Ethical and legal issues in mitochondrial transfer

Abstract

The US National Academies of Science, Engineering and Medicine recently provided conditional endorsement for mitochondrial transfer. While its approach is more conservative in some respects than that of the United Kingdom (which passed its own regulations in 2015), it marks a significant policy development for a potentially large implementer of this emerging intervention. In this perspective, we consider some of the ethical and legal aspects of these policy responses.

Mitochondrial DNA Replacement Techniques to Prevent Human Mitochondrial Diseases

“…However, the term “germinal gene therapy” is usually used to define changes in nuclear genome, not in mitochondrial DNA [ 23 , 55 ]. The authors in favor of MRTs allege that nuclear transfers are “inheritable modifications” but not an intervention in the germline, since they do not affect the nuclear DNA (which contains the information that determines the characteristics of an individual) [ 9 , 54 , 55 , 56 ]. In addition, they argue that mtDNA constitutes a tiny part of the total cell genome (0.1%).…”

Treatment strategies for Leber hereditary optic neuropathy

“…The term "three-parent embryo" is frequently used in the lay press as the mitochondrial genome of the resulting embryo is derived from the donor egg whereas the nuclear genome is inherited from the biological parents. In 2015, mitochondrial replacement therapy was approved by both Houses of Parliament in the United Kingdom as a justifiable reproductive option with the caveat that it should only be carried out in a recognised centre of excellence and with longterm follow-up of the children born using this approach [45]. In contrast, the US Food and Drug Administration (FDA) has concluded that more experimental and safety data are needed before advocating mitochondrial replacement therapy as reproductive option for mitochondrial disease [33,45].…”

“…In 2015, mitochondrial replacement therapy was approved by both Houses of Parliament in the United Kingdom as a justifiable reproductive option with the caveat that it should only be carried out in a recognised centre of excellence and with longterm follow-up of the children born using this approach [45]. In contrast, the US Food and Drug Administration (FDA) has concluded that more experimental and safety data are needed before advocating mitochondrial replacement therapy as reproductive option for mitochondrial disease [33,45]. As the legal and ethical implications of mitochondrial donation was being openly debated, the media reported that maternal spindle transfer had resulted in the birth of a healthy baby boy who carried low levels of the m.8993T>G mtDNA mutation in MTAP6 that had resulted in the premature death of two siblings from Leigh syndrome [46  ].…”

“…As the legal and ethical implications of mitochondrial donation was being openly debated, the media reported that maternal spindle transfer had resulted in the birth of a healthy baby boy who carried low levels of the m.8993T>G mtDNA mutation in MTAP6 that had resulted in the premature death of two siblings from Leigh syndrome [46  ]. Mitochondrial replacement therapy remains controversial and both the regulatory framework and the consequences of modifying the germline need to be carefully considered [45].…”

The right to know one’s genetic origins and cross-border medically assisted reproduction

“…Arguments in favor of such a right to know highlight the fact that the role mitochondrial DNA (mtDNA) plays in development is still uncertain and that there may be “a precautionary case for granting a right to know: just in case it turns out that mtDNA has a greater role biologically than we thought; or just in case it turns out that MT‐conceived children have a strong desire to know who their donor was” [22]. I argue that in the absence of robust longitudinal data regarding the consequences of mitochondrial replacement, it is in the medical and psycho-social best interest of those conceived to have access to information regarding their mitochondria provider, as in the case of egg provision.…”