Three parent babies: Parent #3’s impact may go beyond mitochondria

| June 2, 2015
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Three-parent babies have garnered big headlines in the genetics community for the last year. In February that culminated when the procedure won legal approval for therapeutic use in the UK after nearly a year’s worth of discussion.

The procedure is controversial for a number of reasons. First and foremost, it’s difficult for people to get over the ‘three-parent’ part. There’s often backlash against restructuring concepts of family. While once widely derided, families headed by gay or lesbian parents have become much more widely accepted.

IVF with mitochondrial donation does not just challenge our social constructs of families, but also our biological understandings of them. The procedure is used when a woman has mitochondrial disease. These conditions are often severe enough that a woman suffer numerous miscarriages and still births, if she becomes pregnant at all. Mitochondria are cellular structures involved in metabolism that have their own, tiny genomes. Sperm have zero mitochondria, so the mitochondria in a woman’s egg contains the DNA template for all of her children’s mitochondria.

A second reason 3-parent IVF raises some eyebrows is that it effects future generations. The changes made to the egg will be passed on to female progeny, and their female progeny, and so on. This is called ‘crossing the germline.’ Sperm and eggs are ‘germ’ cells. This is step that many people working in the field are hesitant to cross. There’s been much discussion about the germline in regards to new genome editing techniques because fetuses who are not yet conceived cannot give legal consent for the procedure. Three-parent IVF is the most advanced reproductive technique that would cross the germline and potentially be used by thousands of people. Some worry once its breached in this case, to help women who couldn’t conceive otherwise, it will be easier to do it for other less ethically clear reasons. Jessica Cussins writes at Biopolitical Times:

Mitochondrial replacement would not alter genes in the nucleus. But the prohibition against human germline engineering represents a critical line in the sand. If the [UK] proposal to alter mitochondrial genes is approved, we will have crossed that line; it will be harder to argue against other inheritable genetic modifications in the future.

Beyond these ethical and regulatory questions, there was not much discussion about whether or not the procedure could be done technically. Biologically, mitochondrial data was thought to stick to itself and not to interact with the much larger cache of DNA stored at the nucleus. New studies however show interactions between mitochondrial and nuclear DNA are at play in diabetes and breast cancer. Mitochondrial DNA mutations have also been associated with some mental health conditions.

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However, there is no evidence that 3-parent IVF causes or even accelerates the mutations and interactions linked to disease. There’s very few data points to find evidence. But it might mean that when parents chose their mitochondrial donor, they should also consider her family history of adult diseases like cancer and diabetes. There maybe many more examples of mitochondrial DNAs’ interactions with our environment and nuclear DNA. To put its effects in perspective, mitochondrial DNA codes for 37 genes, largely concerned with energy metabolism. compared to the more than 20,000 genes encoded by nuclear DNA.

There is also the chance, as biologist Emmanuelle Charpentier told Nature, that genetic editing of any sort could leave to chimeric individuals. These people have different DNA in each of their cells. This is more common in populations than we once thought, but only with two sets of DNA. It could lead to some challenging legal and ethical dilemmas, but was largely overlooked:

During the recent debate and approval of legislation allowing mitochondrial replacement approaches for IVF in the UK—which leads to circumstances in which an embryo would receive genetic material from three different individuals—the concept of chimerism having a negative impact on the health and fitness of respective offspring was dismissed for humans.

Right now its extremely difficult to quantify these newly understood risks, or even call them risks at all. But parents considering the procedures must obviously be informed of these potential effects. There is a strong probability that it won’t matter to potential parents who are already betting on an experimental procedure combined with IVF, which is not a sure thing. It may be like adding a grain of uncertainty on top of a mountain of it. Hopefully children born using these procedures will be followed, respectfully and appropriately, to see if any health patterns emerge related to their method of conception.

Meredith Knight is a contributor to the human genetics section for Genetic Literacy Project and a freelance science and health writer in Austin, Texas. Follow her @meremereknight.

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The GLP featured this article to reflect the diversity of news, opinion and analysis. The viewpoint is the author’s own. The GLP’s goal is to stimulate constructive discourse on challenging science issues.

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