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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]

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.

The Abolition of Man, written over 60 years ago by C. S. Lewis, focuses on the importance of objective values. In it, Lewis asserts that a person cannot be fully human without the existence of objective values. He explores the basis for objective values and imagines a scenario in which the pursuit of the control of human nature through scientific technology would by the nature of the project separate itself from objective values and lead to the abolition of man. However, what he imagines might happen by the hundredth century A.D. is beginning to be possible in the twenty first. Research on germline gene transmission in animals suggests that germline genetic modification capable of changing the future of the human genome may be possible in the near future. Germline genetic modification is the focus of an extensive ongoing ethical discussion. This includes issues of safety, justice, and the limitations of human subject research. A major focus in the discussion is the issue of whether germline genetic modification for enhancement is ethically distinct from that done for therapy or prevention and whether genetic enhancement of future generations should be allowed. An analysis of Lewis's thoughts in The Abolition of Man adds an insightful perspective to the contemporary discussion of whether human germline genetic enhancement should be permitted. [ABSTRACT FROM AUTHOR]