In the last month Britain has paved the way for legislation to allow the creation of so-called “three-parent babies”. We thought this was the ideal topic to start our blog with, because it is difficult to comprehend the problem, the solution, and the risks without understanding the background science involved. We don’t want to write very long posts but at the same time we recognise the need to explain the science well, regardless of your scientific background. Below you will see our compromise, which is to write separate explanations for the basic terms and concepts that we think are interesting or important to understand the message.
“Three parent babies” would be the first procedure to address the problem of mitochondrial diseases. Mitochondria
are compartments in the cell located outside the nucleus (see separate explanation) and are hugely important for supplying energy to our cells. Mitochondria are quite peculiar in that they have their own DNA which is inherited only from the mother. Mutations in this DNA can result in multiple issues, including neurological problems (migraine, epilepsy and dementia), muscular failure (strokes, lack of coordination, involuntary movements and extreme muscular weakness) and problems in other organs including the bowel, kidneys, pancreas and liver. Put simply, if there are damaged mitochondria in the egg of the mother, then the baby will get a disease which can be severe and, owing to its genetic origin, will also be incurable.
The solution that science has come up with is to swap the defective mitochondria for healthy ones. This is done by transplanting the nucleus of the mother’s egg (containing its entire nuclear DNA with the genetic information of the mother) into a donor’s egg with loads of healthy mitochondria but that has had its own nucleus removed. This is the cell that is then fertilized by the sperm of the father. Three people involved (mother’s nucleus, donor’s egg and father’s sperm), and hence the name “three parent babies” (see scheme below). This technique has been tested in animal models and has been reported to render healthy baby monkeys which developed into healthy adults. The same research group showed in 2013 that the technique was possible in human cells and resulted in viable eggs which could be fertilized to start dividing. So as far as medical science is concerned, this procedure is a feasible option (the only one available) to get rid of mitochondrial DNA-originated diseases.
That is as far as science can go. However, some long term biological issues remain unsolved. For example, what is the possibility of incompatibilities between the nuclear and the mitochondrial genetic materials? Our bodies are extremely good at controlling what happens in its cells, and we simply do not know if nuclear/mitochondrial mismatch is going to be well tolerated in all cases. There are other issues that I will not develop in this post (we want to keep posts short, but if you want to find out more I encourage you to read this article). So while there is no evidence to suggest that major problems will arise, the truth is that the first babies that result from this procedure will have to be closely monitored over a long period of time, and only in the following generations can we properly assess the risks and benefits associated with this technique.
However, every new procedure entails risk. IVF and organ transplantations (just to mention a couple) were once considered high risk techniques with unknown long term consequences. In my opinion, if there is a medical procedure available to offset a catastrophic illness, patients should be given the choice. This new legislation will provide the legal framework to regulate the procedure, making possible to finally take it to the clinic and potentially cure some extremely debilitating diseases.
Three parent babies (scheme)
What are mitochondria?
Every living organism is built by cells, which are organized like bricks to build all the organs and structures. Each of these cells is quite complex in itself. It has its nucleus, which is a separate “room” where it keeps its genetic information (see nuclear DNA definition). It also has its own little skeleton that allows it to move if it needs to (for example, sperm). And it has its own energy supplier, the mitochondria. Each cell receives food from the blood and burns it, keeps the energy that is generated and chucks the carbon dioxide and water that is left back into the bloodstream to be taken back to the lungs. This process of combustion happens in the mitochondria. Depending of the energetic needs of the cell, it will have more or less mitochondria.
Why do they have their own DNA?
The reason for that is still under discussion, but one of the hypotheses (and my personal favorite!) is that the first mitochondria was a bacterial cell that colonized an ancestor of ours when we were organisms composed by a single cell and formed a symbiosis (two organisms which associate for the mutual benefit). The bacteria would burn energy for the cell, while the cell would provide food and shelter for the bacteria. So yes, the mitochondria used to be an independent organism, which is why it has its own DNA.
And by the way, what is nuclear DNA?
Each cell in an organism has a copy of nuclear DNA: the unique genetic code that describes every aspect of that particular organism. In the same way that we use our code of 26 letters and combine them to form words which then are combined to form sentences, our genetic “book” is composed of repetitions of 4 bases (“letters”) which are combined to form genes which are grouped in chromosomes. This genetic material is very well kept and protected in a separate compartment, the nucleus.
What are mutations?
Mutations are mistakes in the genetic code. For example if in the process of building new DNA for a daughter cell a certain base (letter!) is “misread” and substituted by another base.
Why can’t we screen mitochondrial diseases the same way we screen for other genetic issues?
The majority of people with faulty mitochondria have actually a mix of healthy and faulty mitochondria. This makes it very difficult to screen the gametes and the babies for these diseases; we can’t know what percentage of healthy and faulty mitochondria going to be inherited by each cell. This means that we cannot screen for these diseases the way we screen for many other genetic alterations such as Dawn syndrome. In general diseases only develop if there is a high percentage of unhealthy mitochondria. However, if the mother has a very high percentage of unhealthy mitochondria there is no point in screening!