Thursday, January 05, 2017

Mitochondria replacement risks

No, it's not just conservative reservations about fiddling with genetics that makes me annoyed that this line of work is being pushed by some scientists.

Plenty of scientists worry that it is risky to the potential child.

I can't for the life of me understand why people don't see the problem with this:   when did the interests of  adults who know they have a inheritable major health problem to nonetheless have a child with their own genes start over-riding the obvious moral problem of experimenting in a way that runs a serious risk of creating a child with serious health problems as a result of the experiment? 

The moral thing to do, surely, is for that very small part of the population to not insist on propagating their own (or, particularly, the mother's) genes:  adopt or use egg donation.   With the latter, the mother still gets all the experience of pregnancy, even. 


1 comment:

John said...

Mito-nucleus incompatibility is a real risk. The biochemist Nick Lane, a British biochemist argues in "The Vital Question"(evolution from a bio-energetic perspective - good read) that it may account for many occult miscarriages. The two genomes need to co-operate. Obtain mitochondria from close relatives will probably eliminate most of the risk; though now direct genome mapping is feasible.

...A diseased mitochondrial genome could behave like a super-replicating bully, O'Farrell says, re-emerging and having a large impact on the three-parent baby at any time. It could also affect that child's future offspring.

Perhaps but it contradicts the role of somatic evolution of mitochondria. Damaged mitochondria are subject to mitophagy: broken down because those mitochondria are generating too many free radicals and not enough ATP, easy enough to happen because mtDNA, which is for the respiratory complexes, is very close to the main source of oxidising agents: the electron transport chain. So if anything the damaged mitochondria will be eliminated, leaving the healthy mitochondria to dominate the cells.

Nonetheless it is conceivable that there could be aberrant mitochondria that are not damaged or free radical generating but have consequences for cellular function that can be very dangerous at specific ages. Some neurologic disorders appear to be like that, where eventually there aren't enough optimal mitochondria so eventually energy failure ensues which is collapse of the proton gradient which is death. There is a strong relationship between Parkinson's and mitochondrial death, and I've read studies highlighting how failure of transporting mitochondria back to the cell body, presumably for mitophagy, is blocked early in the development of Alzheimer's, the implication being that these surviving mitochondria should have been killed but are now generating problems for the cell, if only because of inefficient energy generation and the organelles literally pile up in the axon, further inhibiting transport processes!

So yes there are potential risks but this technology is inevitable. We are going to genetic manipulate ourselves at that level of effect. mtDNA only produces 37 proteins but these are critical to optimising the electron transport chain. The structure of respiratory complexes is well understood and the functions are known, it won't be long before someone starts tweaking mtDNA to produce better respiratory complexes. A huge bonus would be eliminating the requirement for oxidative stress to initiate mtDNA transcription.