons to think that this technology should be limited to serious diseases once it is sufficiently proven to be safe and efficient. In (...) fact, opting otherwise would negatively harm human beings’ right to the highest standard of health that unmodified embryos could promote. Therefore, the issue should not be so much to define adequately what a serious disease is, but rather to elucidate whether this concept should play any role beyond the context of preimplantation genetic testing. This paper argues that we should not accept the similarity between technologies such as PGT and HGGM because they face different challenges and offer totally different possibilities. Therefore, we are in urgent need to build a completely new ethical architecture that covers the application of germline editing in human embryos. As a part of that process, a much deeper debate on the necessity of distinguishing different disease types is required. (shrink)

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

The governance of human (germline) genome modification at the international and transnational level -- The regulation of human germline genome modification in Canada (E Kleiderman) -- The regulation of human germline genome modification in the United States (Kerry Macintosh) -- The regulation of human germline genome modification in Mexico (M Medina Arellano) -- The regulation of human germline genome modification in Europe (J Almqvist, C Romano) -- The regulation of human (...) germline genome modification in the United Kingdom (J Lawford Davies) -- The regulation of human germline genome modification in Germany (T Faltus). (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 prospect of using genome technologies to modify the human germline has raised profound moral disagreement but also emphasizes the need for wide-ranging discussion and a well-informed policy response. The Hinxton Group brought together scientists, ethicists, policymakers, and journal editors for an international, interdisciplinary meeting on this subject. This consensus statement formulated by the group calls for support of genome editing research and the development of a scientific roadmap for safety and efficacy; recognizes the ethical challenges involved in clinical (...) reproductive applications of genome editing but, importantly, rejects the idea that human reproductive germline modification is necessarily morally unacceptable; and highlights the importance of meaningful engagement in discussions of genome editing and the development of regulation and oversight mechanisms to govern future uses of such technologies. (shrink)

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)

Bioethics, Volume 36, Issue 5, Page 556-568, June 2022.

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

The 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)

As research involving gene editing continues to advance, we are headed in the direction of being able to modify the human germline. Should we reach a point where an argument can be made that the benefits of preventing unborn children and future generations from inheriting genetic conditions that cause tremendous suffering outweigh the risks associated with altering the human germline, the next step will be to design clinical trials using this technology in humans. These clinical trials will likely (...) require careful follow-up and monitoring of future generations born with altered genes. This paper addresses some of the ethical issues raised by intergenerational monitoring and sets out to show that these issues can be avoided with careful consideration and clinical trial design. (shrink)

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)

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

Liberal proponents of genetic engineering maintain that developing human germline modification technologies is morally desirable because it will result in a net improvement in human health and well-being. Skeptics of germline modification, in contrast, fear evolutionary harms that could flow from intervening in the human germline, and worry that such programs, even if well intentioned, could lead to a recapitulation of the scientifically and morally discredited projects of the old eugenics. Some bioconservatives have appealed as (...) well to the value of retaining our “given” human biological nature as a reason for restraining the development and use of human genetic modification technologies even where they would tend to increase well-being. In this article, I argue that germline intervention will be necessary merely to sustain the levels of genetic health that we presently enjoy for future generations—a goal that should appeal to bioliberals and bioconservatives alike. This is due to the population-genetic consequences of relaxed selection pressures in human populations caused by the increasing efficacy and availability of conventional medicine. This heterodox conclusion, which I present as a problem of intergenerational justice, has been overlooked in medicine and bioethics due to certain misconceptions about human evolution, which I attempt to rectify, as well as the sordid history of Darwinian approaches to medicine and social policy, which I distinguish from the present argument. (shrink)

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

The possibility of performing germline modifications on currently living individuals targets future generations’ health and well-being by reducing the diversity of the human gene pool. This can have two negative repercussions: reduction of heterozygosity, the latter being associated with a health or performance advantage; uniformization of the genes involved in reproductive recombination, which may lead to the health risks involved in asexual reproduction. I argue that germline interventions aimed at modifying the genomes of future people cannot be ethically (...) justifiable if there is no possibility of controlling the intervention either by reversing or altering it, whenever need demands it. This argument is challenged on six different grounds: safety, population versus individual focus, spontaneous mutations, exceptionalism, the intentional pursuit of genetic diversity through germline interventions, and harm reduction potential. (shrink)

Focusing on present‐day possibilities raised by existing technology, I consider the normative aspects of genetically modifying the human germline from a utilitarian standpoint. With reference to a hypothetical case, I examine the probable consequences of permitting a well‐conceived attempt to correct a disease‐associated gene in the human germline using current CRISPR gene‐editing technology. I consider inter alia the likely effects on utility of creating healthy new lives, of discouraging adoption, and of kickstarting a revolution in human germline (...) genetic modification (HGGM). I reject various objections to HGGM, including claims that the risks of genetic harm outweigh the likely benefits. From this utilitarian analysis, I conclude that strong grounds exist to support intervening in the human germline using current technology. Delay in commencing such work will impose a utility cost, because the longer we wait until commencing the HGGM revolution and moving towards a world of increased utility, the greater will be the quantity of suffering accrued meantime through genetically influenced disease. Nevertheless, considering residual safety concerns and the negative publicity engendered by an ethically problematic recent (2018) first attempt at HGGM, it seems prudent—and ultimately generative of the greatest amount of utility—to delay implementing HGGM for a modest period of time, in the order of 1–2 years. (shrink)

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

The ethical issues associated with germline gene modification and embryo research are some of the most contentious in current international science policy debates. In this paper, we argue that new genetic techniques, such as CRISPR, demonstrate that there is an urgent need for China to develop its own regulatory and ethical framework governing new developments in genetic and embryo research. While China has in place a regulatory framework, it needs to be strengthened to include better compliance oversight and (...) explicit criteria for how different types of research should be reviewed by regulatory authorities. We also document a variety of opinions about the new technologies among the public, scholars, and policy makers. China needs to develop its own regulations in coordination with other countries; but it is unlikely that an international consensus will be achieved in this area, given the existing differences in regulations between countries. We should aim at harmonization, not necessarily complete consensus, and the perspective from China is vital when international norms are developed and harmonized. Chinese policy makers and researchers need to be aware of the international discussions, at the same time as the international community is aware of, and accommodates, Chinese positions on important policy options. (shrink)

The 23rd volume in the respected series Ô Basic Bioethics’, this book contains seven original and two reprinted essays and a substantial introductory chapter by the editor. The main concern of the editor, and of several contributors, is to dispel the view that organised reli- gion has been consistently hostile to new biomedical developments. Instead, they emphasise that the practice of medicine is endorsed by the Church and by Jewish tradition. In principle, germline mod- ification might count as an (...) extension of medicine. A consensus emerges in the volume that germline modification would be accept- able if it could be developed and applied with safety and social equity, without destroying any human embryos, and if conducted purely for therapeutic purposes rather than for any form of genetic enhancement. (shrink)

Recent scientific advances in the field of gene editing have led to a renewed discussion on the moral acceptability of human germline modifications. Gene editing methods can be used on human embryos and gametes in order to change DNA sequences that are associated with diseases. Modifying the human germline, however, is currently illegal in many countries but has been suggested as a ‘last resort’ option in some reports. In contrast, preimplantation genetic diagnosis is now a well-established practice within (...) reproductive medicine. Both methods can be used to prevent children from being born with severe genetic diseases. This paper focuses on four moral concerns raised in the debate about germline gene editing and applies them to the practice of PGD for comparison: Violation of human dignity, disrespect of the autonomy and the physical integrity of the future child, discrimination of people living with a disability and the fear of slippery slope towards immoral usage of the technology, e.g. designing children for specific third party interests. Our analysis did not reveal any fundamental differences with regard to the four concerns. We argue that with regard to the four arguments analyzed in this paper germline gene editing should be considered morally as acceptable as the selection of genomes on the basis of PGD. However, we also argue that any application of GGE in reproductive medicine should be put on hold until thorough and comprehensive laws have been implemented to prevent the abuse of GGE for non-medical enhancement. (shrink)

DNA methylation is a repressive epigenetic modification that is essential for development and its disruption is widely implicated in disease. Yet, remarkably, ablation of DNA methylation in transgenic mouse models has limited impact on transcriptional states. Across multiple tissues and developmental contexts, the predominant transcriptional signature upon loss of DNA methylation is the de‐repression of a subset of germline genes, normally expressed in gametogenesis. We recently reported loss of de novo DNA methyltransferase DNMT3B resulted in up‐regulation of (...) class='Hi'>germline genes and impaired syncytiotrophoblast formation in the murine placenta. This defect led to embryonic lethality. We hypothesize that de‐repression of germline genes in the Dnmt3b knockout underpins aspects of the placental phenotype by interfering with normal developmental processes. Specifically, we discuss molecular mechanisms by which aberrant expression of the piRNA pathway, meiotic proteins or germline transcriptional regulators may disrupt syncytiotrophoblast development. (shrink)

Would direct genetic modification of human embryos affect the welfare of future persons? Sparrow’s approach to answering this question fails a core goal of bioethics: to generate perspectives capab...

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)

Metaphors used to describe new technologies mediate public understanding of the innovations. Analyzing the linguistic, rhetorical, and affective aspects of these metaphors opens the range of issues available for bioethical scrutiny and increases public accountability. This article shows how such a multidisciplinary approach can be useful by looking at a set of texts about one issue, the use of a newly developed technique for genetic modification, CRISPRcas9.

Although germline editing has been the subject of debate ever since the 1980s, it tended to be based rather on speculative assumptions until April 2015, when CRISPR/Cas9 technology was used to modify human embryos for the first time. This article combines knowledge about the technical and scientific state of the art, economic considerations, the legal framework and aspects of clinical reality. A scenario will be elaborated as a means of identifying key ethical implications of CRISPR/Cas9 genome editing in humans (...) and possible ways of dealing with them. Unlike most other discussions of CRISPR/Cas9 germline editing, which are generally based on deontological arguments, the focus in this case will be on a consequentialistic argument against certain applications of germline and somatic editing that takes not only the potential benefits and risks but also socioeconomic issues into consideration. The practical need for an indication catalogue, guidelines for clinical trials, and for funding of basic research will be pointed out. It will be argued that this need for regulatory action and discussion does not stem primarily from the fact that CRISPR/Cas9 germline editing is revolutionary in terms of its ethical implications and potential for human therapy, although this is the prevailing view in the current discussion. Understanding the value and interest dependency of arguments put forward by different stakeholders and learning from past debates related to similar technologies might prove a fruitful method of reaching judgments and decisions that come closer to a consensus upon which society as a whole can agree - which after all should be the true goal of an ethical debate and of bioethics. (shrink)

Mitochondrial replacement therapy (MRT) utilises nuclear transfer technology to replace defective mitochondria with healthy ones and thereby minimise the risk of a mitochondrial disease passing from a mother to her child. It promises much but comes with ethical controversy, significant risk of harm and many unknowns. Forming a position on MRT requires accurate information about the current state of knowledge, and an appreciation of the ethical issues at stake. Ethical deliberations will vary depending on the framework used. There are in (...) principle objections to MRT on the grounds of direct harm to human embryos and germline genetic modification. But even without these objections MRT can be weighed in terms of the balance between risks and benefits, alternatives and uncertainties. This paper explores the evidence and lays out the relevant issues to assist such a deliberation. (shrink)

This paper explores the ethics of introducing genome-editing technologies as a new reproductive option. In particular, it focuses on whether genome editing can be considered a morally valuable alternative to preimplantation genetic diagnosis. Two arguments against the use of genome editing in reproduction are analysed, namely safety concerns and germline modification. These arguments are then contrasted with arguments in favour of genome editing, in particular with the argument of the child’s welfare and the argument of parental reproductive autonomy. (...) In addition to these two arguments, genome editing could be considered as a worthy alternative to PGD as it may not be subjected to some of the moral critiques moved against this technology. Even if these arguments offer sound reasons in favour of introducing genome editing as a new reproductive option, I conclude that these benefits should be balanced against other considerations. More specifically, I maintain that concerns regarding the equality of access to assisted reproduction and the allocation of scarce resources should be addressed prior to the adoption of genome editing as a new reproductive option. (shrink)

The discovery of clustered regularly interspaced short palindromic repeats (CRISPR) and the CRISPR-mediated protein 9 (CRISPR-Cas9) immediately revealed numerous potential therapeutic applications. Although CRISPR-Cas9 will most likely be useful for addressing issues such as genetic diseases and related medical issues, use of this modality for germline modification generates complex ethical questions regarding the safety and efficacy, human genetic enhancement, and “designer” babies. In this article, the case of the He Jiankui affair is used as an example of the (...) potential for unregulated use of CRISPR-Cas9 technology. In 2018, Dr He Jiankui reported that he had successfully edited human embryos. This work clearly violates all international principles of bioethics. As such, the purpose of this paper is to explore the ethical challenges inherent in the use of CRISPR-Cas9 for human germline editing from the perspectives of the goals of Islamic law (Maqasid al Shari'a) and the major jurisprudential maxims (Qawaid Fiqhiyyah). We argue that from an Islamic standpoint, the therapeutic application of CRISPR-Cas9 for germline editing may be permissible if the safety and efficacy concerns are resolved and if the principles of Maqasid al-Shari'a are fulfilled. (shrink)

On September 27, 2016 people across the world looked down at their buzzing phones to see the AP Alert: “Baby born with DNA from 3 people, first from new technique.” It was an announcement met with confusion by many, but one that polarized the scientific community almost instantly. Some celebrated the birth as an advancement that could help women with a family history of mitochondrial diseases prevent the transmission of the disease to future generations; others held it unethical, citing medical (...) tourism and consequences for the future of the therapy. The child in question was actually born a few months earlier on April 6, 2016, but the research was published a few months later in the October edition of Fertility and Sterility. The mother carries DNA that could have given the baby Leigh Syndrome, a severe neurological disorder characterized by psychomotor regression that typically results in death between ages two and three.[1] Also known as subacute necrotizing encephalomyelopathy, Leigh Syndrome is caused by genetic mutations in mitochondrial DNA, which causes defective oxidative phosphorylation. Because people with this condition cannot re-form ATP, “demyleniation, gliosis, necrosis, spongiosis, or capillary proliferation”[2] can occur, thereby producing bilateral lesions across the central nervous system. The 36-year-old mother previously had four miscarriages and successfully birthed two children, both of whom survived less than six years due to the syndrome. For religious reasons, the mother opted for Spindle Nuclear Transfer instead of Pronuclear Transfer,[3] which many religious organizations oppose because it entails the destruction of fertilized eggs.[4] In Pronuclear Transfer, both the parent and donor egg are fertilized. The parent’s nuclear material is then removed from the egg containing mutated mitochondria and inserted into the fertilized donor egg—from which the original nuclear material has been removed and destroyed. Spindle Nuclear Transfer, on the other hand, removes the mother’s nuclear material from the egg with unhealthy mitochondria, then implants it into a donor’s egg. The newly created egg is then fertilized with the father’s sperm. This Spindle Nuclear Transfer was performed in Mexico by a team of doctors led by Dr. John Zhang, the founder of the New Hope Fertility Center in New York City. In their report, the doctors outline that five oocytes were successfully reconstituted, four of which developed into blastocysts. Only one was euploid: containing 46 XY chromosomes. Researchers then biopsied that blastocyst and found that the transmission rate of maternal mtDNA was, “5.10 ± 1.11% and the heteroplasmy level for 8993T>G was 5.73%.”[5] This indicates that at the blastocyst stage, around five percent of the mitochondria are from the original maternal egg with the mutation for Leigh Syndrome. After birth, they biopsied different tissues and found that they had an average of less than 1.60 ± 0.92% of transmitted mtDNA from the original maternal egg. The baby is reportedly doing well and the team of doctors concluded that “[h]uman oocytes reconstituted by SNT are capable of producing a healthy live birth. SNT may provide a novel treatment option in minimizing pathogenic mtDNA transmission from mothers to their babies."[6] Even when considered theoretically, Spindle Nuclear Transfer is controversial. Many doctors believe that the risks at this stage of research are too great. Dr. Trevor Stammers, a bioethicist at St. Mary’s University in London, points out: “We do not yet have a clear picture of the interaction between nuclear DNA and mitochondria.”[7] Others hold that faulty mitochondrial DNA can still be transferred during the procedure. Still more argue this technology could create problems because of germline modification.[8] Dr. Paul Knoepfler, a cell biologist at the UC Davis School of Medicine, explains: “Since this is uncharted territory and the children born from this technology would have heritable genetic changes, there are also significant unknown risks to future generations.”[9] However, proponents counter these arguments. They say the benefits outweigh the risks, as “mitochondrial replacement techniques [like Spindle Nuclear Transfer] would eliminate maternal transmission of mitochondrial disease… allowing a woman with a family history of mitochondrial diseases to ensure her children would not be affected.”[10] Additionally, experts say that no symptoms will occur if less than 20% of the transferred mitochondrial DNA is faulty.[11] And while opponents see potential germline modification as a problem, advocates answer that this could stop a family history of mitochondrial disease, which they deem a more serious concern. In this case specifically, however, there are more issues at hand. While the team of doctors did eliminate the possibility of germline modification by selecting a male embryo, there are other ethical concerns. Some argue that this case could be described as “medical tourism.” While New Hope Medical Clinic does maintain a branch in Mexico, Dr. Zhang stated that Mexico has “no rules.”[12] It is a country with underdeveloped regulations, making it difficult to confirm that doctors adhere to widely-held medical and ethical standards. Furthermore, while it is highly unlikely that the child will develop Leigh’s Syndrome, Dr. Dietrich Egli of the New York Stem Cell Foundation says the 5% mitochondrial transfer rate indicates that the technique “was not carried out well.”[13] He points to studies of embryos where the rate of mtDNA transfer was almost ten times lower. Spindle Nuclear Transfer is currently legal in the UK,[14] and many are hoping to see it legalized in the US, although Congress currently prohibits the FDA from considering applications that would entail trials in people.[15] While Dr. Zhang’s work is arguably revolutionary, many wonder if the manner in which this study was performed—in Mexico and with a high mitochondrial transfer rate—will impact the technology’s future in the US. Last week, Dr. Zhang presented the report to scientists gathered in Salt Lake City, saying that while science isn’t a race, it is “in a sense, a race for the family to find a cure, to find hope.”[16] Only time will tell if this study set back other families racing and hoping for a cure. References 1. "Leigh Syndrome." Genetics Home Reference, US National Library of Medicine, 25 Oct. 2016. Accessed 26 Oct. 2016. 2. McKusick, Victor A., and Ada Hamosh. "LEIGH SYNDROME; LS." Online Mendelian Inheritance in Man, Johns Hopkins University, 20 Jan. 2016. Accessed 30 Oct. 2016. 3. Zhang, J, H Liu, S Luo, A Chavez-Badiola, and Z Liu. "First live birth using human oocytes reconstituted by spindle nuclear transfer for mitochondrial DNA mutation causing Leigh syndrome." Fertility and Sterility, vol. 106, no. 3, 2016, pp. e375-76. Accessed 30 Oct. 2016. 4. Sample, Ian. "‘Three-parent’ babies explained: what are the concerns and are they justified?" The Guardian, 2 Feb. 2015. Accessed 30 Oct. 2016. 5. Zhang, et al. 6. Ibid. 7. Knapton, Sarah. "Three-parent babies: the arguments for and against." The Telegraph, 3 Feb. 2015. 8. Ibid. 9. Ibid. 10. "Mitochondrial Replacement Therapy FAQs." New York Stem Cell Foundation Research Institute, New York Stem Cell Foundation. Accessed 30 Oct. 2016. 11. Reardon, Sara. "‘Three-parent baby’ claim raises hopes — and ethical concerns." Nature, 28 Sept. 2016. Accessed 30 Oct. 2016. 12. Hamzelou, Jessica. "Exclusive: World’s first baby born with new “3 parent” technique." New Scientist, 27 Sept. 2016. Accessed 30 Oct. 2016. 13. Reardon, Sara. "‘Three-parent baby’ claim raises hopes — and ethical concerns." Nature, 28 Sept. 2016. Accessed 30 Oct. 2016. 14. "3-Person IVF: A Resource Page." Center for Genetics and Society, 24 Oct. 2016. Accessed 30 Oct. 2016. 15. Ritter, Malcolm. "Baby born with DNA from 3 people, first from new technique." Associated Press, 27 Sept. 2016. Accessed 30 Oct. 2016. 16. Chen, Daphne. "Controversy swirls around first three-parent baby." Deseret News, 19 Oct. 2016. Accessed 30 Oct. 2016. Works consulted Swetlitz, Ike. "FDA urged to approve ‘three-parent embryos,’ a new frontier in reproduction." STAT, 3 Feb. 2016. Accessed 30 Oct. 2016. (shrink)

Given recent advancements in CRISPR‐Cas9 powered genetic modification of gametes and embryos, both popular media and scientific articles are hailing CRISPR’s life‐saving, curative potential for people with serious monogenic diseases. But claims that CRISPR modification of gametes or embryos, a form of germline engineering, has therapeutic value are deeply mistaken. This article explains why reproductive uses of CRISPR, and germline engineering more generally, do not treat or save lives that would otherwise have a genetic disease. Reproductive (...) uses of CRISPR create healthy people whose existence is not inevitable in the first place. Creating healthy lives has distinct and lesser moral value from saving or curing lives that would otherwise have genetic disease. The real value in reproductive uses of CRISPR is in helping a very limited population of people have healthy, genetically related children. This diminished value cannot compete with the concerns in opposition to germline engineering, nor is it worth the investment of research money. (shrink)

In July 2018, the Nuffield Council on Bioethics released the report Genome editing and human reproduction: Social and ethical issues, concluding that human germline modification of human embryos for implantation is not ‘morally unacceptable in itself’ and could be ethically permissible in certain circumstances once the risks of adverse outcomes have been assessed and the procedure appears ‘reasonably safe’. The Nuffield Council set forth two main principles governing anticipated uses and envisions applications that may include health enhancements as (...) a public health measure. This essay provides a critique of three aspects in the Nuffield Council’s Report: its presumption of therapeutic efficacy, its inflation of parental rights to create a certain type of child, and its reliance on a specially commissioned report that appears to distort key definitions in international law. (shrink)

In their paper ‘The “serious” factor in germline modification’, Kleiderman, Ravitsky and Knoppers rightly highlight the ambiguity in the oft-utilised term ‘serious’ in legal discussions of human germline genome modification.1 They suggest interpretation of this term may benefit from a framework based on human rights rather than solely objectivist or constructivist frameworks. In this response, I show the authors provide a narrow and hasty dismissal of objectivist frameworks by defining objectivism broadly as ‘based on biological facts’ (...) early on but later criticising genetic treatment lists, a single narrow implementation of only some of the facts. Furthermore, I will show their consideration of the right to science is biassed towards the material innovations of science, the authors succeed in recognising but fail in elaborating on the knowledge gained from scientific progress; knowledge which may ultimately update moral intuitions and change the nature of ethical conversation across cultures. (shrink)