Some future kids will have three parents to embarrass them

By: Helen Beilinson

In each cell of our bodies, DNA is stored in two places. The nucleus contains nearly all of our genetic material, storing information that ranges from our hair color to how quickly we can break down the food we eat. A few genes are stored in an organelle called the ‘mitochondrion’, known more colloquially as ‘the powerhouse of the cell’. Mitochondria are predominantly in charge of generating their cell’s supply of chemical energy (hence their nickname), but are also involved in a variety of other tasks, such as cell growth and cell death.

Despite being involved in so many functions, mitochondria only have 37 genes (as opposed to the 25,000 in the nucleus). This may sound insignificant, but these genes are critical in ensuring that cells are happy and function properly. Consequently, defects in the function of mitochondria can have major effects on our health, resulting in a set of disorders called mitochondrial diseases. These include Leber’s hereditary optic neuropathy (LHON), which causes loss of vision at early ages and progressive loss of vision due to optic nerve degeneration, and mitochondrial myopathy, a muscle tissue disease. Fifteen percent of mitochondrial diseases are caused by mutations in mitochondrial DNA (the remaining are due to nuclear DNA mutations or other causes).

Mitochondrial diseases are treatable. However, current therapies are predominantly directed toward alleviating symptoms and in order to provide more comfort to the patient. These therapies don’t actually eliminate the cause of the symptoms— particularly mutated mitochondrial DNA. Why is it so hard to target the cause of mitochondrial diseases? Mitochondria are incredibly abundant; nearly half the space inside of heart muscle cells is taken up by mitochondria, and each liver cell contains up to 2000 individual mitochondria. So to target the cause of mitochondrial disease, one would need to eliminate the problem in the original mitochondria that gave rise to the lifetime supply present in all the cells of our bodies. Luckily, scientists have found a trick to do just that.

All of this potentially mutated mitochondrial DNA is inherited from our mothers, because the female egg, unlike sperm, contains all the mitochondria that the offspring will inherit. If a woman’s eggs contain only unhealthy or mutated mitochondria, the egg will usually be killed before it can further develop into a fetus. This is a common protective strategy used to eliminate fertilized eggs with any number of defects that could cause disease in the fetus. There are rare cases where the fetus will continue to birth with such inherited diseases. Luckily, accumulated knowledge about mitochondrial diseases and advancements in cellular biology have led to an invention that helps prevent infertility in women with defective mitochondria and protects their children from inheriting mitochondrial diseases.

This method, called three-parent in vitro fertilization (TPIVF), is essentially a twist on in vitro fertilization, where an egg is mixed with a sperm in a dish, outside of a body, and this fertilized egg is then implanted into a woman’s uterus. Unlike traditional in vitro fertilization, however, fertilized eggs generated through TPIVF contain DNA from three parents (hence the name). In this method, the nucleus from an egg with healthy mitochondria is removed and replaced by the nucleus from an egg with unhealthy mitochondria. This egg, composed of the mitochondrial DNA of parent A and the nuclear DNA of parent B, is then fertilized by sperm of parent C. In this way, a woman whose eggs contain mutated mitochondria is still able to conceive a child whose nuclear DNA is half her own.

At the beginning of February, the United Kingdom became the first country to legalize this method of in vitro fertilization. As early as January of next year, children will be born with three biological parents. As wonderful as this method is at preventing disease and infertility, it raises a lot of ethical issues, which are the predominant reason as to why TPIVF hasn’t been legalized in countries other than the UK.  Allowing for such extreme genetic modification of offspring opens the door to acceptance of “designer babies”. The idea of designer babies is that with advancements in basic cellular biology, people may start wanting to manipulate the genetic make up of their future children to personally select for features such as blue vs. brown eyes, curly vs. straight hair, etc. To my knowledge, in vitro fertilization, be it two or three parent, has thus far only been used to allow couples experiencing infertility or those whose offspring have a high risk of debilitating disease to give birth to healthy children. However, there will always be the question of whether such manipulations will lead to something more extreme.

TPIVF is an incredible advancement that highlights how far cellular, genetic, and developmental biology have come. Nevertheless, with great power comes great responsibility (thanks, Voltaire). It will definitely be interesting to see where our new abilities to genetically modulate offspring will lead.