Mitochondrial transfer: Ethical, legal and social implications in assisted reproduction

Three to one – an ethicolegal outline of mitochondrial donation in the South African context

“…In the case of mitochondrial donation, it could be argued that the manipulation of genetic material is aimed at ultimately achieving the reproduction of a human being, and could also fall within the objectives of 'therapeutic purpose' (i.e., healing mitochondrial disease) as per the definition of therapeutic cloning. While the science indicates that maternal spindle transfer and pronuclear transfer (the two most promising types of nuclear transfer to prevent mitochondrial disorders) do not amount to reproductive cloning, [8,9] the current ambiguous definition of reproductive cloning in the NHA does little to provide solid clarity regarding what is and what is not legally permitted. It is further prudent to distinguish reproductive adult cloning from reproductive embryo cloning.…”

“…It is further prudent to distinguish reproductive adult cloning from reproductive embryo cloning. According to Reznichenko et al: [9] 'Adult cloning involves the transfer of adult (diploid) nuclear material into an enucleated oocyte. In contrast, the cell to be transferred in embryo cloning originates from an embryo.…”

“…Several ethical questions have been raised and flagged as concerns in the past regarding mitochondrial donation [1,4,9,10] The following discussion includes a few key points that require further analysis, specific to the SA context.…”

“…[14] As a result, these techniques introduced the 'three-parent embryos' , 'three-parent babies' and 'three-person IVF' debate, with the implication that the children born from the use of these techniques may suffer from psychosocial problems as a result of having more than two parents. [10] However, if the child only inherits mitochondrial DNA from the donor (<30 genes) and all its nuclear DNA (>20 000 genes) from the intending parents, [9] it could be argued that the 'three' terminology is merely used to garner public interest and excitement and spur controversy, at the expense of accuracy. Similarly, debates around mitochondrial donation in the UK, prior to its legalisation, regularly drew upon figurative and emotive language.…”

Could we offer mitochondrial donation or similar assisted reproductive technology to South African patients with mitochondrial DNA disease?

“…[3] In both these scenarios, the offspring inherit their nuclear DNA (nDNA) from the gametes contributed by both parents but their mtDNA from another female (donor), introducing the threeparent scenario that has sparked controversy and debate. [4,5] Mitochondrial DNA has several properties that distinguish it from nDNA: it is strictly maternally inherited and does not undergo recombination; it is not wrapped around histone proteins for protection, and is consequently exposed to high levels of mutationgenerating free radicals; and there are many copies per cell, ranging from two up to several thousand. In addition, the mutation rate in mtDNA is about 10 times greater than in nDNA, and replication errors are less likely to be repaired.…”