[3-parent embryo"] MYTH replacement therapy: MPs debate the science of mitochond

by Dr Ted Morrow

The regulatory path to clinical trials of mitochondrial replacement therapy (MRT) was recently debated in the House of Commons. MRT is under development in the UK as a way of potentially eliminating mitochondrial disease. The techniques essentially swap diseased mitochondria in the unfertilised or fertilised eggs of affected women for putatively healthy ones obtained from a donor. The outcome is unknown and evidence from animals suggest mismatching may occur between the nuclear DNA from the mother and the mitochondrial DNA (mtDNA) derived from the donor (1). The debate was called by a group of backbenchers that are unhappy about the pace with which the Government is apparently moving towards changing the regulations. The split in views in the chamber was fairly even.
 

From my perspective as a research scientist, what I found most interesting was how the science behind mitochondrial disease and MRT was discussed. Genetics is an extremely complex subject; while scientists are still unsure how genes and genomes cause disease and impact on our physical appearance and personality, there are clearly misconceptions about mitochondrial genetics repeated during the debate that are not supported by current scientific evidence.
 

For example, David Willets, the former minister for universities and science, who is widely respected within the scientific community, employed the much-used analogy that mitochondria are like batteries for the cell. He followed on to claim therefore that the DNA within 'does not affect identity'. It's true that mitochondria (the cellular subcomponent or organelle) are absolutely where energy is made available for all other cellular processes and so perhaps can be thought of as the cell's 'batteries'. But mtDNA is not a battery and the influence of genes in mtDNA on traits beyond battery-like function is well established (2).

Does mtDNA influence an individual's identity then? In its review, the Nuffield Council on Bioethics thought not, but the answer to this question depends on how you define identity (3). Genetic variation in the mitochondrial genome has been shown to influence a range of traits including cognition, fertility, ageing and lifespan (1); arguably these are indeed part of an individual's personal identity, they are certainly an important part of an individual's characteristics (consider, for example, contemporary ideas about masculinity).

Chi Onwurah supplemented this idea with actual numbers of genes involved: '13 out of 23,000' would be replaced (4). The numbers are approximately correct, but the mitochondrial genes are all essential – in contrast to many of the genes in the nuclear DNA. Consider for example the Y chromosome, which contains a couple of hundred genes, and yet half of the population do quite well without any of them (females). It is therefore a contradiction to claim that mtDNA is not important for an individual's characteristics (scientists call this the phenotype) while at the same time acknowledging that changes in the mitochondrial genetic code are important for an individual's risk of disease (again part of an individual's phenotype).

A second point of contention was whether MRT constituted a form of genetic modification (GM). This is a highly charged subject and there were several MP's that were adamant that it is not. The Department of Health's definition of GM is 'the germ-line modification of nuclear DNA (in the chromosomes)', thereby specifically excluding the mitochondrial genome. They do however state that MRT is a form of germ-line modification. This makes no sense logically or scientifically, since it is modification of the germ-line that is a key defining feature of genetic modification (also a point of confusion for the chief medical officer, Dame Sally Davies (5)). It has been argued that since the entire mitochondrial genome is replaced as a whole it does not constitute GM, but there will be differences between the sequences of the mtDNA removed and donated, and these will enter the germ-line.

How will accepting these points make a difference in the debate? First, if the general public and MPs understand that mtDNA does much more than just provide the genetic code for making more battery parts, then the idea of tinkering with the genetics of mitochondria may be a much less appealing prospect. Genetic modification is obviously a highly contentious proposal for the human germ-line. I can envisage scenarios where GM in humans could perhaps be justifiable (e.g. correcting point mutations) and ethical, but an informed debate on these issues, whether in Parliament or elsewhere, needs to start with the facts, and at the moment those facts do not seem to be filtering through.

SOURCES & REFERENCE

Dr. Ted Morrow is Senior Research Fellow, University of Sussex.
 

[Note:  Again, excellent and accurate scientific points critical to understanding this particular technique proposed for “3-parent embryos”.  Yes, the “human genome” is defined by ALL of the DNA in a human cell -- both the nuclear DNA and the mitochondrial DNA.  It is NOT defined merely in terms of the nuclear DNA (scientific references on request).  And therefore yes, the new “foreign” (donated) mitochondrial genes will become part of the genome of that a-sexually reproduced human embryo, and thus part of his/her “germ line” cells (oocytes or sperms).  Therefore, to use mitochondrial transfer would not just affect the individual human embryo thus a-sexually reproduced;  those new “foreign” mitochondrial genes will be passed down through that future adult’s generations -- along with any possible mutations and diseases caused by those new “foreign genes” -- which remain unknown.  I would also point out that “The” Human Genome Project --  which itself is a myth (scientific references on request) -- has still, after decades, only decoded about 15% of “the” human genome (which they define as ONLY NUCLEAR DNA) and the samples used were pooled from dozens of individuals from around the world, etc. --  thus how much do scientists really know about the genetic effects of this mitochondrial replacement technique on the individual human embryo a-sexually reproduced or on his/her future generations if they don’t know accurately what a human genetic code consists of?  Doesn’t take a rocket scientist ... The article first appeared here.  -- DNI]