The Science Behind the Procedure
by Halima Hassan
On February 3rd, politicians in the UK came together to become the first country to approve a motion that would change the limits of assistive reproductive technology forever.
The mitochondrial donation in vitro fertilization technique, more popularly referred to as the ‘three parent babies’ technique, is a procedure which allows couples to have children without mitochondrial diseases. Mitochondria are organelles present in the majority of our cells, responsible for producing the energy we need to function. They contain a small amount of genetic material; overall the sum of mitochondrial DNA is just 0.054% of all DNA. Because of the important role mitochondria have, inherited mitochondrial diseases, which result from mutations in the mitochondrial DNA, are severe and lead to a low quality of life. What this procedure enables is an opportunity for couples observed to carry harmful mitochondrial mutations to have disease free children that are genetically theirs. This revolutionary technique could transform the lives of many people, allowing those who previously thought they could not conceive healthy children to do so, and for those children to lead full lives. An example of an inherited mitochondrial disease is Leber’s hereditary optic neuropathy (LHON). Inheriting LHON leads to the degeneration of retinal ganglion cells and their axons resulting in acute or sub acute loss of central vision. This disease, as with most inherited mitochondrial diseases, affects predominantly adult males. This is because transmission of inherited mitochondrial diseases is through the mother, as only the egg contributes mitochondria to the embryo.
To outline this technique: the isolated nucleus from the egg of the mother is inserted into an enucleated (nucleus-lacking) egg of another woman, with healthy mitochondria. If this nuclear transfer is done prior to fertilization with sperm from the father, it is called ‘Maternal Spindle Transfer.’ If the nuclear transfer into an enucleated egg from a healthy donor occurs after fertilization, it is called ‘Pronuclear transfer.’ This technique was developed by scientist Doug Turnbull, Professor of Neurology at Newcastle University, and the findings were published in 2010.
The approval of this technique by the UK government has simply made the issue legal in the eyes of the UK authority; individual licenses are yet to be issued to facilities that can provide mitochondrial donation to families. In order for a facility to be approved and licensed they would have to demonstrate that they have the appropriate knowledge to carry out the procedure safely and effectively. Treatment for patients would require approval on a case-by-case basis, based on scientific evidence and advice submitted to the facility in question.
It is important to note that mitochondrial diseases caused as a result of mutations in the mitochondrial genome, which this technique would successfully prevent, only represent 15% of all mitochondrial diseases. Without getting into too much detail, many of the proteins mitochondria require to function correctly are encoded by nuclear DNA. Therefore if a mutation in the nuclear genome affects a protein destined for the mitochondria, a whole host of other diseases can arise. Notwithstanding this limitation, the new treatment should be an appreciated addition to fertility clinics.
Those lacking a biological background may well interpret, from the headline alone, the procedure to be one that generates a baby from three parents…
The initial concerns and hesitations regarding passing this motion were based on the incorrect belief that this technique would indeed result in three parent babies; a belief based on ignorance of the differences between mitochondrial and nuclear DNA. Not only has this gross mislabelling confused politicians, but also many ordinary people who accessed these reports and headlines. Inaccurate headlines like this can lead to reduced public acceptance and can raise fear among the target patient group for this treatment. Although very few articles condemned the technique, headlines alone can act to denigrate someone’s work and instill negative connotations into the minds of readers. Those lacking a biological background may well interpret, from the headline alone, the procedure to be one that generates a baby from three parents, not understanding that the egg donor is only contributing mitochondria to the future child and nothing else. It is nuclear DNA that determines our appearance and personality and this technique will keep nuclear DNA, from the two parents, intact.
A further controversy has been the existence of a study by a group in China where the procedure had been performed, which has not yet happened in the West, with tragic consequences. The treatment was carried out by an American clinician on a single patient in China and as a result the patient became pregnant with triplets, one of whom was aborted and the other two born prematurely and died. It is important to note however that the clinician attributed the outcome entirely to multiple pregnancy and obstetric complications and not to the method of conception.
Mitochondrial donation has, overall, been well received as shown by the approval of the UK government and the fact that this has stimulated many countries to also reconsider their policies in embryonic research. This acceptance can be attributed to great science communication and increased public engagement of the scientists involved.
Professor Turnbull has, since the early days of developing this technique, publicly advocated for it, speaking to potential patients, church groups, the media and politicians to build support for mitochondrial donation. Ultimately it is only with support from the public that any scientific finding could be incorporated into society and change lives for the better. Turnbull mastered scientific communication and learned how to communicate his findings accurately but in a way that can be easily understood by the layman. What Turnbull’s plight has shown is how crucial scientific communication and public engagement of scientists remains to be for the progression of science itself. Without engagement, a scientist’s work may remain in the confines of a lab and never impact lives like science should.
“We have within our reach the possibility of eradicating mitochondrial disease…”
For the few who remain skeptical, it is important to remind them of a procedure that when it was first approved was met with a lot of hostility and is today widely embraced: In Vitro Fertilization (IVF). IVF brought hope into many lives and if anything, mitochondrial donation is simply the next step in allowing families to have their own biological children. With time, I think mitochondrial donation will too be viewed in such a positive light.
I would like to conclude this piece with a quote from Luciana Berger, minister of public health to the UK government:
“We have within our reach the possibility of eradicating mitochondrial disease from families who have been blighted by it for generations: families who have endured a disease for which there is no cure, who have suffered daily battles with painfully debilitating symptoms, and who have sadly lost their children prematurely. Those families have had to face up to the risk, and perhaps the certainty, that to be a parent must come at the expense of a difficult and, in too many cases, painful life for their children. Not only would children born through such techniques be free of such conditions, but so would their children and grandchildren. This treatment would break a chain of misery that would otherwise have ruined generations of lives.”