Tuesday 24th February 2015: Holly sits anxiously in her living room. Her husband, Chris, sits by her side as she fidgets nervously, waiting for the verdict. Today is the day. In a few hours time, the House of Lords will decide whether or not to amend the 2008 Human Fertilisation and Embryology Act which would legalise a controversial IVF treatment allowing the creation of so-called ‘3 parent babies’. The technique has been described by The Telegraph as ‘unethical, scary and wrong’ but for Holly, and many other women in the UK, it’s a beacon of hope.
The technique, being developed by Newcastle upon Tyne Hospitals NHS Foundation Trust and Newcastle University, is designed to help mothers who are at risk of transmitting a mitochondrial disease to their children to have healthy babies. Mitochondrial defects affect approximately 1 in every 200 children born in the UK with 1 in 4,300 children born in the UK suffering from a mitochondrial disease. There is currently no cure and unfortunately many of the children who suffer from mitochondrial diseases die in early infancy. One couple in particular have suffered more than most losing all 7 of their children to one of these devastating conditions. If the amendment is approved, the UK will be the first country in the world to legalise the pioneering technique providing some much needed hope to couples like Chris and Holly. But what exactly is a mitochondrial disease?
Commonly referred to as the power house of the cell, mitochondria are essential for normal cellular function. They convert the energy from the food we eat into a form that is useful to our cells, ATP. This energy is then used to power hundreds of different processes across our bodies. This is why dysfunctions to the mitochondria can cause a wide variety of problems from muscle weakness and vision abnormalities to recurring headaches and seizures.
Mitochondria are unique in that they are the only structure within our cells that contain their own DNA. This means that their function depends both on our genomic DNA, which we inherit from our biological parents, and our mitochondrial DNA (mtDNA). A mutation in either of these can lead to a huge array of mitochondrial diseases including diabetes mellitus and deafness, mitochondrial myopathy and Leigh syndrome. The most difficult to diagnose and treat are mutations which occur within the mtDNA. This is because unlike the single copy of genomic DNA that each of our cells posses, mitochondria have thousands of copies of their genome and it’s the number of these copies that contain the mutation that determines which clinical symptoms a person will present with. People with a large number of mutations may suffer from multiple, severe symptoms whereas people with only a few mutations may never even know they have one.
It’s also extremely difficult to predict how these mutations will affect our children. Unlike genomic DNA, mtDNA is only inherited from our mothers which means that although an mtDNA disease can affect both men and women, only women are able to pass the mutation on to their children (this isn’t the case if the mutation is in the genomic DNA which can be passed on by both men and women equally). The situation is complicated further in that each oocyte (egg) a female creates contains different mitochondria with different amounts of the mutation. This means that one child may present with a mitochondrial disease whilst another doesn’t.
This ‘genetic bottlenecking’ is a natural mechanism of limiting the effects of mtDNA mutations by ensuring that at least some of our offspring will be defect free. As we’ve already heard however, this genetic lottery doesn’t favour everyone.
The uncertainty around the inheritance of mtDNA diseases can cause severe anxiety for couples like Chris and Holly when thinking about starting a family. Holly is lucky. Thanks to the genetic bottlenecking described above, she has relatively few copies of the mutated mtDNA meaning that she doesn’t suffer from a clinically visible mitochondrial disease. She has however seen first-hand how devastating these conditions can be. Holly’s mother, Lynn, suffers from ‘mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes’, an mtDNA disease more easily referred to as MELAS. The symptoms of MELAS can include extreme fatigue, vomiting, abdominal pain and seizures to name but a few, making day to day life extremely difficult for suffers of this condition. As mtDNA mutations are inherited from our mothers, Holly is a carrier of the disease and was absolutely devastated when she found out that she could pass it on to her children.
If the House of Lords approves the amendment, ‘mitochondrial donation’ could allow her to have healthy, disease free children by having ‘normal’ mitochondria donated from an unaffected female. Although the technique is commonly referred to as mitochondrial donation, the process being developed in Newcastle actually involves taking the pro-nucleus from the fertilised egg of the affected mother and transferring it into the donor’s fertilised egg which has had its own pro-nucleus removed. (The pro-nucleus is simply the nucleus of both the mother’s egg and the father’s sperm before they fuse to form a single nucleus). The donor cell, containing the healthy mitochondria and the affected mother’s pro-nucleus, is then transplanted back into the affected mother in a procedure similar to IVF.
The media have had a field day with the term ‘3 parent baby’ but in actual fact, the amount of mtDNA in the mitochondria equates to about 0.1% of the cell’s genetic material and has no affect on a person’s traits such as height, speed or intelligence. These are all inherited from our biological parents via the genomic DNA found within the nucleus. Perhaps it would more accurate and less outrageous then to refer to them as ‘2.1 parent babies’ but unfortunately, I can’t see that phrase catching on quite as well.
Despite the controversy over creating children with genetic material from three ‘parents’, the House of Lords actually passed the amendment with a majority of 280 to 48 in February 2015 with the legislation change occurring in October 2015. Although now legal, the technique is heavily regulated and approval is need by the Human Fertilisation and Embryology Authority (HFEA) before centres can carry out the procedure. The team at Newcastle, who were pioneers in developing the technique, were the first to apply for a licence when the process opened in December 2016 and were granted the first ever licence by the HFEA earlier this year in March 2017. They hope to provide the treatment for up to 25 carefully selected women a year to help prevent the transmission of mitochondrial DNA diseases from mother to child.
Now, two years on from that fateful day in their living room, Holly and her husband finally have some hope of having a happy, healthy family without the worry of what future awaits their unborn child. If she passes the pre-treatment screening, Holly is hoping to undergo the treatment in the near future and described the technique as a “huge relief” both for herself and for the many families in the UK affected by mitochondrial diseases. There are still plenty of sceptics who question both the effectiveness and ethicality of mitochondrial donation but with the UK leading the way, perhaps more countries will now consider legalising this extraordinary advancement in science and medicine. Only time will tell.
I hope you enjoyed my take on the media’s famous ‘3 parent baby’ story. Below you can find some greats links to more reading material on the topic as well as links to the pages I sourced my figures from.