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The Truth about Mitochondrial Replacement

by Françoise BaylisImpact Ethics
February 23rd, 2015

via wikimedia commons Ragged red fibres - gtc - very high mag.jpg Uploaded by Nephron

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The United Kingdom’s House of Commons recently voted to amend the Human Fertilisation and Embryology Act 2008 to permit heritable genetic modification using a technology called mitochondrial replacement. This technology involves the creation of an embryo using the genetic material from three individuals: a man who contributes nuclear DNA; a woman who contributes nuclear DNA; and a woman who contributes mitochondrial DNA.

Usually, embryos are created using the sperm of one man and the egg of one woman. The sperm contains nuclear DNA and the egg contains both nuclear and mitochondrial DNA. Some women, however, have diseased mitochondrial DNA. If these women reproduce, they could pass their mitochondrial disease along to their children. This could mean serious health problems for these children including neurodegenerative disease, stroke-like episodes, blindness, and muscular dystrophy. To avoid the birth of children with these types of mitochondrial diseases, scientists want to replace the woman’s unhealthy mitochondrial DNA with healthy mitochondrial DNA from an egg donor, and then create a healthy embryo using IVF. The donated mitochondrial DNA would be passed on to the children, and the children’s children, and so on for generations. This vertical transmission of mitochondrial DNA from one generation to the next has given rise to the debate about the ethics of heritable genetic modification.

In the wake of the House of Commons historic vote (382 to 128 in favour of amending the Human Fertilisation and Embryology Act), Gillian Lockwood, the medical director of the Midland fertility clinic, maintains there is a need to educate those who still “have anxieties” about mitochondrial replacement technology. This is an interesting perspective given that for the past several years the UK public has had plenty of education (some would say indoctrination) by scientific and government organizations about the “need” for this technology so that families can have healthy genetically-related children free of mitochondrial disease.

'Ragged red fibres - gtc - very high mag' by Nephron

“Ragged red fibres – gtc – very high mag” by Nephron

To put this “need” in perspective, recent calculations suggest that mitochondrial replacement could benefit about 150 births per year in the UK. This would be the case if all women at risk of having a child with mitochondrial disease chose to reproduce using mitochondrial replacement and IVF. Quite clearly, however, it is highly unlikely that this number of women would choose to reproduce in this way – because of the risks to themselves and their potential offspring, as well as the costs involved.

First, women with mitochondrial disease who become pregnant are at increased risk of pregnancy complications including gestational diabetes, pre-eclampsia, and preterm delivery. Second, the short- and long-term risks to children born after mitochondrial replacement are unknown and may take years to identify. This is especially so as this new technology will be offered as a therapy, outside the context of a clinical trial where careful long-term follow-up to identify and deal with unintended consequences could be mandated. Third, mitochondrial replacement and IVF are not cheap. At this time, the cost of mitochondrial replacement is unknown. The cost of one IVF cycle is between £4000 and £8000, and a woman might need as many as four IVF cycles to become pregnant (the success rate of IVF in the UK is estimated at 25% per cycle). For these and other reasons, some women might take their chances with natural reproduction, some women might chose IVF with donated eggs, some women might choose adoption or foster care, and some women might remain child-free.

Why highlight these facts? Because the pursuit of all scientific and medical advances comes with opportunity costs. The time, talent, and energy devoted to possibly helping “less than 150 women per year” have healthy genetically-related children free of mitochondrial disease (when there are other available options) could be better spent on other public health goals that would benefit considerably more people.

In response to this claim, some might argue that mitochondrial replacement is not just about helping (less than) 150 women per year who have mitochondrial disease. Indeed, Shoukhart Mitalipov (the first scientist to clone human embryonic stem cells) has suggested that mitochondrial replacement might be useful in treating age-related infertility, which affects thousands of women per year in the UK and around the world.

As well, there are those who might insist that this technology is an important scientific breakthrough, the benefits of which cannot be known or anticipated. This may well be true, but just as we can’t know or anticipate the benefits, we can’t know or anticipate the harms.

If we are to have honest conversation about the possible future benefits and harms of mitochondrial replacement, we should start by acknowledging that discussions to date have been a distraction. Arguably, framing the science as primarily a benefit for families at risk of mitochondrial disease has been a sophisticated advertising campaign to garner public support for legislative change to ultimately allow human cloning for reproductive purposes. The real ethical issue is volitional evolution (the intentional genetic shaping of human purpose) about which considerable, informed ethical debate is both needed and warranted.

Being honest about the past will better enable us to be honest about the future.

Addendum: In Canada, the use of mitochondrial replacement to create a human being is illegal. The Assisted Human Reproduction Act 2004 prohibits altering “the genome of a cell of a human being or in vitro embryo such that the alteration is capable of being transmitted to descendants.”

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