Despite recent claims in New Scientist, there is no evidence mitochondrial replacement is unsafe, says an adviser to the UK government on this topic
The UK government will shortly submit regulations on mitochondrial replacement to Parliament for debate and a vote on whether the techniques can be used in the clinic. Their goal is to avoid children being born with serious diseases due to mutations in mitochondrial DNA (mtDNA) carried by their mothers.
For the past four years I have been a member of the panel that has provided independent advice to the government on this topic. It is our considered view that the techniques are not unsafe and are likely to be effective. As long as these views are not contradicted by further research currently under way, they should be made available.
However, a recent article in New Scientist on some of the properties of mitochondria, together with an accompanying leader, claimed that "we may have seriously underestimated the influence that mitochondria have" and that "recent research suggests that they play a key role in some of the most important features of human life", and are not just simply the cell's power plants.
The leader concludes by saying that the "emerging science and the issues it raises have not had a proper airing" and "need to be brought to parliament's attention, debated and settled before a decision is made".
I was rather taken aback by this, given our almost four years of work exploring all the issues relating to the science, safety, efficacy and ethics, and to conduct an informed public debate in the UK.
Amazing biology
"We" are fully aware of the amazing biology in which mitochondria are involved in addition to their main function of generating energy, including their roles in steroid synthesis and cell death, and their complex behaviour when they replicate, fuse or change shape and position within cells. People with mitochondrial diseases can experience a myriad of symptoms related to these functions. None, however, is relevant to mitochondrial replacement.
Mitochondrial replacement (MR) involves transplanting the nuclear DNA of an unfertilised or fertilised egg (zygote) from the woman at risk of having affected children to a donor egg or zygote with its nuclear DNA removed; the donor has normal mtDNA. The resulting child will have nuclear DNA from the patient and her partner, and mtDNA from the donor.
The scientific review considered many issues in depth. But, with respect to the issues raised in the article, the following questions are the only ones that are relevant:
Is a trait attributed to mitochondria one that is encoded by nuclear or mitochondrial DNA? If nuclear, then it is not relevant to MR because all these traits – and we know there are at least 1000 nuclear genes encoding products required for mitochondrial functions – will be inherited by the child in exactly the same way as if MR had not been used.
Effect on the child
If a trait is encoded by mtDNA, will mitochondrial replacement have any consequences for the child's future that are different from those of natural reproduction? If so, are the consequences worth worrying about, especially given that without replacement the child would suffer from a debilitating disease and die young?
We know that variation in mtDNA can alter mitochondrial function. Notably, variations in the 37 well-studied genes in the mitochondrial genome have been associated with subtle differences in energy metabolism, such as the ability to cope at high altitudes.
Is this relevant? Any effect of mtDNA variation has to be considered in the light of the extensive variation in the nuclear genes that impact on mitochondrial function. Will variation in mtDNA make itself heard above the noise of this variation in nuclear DNA? The answer is probably not.
But let us assume that a child born after MR has slightly different energy metabolism compared to his or her parents. Will this matter? Assuming the child is healthy, I very much doubt it will concern anyone.
Humanin
What about other possible mtDNA-encoded traits? The New Scientist article discusses the role of "humanin" and of non-coding RNAs encoded in mtDNA. Are either of these likely to be relevant?
Humanin is a peptide (a short chain of amino acids) that was discovered in a screen for biomolecules that might protect against the neurodegeneration seen in Alzheimer's disease. It was given its emotive name in the hope that it would restore humanity to Alzheimer's patients.
As to its function, we don't really know. Research papers report it acting both inside and outside of cells and having protective effects against several types of neurodegeneration, stroke, heart and cardiovascular disease, cancer, and death of cells in the testis. It has also been reported to be involved in the action of insulin, and declining humanin levels in blood plasma are claimed to be associated with ageing.
I am a little suspicious when something is said to be so powerful. Nevertheless, even if humanin is able to carry out a fraction of all these functions, then it would be important.
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