Mom, Dad, and Mitochondria

Mom, Dad, and Mitochondria

    A baby born in May of this year joins the ranks of only 30-501 other people in the world whose personal genetic code comes from three different people: a mother, father, and a mitochondrial donor. Using a method of cytoplasmic transfer called mitochondrial replacement therapy, these unique individuals were conceived by the success of a relatively recent innovation that involves replacing the mitochondria in a mother’s egg with that of a donor.1 This method allows parents who would otherwise pass fatal or highly debilitating mitochondrial defects onto their children to conceive naturally. It is also, however, plagued by controversy. Only fully legal in the UK,2 the procedure has been praised and lambasted by scientists and everyday folk alike.

           In the US, a baby girl was born in 19973 by mitochondrial replacement therapy, the first to be born through the procedure. She remains healthy today as a testament to the method’s potential benefits.  However, in 2001, the FDA began classifying the procedure as a form of genetic therapy,4 a distinction which comes with a host of further possible bioethical concerns. In 2002, the FDA barred the practice, leading the family and doctors involved in the most recent mitochondria replacement birth to travel to Mexico to carry out the procedure,5 where regulations are less stringent.

In February of this year, a US panel of scientists and bioethicists from US National Academies of Sciences, Engineering, and Medicine gave the matter further consideration and extended their recommendation that mitochondrial replacement therapy be allowed, with some stipulations. The conditions include only allowing clinical trials to be carried out on male babies,6 since mitochondria is inherited by the mother, meaning that any possible negative effects of the procedure would not be passed on to further generations. The opinion of the panel is a deciding factor in many federal regulations, giving hope that the official mandate may be overturned.

           As nations continue to consider and revise regulations around mitochondrial replacement therapy and other gene therapies, the arguments both in favor of and in opposition to these procedures remain relatively constant. The potential benefits are huge; 1 out of 5,000 to 10,000 people born will develop symptomatic mitochondrial diseases,7 many of which could be prevented by the therapy. Multiplying this across the global population, millions of lives could be saved, or quality of lives significantly improved.

            The concerns, however, are equally powerful. A study carried out in the US has shown that the therapy may result in missing X chromosomes, and at least one child developed cognitive defects.1 Researchers at the University of Tubingen in Germany suggest that mitochondrial and nuclear DNA may be incompatible between individuals,4 as shown in various lab animals. However, this was countered with other examples of mitochondrial and nuclear DNA gene transfer between humans that carried no negative effects.4  Concerns have also been raised about the identity of the ‘third parent’, and the possible emotional consequences that it may bring about in the individuals involved. In cases conducted so far, families of mitochondrial recipients have not known the identity of the donor, and children bear no physical resemblance to the donor.

The minutia of the procedure, however, are far less concerning to many than its theoretical implications. On a broad scale, gene therapy and its various applications (including mitochondrial replacement therapy), carry the weight of future applications to human DNA editing. As a race, we retain a healthy awareness that alterations to our DNA, and by extension our being as we know it, is a step into uncharted territory. Changing a human’s genetic makeup not only affects one person, but each of the following generations; this is known as the germ line.1 Crossing this line means that abnormal DNA created by gene therapy has the potential to spread to thousands of offspring in years to come. In the case of mitochondrial replacement therapy, less than 0.1% of a mitochondrial donor’s DNA is identifiable in a recipient’s total genetic makeup.5 In some cases, the donor’s DNA is not detectable in the recipient at all.1 However, with mitochondria replacement research having only been conducted in the past 20 years, and accounting for less than 100 births,1 therapy remains solidly in the category of ‘uncharted territory’.

Uncharted territory, however, is exactly what medical advancement is. No therapy or treatment ever has been, or ever will be, developed under the assurance of decades of successful trials. It takes decades of trials to prove success. While every medical therapy takes time to be developed (according to the FDA, it takes an average of ten years for a drug to be approved 8), their development is allowed, despite the risk they all carry, because of the potential benefit to human health. In this regard, mitochondrial replacement therapy is no different. Out of known births occurring as a result of the therapy, only two miscarriages have been linked to the procedure.1 To be sure, two miscarriages are two miscarriages too many. However, in a time when common over-the-counter painkillers have been shown to cause an 80% increase in the risk of miscarriage,9 it seems that the risk is far outweighed by the benefit it may have to the 4,000 children who are born in the US alone with deleterious mitochondrial defects.4 Rather, it is far more likely that development of the therapy is held back by reservations about its implications in gene alteration.

In public imagination, the terms ‘gene therapy’ and  ‘gene editing’ often conjure up images of designer babies and genetically engineered super-humans. While these ideas will likely remain fiction for some time, behind them lays the more realistic concern of unknown effects that even slight gene alterations may have on generations down the road. Like the use of euthanasia to end life, IVF to conceive children in a test tube, and cryogenics to preserve human tissue, gene therapy is controversial because it seems, in a word, unnatural. The human conscience is at the core of bioethics, guiding the way towards or away from a practice. However, what at the outset seems aversion to the unnatural is often revealed to be a natural fear of the unknown. Medical advancement is made in the face of these concerns, proceeding with caution and respect for human life. At present, mitochondrial replacement therapy results in extremely small, and in some cases undetectable, changes to DNA. The known risk to human life is minimal, and the benefit is potentially huge. If we are able to take a step forward to allow clinical research in this area, it has the potential to markedly reduce the effects of mitochondrial diseases in an ethical and responsible manner.



1 Pritchard, Charlotte. “The girl with three biological parents.” BBC, 1 September 2014,

2 Couzin-Frankel, Jennifer. “Unanswered questions surround baby born to three parents.” Science, 27 September 2016,

3 Connor, Steve. “Three child babies: ‘As long as she’s healthy, I don’t care’ says mother of IVF child.” Independent, 25 August 2014,

4 Hayden Check, Erica. “Regulators weigh benefits of ‘three-parent’ fertilization.” Nature, 25 October 2013,

5 Roberts, Michelle. “First ‘three person baby’ born using new method.” BBC, 27 October 2016,

6 Vogel, Gretchen. “For boys only? Panel endorses mitochondrial therapy, but says start with male embryos.” Science, 3 February 2016,

7 “UMDF position & clinical status of mitochondrial replacement therapy to prevent transmission of mtDNA diseases.” United Mitochondrial Disease Foundation, September 2016,

8 “How long does it the FDA take to approve a drug?.” US Department of Veteran Affairs,

9 Greene, Alan. “Common over-the-counter Medicines and Miscarriage.”, 22 September 2005,




Obese Individuals are not Second-Class Patients

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