Mitochondrial disease is an incredibly debilitating disease which stems from mistakes in the mitochondrial DNA. Recently, a new treatment has been pioneered, allowing children to be born free of the defective organelles. The original mitochondria are replaced with newer, healthier versions. However, these healthy mitochondria are donated by a third woman, hence the sobriquet “three parent babies”.
A brief intro to the role of mitochondria: why do we need them?
Mitochondria are sometimes given the name ‘the powerhouse of the cell’, which is quite an accurate description of these innumerable organelles. When we eat, food is broken down into its constituents, and as we all know carbohydrates give you energy. This occurs due to the constant bombardment with enzymes, starting from the mouth and continuing tirelessly to the intestines. This is because they are broken down into sugars such as glucose or sucrose etc. These sugars are essential to life, as the stored chemical energy is transposed into a usable form- ATP.
The production of ATP is a complicated mechanism to say the least, but for the time being lets simplify it to this: the simple molecules as described are transported from the intestines (where they absorbed) to the appropriate areas, where sugars are sent to the trusted mitochondria within the cells (after taking in the molecules via endocytosis at the cell surface membrane, they are then packaged into small compartments called vesicles, and finally are transported to mitochondria on the cytoskeleton, which the collective name for the enormous 3D mesh of proteins inside the cell which are responsible for moving organelles around inside cells among other things).
Once the sugars are inside the mitochondria, they are processed to create charged molecules, which combine with oxygen to produce ATP, a mechanism known as oxidative phosphorylation.
Going back to the main topic of this post, ATP is used as a vital energy source. Energy is needed for all metabolic reactions (reactions that occur inside living organisms), and thus you can conclude that the workings of all organs, tissues etc rely on this crucial supply of ATP. However, what would happen if this supply was compromised?
This is the underlying cause of mitochondrial disease, a terribly debilitating condition which one in every 6,500 children are born with in the UK.
Mitochondria are unique in the sense that they contain their own specific DNA: mtDNA. This is solely found within the mitochondria and codes for its functions such as respiration. Nuclear DNA, however, is found (as the name states) within the nucleus, which is the conventional DNA everyone knows and loves. This nuclear DNA contributes to your characteristics.
When a mitochondria is damaged, for example through random mutations of a gene, its ability to produce ATP is severely reduced. As a result, all the organs that require high volumes of energy to function are affected dramatically, leading to heart failures, muscular dystrophy (weakened muscles), steep cognitive decline, other brain complications and many more immobilizing effects. Most patients with mitochondrial disease die before the age of 20, with one woman losing seven children as a result.
What I find fascinating about mitochondria is that the mitochondrial DNA, mtDNA, is derived exclusively from your mother, matrilineal. This can have dire consequences for any potential offspring, as if a mother has faulty mitochondria, so too will the child.
Yet this is about to change: innovative techniques to tackle this disease are already known, and earlier this year MP’s have voted in favour of the new treatment, which makes the UK the first country to legalise it.
There is much controversy about the treatment, and I will try to sum up the cause.
In treating mitochondrial disease, the method proposed is to essentially replace all faulty mitochondria with healthy ones. There are two ways this is carried out:
1) Pronuclear transfer: after fertilisation
At one day old, after the sperm has fertilised the egg, the nuclei of both have not yet fused. This is called the ‘pronuclei’. Two pronuclei are formed, one from the intended parents and a second one from a donor. The donor is selected so the mitochondria are healthy and undamaged. Since the faulty mitochondria are found within the egg’s cytoplasm, this cytoplasm must be replaced. The intended pro-nuclei of the parent’s are extracted and inserted into a donor egg, whose donor pro-nuclei has been removed and discarded. The embryo goes on to develop fully, and healthy donor mitochondria now becomes inheritable for the future, to be passed forevermore down the germline. Now you can see why this treatment has been dubbed “three parent babies”: a third party’s DNA has been introduced (in the form of mtDNA) to replace the mother’s faulty version.
2) maternal spindle transfer: before fertilisation
This method works with eggs prior to fertilisation. The intended mother’s egg and a donor egg is collected. The spindle, a stage of meiosis, is removed from both the mother’s egg and the donor’s egg, and the donor spindle is discarded. Then, the mother’s spindle is inserted into an empty donor egg which contains the healthy mitochondria. This egg proceeds to be fertlilised and develop into an embryo.
So now we know the basics of this treatment. But why has there been so much concern? Since the child in question will contain genetic information from three people, many ethical issues have been raised.
In the run up to the legalising of this treatment, many heated debated took place within parliament and the medical profession. One of the main arguments against it was the idea of genetically modifying humans- are we one step closer to designer babies? Could we be travelling down a slippery slope, whereby further similar treatments are legalised, ultimately leading to parents choosing eye colour? In my opinion, this argument is based on a few crucial incorrect assumptions. Firstly, mitochondria are separate structures from the nucleus, and as previously mentioned mitochondrial DNA only determines the function of mitochondria. There are no genes within mtDNA that contribute to any apparent personality or appearance. Secondly, there are 37 genes on mitochondria, which accounts for 0.002% of the 25,000 genes on the human genome. This is such a minuscule value that the effects would be minimal. Furthermore, strict regulations would monitor areas such as genetic engineering, ensuring that tinkering with nuclear DNA is strictly prohibited.
The main drive for this treatment is the obvious: it will save those unlucky individuals from the enervating pain and complications arising from the disease. This reason alone is ample support for the treatment. The parents too would benefit immensely, as they wouldn’t have to watch their child die such a painful death.
In my opinion, the other arguments against such as destruction of embryo’s and unpredictable long term impacts have very little weight compared to the relief and unimaginable joy this treatment would bring to the potential suffers. Thus, I would agree with legalising this treatment, to better the lives of the suffers who would otherwise have no alternative.