In a recent clinical exam, I came across a patient with a disease called Kearns-Sayer syndrome. I examined him and found he had a complex ophthalomeglia (paralysis of the eye muscles causing problems with vision) and was mentally handicapped – amongst other clinical signs and symptoms – but I still could not come to the diagnosis mentioned above. After spectacularly failing this exam, I looked up this so-called Kearns-Sayer syndrome and read with interest that this was among a collection of rare diseases called the mitochondrial diseases.
You may remember hearing about mitochondria during your high school days. They are important components of every cell and responsible for creating the majority of the energy for a cell to function.
Interestingly, it is believed that a long time ago mitochondria were in fact separate cells from our own. Billions of years ago, when most life on earth was indeed cellular, mitochondria merged with our ancestral cells to form our present day cells. This process is called symbiosis and it occurs when there is a shared biological benefit. Mitochondria have their own DNA and genes, 37 to be precise, and it is the mutation of these genes that causes serious diseases such as Kearns-Sayer.
When a baby is conceived, it is always the mother who passes on the mitochondrial genes from the material within the egg cell. While mitochondrial DNA also exists in a sperm cell, its amount is smaller and is deliberately destroyed by specific mechanisms in the embryo. Therefore paternal mitochondrial DNA cannot be inherited, which leads to a few interesting consequences and has also been suggested as one explanation for the shorter lifespan of males compared to females.
An even more serious issue, however, emerges when the mother’s mitochondrial DNA is damaged. In addition to Kearns-Sayer syndrome, many other mitochondrial diseases have been reported which can result from mutations in the maternal mitochondrial DNA. Does this mean these mothers will never have children?
Recently, there has been a lot of attention in the media about the creation of three-person babies. This procedure is believed to avoid the passing of faulty mitochondrial genes from mother to baby. There are 2 main methods to do this.
The first method is called Pronuclear Transfer. When a sperm has fertilized an egg, the resulting cell is called a zygote. The nucleus of the zygote is removed and inserted into a new nucleus-free egg. The mitochondrial DNA is found in the cytoplasm of the new egg so the baby will be born with the DNA of their mother but the mitochondrial DNA of another woman.
The second method is called Maternal Spindle Transfer. In this procedure the nucleus is removed from an egg cell and inserted into a new nucleus-free egg. This manipulated egg is then fertilized by sperm.
There are obvious ethical concerns with these methods, especially regarding the physical and psychological well-being of the children. How will the fact that they have two genetic mothers affect their upbringing and sense of identity? Is it ethical to literally re-write a person’s genetic code for the sake of health benefits?
Or rather biological questions, such as: are there consequences for cognitive ability, fertility or aging in these kids – all traits that mitochondria have been reported to have an influence on. Or how does the mitochondrial genome interact with the nuclear genome? Can the genetic material of two mothers work alongside in an efficient and compatible way? These issues are currently being investigated but the general consensus is that the procedure is safe enough to offer to patients in a treatment setting and within a regulatory framework.
Based on these reports, the UK government has reached an agreement last year to legalize the procedure and will therefore be the first country in the world to go ahead with mitochondria replacement. This is all the more satisfying as the procedures were pioneered in the UK at Newcastle University.
In the future, diseases like Kearns-Sayer might be prevented and these families saved from going through hardship and suffering. It will also mean that young medics like myself will hopefully not have to see diseases like this in our exams again.