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The ‘one‐way’ expert model of science communication is out of date. The new dialogue model requires from scientists more than just providing expert knowledge to the publics.

Biomedical research often raises ethical questions that are usually addressed ad hoc or in retrospective. Real-time ethical engagement as part of research may be better suited to identify ethical issues.

Recent developments in the field of mitochondrial replacement technique (MRT) research and clinical practice have raised ethical concerns worldwide. We argue that the future use of MRTs requires a concerted effort among the global research and clinical community to implement and enforce responsible innovation and governance.

Recent developments in stem cell research and genomics have made it possible to grow mini‐organs, so‐called organoids, in culture. Organoids are self‐assembling three‐dimensional structures that closely resemble the architecture and function of real organs and are seen as one of the most significant developments in stem cell research with a wide range of applications in research and in the clinic. However, the relevant ethics for organoid technology have not been sufficiently addressed. First, the moral and legal status of organoids deserves further exploration. Second, organoid biobanking calls for the development of adequate consent procedures in both research and clinical applications. Third, the concept of mixed models in biobanking of organoids requires distinct governance structures. Fourth, we anticipate ethical challenges related to clinical translation. Further interdisciplinary discussion is required to stimulate morally responsible innovation. > As organoid biobanking is growing rapidly, it should be scrutinized whether and to what extent organoids give new twists to the ethical challenges in stem‐cell research and analogous fields. Organoids can be grown from several types of stem cells, including induced pluripotent stem cells (iPSCs), human embryonic stem cells (hESCs) and adult stem cells for a wide variety of organs including gut, kidney, pancreas, liver, brain, and retina, among others. These mini‐organs can be stored in biobanks and used for fundamental research, precision medicine, and regenerative medicine [1], [2]. Cerebral organoids can be used to understand brain development, and mini‐guts can serve as a personalized drug‐testing tool for cystic fibrosis (CF) [2], [3]. Mini‐livers could form a complement to current organ transplantation to restore liver function of patients with metabolic liver disease [2]. Stem cell research, and the use of embryonic stem cells in particular, has raised a fierce ethical debate, which mainly revolved around the moral …

Cancer patients participating in studies involving experimental or diagnostic next-generation sequencing (NGS) procedures are confronted with the possibility of unsolicited findings. The Center for Personalized Cancer Treatment (CPCT), a Dutch consortium of cancer centers, is offering centralized large-scale NGS for the discovery of somatic tumor mutations with their germline DNA as reference. The CPCT aims to give all cancer patients with advanced disease stages access to tumor DNA analysis in order to improve selection for experimental therapy. In this article, our experiences at the CPCT will serve as an example to discuss the ethical and practical aspects regarding the management of unsolicited findings in personalized cancer research and treatment. Generic issues, relevant for all researchers in this field are discussed and illustrated by description of three patients faced with an unsolicited DNA finding, while they intended to be candidate for future anticancer treatment by participating in a trial that included NGS of both somatic and germline DNA. As options for DNA analysis expand and costs decrease rapidly, more and more patients are offered large-scale NGS testing. After reviewing current recommendations in literature, we conclude that classical informed consent procedures need to be adapted to become more explicit in asking patients if they want to be informed about unsolicited findings and if so, what level of detail of genetic risk information exactly they want to be returned after the analysis.

Item does not contain fulltext The FAIR guiding principles for research data stewardship (findability, accessibility, interoperability, and reusability) look set to become a cornerstone of research in the life sciences. A critical appraisal of these principles in light of ongoing discussions and developments about data sharing is in order. The FAIR principles point the way forward for facilitating data sharing more systematically-provided that a number of ethical, methodological, and organisational challenges are addressed as well.

This study explored individuals' preferences for genetic testing for colorectal cancer (CRC) in a screening situation and their willingness to participate in genetic testing for Lynch syndrome, familial adenomatous polyposis (FAP), and familial colorectal cancer (FCC). For that purpose, 532 respondents aged 55-65 years completed a Discrete Choice Experiment. Using panel latent class models, the preferences for two screening situation characteristics (the probability of being genetically predisposed and the probability of developing CRC) and screening test characteristics (the frequency of preventive colonoscopies and CRC survival) were estimated. Based on these preferences, respondents' willingness to participate in the three screening initiatives was estimated. Lower-educated respondents and respondents who express serious anxiety and worries found colonoscopy frequency and the probability of developing CRC relatively more important and survival relatively less important compared with higher-educated respondents and respondents who express no anxiety and worries. These differences in preferences resulted in opposite preferences for participation in FCC and FAP screening. In conclusion, the general population is willing to participate in genetic screening for CRC. If individuals are suspected of genetic or familial CRC, they should at least be informed about their increased risk of being genetically predisposed and about the importance of participating in all preventive follow-up colonoscopies in order to maximize survival.

Nature Biotechnology asks selected members of the international community to comment on the ethical issues raised by the prospect of CRISPR-Cas9 engineering of the human germline.

The introduction of novel diagnostic techniques in clinical domains such as genomics and radiology has led to a rich ethical debate on how to handle unsolicited findings that result from these innovations. Yet while unsolicited findings arise in both genomics and radiology, most of the relevant literature to date has tended to focus on only one of these domains. In this article, we synthesize and critically assess similarities and differences between “scanning the body” and “sequencing the genome” from an ethical perspective. After briefly describing the novel diagnostic contexts leading to unsolicited findings, we synthesize and reflect on six core ethical issues that relate to both specialties: Terminology; benefits and risks; autonomy; disclosure of unsolicited findings to children; uncertainty; and filters and routine screening. We identify ethical rationales that pertain to both fields and may contribute to more ethically sound policies. Considerations of preserving public trust and ensuring that people perceive healthcare policies as fair also support the need for a combined debate.

The inclusion of children's samples in biobanks brings forward specific ethical issues. Guidelines indicate that children should be involved in the consent procedure. It is, however, unclear how to allocate an appropriate role for children. Knowledge of current practice will be helpful in addressing this issue. Therefore, we conducted an international multiple-case study on the child's role in consent procedures in pediatric biobanks. Four biobanks were included: (1) LifeLines, (2) Prevention and Incidence of Asthma and Mite Allergy (PIAMA), (3) Young-HUNT3 and (4) the Oxford Radcliffe Biobank contribution to the Children's Cancer and Leukaemia Group tissue bank (ORB/CCLG). Four themes linked to the child's role in the consent procedure emerged from the multiple-case study: (1) motives to involve the child, (2) informing the child, (3) the role of dissent, assent and consent and (4) voluntariness of children to participate. We conclude that biobank characteristics influence the biobank's motives to include children in the consent procedure. Moreover, the motives to include children influence how the children are involved in the consent procedure, and the extent to which children are able to make voluntary decisions as part of the consent procedure. This insight is valuable when designing pediatric biobank governance.

The world has been startled by the irresponsible experiment of He Jiankui, who used CRISPR to genetically modify human embryos. In this viewpoint, we explore the phenomenon of moral luck in medicine and its bearing on the limits of simple judgements of the kind “everything that ends well is well” or “someone broke the rules, and is therefore blameworthy”. The risks involved in scientific and medical experiments are often brushed aside, when they turn out well. The clinical application of CRISPR in the human germline is presently too risky to be used without more preclinical research and unacceptable without broader societal support, which justifies the call for a moratorium by the scientific community. However, such policies do not determine how to assess cases, where someone was willing to take such risks beyond all rules, guidelines and regulation and succeeds. The policies including the proposed moratorium are as unanimous about the undesirability of current applications of clinical germline editing as they are about the potential importance of this research. What if this potential is achieved by breaking the rules? The paradox of moral luck impinges on this debate. In our analysis, we rebut simplified judgments and advocate a more balanced view on the relation between moral responsibility and the societal consequences of medicine.

Rapid advances in genomic technologies and their increasing clinical application are driving the need for a policy on whether to recontact patients to inform them of new genetic discoveries that may have relevance to their health. Importantly, the duty to recontact is context-specific, and professionals should be offered guidance accordingly. The clinical application of genomic technologies is driving new discoveries that may be relevant to individuals who have previously undergone genetic testing. This Comment highlights the need for a framework to decide whether to recontact patients and inform them of new genetic findings.

With the rapid development of next-generation sequencing (NGS) technologies, among them whole exome and whole genome sequencing, it is now possible and affordable to sequence genomes in a short per...

Parents' preferences for unsolicited findings (UFs) from diagnostic whole-exome sequencing (WES) for their children remain largely unexplored. Our aim was to gain insight into parental considerations favoring acceptance/decline of UFs pertaining to their child. We conducted 20 qualitative, semistructured interviews with parents (n=34) of children with a developmental delay, aged

Ever since genetic testing is possible for specific mutations, ethical debate has sparked on the question of whether professionals have a duty to warn not only patients but also their relatives that might be at risk for hereditary diseases. As next generation sequencing swiftly finds its way into clinical practice, the question who is responsible for conveying unsolicited findings to family members becomes increasingly urgent. Traditionally, there is a strong emphasis on the duties of the professional in this debate. But what is the role of the patient and her family? In this article, we discuss the question of whose duty it is to convey relevant genetic risk information concerning hereditary diseases that can be cured or prevented to the relatives of patients undergoing NGS. We argue in favor of a shared responsibility for professionals and patients and present a strategy that reconciles these roles: a moral accountability nudge. Incorporated into informed consent and counseling services such as letters and online tools, this nudge aims to create awareness on specific patient responsibilities. Commitment of all parties is needed to ensure adequate dissemination of results in the NGS era. This article is protected by copyright. All rights reserved.

Medical research is increasingly becoming data-intensive; sensitive data are being re-used, linked and analysed on an unprecedented scale. The current EU data protection law reform has led to an intense debate about its potential effect on this processing of data in medical research. To contribute to this evolving debate, this paper reviews how the dominant 'consent or anonymise approach' is challenged in a data-intensive medical research context, and discusses possible ways forwards within the EU legal framework on data protection. A large part of the debate in literature focuses on the acceptability of adapting consent or anonymisation mechanisms to overcome the challenges within these approaches. We however believe that the search for ways forward within the consent or anonymise paradigm will become increasingly difficult. Therefore, we underline the necessity of an appropriate research exemption from consent for the use of sensitive personal data in medical research to take account of all legitimate interests. The appropriate conditions of such a research exemption are however subject to debate, and we expect that there will be minimal harmonisation of these conditions in the forthcoming EU Data Protection Regulation. Further deliberation is required to determine when a shift away from consent as a legal basis is necessary and proportional in a data-intensive medical research context, and what safeguards should be put in place when such a research exemption from consent is provided.

The International Society for Stem Cell Research (ISSCR) presents its 2016 Guidelines for Stem Cell Research and Clinical Translation (ISSCR, 2016). The 2016 guidelines reflect the revision and extension of two past sets of guidelines (ISSCR, 2006, ISSCR, 2008) to address new and emerging areas of stem cell discovery and application and evolving ethical, social, and policy challenges. These guidelines provide an integrated set of principles and best practices to drive progress in basic, translational, and clinical research. The guidelines demand rigor, oversight, and transparency in all aspects of practice, providing confidence to practitioners and public alike that stem cell science can proceed efficiently and remain responsive to public and patient interests. Here, we highlight key elements and recommendations in the guidelines and summarize the recommendations and deliberations behind them., Highlights • The ISSCR presents its new Guidelines for Stem Cell Research and Clinical Translation • The guidelines outline core principles and best practices for the field • Recommendations drive rigor and transparency in all aspects of stem cell research • The guidelines build widespread confidence in the integrity of the research enterprise, The International Society for Stem Cell Research (ISSCR) presents its 2016 Guidelines for Stem Cell Research and Clinical Translation (ISSCR, 2016). The 2016 guidelines reflect the revision and extension of two past sets of guidelines (ISSCR, 2006; ISSCR, 2008) to address new and emerging areas of stem cell discovery and application and evolving ethical, social, and policy challenges. These guidelines provide an integrated set of principles and best practices to drive progress in basic, translational, and clinical research. The guidelines demand rigor, oversight, and transparency in all aspects of practice, providing confidence to practitioners and public alike that stem cell science can proceed efficiently and remain responsive to public and patient interests. Here, we highlight key elements and recommendations in the guidelines and summarize the recommendations and deliberations behind them.

At the moment, there are many collections of human biological samples stored for medical—scientific research purposes that include samples from children [1]. These pediatric biobanks facilitate research, which is considered important for improving (pediatric) health care by generating biomedical knowledge [2,3]. However, pediatric biobank research gives rise to specific ethical issues. At the time of inclusion, many children cannot, or are legally not allowed to, consent for themselves, and typically parental permission is required. Samples may still be stored and used by biobanks when children become autonomous adults. The question arises whether children should be re-contacted to obtain their own consent, or give the opportunity to withdraw their samples, when they reach adulthood. Often, this is referred to as re-consent [4–6]. This term, however, is a misnomer, since the child has not consented in the first place. We therefore use the terms re-contact and consent. In practice, biobanks have adopted different approaches to re-contact and consent. A study on six birth cohort studies found that only the cohorts that follow children into adolescence or past childhood recognize a need to seek consent as the child matures [7], or biobanks attribute a role to parents/guardians to inform their child about the tissue that has been stored and used for research [8]. Furthermore, our international case study on consent procedures in pediatric biobanking [9] shows that regulation plays a key role when pediatric biobanks design their consent procedures. However, major guidelines do not provide sufficient guidance on re-contact and consent [10–12], and there is only very limited literature that analyses the issue in depth [4–6,13]. Given the fact that biobanks already include pediatric samples, and in light of the rapid developments in biobank research, it is important to address the issue of re-contact and consent now. In this paper, we discuss the arguments in favor and against re-contacting participants at maturity and examine different re-contact policies that can be considered.

Next-generation sequencing (NGS) can be used to generate information about a patient's tumour and personal genome. This powerful diagnostic tool provides solicited and unsolicited hereditary genetic (risk) information that could have consequences for cancer patients and their quality of life. A well-defined approach for returning appropriate genetic risk information is needed in personalized cancer care. A qualitative design with semi-structured interviews was used. We conducted interviews with 24 Dutch patients with different types of cancer, both NGS-experienced and NGS-inexperienced, to learn their intentions, needs and preferences towards receiving unsolicited genetic information obtained using NGS. Almost all participants had a positive attitude towards receiving unsolicited findings. After receiving comprehensive background information on NGS, including a binning model of four categories of unsolicited findings, most participants preferred to receive only subsets of genetic information. Their main concern was their own and others' (including family members) ability to cope with (the increased risk of having) a genetic disorder. Providing background information gave cancer patients the opportunity to select subsets of findings and increased their ability to make an informed choice. Special attention is needed for social and emotional factors to support the patients themselves and when communicating test results with their family members.

In this article, we discuss sex selection not intended to help a couple avoid having a child with a severe genetic disorder, but to avoid possible health risks further along the line of generations. Sex selection may be put to this use in the context of preventing mito- chondrial DNA disorders by means of preimplantation genetic diagnosis (PGD) and possibly in the future also through nuclear transfer (NT; also known as mitochondrial gene replacement). A relevant analogy can be found in the context of PGD for X-linked diseases, where sex selection against healthy female carrier embryos would have the same 2-fold purpose of (i) avoiding difficult reproductive decisions for the future child and (ii) avoiding transmission of the mutation to a possible third generation. Because sex selection would still be done for reasons of health, this application should not give rise to the moral concerns associated with sex selection for non-medical reasons. However, the proportionality of adding the relevant procedures to PGD or NT is a relevant concern. We discuss post- and preconceptional sex selection strategies. We conclude that if PGD is already part of the procedure, either as the central technology or as a back-up test after NT, pre- ferentially transferring male embryos could in principle be a morally acceptable way of reducing possible burdens and risks. To start an IVF/ PGD-cycle especially for this purpose would be disproportional. The alternative approach of preconceptional sex selection may be morally justified as a means to increase the chances of obtaining male embryos.

Should professionals systematically screen whole-genome sequencing (WGS) data to check for life-threatening mutations? Alternatively, should genome analysis focus on the primary reason for testing – that is, aiming to achieve precision medicine? We present an ethical review of the arguments and compare the act of searching for mutations with disclosing mutations that are discovered incidentally.

This paper discusses the pros and cons of introducing PGD for mitochondrial DNA (mtDNA) disorders such as NARP (Neurogenic muscle weakness, Ataxia, Retinis Pigmentosa)/Leigh, MELAS (Mitochondrial myopathy, Encephalopathy, Lactic acidosis, and Stroke-like episodes), private mtDNA mutations and LHON (Leber Hereditary Optic Neuropathy). Although there is little experience with PGD for mtDNA disorders, it is reasonable to assume that in many cases, the best one can achieve is the selection of the 'least' affected embryos for transfer. So instead of 'promising' parents a healthy child, PGD in these cases can only aim at reducing reproductive risk. From an ethical point of view, this raises challenging questions about parental and medical responsibilities. The main argument in favour of PGD is that it offers couples at risk the opportunity of reducing their chances of having a severely affected child. Potential objections are manifold, but we conclude that none of them supplies convincing moral arguments to regard risk-reducing PGD as unacceptable. Nevertheless, introducing this new application of PGD in clinical practice will raise further complex issues of determining conditions for its responsible use.

Advances in genome sequencing together with the introduction of personalized medicine offer promising new avenues for research and precision treatment, particularly in the field of oncology. At the same time, the convergence of genomics, bioinformatics, and the collection of human tissues and patient data creates novel moral duties for researchers. After all, unprecedented amounts of potentially sensitive information are being generated. Over time, traditional research ethics principles aimed at protecting individual participants have become supplemented with social obligations related to the interests of society and the research enterprise at large, illustrating that genomic medicine is also a social endeavor. In this review we provide a comprehensive assembly of moral duties that have been attributed to genomics researchers and offer suggestions for responsible advancement of personalized genomic cancer care.

Data sharing is an essential element of research; however, recent scientific and social developments have challenged conventional methods for protecting privacy. Here we provide guidance for determining data sharing thresholds for human pluripotent stem cell research aimed at a wide range of stakeholders, including research consortia, biorepositories, policy-makers, and funders. The International Stem Cell Forum and the Stem Cell Network of Canada.

Embarking toward a new option Mitochondrial DNA (mtDNA) disorders often result in severe diseases involving defects in cellular energy production.1 In the absence of effective treatment, helping carriers of mtDNA mutations to bear healthy, genetically related children has been a key focus. To this end, the UK Parliament voted last February to permit a novel reproductive genetic technology to prevent the transmission of mitochondrial disease, also known as mitochondrial gene transfer (MGT). MGT transfers the nuclear DNA of a woman's egg carrying an mtDNA mutation into a donor oocyte with healthy mitochondria. The transfer can be performed either before in vitro fertilization (by switching the nuclei of diseased and healthy oocytes) or after (by transferring the pronuclei of the affected woman's zygote).2 Because children inherit all mitochondria from their mothers' eggs, such transfers would in theory prevent maternal transmission of mtDNA disease while preserving the genetic link between affected mothers and their offspring. If successful, MGT could be a valuable addition to current reproductive options for carriers of mtDNA mutations in the United Kingdom and elsewhere. At present, the US Food and Drug Administration has requested that the Institute of Medicine (IOM) produce a consensus report regarding the ethical and policy issues related to MGT. In weighing whether to proceed down the road to MGT, might the United States benefit from the UK experience as a reliable course to follow? Context matters Last month, the ethical and policy considerations of MGT were discussed at the first IOM public workshop in Washington, DC (http://www.iom.edu/Activities/Research/MitoEthics/2015-MAR-31.aspx). A wide array of ethical and regulatory challenges were examined, among which were the moral significance of modification of the mitochondrial genome, questions of kinship and identity, and the science and ethics of first human use. Although we acknowledge that the United Kingdom has made pioneering steps toward MGT, we do not think that the regulatory lessons learned there can serve as an immediate road map for the US context. We observe at least three differences that make a copy-and-paste transposition of the UK decision impossible at this point. First, in the United States there is no federal legislation that regulates assisted reproductive technology and no formal review system in place specifically for the creation and use of research embryos.3 By contrast, the UK Human Fertilization and Embryology Authority (HFEA) has strict oversight and will regulate the development and use of MGT by means of a licensing system. Second, the Dickey-Wicker Amendment in the United States prohibits federal funding for any scientific research that would create and/or destroy human embryos in the process—activities that are necessary to study preclinically any assisted-reproduction techniques such as MGT. UK researchers, by contrast, can rely on their own government's funding support, rendering their drive to develop MGT relatively unencumbered both financially and politically. Third, the United Kingdom is the first country to move MGT forward after extensive ethical and political debate. The US political and social landscape is different, and there is less experience to date in facilitating similarly widespread and deep social discourses over emerging biotechnologies such as MGT. In short, the United States does not currently have the regulatory, funding, and deliberative framework in place to fully support MGT. Indeed, the United Kingdom is driving ahead with this new technology largely because it already has clearly marked lanes and traffic signals for the delivery of such scientific innovation to the clinic. Furthermore, citizens in the United Kingdom might be more open than those in the United States to the use of novel assisted-reproduction technologies—a quirky cultural convention that many Americans might equate with “driving on the wrong side of the road.” The IOM Committee will need to embrace and acknowledge these differences in its report. Follow the middle lane Needless to say, whether in the United Kingdom or the United States, first-in-human use of MGT will be replete with risks and uncertainties, because the needed evidence to reliably predict risk and benefit (i.e., testing in humans) is missing. The bold leap from bench to bedside needs sufficient preclinical evidence and careful, long-term, interdisciplinary research, including more ethics research. Although research ethics has made several efforts to better appreciate the risks and benefits of medical research, less work has been done to determine when an acceptable risk–benefit balance has been reached. One must find a balance here between taking appropriate precautions and not unnecessarily hampering innovation.4 We conclude by listing the three distinct precautionary lanes that the United States might take in pursuing MGT. Those favoring the left lane will regard risk and uncertainty as rooted merely in the (temporary) lack of scientific data. The go/no go decision here would be based on both further research and where one sets the threshold for having “sufficient” information about the risks. Those favoring the right lane are much more cautious. They are prepared to take the next exit to find alternative avenues to MGT for preventing mitochondrial disease. Right-lane drivers are inherently distrustful of new technologies, and distrustful of our ability to control or reverse the harms caused by them. In this case, the go/no go decision will be based on whether other approaches can be identified that are intrinsically less risky. Between the right and left lanes is the middle lane. Finally, those favoring the middle lane view uncertainty as a persistent characteristic of all science, not merely a temporary condition. Thus, other social values and ethical considerations aside from one's faith in scientific and safety data will be necessary to inform the go/no go decision. We recommend that the United States follow the middle lane in pursuing MGT. A cautionary approach means that a wide variety of concerns should be taken seriously—wider than safety and efficacy alone—and that one should not to be so anxious about the way forward that progress itself becomes impossible.

Assent is a relatively young term in research ethics, but became an often mentioned ethical requirement in current pediatric research guidelines. Also, the European Society of Human Genetics considers assent an important condition for the inclusion of children in biobanks. However, although many emphasize the importance of assent, few explain how they understand the concept and few have elaborated on the underlying grounds. In this paper, we will discuss the different underlying ethical principles of assent. In the first category, assent appears to be derived from informed consent. This understanding is grounded in respect for autonomy and protection against harm. We conclude that this interpretation of assent is not of added value as a majority of children cannot be considered competent to make autonomous decisions. In addition, other safeguards are more appropriate to protect children against harm. The grounds from the second category can be classified as engagement grounds. These grounds do justice to the specifics of childhood and are of added value. Furthermore, we argue that it follows that both the content and the process of assent should be adjusted to the individual child. This can be referred to as personalized assent. Personalized assent is an appeal to the moral responsibility and integrity of the researcher.

This article discusses whether and when researchers have a moral obligation to feedback individual genetic research results. This unsettled debate has rapidly gained in urgency in view of the emergence of biobanks and the advances in next-generation sequencing technology, which has the potential to generate unequalled amounts of genetic data. This implies that the generation of many known and unknown genetic variants in individual participants of genetics/genomics research as intentionally or collaterally obtained byproducts is unavoidable. As we conclude that valid reasons exist to adopt a duty to return genetic research results, a qualified disclosure policy is proposed. This policy contains a standard default package, possibly supplemented with (one or more of) three additional packages. Whereas the default package, containing life-saving information of immediate clinical utility, should be offered routinely and mandatory to all research participants, offering (one of) the three additional packages is context-specific. Such a qualified disclosure policy in our opinion best balances the potential benefits of disclosure with the potential risks for research participants and the harms of unduly hindering biomedical research. We appeal to the genetics community to make a joint effort to further refine the packages and set thresholds for result selection.

Preclinical experiments are currently performed to examine the feasibility of several types of nuclear transfer to prevent mitochondrial DNA (mtDNA) disorders. Whereas the two most promising types of nuclear transfer to prevent mtDNA disorders, spindle transfer and pronuclear transfer, do not amount to reproductive cloning, one theoretical variant, blastomere transfer does. This seems the most challenging both technically and ethically. It is prohibited by many jurisdictions and also the scientific community seems to avoid it. Nevertheless, this paper examines the moral acceptability of blastomere transfer as a method to prevent mtDNA disorders. The reason for doing so is that most objections against reproductive cloning refer to reproductive adult cloning, while blastomere transfer would amount to reproductive embryo cloning. After clarifying this conceptual difference, this paper examines whether the main non-safety objections brought forward against reproductive cloning also apply in the context of blastomere transfer. The conclusion is that if this variant were to become safe and effective, dismissing it because it would involve reproductive cloning is unjustified. Nevertheless, as it may lead to more complex ethical appraisals than the other variants, researchers should initially focus on the development of the other types of nuclear transfer to prevent mtDNA disorders.

The prospect of using mitochondrial gene replacement to conceive children free of mitochondrial disease highlights the need for a sound ethical framework for reproductive genetic technology, say Annelien Bredenoord and Peter Braude

Despite extensive debate, there is no consensus on whether individual genetic data should be disclosed to research participants. The emergence of whole-genome sequencing methods is increasingly generating unequalled amounts of genetic data, making the need for a clear feedback policy even more urgent. In this debate two positions can be broadly discerned: a restrictive disclosure policy ('no feedback except life-saving data') and an intermediate policy of qualified disclosure ('feedback if the results meet certain conditions'). We explain both positions and present the principal underlying arguments. We suggest that the debate should no longer address whether genetic research results should be returned, but instead how best to make an appropriate selection and how to strike a balance between the possible benefits of disclosure and the harms of unduly hindering biomedical research.

In this second edition of Genetic Dilemmas: Reproductive Technology, Parental Choices, and Children's Futures, Dena Davis explores the scope and limits of parental reproductive autonomy. Reproductive autonomy is by many perceived as being one of the leading values in reproductive genetic technology. It is usually defined as the right to control one's own procreation unless good and sufficient reasons exist for denying a person that control. The rationale behind this principle is that in a liberal democratic society, the presumption is that people should be free to make their own choices according to their own values. Although most will accept this (negative) right to control one's own procreation, it is less clear whether this also implies a positive right to assistance to realize those reproductive rights and a correlating duty of the physician.Davis argues that parental decision making should be curbed when parental choices may infringe on the child's future autonomy. She conceptualizes the child's autonomy as, what Feinberg coined, “the child's right to an open future,” meaning a right to have one's future options kept open until one is capable of making one's own decisions. This implies that parents should not deliberately constrain the ability of their (future) children to make a wide variety of life choices when they are adults.With this framework, she explores and reviews the recent developments in reproductive and genetic technologies, ranging from genetic testing of minors, embryo selection, and sex selection to reproductive cloning. She consistently argues that a potential infringement of a child's right to an open future forms an appropriate threshold for allowing certain practices. According to Davis, sex selection for nonmedical reasons should, for example, be discouraged because if future parents have such a strong preference for a certain gender that they go through techniques such as sperm sorting and artificial insemination, they are likely to raise the child against the backdrop of strong gender-role expectations. This kind of gender stereotyping would threaten to violate the child's right to an open future.Another contentious issue extensively addressed by Davis regards the question to what extent parents may choose to have a deaf child, for example by means of IVF and preimplantation genetic diagnosis. This leads to an interesting review on the “disability debate,” including the question what disability actually is.For a European reader, the debate on whether reproductive genetics should be regulated remains an intriguing one, because the European and US approaches toward (non)regulation are very different. In the last decades, many European countries accepted laws governing issues such as embryo research, sex selection, and genetic testing. Some laws were updated last years, such as the UK Human Fertilisation and Embryology Bill—which is included in this second edition.This lucid and well-written book is accessible to a wide audience of readership—despite the fact that Davis does not avoid the philosophical conundrums inherent to the ethics of reproductive genetics. Particularly in the first part of the book, Davis frequently makes use of case examples. I would recommend this book to all people interested in the ethical complexities of parental and reproductive decision making, ranging from families and policymakers to genetic counselors and clinicians.

Although a scientific and ethical debate about the possible reproductive options for carriers of mitochondrial DNA (mtDNA) mutations is developing, not much information regarding the views and experiences of professionals exists. This paper explores the attitudes and experiences of professionals involved on a daily basis with their patients' reproductive decision-making in the context of mtDNA disease. Qualitative international multicenter design using in-depth semi-structured interviews with 20 professionals has been utilized. We identified four main themes emerging from the interviews. Firstly, we illustrate the discussion among professionals as to what extent mitochondrial genetics differs from other areas in genetics, both technically and ethically. Secondly, we show the discomfort and doubts of professionals when an mtDNA mutation is involved, because of the uncertainty remaining after testing. Thirdly, we discuss how professionals struggle with the tension between, on the one hand, the ideal of reproductive autonomy and, on the other hand, the reality of their professional responsibility and complex clinical decision-making. Fourthly, we delineate the strategies used by professionals in order to make attempts to control uncertainty. This paper illustrates the impact on professionals of reproductive decision-making in the context of mtDNA disease. It shows their feelings of discomfort when interpreting and explaining uncertain or ambiguous data and may be perceived as an example of how professionals deal with the inherent limitations in genetic knowledge representing the state of the art. Insight into the experiences of professionals may contribute to a further improvement of reproductive genetic counseling in the context of mtDNA disorders.

Although morally acceptable in theory, preimplantation genetic diagnosis (PGD) for mitochondrial DNA (mtDNA) disorders raises several ethical questions in clinical practice. This paper discusses the major conditions for good clinical practice. Our starting point is that PGD for mtDNA mutations should as far as possible be embedded in a scientific research protocol. For every clinical application of PGD for mtDNA disorders, it is not only important to avoid a 'high risk of serious harm' to the future child, but also to consider to what extent it would be possible, desirable and proportional to try to reduce the health risks and minimize harm. The first issue we discuss is oocyte sampling, which may point out whether PGD is feasible for a specific couple. The second issue is whether one blastomere represents the genetic composition of the embryo as a whole -- and how this could (or should) be investigated. The third issue regards the cutoff points below which embryos are considered to be eligible for transfer. We scrutinize how to determine these cutoff points and how to use these cutoff points in clinical practice -- for example, when parents ask to take more or less risks. The fourth issue regards the number of cycles that can (or should) justifiably be carried out to find the best possible embryo. Fifth, we discuss whether follow-up studies should be conducted, particularly the genetic testing of children born after IVF/PGD. Finally, we offer the main information that is required to obtain a truly informed consent.

BACKGROUND: Mitochondrial DNA (mtDNA) disorders are an important cause of human diseases. In view of the limitations of prenatal diagnosis and preimplantation genetic diagnoses, alternatives such as ooplasmic transfer (OT) and nuclear transfer (NT) have been proposed to prevent the transmission of mtDNA mutations. Both OT and NT are radical in the sense that they do not entail genetic selection, but genetic intervention to correct the genetic cause of the disease. METHODS: After interviews with experts in the field, the relevant literature was searched and analyzed. Bioethical issues were divided into conceptual and normative points. RESULTS: OT is the transfer of normal mitochondria to a carrier’s oocyte containing mutant mtDNA. In case of NT, a donated oocyte is enucleated and replaced with the nuclear DNA from a woman carrying a mtDNA mutation. NT can be performed both before and after in vitro fertilization, respectively, with the nucleus of an unfertilized oocyte, with the pronuclei of the zygote, or with the nucleus of a blastomere of an embryo. Conceptual questions regard whether these techniques amount to germ-line modification and human cloning. Normative questions concern, among others, the significance of intervening in the mtDNA, the implications of having ‘three genetic parents’, the ethics of oocyte donation and the health and safety risks for children conceived as a result of one of these techniques. CONCLUSIONS: Further interdisciplinary debate and research is needed to determine whether a clinical application of OT and NT can be morally justified, and if so, under which conditions.

We kindly appreciate the chance to reply to Waligora’s1 comments on what we call personalized assent. Assent understood from an engagement point of view does justice to the specifics of childhood. In practice, this can be translated into personalized assent, which means that both the process and the content of the assent procedure are dynamic and adjusted to the individual child and research context.2