Search

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

Abstract Background Recent studies have proved the role of autophagy in mesenchymal stem cell (MSCs) function and regenerative properties. How and by which mechanism autophagy modulation can affect the juxtacrine interaction of MSCs should be addressed. Here, the role of autophagy was investigated in the formation of tunneling nanotubes (TNTs) and homotypic mitochondrial donation. Methods MSCs were incubated with 15 µM Metformin (Met) and/or 3 µM 3-methyladenine (3-MA) for 48 h. The formation of TNTs was assessed using bright-field and SEM images. The mitochondria density and ΔΨ values were monitored using flow cytometry analysis. Using RT-PCR and protein array, the close interaction and shared mediators between autophagy, apoptosis, and Wnt signaling pathways were also monitored. The total fatty acid profile was assessed using gas chromatography. Result Data indicated the increase of TNT length and number, along with other cell projections after the induction of autophagy while these features were blunted in 3-MA-treated MSCs (p 0.05). We found that the inhibition/stimulation of autophagy can affect the protein, and transcription levels of several mediators related to Wnt and apoptosis signaling pathways involved in different cell bioactivities. Data confirmed the profound increase of mono and polyunsaturated/saturated fatty acid ratio in MSCs exposed to autophagy stimulator. Conclusions In summary, autophagy modulation could affect TNT formation which is required for homotypic mitochondrial donation. Thus, the modulation of autophagy creates a promising perspective to increase the efficiency of cell-based therapies.

Background: Recent studies have proved the role of autophagy in mesenchymal stem cell (MSCs) function and regenerative properties. How and by which mechanism autophagy modulation can affect the juxtacrine interaction of MSCs should be addressed. Here, the role of autophagy was investigated in the formation of tunneling nanotubes (TNTs) and homotypic mitochondrial donation. Methods: MSCs were incubated with 15 µM Metformin (Met) and/or 3 µM 3-methyladenine (3-MA) for 48 h. The formation of TNTs was assessed using bright-field and SEM images. The mitochondria density and ΔΨ values were monitored using flow cytometry analysis. Using RT-PCR and protein array, the close interaction and shared mediators between autophagy, apoptosis, and Wnt signaling pathways were also monitored. The total fatty acid profile was assessed using gas chromatography. Result: Data indicated the increase of TNT length and number, along with other cell projections after the induction of autophagy while these features were blunted in 3-MA-treated MSCs (p < 0.05). Western blotting revealed the significant reduction of Rab8 and p-FAK in 3-MA-treated MSCs (p < 0.05), indicating the inhibition of TNT assembly and vesicle transport. Likewise, the stimulation of autophagy increased autophagic flux and mitochondrial membrane integrity compared to 3-MA-treated MSCs. Despite these findings, protein levels of mitochondrial membrane Miro1 and 2 were unchanged after autophagy inhibition/stimulation (p > 0.05). We found that the inhibition/stimulation of autophagy can affect the protein, and transcription levels of several mediators related to Wnt and apoptosis signaling pathways involved in different cell bioactivities. Data confirmed the profound increase of mono and polyunsaturated/saturated fatty acid ratio in MSCs exposed to autophagy stimulator. Conclusions: In summary, autophagy modulation could affect TNT formation which is required for homotypic mitochondrial donation. Thus, the modulation of autophagy creates a promising perspective to increase the efficiency of cell-based therapies. [ABSTRACT FROM AUTHOR]

In this article, we explore the legalisation of mitochondrial donation in the UK as the latest iteration of an established sociotechnical imaginary of permissive yet highly scrutinised human embryo research in the country. The focus of our analysis is the work of the UK House of Commons Science and Technology Select Committee as it contributed to the debates and ultimately played a role in enabling the UK to become the first country in the world to legalise clinical use. Mitochondrial donation is a reproductive technology which could allow women with mitochondrial disease to have healthy, genetically related children. From 2011, an extensive process of inquiry was launched in the UK to assess safety, ethics and public attitudes. We analyse video and transcripts of the meeting, and interviews with panellists to explore three themes: contesting scientific interpretation, the labour of alignment and resolution. We demonstrate how micro-interactions during the meeting, and the broader structure of the meeting itself, aligned with the UK sociotechnical imaginary of a permissive but scrutinising approach to human embryo regulation. We conclude that the event was one element of a larger process of review that together worked to render mitochondrial donation as knowable, ethical, desirable and sanctionable. [ABSTRACT FROM AUTHOR]

Changes to Australian law in 2022 made Australia the second country to expressly permit the clinical use of mitochondrial donation (MD), a technology that makes heritable changes to the human genome. This paper considers these changes in the context of Australia's broader controls on human embryo use to provide insights into future regulatory responses to other emerging genetic technologies, which could be used in reproduction. [ABSTRACT FROM AUTHOR]

Mitochondrial donation is an assisted reproductive technology used to minimize the risk of transmitting serious mitochondrial diseases from mother to child. The aim of this research is to examine the Australian legal landscape regarding mitochondrial donation. This research uses a literature review research method. The data collection technique in this research is literature study. The data that has been collected is then analyzed in three stages, namely data reduction, data presentation and drawing conclusions. The results show that Western Australian legislation (external site) currently prohibits the use of embryos containing the genetic material of more than two people, and this is one of the reasons why mitochondrial donation is not currently legal in Western Australia. In 2021, following a Senate Committee Review and Community Consultation, the Commonwealth Government introduced the Mitochondrial Donation Law Reform Bill (Maeve's Law) (2021) which proposes a phased approach to amending Commonwealth laws that currently make mitochondrial donation illegal. The bill was passed on 30 March 2022. Assisted reproductive technology legislation is under review in Western Australia and the Western Australian Government has committed to engaging in national consultation on new technologies, including mitochondrial donation. [ABSTRACT FROM AUTHOR]

Recently, Australia became the second jurisdiction worldwide to legalize the use of mitochondrial donation technology. The Mitochondrial Donation Law Reform (Maeve's Law) Bill 2021 allows individuals with a family history of mitochondrial disease to access assisted reproductive techniques that prevent the inheritance of mitochondrial disease. Using inductive content analysis, we assessed submissions sent to the Senate Committee as part of a programme of scientific inquiry and public consultation that informed drafting of the Bill. These submissions discussed a range of bioethical and legal considerations of central importance to the political debate. Significantly, submissions from those with a first-hand experience of mitochondrial disease, including clinicians and those with a family history of mitochondrial disease, were in strong support of this legislation. Those in support of the Bill commended the two-staged approach and rigorous licencing requirements as part of the Bill's implementation strategy. Submissions which outlined arguments against the legislation either opposed the use of these techniques in general or opposed aspects of the implementation strategy in Australia. These findings offer a window into the ethical arguments and perspectives that matter most to those Australians who took part in the Senate inquiry into mitochondrial donation. The insights garnered from these submissions may be used to help refine policy and guidelines as the field progresses. [ABSTRACT FROM AUTHOR]

Angiogenesis is a complex process that involves the expansion of the pre‐existing vascular plexus to enhance oxygen and nutrient delivery and is stimulated by various factors, including hypoxia. Since the process of angiogenesis requires a lot of energy, mitochondria play an important role in regulating and promoting this phenomenon. Besides their roles as an oxidative metabolism base, mitochondria are potential bioenergetics organelles to maintain cellular homeostasis via sensing alteration in oxygen levels. Under hypoxic conditions, mitochondria can regulate angiogenesis through different factors. It has been indicated that unidirectional and bidirectional exchange of mitochondria or their related byproducts between the cells is orchestrated via different intercellular mechanisms such as tunneling nanotubes, extracellular vesicles, and gap junctions to maintain the cell homeostasis. Even though, the transfer of mitochondria is one possible mechanism by which cells can promote and regulate the process of angiogenesis under reperfusion/ischemia injury. Despite the existence of a close relationship between mitochondrial donation and angiogenic response in different cell types, the precise molecular mechanisms associated with this phenomenon remain unclear. Here, we aimed to highlight the possible role of mitochondria concerning angiogenesis, especially the role of mitochondrial transport and the possible relation of this transfer with autophagy, the housekeeping phenomenon of cells, and angiogenesis. [ABSTRACT FROM AUTHOR]

Changes to Australian law in 2022 made Australia the second country to expressly permit the clinical use of mitochondrial donation (MD), a technology that makes heritable changes to the human genome. This paper considers these changes in the context of Australia’s broader controls on human embryo use to provide insights into future regulatory responses to other emerging genetic technologies, which could be used in reproduction.

Summary: According to the World Health Organization, the female reproductive age lasts up to 49 years, but problems with the realization of women's reproductive rights may arise much earlier. Significant numbers of factors affect the state of reproductive health: socioeconomic, ecological, lifestyle features, the level of medical literacy, and the state of the organization and medical care quality. Among the reasons for fertility decline in advanced reproductive age are the loss of cellular receptors for gonadotropins, an increase in the threshold of sensitivity of the hypothalamic-pituitary system to the action of hormones and their metabolites, and many others. Furthermore, negative changes accumulate in the oocyte genome, reducing the possibility of fertilization, normal development and implantation of the embryo and healthy offspring birth. Another theory of ageing causing changes in oocytes is the mitochondrial free radical theory of ageing. Taking into account all these age-related changes in gametogenesis, this review considers modern technologies aimed at the preservation and realization of female fertility. Among the existing approaches, two main ones can be distinguished: methods allowing the preservation of reproductive cells at a younger age using ART intervention and cryobanking, as well as methods aimed at improving the basic functional state of advanced-age women's oocytes and embryos. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Heritable human genome editing is a form of modification of the human genome that will be inherited by progeny of the person whose DNA has been edited. Editing human genomes in ways that are heritable is currently prohibited in many countries throughout the world, including in Australia. This section starts with an examination of the historical backdrop to Australia's current laws relating to heritable human genome editing, with particular focus on how technological advances and community responses have shaped our legislative environment for innovative artificial reproductive technologies. The section then examines how community responses to current developments in heritable human genome editing might shape future law reform. The aim is to provide a foundation for examining how the future regulatory environment for heritable human genome editing in Australia might be shaped in ways that are responsive both to technological developments and to contemporary ethical norms and social values. [ABSTRACT FROM AUTHOR]

Ovarian cancer is characterized by early metastatic spread. This study demonstrates that carcinoma-associated mesenchymal stromal cells (CA-MSCs) enhance metastasis by increasing tumor cell heterogeneity through mitochondrial donation. CA-MSC mitochondrial donation preferentially occurs in ovarian cancer cells with low levels of mitochondria ("mito poor"). CA-MSC mitochondrial donation rescues the phenotype of mito poor cells, restoring their proliferative capacity, resistance to chemotherapy, and cellular respiration. Receipt of CA-MSC-derived mitochondria induces tumor cell transcriptional changes leading to the secretion of ANGPTL3, which enhances the proliferation of tumor cells without CA-MSC mitochondria, thus amplifying the impact of mitochondrial transfer. Donated CA-MSC mitochondrial DNA persisted in recipient tumor cells for at least 14 days. CA-MSC mitochondrial donation occurs in vivo , enhancing tumor cell heterogeneity and decreasing mouse survival. Collectively, this work identifies CA-MSC mitochondrial transfer as a critical mediator of ovarian cancer cell survival, heterogeneity, and metastasis and presents a unique therapeutic target in ovarian cancer. [Display omitted] • CA-MSCs donate mitochondria to ovarian cancer cells with low endogenous mitochondria • Mitochondrial donation enhances cancer cell proliferation, chemoresistance, and OXPHOS • Donated mito-to-nuclear signaling drives ANGPTL3 secretion, which increases tumor cell growth • Mito donation enhances metastasis and clonal heterogeneity in vivo Frisbie et al. demonstrate that stromal-to-tumor cell mitochondrial transfer drives ovarian cancer metastasis and clonal heterogeneity. Carcinoma-associated mesenchymal stem cells donate mitochondria to vulnerable tumor cells, enhancing tumor cell proliferation, chemoresistance, and respiratory capacity and triggering ANGPTL3 secretion to further promote tumor growth. These findings offer a potential therapeutic target for ovarian cancer. [ABSTRACT FROM AUTHOR]

There seems to be a consensus that enucleated oocyte donation (EOD) should only be used to reduce the risk of having a child with mitochondrial disorders. However, this paper argues that in the initial phase in which we are at the moment, EOD should first be used to remedy infertility caused by poor oocyte quality or poor embryonic development. That learning period will allow researchers to improve their technical skills and the knowledge of the best procedure before starting on high-risk cases. Mitochondrial carryover of pathologic mtDNA is the main cause of concern for the offspring. That risk does not exist in infertility cases. The application of EOD to treat infertility should at present be performed in a clinical research setting to obtain more evidence about efficacy and safety. [ABSTRACT FROM AUTHOR]

Mitochondrial DNA (mtDNA), as its name implies, is an embodiment of the mitochondrial genetic information that constitutes about 1% of the mammalian genome. It fills a vital niche in tracing matrilineality; the mtDNA is inherited solely from the mother and plays a crucial role in genealogical research. Even a single mutation in the mtDNA can have debilitating and life-altering consequences. Mothers carrying mtDNA mutations will inevitably pass it on to the future generation. Three-parent In vitro fertilization (IVF), a breakthrough technique, shows promising potential to prevent mothers with mtDNA defects from passing it on to their future generation, while also maintaining the genetic link to their posterity. In this review, I delve into the intricacies of this technique, compare and analyze the difference between maternal spindle transfer and pronuclear transfer, discuss the prospective therapeutic effects, and highlight the ethical concerns surrounding this procedure. Considering the various challenges and ethics of this contentious technique, the paper seeks to answer the rousing question – Is three-parent IVF the answer to preventing mitochondrial defects?

The aim of this study was to evaluate if cytoplasmic transfer can improve fertilization and embryo quality of women with oocytes of low quality. During ICSI, 10–15% of the cytoplasm from a fresh or frozen young donor oocyte was added to the recipient oocyte. According to the embryo quality, we defined group A as patients in which the best embryo was evident after cytoplasmic transfer and group B as patients in which the best embryo was evident after a simple ICSI. We investigated in the period of 2002–2018, 125 in vitro fertilization cycles involving 1011 fertilized oocytes. Five hundred fifty-seven sibling oocytes were fertilized using ICSI only and 454 oocytes with cytoplasmic transfer. Fertilization rates of oocytes were 67.2% in the cytoplasmic transfer and 53.5% in the ICSI groups (P < 0.001). A reduction in fertilization rate was observed with increased women age in the ICSI but not in the cytoplasmic transfer groups. The best embryo quality was found after cytoplasmic transfer in 78 cycles (62.4%) and without cytoplasmic transfer in 40 cycles (32%, P < 0.001). No significant differences were detected between the age, hormonal levels, dose of stimulation drugs, number of transferred embryos, pregnancy rate and abortion rate between A and B groups. Cytoplasmic transfer improves fertilization rates and early embryo development in humans with low oocyte quality. All 28 children resulting from cytoplasmic transfer are healthy. [ABSTRACT FROM AUTHOR]

Since mitochondrial replacement techniques (MRT) were developed and clinically introduced in the United Kingdom (UK), there has been much discussion of whether these lead to children borne of three parents. In the UK, the regulation of MRT has dealt with this by stipulating that egg donors for the purposes of MRT are not genetic parents even though they contribute mitochondrial DNA (mtDNA) to offspring. In this paper, I examine the way that the Human Fertilisation and Embryology Act in the UK manages the question of parentage. I argue that the Act breaks the link typically made between genetic causation and genetic parenthood by redefining genetic causation solely in terms of nuclear genetics. Along with this, mtDNA is construed as a kind of supplement to the nuclear family. Drawing on the account of the supplement developed by Jacques Derrida, I argue that mtDNA and the women who donate it are seen as both essential to establishing the nuclear family but also exterior to and insignificant for it. [ABSTRACT FROM AUTHOR]

The article offers Parliamentary news brifs from Australia and discusses the Mitochondrial Donation Law Reform (Maeve's Law) Bill 2021 that amends Prohibition of Human Cloning for Reproduction Act 2002 and Freedom of Information Act 1982 and Prohibition of Human Cloning for Reproduction Act 2002. It offers views of several legislators including Julian Leeser, Kevin Andrews, and Matthew Canavan on the bill.

Mitochondrial DNA (mtDNA), as its name implies, is an embodiment of the mitochondrial genetic information that constitutes about 1% of the mammalian genome. It fills a vital niche in tracing matrilineality; the mtDNA is inherited solely from the mother and plays a crucial role in genealogical research. Even a single mutation in the mtDNA can have debilitating and life-altering consequences. Mothers carrying mtDNA mutations will inevitably pass it on to the future generation. Three-parent In vitro fertilization (IVF), a breakthrough technique, shows promising potential to prevent mothers with mtDNA defects from passing it on to their future generation, while also maintaining the genetic link to their posterity. In this review, I delve into the intricacies of this technique, compare and analyze the difference between maternal spindle transfer and pronuclear transfer, discuss the prospective therapeutic effects, and highlight the ethical concerns surrounding this procedure. Considering the various challenges and ethics of this contentious technique, the paper seeks to answer the rousing question - Is three-parent IVF the answer to preventing mitochondrial defects?. [ABSTRACT FROM AUTHOR]

Mitochondrial disorders manifest enormous genetic and clinical heterogeneity - they can appear at any age, present with various phenotypes affecting any organ, and display any mode of inheritance. What mitochondrial diseases do have in common, is impairment of respiratory chain activity, which is responsible for more than 90 % of energy production within cells. While diagnostics of mitochondrial disorders has been accelerated by introducing Next-Generation Sequencing techniques in recent years, the treatment options are still very limited. For many patients only a supportive or symptomatic therapy is available at the moment. However, decades of basic and preclinical research have uncovered potential target points and numerous compounds or interventions are now subjects of clinical trials. In this review, we focus on current and emerging therapeutic approaches towards the treatment of mitochondrial disorders. We focus on small compounds, metabolic interference, such as endurance training or ketogenic diet and also on genomic approaches. [ABSTRACT FROM AUTHOR]

Human oocytes have an abundance of mitochondria that have their own genome. Mitochondrial functions are exerted through evolutionarily-developed interactions between the nucleus and mitochondria. Since 1996, fertility clinics have practiced various types of germline mitochondrial DNA (mtDNA) modification that alter the composition of mtDNA copies in oocytes or zygotes using micromanipulation. Experimental reproductive medicine has primarily intended to treat intractable infertility and has been used to prevent the maternal transmission of a pathogenic mtDNA mutation to offspring. In some cases, it has helped parents have a healthy genetically-related child; in others, it has resulted in miscarriages, aneuploid fetuses, or developmental disorders in the offspring. Adverse events have raised ethical controversy, leading to restrictive or prohibitive policies in the USA and China. Conversely, the UK recently became the first nation to explicitly permit two types of germline mtDNA modification (termed mitochondrial donation) for the sole purpose of preventing serious mitochondrial disease in offspring. The aim of this review is three-fold: first, to reshape the medical concept and evolution of germline mtDNA modification, while revisiting 14 clinical cases. Second, to analyse the legality of mtDNA modification, focussing on 16 Western countries. Finally, to consider the ethical aspects, including permissible cases, reproductive options, use of preimplantation and prenatal testing, and the humane follow-up of resultant children. The clinical use of germline mtDNA modification will likely become legal, at least for use in preventative medicine, in some countries. However, the potential clinical, ethical, and evolutionary implications mean that caution is required when considering its wider application.

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. [ABSTRACT FROM AUTHOR]

The article describes the developing technologies for the production of «designer embryos» also known as genetically improved babies. The authors briefly review these technologies with a special emphasis on their medical, legal and bioethical aspects. We propose and substantiate the point of view why some of these approaches may be illegal.

Reproductive rights in South Africa have traditionally focused on the rights of individuals to avoid reproduction. However, with an increase in the use of assisted reproductive technologies (ART), there has been a shift in the focus on reproductive rights from the rights of individuals to avoid reproduction to the rights of individuals to reproduce noncoitally. With the emergence of new technologies, reproduction by noncoital means and the right to engage in these new technologies is becoming more prevalent. This raises two questions. The first question is whether such a right exists. The recent Constitutional Court decision in AB v Minister of Social Development 2017 3 BCLR 267 (CC) suggests that it does, but only if the person claiming this right is physically involved in the reproductive process. Ostensibly this excludes those who cannot contribute to the reproduction of a child. The second question raised pertains to the impact of this right on specific forms of ART, namely mitochondrial transfer, posthumous reproduction and embryo donation. While the first two forms of ART would meet the criteria set down in AB, embryo donation would not. Individuals denied access to embryo donation could thus not rely on either the right to reproductive autonomy or the right to privacy to aid them. Fortunately the existing legal framework provides some assistance to these individuals, although sadly the same legislative framework does not support the use of mitochondrial transfer and posthumous reproduction. In this respect there is incongruence between rights and legislation, which has only been exacerbated by the recent Constitutional Court decision. What is thus needed is clarity on the meaning of certain rights in respect of certain forms of ART as well as legislative reform to reflect the clarified position.

Conferences are important performative sites. Here we detail a UK science policy conference debating the novel biomedical techniques CRISPR/cas9 and mitochondrial donation. Both techniques have received significant attention from scientists and bioethicists about their clinical potential, social implications, and the prospects of genetic and germline modification. In many countries the policy debates on regulating both technologies is ongoing and operating in tandem. The UK, however, is operating in a distinct policy context in that mitochondrial donation was formally legalized under license in 2015, meaning the British CRISPR/cas9 debates occur in the light of a confirmed policy position on mitochondrial donation. Our analysis of the Progress Educational Trust 2015 annual conference ‘From Three-Person IVF to Genome Editing’ argues that this event conducted important staging work in articulating the relationship between these two technologies in the UK. These efforts constitute what we call a ‘transition performance’ that (i) enacted the successful resolution of the mitochondrial donation policy debate, (ii) performed the success of British biomedical politics, and (iii) opened the space for a public debate on CRISPR/cas9 in line with a specifically configured set of legitimacy practices. Subsequently the conference contrasts to many other conferences that fit what we term a ‘continuity performance’ that seek to assert consistency and progress through iteration. We close by articulating further applications and developments of these notions in Science and Technology Studies.

Study Question: Does an informed group of citizens endorse the clinical use of mitochondrial donation in a country where this is not currently permitted?Summary Answer: After hearing balanced expert evidence and having opportunity for deliberation, a majority (11/14) of participants in a citizens' jury believed that children should be able to be born using mitochondrial donation.What Is Known Already: Research suggests that patients, oocyte donors and health professionals support mitochondrial donation to prevent transmission of mitochondrial disease. Less is known about public acceptability of this novel reproductive technology, especially from evidence using deliberative methods.Study Design, Size, Duration: This study comprised a citizens' jury, an established method for determining the views of a well-informed group of community members. The jury had 14 participants, and ran over one and a half days in 2017.Participants/materials, Setting, Methods: Jurors were members of the public with no experience of mitochondrial disease. They heard and engaged with relevant evidence and were asked to answer the question: 'Should Australia allow children to be born following mitochondrial donation?'Main Results and the Role Of Chance: Eleven jurors decided that Australia should allow children to be born following mitochondrial donation; 7 of whom added conditions such as the need to limit who can access the intervention. Three jurors decided that children should not (or not yet) be born using this intervention. All jurors were particularly interested in the reliability of evidence, licensing/regulatory mechanisms and the rights of children to access information about their oocyte donors.Limitations, Reasons For Caution: Jurors' views were well informed and reflected critical deliberation and discussion, but are not intended to be representative of the whole population.Wider Implications Of the Findings: When presented with high quality evidence, combined with opportunities to undertake structured deliberation of novel reproductive technologies, members of the public are able to engage in detailed discussions. This is the first study to use an established deliberative method to gauge public views towards mitochondrial donation.Study Funding/competing Interest(s): This study was funded by a University of Sydney Industry and Community Collaboration Seed Award (2017), which was awarded contingent on additional funding from the Mito Foundation. Additional funding was provided by the Mito Foundation. The Foundation was not involved in jury facilitation or deliberation, nor analysis of research data.Trial Registration Number: Not applicable. [ABSTRACT FROM AUTHOR]

Mmt is a framework for designing and implementing formal systems in a way that systematically abstracts from theoretical and practical aspects of their type of theoretical and logical foundations. Thus, definitions, theorems, and algorithms can be stated independently of the foundation, and language designers can focus on the essentials of a particular foundation and inherit a large-scale implementation from Mmt at low cost. Going beyond the similarly motivated approach of meta-logical frameworks, Mmt does not even commit to a particular meta-logic—that makes Mmt level results harder to obtain but also more general. We present one such result: a type reconstruction algorithm that realizes the foundation-independent aspects generically relative to a set of rules that supply the foundation-specific knowledge. Maybe surprisingly, we see that the former covers most of the algorithm, including the most difficult details. Thus, we can easily instantiate our algorithm with rule sets for several important language features including, e.g., dependent function types. Moreover, our design is modular such that we obtain a type reconstruction algorithm for any combination of these features. [ABSTRACT FROM AUTHOR]

Background The first live birth following the use of a new reproductive technique, maternal spindle transfer (MST), which is a mitochondrial replacement technique (MRT), was accomplished by dividing the execution of the MST procedure between two countries, the USA and Mexico. This was done in order to avoid US legal restrictions on this technique. Sources of data Academic articles, news articles, documents obtained through freedom of information requests, laws, regulations and national reports. Areas of agreement MRTs are new reproductive techniques that present novel ethical and legal challenges, since genetic material from three people is employed to create a child. Areas of controversy Could the first MST procedure that culminated in a live birth negatively impact reproductive medicine in Mexico? Growing points The USA and Mexico need specific and clear legislation on MRTs, in order for such techniques not to be governed by prior existing legislation on assisted reproduction that is inadequate for dealing with the new challenges that these techniques present. Areas timely for developing research There is a pressing need for work to be done on the international governance of new reproductive techniques. [ABSTRACT FROM AUTHOR]

Background: Mitochondrial DNA (mtDNA) diseases are a group of maternally inherited genetic disorders caused by a lack of energy production. Currently, mtDNA diseases have a poor prognosis and no known cure. The chance to have unaffected offspring with a genetic link is important for the affected families, and mitochondrial replacement techniques (MRTs) allow them to do so. MRTs consist of transferring the nuclear DNA from an oocyte with pathogenic mtDNA to an enucleated donor oocyte without pathogenic mtDNA. This paper aims to determine the efficacy, associated risks, and main ethical and legal issues related to MRTs. Methods: A bibliographic review was performed on the MEDLINE and Web of Science databases, along with searches for related clinical trials and news. Results: A total of 48 publications were included for review. Five MRT procedures were identified and their efficacy was compared. Three main risks associated with MRTs were discussed, and the ethical views and legal position of MRTs were reviewed. Conclusions: MRTs are an effective approach to minimizing the risk of transmitting mtDNA diseases, but they do not remove it entirely. Global legal regulation of MRTs is required.

ARGUMENTATION STRATEGIES IN THE DEBATE ON MITOCHONDRIAL DONATION Bioethical aspects of mitochondrial donation have recently become one of the most debated issues. The growing interest in the philosophical and bioethical problems it generates has become even more visible since mitochondrial donation was legally allowed in Great Britain in 2015. In this paper we will take a closer look at the arguments employed in the debate, such as 1) argument from uncertainty closely connected with an obligation to use safe and already known alternative medical procedures; 2) the threat of losing personal identity; 3) the fear of creating a child of three parents; 4) detrimental outcome of manipulation in the human germ line. We will analyze the arguments showing that they are in fact the result of the lack of precision in employing medical terminology, the simplification of argumentation or the manifestation of ‘status quo bias’.

Abstract: The Institute of Medicine has recently endorsed arguments put forward by John Appleby calling for mandatory sex selection against female offspring in the initial trials of mitochondrial replacement techniques. In this paper I argue that, despite this endorsement, the reasons offered by Appleby for mandatory sex selection are inadequate. I further argue that plausible revisions to Appleby's arguments still fail to convincingly defend such an intrusive policy. While I remain neutral about whether intending parents making use of mitochondrial replacement techniques ought to have access to sex selection, I conclude that to date the case for mandatory sex selection has not been satisfactorily made. [ABSTRACT FROM AUTHOR]

Mitochondrial Replacement Therapy is an ethically controversial procedure that allows women with genetically transmitted mutations in their mitochondria to have healthy children. Using this procedure, healthy mitochondria from a third party can be donated in the fertilization process to create a healthy child from three genetic "parents". There is much concern about the safety and ethics of this procedure and presenting the Catholic and Jewish perspectives of Mitochondrial Replacement Therapy can offer insights into the morally complexity of the ethical issues surrounding this innovative medical procedure. [ABSTRACT FROM AUTHOR]

In 2015, the UK was the first country to legalize the mitochondrial donation and replacement procedure, which allows three-parent in vitro fertilization, and results in three-parent embryos. In March 2017, the UK Human Fertilisation and Embryology Authority issued its first licence for the mitochondrial donation and replacement procedure to the Newcastle Fertility Centre under the Human Fertilisation and Embryology (Mitochondrial Donation) Regulations 2015/572. This article focuses on one fundamental ethical and a legal challenge that this legislation overlooks: the right of the conceived children to know and trace their genetic origins. The article argues that this is a natural and basic human right, which is guaranteed by legal documents in the UK and internationally, and is also morally justified. The Human Fertilisation and Embryology (Mitochondrial Donation) Regulations 2015/572 discriminate against three-parent persons by negating their right to know and trace their genetic origins. The article concludes with a justification for the specific amendment of the regulations so as to remedy the said unjust discrimination and violation of the natural and basic right to know and trace one's genetic origins. [ABSTRACT FROM AUTHOR]