tag:theconversation.com,2011:/ca/topics/mitochondrial-disease-1321/articlesMitochondrial disease – The Conversation2022-02-08T23:37:42Ztag:theconversation.com,2011:article/1766682022-02-08T23:37:42Z2022-02-08T23:37:42Z‘Maeve’s law’ would let IVF parents access technology to prevent mitochondrial disease. Here’s what the Senate is debating<figure><img src="https://images.theconversation.com/files/445252/original/file-20220208-23-vygwrj.png?ixlib=rb-1.1.0&rect=0%2C0%2C577%2C445&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><span class="source">Courtesy of Louise Hyslop & Mary Herbert, Univ. Newcastle upon Tyne</span></span></figcaption></figure><p>The Senate is this week debating “Maeve’s law” – a proposal to legalise access to new assisted reproductive techniques that will reduce the risk of parents passing on mitochondrial disease to their children.</p>
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<a href="https://images.theconversation.com/files/445246/original/file-20220208-36472-1c86l4h.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Maeve and Sarah Hood" src="https://images.theconversation.com/files/445246/original/file-20220208-36472-1c86l4h.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/445246/original/file-20220208-36472-1c86l4h.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=800&fit=crop&dpr=1 600w, https://images.theconversation.com/files/445246/original/file-20220208-36472-1c86l4h.jpeg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=800&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/445246/original/file-20220208-36472-1c86l4h.jpeg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=800&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/445246/original/file-20220208-36472-1c86l4h.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1005&fit=crop&dpr=1 754w, https://images.theconversation.com/files/445246/original/file-20220208-36472-1c86l4h.jpeg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1005&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/445246/original/file-20220208-36472-1c86l4h.jpeg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1005&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">Maeve with her mother Sarah Hood.</span>
<span class="attribution"><span class="source">Photo courtesy of the Hood family</span>, <span class="license">Author provided</span></span>
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<p>The legislation, formally called the <a href="https://www.aph.gov.au/Parliamentary_Business/Bills_LEGislation/Bills_Search_Results/Result?bId=r6697">Mitochondrial Donation Law Reform (Maeve’s Law) Bill 2021</a>, is named after Maeve Hood, a six-year-old Victorian girl who lives with Leigh syndrome – a disorder in which the body’s cells fail to produce enough energy. Tragically, Maeve is unlikely to survive beyond childhood. </p>
<p>This week’s expected vote will be the first conscience vote in the Senate since the historic reforms to allow <a href="https://theconversation.com/australia-has-finally-achieved-marriage-equality-but-theres-a-lot-more-to-be-done-on-lgbti-rights-88488">marriage equality in 2017</a>, and is already being passionately debated. </p>
<p>But the issues raised are unlikely to be new. These reforms have already undergone <a href="https://www.nhmrc.gov.au/mitochondrial-donation-0">extensive community consultation</a> and been <a href="https://www.theguardian.com/australia-news/2021/dec/01/controversial-mitochondrial-donation-legalised-after-conscience-vote">approved by the House of Representatives</a>. </p>
<h2>What is mitochondrial donation?</h2>
<p>Mitochondria are energy-producing structures inside cells, which have their own DNA and are separate from the cell nucleus containing the bulk of the cell’s DNA (called “nuclear DNA”). Mitochondrial DNA is inherited entirely from the mother’s egg, so if a mother has mutations in her mitochondrial DNA she is at risk of passing life-threatening conditions to her baby.</p>
<p>Conceiving a baby via mitochondrial donation involves implanting the mother’s nuclear DNA into a healthy egg from which the nuclear genes have been removed, and using this egg for in-vitro fertilisation (IVF) with a sperm. Alternatively, a procedure called pronuclear transfer can be used early in the fertilisation process a few hours after the sperm has entered the egg, but before the parental genomes come together and the fertilised egg officially becomes an embryo. </p>
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<a href="https://images.theconversation.com/files/445254/original/file-20220208-27-x3p9ju.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Schematic diagram of mitochondrial donation" src="https://images.theconversation.com/files/445254/original/file-20220208-27-x3p9ju.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/445254/original/file-20220208-27-x3p9ju.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=464&fit=crop&dpr=1 600w, https://images.theconversation.com/files/445254/original/file-20220208-27-x3p9ju.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=464&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/445254/original/file-20220208-27-x3p9ju.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=464&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/445254/original/file-20220208-27-x3p9ju.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=584&fit=crop&dpr=1 754w, https://images.theconversation.com/files/445254/original/file-20220208-27-x3p9ju.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=584&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/445254/original/file-20220208-27-x3p9ju.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=584&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="attribution"><span class="source">Mito Foundation</span></span>
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<p>A child born via mitochondrial donation would inherit a mixture of their mother’s and father’s nuclear DNA as usually occurs, along with the healthy mitochondrial DNA from the egg donor.</p>
<p>As a result, mitochondrial donation has sometimes been described as creating “three-parent babies”. But “<a href="https://theconversation.com/3-parent-ivf-could-prevent-illness-in-many-children-but-its-really-more-like-2-002-parent-ivf-126591">2.002-parent babies</a>” would arguably be more accurate, given there are only 37 mitochondrial genes, compared with at least 20,000 in our nuclear DNA.</p>
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Read more:
<a href="https://theconversation.com/3-parent-ivf-could-prevent-illness-in-many-children-but-its-really-more-like-2-002-parent-ivf-126591">3-parent IVF could prevent illness in many children (but it's really more like 2.002-parent IVF)</a>
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<p>Australian law currently bans the creation of a human embryo that involves genetic material from more than two people. The ban was introduced almost 20 years ago amid fears IVF and embryo research would lead to “designer babies” and cloning. Maeve’s law would change this situation specifically to allow mitochondrial donation to prevent mitochondrial disease.</p>
<p>Debate around the issue has focused on a range of questions, such as: is there a risk the child could still end up with mutant mitochondrial DNA? Are there ethical issues centred on the unborn baby’s inability to give consent? What are the egg donor’s rights? Does the procedure carry other health or genetic risks?</p>
<h2>The expert view</h2>
<p>In the United Kingdom, where mitochondrial donation research was pioneered, four scientific reviews by the Human Fertilisation and Embryology Authority and an investigation by the Nuffield Council on Bioethics were conducted between 2011 and 2016. These reviews delivered an overall conclusion that the benefits outweigh the harms if regulated appropriately, and Britain <a href="https://theconversation.com/decision-to-allow-three-person-ivf-should-be-welcomed-37192">legalised mitochondrial donation</a> in 2015. </p>
<p>In Australia, mitochondrial donation has been considered by a <a href="https://www.nhmrc.gov.au/mitochondrial-donation-0">series of inquiries</a>, including a 2018 Senate inquiry and a National Health and Medical Research Council (NHMRC) review, which considered these issues with fresh eyes.</p>
<p>In response, the government drafted Maeve’s law, which underwent a series of reviews and public consultations, and gained the support of <a href="https://www.mcri.edu.au/sites/default/files/media/documents/mitochondrial_donation_open_letter.pdf">60 leading Australian experts</a>.</p>
<h2>Does the public support it?</h2>
<p>One challenge in gauging public support is to measure true community sentiment, rather than inviting submissions that merely serve as a forum for people with existing strongly held views either for or against mitochondrial donation.</p>
<p>To address this challenge, researchers convened a <a href="https://academic.oup.com/humrep/article/34/4/751/5377828">citizens’ jury</a> in 2017, and the NHMRC held a <a href="https://www.nhmrc.gov.au/mitochondrial-donation-0#download">citizens’ panel</a> in 2019 to evaluate attitudes to mitochondrial donation. Both offered qualified support for allowing the technology.</p>
<h2>What topics are likely to be contentious in the Senate debate?</h2>
<p>The Senate will likely revisit amendments that were defeated in the House of Representatives in December. These include a proposal only to allow the technique in which the mother’s DNA is implanted into the donor egg <em>before</em> fertilisation with the father’s sperm.</p>
<p>This suggestion is a response to fears that pronuclear transfer would lead to increased rates of embryo destruction.</p>
<p>But these early fertilised eggs – also called zygotes – do not meet the legal or biological definition of an embryo, and most embryologists do not regard this technique as leading to more loss of embryos than other assisted reproductive technologies. What’s more, banning this approach could greatly compromise the development of mitochondrial donation in Australia.</p>
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<a href="https://images.theconversation.com/files/445256/original/file-20220208-32038-1qki08t.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Zygote undergoing pronuclear transfer" src="https://images.theconversation.com/files/445256/original/file-20220208-32038-1qki08t.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/445256/original/file-20220208-32038-1qki08t.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=469&fit=crop&dpr=1 600w, https://images.theconversation.com/files/445256/original/file-20220208-32038-1qki08t.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=469&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/445256/original/file-20220208-32038-1qki08t.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=469&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/445256/original/file-20220208-32038-1qki08t.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=589&fit=crop&dpr=1 754w, https://images.theconversation.com/files/445256/original/file-20220208-32038-1qki08t.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=589&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/445256/original/file-20220208-32038-1qki08t.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=589&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">A zygote about to have its nuclear DNA removed and transferred to a donor egg, roughly 20 hours before division to form a two-cell embryo. Arrows show the mother’s and father’s DNA, called ‘pronuclei’. These remain separate until later in the process, hence why the zygote is not considered an embryo.</span>
<span class="attribution"><span class="source">Courtesy of Louise Hyslop & Mary Herbert, Univ. Newcastle upon Tyne</span></span>
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<p>Maeve’s law will still require researchers to account to NHMRC for eggs and embryos used in their research, to seek ways to minimise the numbers used, and to report to Parliament on an annual basis.</p>
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Read more:
<a href="https://theconversation.com/disputes-over-when-life-begins-may-block-cutting-edge-reproductive-technologies-like-mitochondrial-replacement-therapies-146254">Disputes over when life begins may block cutting-edge reproductive technologies like mitochondrial replacement therapies</a>
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<h2>If not now, when?</h2>
<p>While we need to respect differing attitudes to IVF and embryo research, we believe most experts and members of the public recognise the importance of giving couples who are at risk of mitochondrial disease the best chance of having a healthy child.</p>
<p>Maeve’s law has been carefully written to ensure a cautious introduction and evaluation of mitochondrial donation technology. The technology will be in a clinical trial setting for at least ten years, during which time the health of babies born using these techniques will be carefully monitored. </p>
<p>The science supports it. The community support it. People who are affected by mitochondrial disease have long supported it. We call on Senators to support it.</p><img src="https://counter.theconversation.com/content/176668/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>David Thorburn receives funding from NHMRC, MRFF, the US Department of Defense Congressionally Directed Medical Research Program, the Royal Children's Hospital Research Foundation and the Mito Foundation for research on mitochondrial and other rare diseases. He is a founding Director of the Mito Foundation and a former Chair of its Scientific & Medical Advisory Panel. He was a member of the NHMRC Expert Working Committee on Mitochondrial Donation and engaged with the reviews referred to in this article.</span></em></p><p class="fine-print"><em><span>Megan Munsie receives funding from ARC, MRFF, the Novo Nordisk Foundation. She is the Vice President of the Australasian Society for Stem Cell Research, non-executive director of the National Stem Cell Foundation of Australia and a member of ethics and policy advisory committees for several national and international organisations including the International Society for Stem Cell Research (ISSCR). She co-authored recently published ISSCR Guidelines that support clinical research for mitochondrial donation.</span></em></p>Parents at risk of passing on genetic disease to their children via mutations in the mother’s mitochondrial DNA could soon use a new IVF-based treatment involving healthy donor mitochondria.David Thorburn, co-Group Leader, Brain & Mitochondrial Research, Murdoch Children's Research InstituteMegan Munsie, Professor Emerging Technologies (Stem Cells), The University of MelbourneLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1265912019-11-11T03:23:04Z2019-11-11T03:23:04Z3-parent IVF could prevent illness in many children (but it’s really more like 2.002-parent IVF)<figure><img src="https://images.theconversation.com/files/300804/original/file-20191108-10961-1saxnlu.jpg?ixlib=rb-1.1.0&rect=8%2C8%2C5742%2C3819&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Australians can now have their say on the issues around mitochondrial donation.</span> <span class="attribution"><span class="source">From shutterstock.com</span></span></figcaption></figure><p>Mitochondrial donation is an assisted reproductive technology sometimes described as “three-parent IVF”. It’s designed for women at high risk of passing on faulty mitochondrial DNA and having a child with severe mitochondrial disease. </p>
<p>Mitochondrial diseases comprise <a href="https://www.sciencedirect.com/science/article/pii/S014067361830727X?via%3Dihub">at least 300 different genetic conditions</a> which affect the energy-producing structures within human cells, impacting organ function.</p>
<p>Mitochondrial donation involves combining the 20,000 or so unique nuclear genes from the mother with the same number from the father – but replacing the mother’s 37 unique mitochondrial DNA genes with mitochondria from a donor egg. </p>
<p>In terms of genetic contribution (physical and personality traits), it would be more accurate to call mitochondrial donation “2.002-parent IVF”.</p>
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Read more:
<a href="https://theconversation.com/meet-mama-papa-and-mama-how-three-parent-ivf-works-15725">Meet mama, papa and mama: how three-parent IVF works</a>
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<p>Mitochondrial donation was legalised <a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(18)31868-3/fulltext">in the UK</a> in 2015. Now, Australia is considering introducing it.</p>
<p>Couples would be able to access the procedure if the mother has a family history of mitochondrial DNA disease, which may apply to <a href="https://www.nejm.org/doi/10.1056/NEJMc1500960?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dwww.ncbi.nlm.nih.gov">about 60 births</a> in Australia each year. </p>
<h2>Mitochondrial disease</h2>
<p>Mitochondria are small structures within our cells that regulate many aspects of metabolism. In particular, they convert sugars, fats and proteins into a form of energy our cells can use.</p>
<p>At least <a href="https://academic.oup.com/brain/article/126/8/1905/307996">one in 5,000 babies</a> will be affected by a severe mitochondrial disease during their lifetime. Problems in mitochondrial energy generation can present at any age and affect any organ system, alone or in combination.</p>
<p><a href="https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD004426.pub3/full">We don’t have effective therapies</a> so, tragically, most affected children die before age five from respiratory failure, heart failure, liver failure or other causes.</p>
<p>More than half of patients don’t develop symptoms until adulthood. But they can suffer debilitating symptoms such as muscle weakness, diabetes, deafness, blindness, strokes, seizures, heart failure, kidney disease and <a href="https://www.nature.com/articles/nrdp201680">early death</a>.</p>
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Read more:
<a href="https://theconversation.com/viewpoints-the-promise-and-perils-of-three-parent-ivf-18402">Viewpoints: the promise and perils of three-parent IVF</a>
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<p>In about half of patients with mitochondrial disorders, the cause is a problem in one of the 20,000 nuclear genes we inherit from each parent. This is the case with other inherited diseases such as cystic fibrosis and thalassaemia. </p>
<p>In the other half it’s due to a problem in one of the 37 genes in the circular chromosome of mitochondrial DNA that lies outside the nucleus and is <a href="https://www.nature.com/articles/nrdp201680">inherited only from the mother’s mitochondria</a>. This is where mitochondrial donation can help.</p>
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<img alt="" src="https://images.theconversation.com/files/300805/original/file-20191108-10901-1dfdhx9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/300805/original/file-20191108-10901-1dfdhx9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/300805/original/file-20191108-10901-1dfdhx9.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/300805/original/file-20191108-10901-1dfdhx9.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/300805/original/file-20191108-10901-1dfdhx9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/300805/original/file-20191108-10901-1dfdhx9.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/300805/original/file-20191108-10901-1dfdhx9.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<span class="caption">Mitochondria play an important role in regulating our metabolism.</span>
<span class="attribution"><span class="source">From shutterstock.com</span></span>
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<p>While couples with a family history of conditions like muscular dystrophy or cystic fibrosis can use IVF technologies to have a child who will not be affected, these options are generally <a href="https://www.nature.com/articles/nbt.3997">unreliable for the prevention of mitochondrial DNA disease</a>. </p>
<p>This procedure would offer Australian couples with a family history of mitochondrial DNA disease access to a reproductive technology to facilitate conception of a healthy child genetically related to both parents.</p>
<h2>Safety and effectiveness</h2>
<p>Mitochondrial donation can be performed <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5890307/">either prior to or shortly after</a> fertilisation. In both cases, <a href="https://academic.oup.com/humrep/article/22/4/905/695880">this is before</a> the fertilized egg becomes an embryo.</p>
<p>However, a small number of maternal mitochondria are carried over, leaving the potential for <a href="https://www.nature.com/articles/nature18303">reversion to mutant mitochondrial DNA</a>. </p>
<p>It’s also possible the donor mitochondrial DNA will be incompatible with the parents’ nuclear genes, potentially causing disease. </p>
<p>Girls born following mitochondrial donation will pass on the donor mitochondrial DNA to any descendants. If any mutant mitochondrial DNA was carried over, it could potentially cause disease in her descendants. </p>
<p>For this reason a review in the United States recommended the procedure should be restricted to implanting <a href="http://www.nationalacademies.org/hmd/Reports/2016/Mitochondrial-Replacement-Techniques.aspx">male embryos only</a>.</p>
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Read more:
<a href="https://theconversation.com/explainer-what-are-mitochondria-and-how-did-we-come-to-have-them-83106">Explainer: what are mitochondria and how did we come to have them?</a>
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<p>A number of scientists have suggested the proposed safety issues may be less relevant to clinical practice because they were based on, for example, <a href="https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1004315">inbred mouse models</a> or <a href="https://www.nature.com/articles/nbt.3997">human embryonic stem cells</a> cultured in the lab.</p>
<p>Some reassurance may also be found in studies describing <a href="https://www.nature.com/articles/nature08368">macaque monkeys</a> born following mitochondrial donation. Meanwhile, human studies have reported apparently healthy children being <a href="https://www.clinicalkey.com.au/#!/content/playContent/1-s2.0-S147264831730041X?returnurl=https:%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS147264831730041X%3Fshowall%3Dtrue&referrer=https:%2F%2Fwww.ncbi.nlm.nih.gov%2F">born following mitochondrial donation</a> or what’s called <a href="https://www.clinicalkey.com.au/#!/content/playContent/1-s2.0-S1472648316305569?returnurl=https:%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS1472648316305569%3Fshowall%3Dtrue&referrer=https:%2F%2Fwww.ncbi.nlm.nih.gov%2F">ooplasmic transfer</a> of a small proportion of mitochondria from a donor egg.</p>
<p>But those human studies avoided regulatory scrutiny and are limited by poor scientific design, while the macaque studies have not been followed through to adulthood yet. So some uncertainty remains about the safety and effectiveness of mitochondrial donation. </p>
<h2>Lessons from the UK</h2>
<p>The approval process in the UK included four separate scientific reviews. A <a href="https://www.nature.com/articles/nbt.3997">panel of embryologists and geneticists</a> considered data on human embryos, mice and monkeys that had undergone mitochondrial donation. They concluded the likely risks were low and it was safe <a href="https://www.hfea.gov.uk/media/2611/fourth_scientific_review_mitochondria_2016.pdf">to proceed cautiously</a>. </p>
<p>Mitochondrial donation in the UK is regulated to ensure the procedure is only used <a href="https://www.hfea.gov.uk/media/2611/fourth_scientific_review_mitochondria_2016.pdf">for prevention of severe mitochondrial DNA disease</a>, where the benefit to risk ratio is strong. It specifically excludes <a href="https://www.sciencedirect.com/science/article/pii/S2405661818300030?via%3Dihub">experimenting with the procedure to treat fertility</a>, which has been proposed by some IVF groups. The benefits versus risks in this case are less clear.</p>
<p>Many international experts on mitochondrial biology and disease supported the approach taken in the UK. We recommend Australia take a similar path.</p>
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Read more:
<a href="https://theconversation.com/safety-in-numbers-how-three-parents-can-beat-genetic-diseases-2524">Safety in numbers: how three parents can beat genetic diseases</a>
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<p>Following <a href="https://www.aph.gov.au/Parliamentary_Business/Committees/Senate/Community_Affairs/MitochondrialDonation/Report">an Australian Senate Inquiry in 2018</a>, the <a href="https://www.aph.gov.au/Parliamentary_Business/Committees/Senate/Community_Affairs/MitochondrialDonation/Government_Response">government</a> tasked the National Health and Medical Research Council with providing expert input on legal, regulatory, scientific and ethical issues, as well as conducting public engagement. </p>
<p>Research suggests many Australians <a href="https://academic.oup.com/humrep/article/34/4/751/5377828">are likely to support this approach</a>, but further public input is important to guide legislative change. This includes consideration of ethical issues such as the rights and interests of the egg donor.</p>
<p>We encourage interested parties to engage with the <a href="https://www.nhmrc.gov.au/about-us/leadership-and-governance/committees/mitochondrial-donation">public consultation process</a> before submissions close on November 29.</p><img src="https://counter.theconversation.com/content/126591/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>David Thorburn receives funding from NHMRC, the US Department of Defense Congressionally Directed Medical Research Program and the Mito Foundation. He is a founding Director of the Mito Foundation and Chair of its Scientific & Medical Advisory Panel. </span></em></p><p class="fine-print"><em><span>John Christodoulou receives funding from NHMRC and the US DOD, as well as a number of disease specific organisations.
He is a founding Director of the Mito Foundation</span></em></p>Should Australia allow the creation of babies with DNA from more than two people? This reproductive technology could prevent babies being born with mitochondrial disease, so the simple answer is yes.David Thorburn, co-Group Leader, Brain & Mitochondrial Research, Murdoch Children's Research InstituteJohn Christodoulou, Director, Genetics Research Theme, Murdoch Children's Research InstituteLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1076412018-11-28T15:10:02Z2018-11-28T15:10:02ZStudy shows mitochondrial DNA can be passed through fathers – what does this mean for genetics?<figure><img src="https://images.theconversation.com/files/247501/original/file-20181127-76764-c9uxf1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/cellular-organelle-mitochondria-3d-illustration-706973239?src=O-u9LHsAO6haC07Few8OpA-1-15">3D man/Shutterstock</a></span></figcaption></figure><p>Some things you learn in school turn out <a href="https://theconversation.com/five-science-facts-we-learnt-at-school-that-are-plain-wrong-33258">not to be true</a>, for example that there are just five senses or three states of matter. Now cutting-edge research has added to the list by proving the mitochondria (the power sources in our cells) comes from both our parents and not – as biology students are taught – just from our mothers.</p>
<p>The research, <a href="http://www.pnas.org/cgi/doi/10.1073/pnas.1810946115">published in PNAS</a>, showed conclusively that, in three unrelated families, mitochondria from the father’s sperm had been passed to the children over several generations. Overturning scientific understanding about this fundamental “truth”, opens the possibility for better treatment of mitochondrial disorders, which blight many families with devastating disease. </p>
<p>Mitochondria convert the sugars, fats and proteins that we eat into the molecules our cells use to power themselves. So <a href="http://mitochondrialdisease.nhs.uk/patient-area/what-mitochondrial-disease/">when they go wrong</a>, the result is often catastrophic, resulting in lifelong problems or even the death of an affected baby in the womb.</p>
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<p><a href="http://www.newcastle-mitochondria.com/patient-and-public-home-page/melas/">MELAS syndrome</a>, for example, begins in early childhood and results in seizures and dementia. <a href="https://ghr.nlm.nih.gov/condition/kearns-sayre-syndrome">Kearns-Sayre syndrome</a> causes problems with sight and hearing, potentially leaving the sufferer blind and deaf.</p>
<p>Most of a cell’s DNA is contained in its nucleus but mitochondria sit separately inside the cell and have their own DNA. This is because mitochondria are thought to have started as <a href="https://www.nature.com/scitable/topicpage/the-origin-of-mitochondria-14232356">separate organisms</a>, which entered early cells about 1.45 billion years ago and never left. They reproduce themselves and move from one generation to another by “hitching a lift” in the egg.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/247502/original/file-20181127-76743-lgxtq0.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/247502/original/file-20181127-76743-lgxtq0.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/247502/original/file-20181127-76743-lgxtq0.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/247502/original/file-20181127-76743-lgxtq0.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/247502/original/file-20181127-76743-lgxtq0.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/247502/original/file-20181127-76743-lgxtq0.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/247502/original/file-20181127-76743-lgxtq0.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=566&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<span class="caption">Mitochondria are the power sources of a cell.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/3d-rendered-illustration-human-cell-crosssection-1215277975?src=2LMaSyJqo8gCmhb0kn0kZQ-1-46">Sebastian Kaulitzk/Shutterstock</a></span>
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<p>During fertilisation, the father’s sperm transfers his DNA into an egg, but few or none of the sperm’s mitochondria get in. If any do, then there are mechanisms designed <a href="https://www.sciencedirect.com/science/article/pii/S1534580714002044">to destroy them</a>. The new research found that, in a small number of families, the mitochondria from the father that found its way into the egg were not destroyed, though we don’t yet know enough to say why. There was also some evidence this mitochondrial DNA from the father may have then been copied as the fertilised egg grew into an embryo even more than that from the mother.</p>
<p>There’s a chance that previous research may have also found examples of mitochondria being passed on from fathers but that these results were discounted and assumed to be the result of sample contamination. But with ever-increasing <a href="https://www.omicsonline.org/open-access/generations-of-sequencing-technologies-from-first-to-next-generation-0974-8369-1000395.php?aid=87862">technological advances</a>, cheaper and more in-depth DNA analysis is possible. So it’s likely that more and more cases will now be reported.</p>
<p>This work could affect scientists studying the movement of humans around the planet. Human mitochondrial DNA tends to <a href="https://www.omicsonline.org/open-access/mitochondrial-dna-a-tool-for-phylogenetic-and-biodiversity-search-in-equines-2332-2543-S1-006.php?aid=63938">alter very little</a> over time because even tiny changes <a href="https://www.forbes.com/sites/quora/2017/02/02/how-can-mutations-in-mitochondrial-dna-affect-the-human-body/#62c6962237d4">are often fatal</a> so aren’t passed on to future generations. This means a person’s mitochondrial DNA is likely to be very similar to that of their distant ancestors and other people from their ethnic group.</p>
<p>So by studying mitochondrial DNA in different populations, scientists have also been able to <a href="https://www.scientificamerican.com/article/how-do-researchers-trace/">follow how these groups</a> have moved around the world and even to identify a potential common female ancestor for all humans, known as “<a href="https://www.sciencedaily.com/releases/2010/08/100817122405.htm">mitochondrial Eve</a>”. All of this work has, however, been based on the “fact” that mitochondria pass down the female line only, something we now know to be wrong.</p>
<h2>Better treatments</h2>
<p>The most significant implications of these findings are staggering, because a better understanding of how mitochondria are passed on gives us a much better chance of developing treatments for mitochondrial disorders. It may even be possible to encourage properly functioning mitochondria to multiply inside a fertilised egg at the expense of the broken ones.</p>
<p>Any treatment would likely be controversial, because it would involve <a href="https://theconversation.com/five-reasons-we-should-embrace-gene-editing-research-on-human-embryos-51474">influencing someone’s DNA</a> in a way that would be inherited by subsequent generations. But the only other current treatment is equally controversial and involves inserting the nucleus from a fertilised egg into a donor egg containing normal mitochondria. This is often described as producing “three-parent babies” and is not permitted in most countries, although the <a href="https://theconversation.com/worlds-first-three-parent-baby-raises-questions-about-long-term-health-risks-66189">first such baby was born in April 2016</a>. So manipulating the parent’s mitochondria instead may be seen as more preferable.</p>
<p>When it comes to our use of mitochondrial DNA to study human evolution and migration, the rarity of the cases identified by the new study means it won’t significantly impact our understanding in this area. But if further research suggests that the inheritance of fathers’ mitochondrial DNA is more common, our whole understanding of human migration may need to be adjusted.</p><img src="https://counter.theconversation.com/content/107641/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Michael Porter does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>We previously thought mitochondrial DNA could only be passed on by mothers.Michael Porter, Lecturer in Molecular Genetics, University of Central LancashireLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/979912018-06-15T10:47:43Z2018-06-15T10:47:43ZHow can a baby have 3 parents?<figure><img src="https://images.theconversation.com/files/222444/original/file-20180608-191954-ugwriv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/baby-crying-after-birth-labor-room-548487937?src=ExK4m7GEK_Vl44wg0TshCQ-1-8">By Fakhrul Najmi</a></span></figcaption></figure><p>It seems impossible, right? We have been taught from the time we were young that babies are made when a sperm and an egg come together, and the DNA from these two cells combine to make a unique individual with half the DNA from the mother and half from the father. So how can there be a third person involved in this process? </p>
<p>To understand the idea of three-parent babies, we have to talk about DNA. Most people are familiar with the double helix-style DNA which make up the 23 pairs of chromosomes that are found in the nucleus of every cell in our body. It provides the instructions for building an entire organism and the proteins that drive our existence from conception until death. However, the DNA in the nucleus is not the only kind of DNA required for us to exist. There is also DNA tucked away in little compartments called mitochondria, that are found inside all of the cells in your body. </p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/222442/original/file-20180608-191947-a49y37.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/222442/original/file-20180608-191947-a49y37.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/222442/original/file-20180608-191947-a49y37.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=531&fit=crop&dpr=1 600w, https://images.theconversation.com/files/222442/original/file-20180608-191947-a49y37.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=531&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/222442/original/file-20180608-191947-a49y37.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=531&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/222442/original/file-20180608-191947-a49y37.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=667&fit=crop&dpr=1 754w, https://images.theconversation.com/files/222442/original/file-20180608-191947-a49y37.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=667&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/222442/original/file-20180608-191947-a49y37.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=667&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">This is a cross section of an animal cell showing the location of the mitochondria, the brown bean-shaped structures. The 23 chromosomes are housed in the innermost compartment of the cell – the nucleus.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-vector/human-animal-cell-cross-section-structure-213232894?src=hh5y4IwJzzN1eY1KM1OWqw-1-5">Designua/shutterstock.com</a></span>
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<p>Remember the mitochondria? Dig deep back to middle or high school biology class. It was that bean-shaped organelle often drawn with a squiggly line on it and called the powerhouse of the cell. Each cell in the body, including eggs and sperm, requires energy to carry out all of its functions. Cells without functional mitochondrial DNA (mtDNA) are like cars without gas. </p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/222446/original/file-20180608-191965-zai8oe.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/222446/original/file-20180608-191965-zai8oe.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/222446/original/file-20180608-191965-zai8oe.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=578&fit=crop&dpr=1 600w, https://images.theconversation.com/files/222446/original/file-20180608-191965-zai8oe.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=578&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/222446/original/file-20180608-191965-zai8oe.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=578&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/222446/original/file-20180608-191965-zai8oe.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=726&fit=crop&dpr=1 754w, https://images.theconversation.com/files/222446/original/file-20180608-191965-zai8oe.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=726&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/222446/original/file-20180608-191965-zai8oe.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=726&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">This is a cross section of a mitochondrion. These are referred to as the powerhouses of the cell. They contain their own DNA and produce energy for the cell.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-vector/structure-mitochondrion-organelle-found-most-eukaryotic-253622641?src=qKD3rMu-w9oN795_Ges2zw-1-32">CLUSTERX/shutterstock.com</a></span>
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<p>Unlike nuclear DNA, mtDNA is not created by the combination of male and female DNA. Instead, mitochondria are only inherited from your mother, meaning that ones that are in the fertilized egg are the ones that will be replicated in every cell of your body during your development and for the rest of your life. </p>
<p>Just like nuclear DNA, mtDNA can have mutations that can lead to very serious, debilitating diseases, and in some cases, infertility for a woman carrying the defective mitochondria. Enter the third parent.</p>
<h2>The third parent</h2>
<p><a href="https://doi.org/10.1016/j.rbmo.2017.01.013">In 2016, a baby was born to a couple</a> who had struggled with the consequences of mtDNA mutations that cause Leigh syndrome, a progressive neurometabolic disorder. When defective mitochondria of the woman’s egg were replaced with mitochondria from a donor who did not carry the mutation, the resulting child carried DNA from three people: the female nuclear DNA donor, the male nuclear DNA or sperm donor, and the female mitochondria donor. This was the first baby born using this technique.</p>
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<a href="https://images.theconversation.com/files/223285/original/file-20180614-32327-1ckkl3v.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/223285/original/file-20180614-32327-1ckkl3v.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/223285/original/file-20180614-32327-1ckkl3v.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=338&fit=crop&dpr=1 600w, https://images.theconversation.com/files/223285/original/file-20180614-32327-1ckkl3v.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=338&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/223285/original/file-20180614-32327-1ckkl3v.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=338&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/223285/original/file-20180614-32327-1ckkl3v.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=424&fit=crop&dpr=1 754w, https://images.theconversation.com/files/223285/original/file-20180614-32327-1ckkl3v.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=424&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/223285/original/file-20180614-32327-1ckkl3v.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=424&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">How to make a three-parent baby: 1) The egg from the mother contains the DNA (yellow circle) and faulty mitochondria (red ovals). 2) The DNA is removed from the mother’s egg using a very small pipette. 3) The DNA is removed from the mitochondrial donor egg leaving behind the healthy mitochondria (green ovals). 4) The DNA from the mother is transferred to the donor egg with the healthy mitochondria. 5) The result is an egg that has the nuclear DNA from the mother and mitochondrial DNA from the egg/mitochondria donor, which can then be fertilized with the father’s sperm. 6) As the cells replicate during embryo development, each cell will have the combined mother and father’s DNA in the nucleus of the cells and the egg donor’s mitochondria and associated mtDNA. Note: Fertilization can occur before or after transfer of DNA to the donor egg. If it happens before then both the mother and the father’s DNA will be transferred to the donor egg after the donor DNA has been removed. If it occurs after, then the egg will be fertilized after the mother’s DNA is transferred into the donor egg, as described here.</span>
<span class="attribution"><span class="source">Jennifer Barfield</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
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<p>This technique, termed mitochondrial replacement, can be thought of like an organ transplant, or rather organelle transplant. However, there are some <a href="http://doi.org/10.1001/jama.2016.20935">significant differences</a> that have created concern among legislators, resulting in <a href="https://www.congress.gov/bill/114th-congress/house-bill/2029/text">a ban on mitochondrial replacement in the U.S.</a>. </p>
<p>Unlike an organ transplant, the effects of mitochondrial replacement will persist in future generations of offspring if the resulting baby is a female and she chooses to have children – males do not pass on their mitochondria. Also, the replacement will affect every tissue in the body, rather than just one body system, such as the cardiovascular system after a heart transplant. </p>
<p>Even so, these donated mitochondria are naturally occurring and already persisting in our population. They are not genetically engineered or altered in any way. Thus, as long as they are functioning properly, there is no demonstrated risk to the offspring from a health standpoint beyond the naturally occurring risks of spontaneous mutations, <a href="http://doi.org/10.1038/525444a">though this is a point of debate</a>.</p>
<p>Since 2016, it’s difficult to say how many of these three-parent procedures have been done and how many resulted in successful pregnancies. But with the recent birth of a baby in the Ukraine that involved three parents, many countries are now exploring if and how to use this technology. The ban in the U.S. has halted the use here but other countries have made different decisions; the U.K. has approved it.</p>
<h2>Is the mitochondrial donor a parent?</h2>
<p>So how much a parent is a woman who donates her mitochondria? </p>
<p>The short answer is not much. More than <a href="https://ghr.nlm.nih.gov/primer/basics/gene">99 percent of the proteins in your body are encoded by the DNA in the nucleus of your cells</a>. Traits such as hair color, eye color and height, for example, are all encoded by nuclear DNA, while genes written on mtDNA are primarily related to <a href="https://doi.org/10.1016/S0005-2728(98)00161-3">energy production and metabolism</a>. </p>
<p>Thus three-parent babies will still resemble the men and women whose sperm and egg combined to produce the 23 chromosomes in the nucleus of that first cell. It’s important for people to understand these distinctions as headlines announcing births of three-parent babies will likely continue to surface. Speculation of what it means could run rampant without understanding the underlying science. </p>
<p>One thing is certain: For women who struggle with infertility caused by mutations in their mitochondrial DNA, or have the potential to pass on significant mitochondrial genetic defects, <a href="http://doi.org/10.1001/jama.2016.20935">this new technique provides hope</a> that they may one day be able to have a healthy child that is a genetic representation of them and their partner – with a little help from a third party.</p><img src="https://counter.theconversation.com/content/97991/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Jennifer Barfield does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>The concept of three-parent babies defies what we learned in health class. But how and when is the third parent involved? At what stage? Jennifer Barfield gives us an update on the birds and the bees.Jennifer Barfield, Assistant Professor, Assisted Reproductive Technologies, Colorado State UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/927942018-03-22T10:42:06Z2018-03-22T10:42:06ZMitochondria mutation mystery solved: Random sorting helps get rid of duds<figure><img src="https://images.theconversation.com/files/211047/original/file-20180319-31633-1sxhx6g.jpg?ixlib=rb-1.1.0&rect=2%2C16%2C590%2C453&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">When a cell divides, mitochondria are randomly allotted to the resulting new cells.</span> <span class="attribution"><a class="source" href="https://www.flickr.com/photos/wellcomeimages/25937295324">Odra Noel. Wellcome Images</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc/4.0/">CC BY-NC</a></span></figcaption></figure><p>You probably know about the 23 pairs of chromosomes safely stowed in your cells’ nuclei. That’s where the vast majority of your genes can be found. But there are 37 special genes — a very tiny fraction of the human genome — located in mitochondria, the structures inside your cells that breathe and produce energy.</p>
<p>Repeated copying of mitochondrial DNA introduces errors; if not kept in check, these mutations can give rise to incurable diseases like <a href="https://ghr.nlm.nih.gov/condition/leigh-syndrome">Leigh syndrome</a> and <a href="https://ghr.nlm.nih.gov/condition/leber-hereditary-optic-neuropathy">Leber’s optic neuropathy</a>. Worldwide, <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4737121/">more than 1 in 10,000</a> people are affected by disorders resulting from mitochondrial genome defects.</p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/211067/original/file-20180319-31614-14j8noq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/211067/original/file-20180319-31614-14j8noq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/211067/original/file-20180319-31614-14j8noq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=671&fit=crop&dpr=1 600w, https://images.theconversation.com/files/211067/original/file-20180319-31614-14j8noq.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=671&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/211067/original/file-20180319-31614-14j8noq.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=671&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/211067/original/file-20180319-31614-14j8noq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=843&fit=crop&dpr=1 754w, https://images.theconversation.com/files/211067/original/file-20180319-31614-14j8noq.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=843&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/211067/original/file-20180319-31614-14j8noq.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=843&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Mitochondrial DNA is inherited only from the mother, based on what mitochondria happen to be in the egg.</span>
<span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:Mitochondrial_DNA_lg.jpg">National Human Genome Research Institute</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>Unlike nuclear chromosomes that we get from both parents, only mothers’ mitochondria are passed on to offspring. This makes the usual process of sexual recombination, in which pieces of maternal and paternal chromosomes combine to repair genome defects, impossible. For decades, biologists predicted that without this repair mechanism, mitochondrial genes should rapidly accumulate harmful mutations and <a href="http://rspb.royalsocietypublishing.org/content/early/2009/02/09/rspb.2008.1758.short">lose their function</a>.</p>
<p>Despite these predictions, mitochondrial disorders in humans, while debilitating, are relatively rare. A <a href="https://doi.org/10.1038/s41556-017-0017-8">set of experiments</a> with human embryos has recently found low levels of mitochondrial mutations in most of the studied cells, that, strikingly, were otherwise perfectly healthy. If mitochondrial defects are so common, what keeps them from reaching dangerous disease-causing levels?</p>
<h2>Dealing out mitochondria by chance</h2>
<p>A typical human cell contains hundreds of mitochondria. Each mitochondrion in turn has many genome copies jointly responsible for <a href="https://en.wikipedia.org/wiki/Cellular_respiration">energy production</a>. If only a few of these copies become faulty, the rest of the mitochondria can still produce enough energy, and the cell does perfectly fine. In fact, some of the most severe disorders develop only when <a href="https://doi.org/10.1111/dgd.12420">60 to 90 percent</a> of mitochondria within each cell become mutated. This means that low levels of mitochondrial mutations are essentially invisible, and can lurk within human cells for generations without causing a disease. </p>
<p>Recent <a href="https://doi.org/10.1534/genetics.117.300273">theoretical work</a> by <a href="https://scholar.google.com/citations?user=yi-SnYcAAAAJ&hl=en&oi=ao">me</a> and my colleagues predicted a number of solutions that likely evolved to expose and eventually eliminate these hidden defects. The general principle we proposed is based on simple sorting of healthy and faulty mitochondria.</p>
<p>Whenever a cell within a developing embryo divides, mitochondria are partitioned into the two daughter cells more or less randomly. By chance, one of the two daughter cells inherits more mitochondrial defects than the other. Initially, this difference is barely noticeable. But repeat the process many times and a sizeable proportion of all daughter cells will have enough mutations to ensure that the cell does not survive. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/211432/original/file-20180321-165583-11ye0fl.PNG?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/211432/original/file-20180321-165583-11ye0fl.PNG?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/211432/original/file-20180321-165583-11ye0fl.PNG?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=277&fit=crop&dpr=1 600w, https://images.theconversation.com/files/211432/original/file-20180321-165583-11ye0fl.PNG?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=277&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/211432/original/file-20180321-165583-11ye0fl.PNG?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=277&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/211432/original/file-20180321-165583-11ye0fl.PNG?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=348&fit=crop&dpr=1 754w, https://images.theconversation.com/files/211432/original/file-20180321-165583-11ye0fl.PNG?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=348&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/211432/original/file-20180321-165583-11ye0fl.PNG?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=348&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">The mitochondria make copies in preparation for a cell dividing. Which version winds up in each daughter cell is essentially random. By chance, the bottom cell has even fewer of the red version than the original cell.</span>
<span class="attribution"><a class="source" href="https://doi.org/10.1371/journal.pbio.2000410">Radzvilavicius et al</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>On the opposite side of the spectrum, this leaves cells that have fewer mutations even than the original cell that started dividing. This simple mechanism of cell division and random sorting of mitochondria can therefore produce cells packed with healthy mitochondria that can then go on to divide further and to eventually produce mutation-free reproductive cells (eggs in females).</p>
<p>But there’s more. Scientists now believe that many features of the human reproductive system evolved to increase the efficiency of this random mitochondrial sorting. For instance, mutations would pile up faster if both paternal and maternal mitochondria were inherited by the offspring – mixing of two unrelated types of organelles would make it easier for rare defects to hide. It is very likely that we inherit mitochondrial genes only from our mothers precisely because it slows down the accumulation of defective genes.</p>
<p>The number of genome replication cycles also matters, because new defects are introduced each time genes are copied. In a paper published in 2016, my colleagues and I suggest this <a href="https://doi.org/10.1371/journal.pbio.2000410">could be the reason</a> why the number of cell divisions to produce an egg in females is strictly limited to 24. In males – whose mitochondria are not transmitted to the offspring – sperm are produced continually with more than 400 cell divisions by the age of 30. By capping the number of times a cell divides before an egg is made, females reduce the risk of introducing new copying errors in their mitochondrial genes.</p>
<p>Likewise, theory predicts that random sorting of healthy and sickly mitochondria works best when the number of mitochondria in a cell is low. With only a few mitochondria, even slightly defective genes cannot hide; their harmful effects are immediately obvious at the level of the cell, which can then be eliminated.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/211068/original/file-20180319-31596-p49o9j.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/211068/original/file-20180319-31596-p49o9j.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/211068/original/file-20180319-31596-p49o9j.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/211068/original/file-20180319-31596-p49o9j.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/211068/original/file-20180319-31596-p49o9j.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/211068/original/file-20180319-31596-p49o9j.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/211068/original/file-20180319-31596-p49o9j.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/211068/original/file-20180319-31596-p49o9j.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=566&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Less hearty mitochondria may already be getting weeded out in an eight-cell embryo.</span>
<span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:Embryo,_8_cells.jpg">eked</a></span>
</figcaption>
</figure>
<h2>Observing what theory predicts</h2>
<p>Confirming these predictions, a recent study involving human embryos has indeed discovered that the <a href="https://doi.org/10.1038/s41556-017-0017-8">number of mitochondria is sharply reduced throughout development</a> – from 1 million in a fertilized egg to only around 1,500 per cell in a 4-week-old embryo. Researchers also found that cells taken from older embryos had fewer mitochondrial mutations, meaning that cells with the most defects were somehow eliminated throughout embryonic development.</p>
<p>It is not yet clear how cells with the most mitochondrial mutations are selectively removed in human embryos. But because most of the harmful mutations were eliminated at the stage of embryonic development when cells start breathing more actively, scientists think that damaged mitochondria simply fail to produce enough energy for the cell to survive. </p>
<p>Many questions remain. For instance, why do cells with high levels of defective mitochondria sometimes escape these quality-control mechanisms, resulting in incurable disorders? Ultimately, greater understanding of these mechanisms should suggest better ways of estimating the risk of mitochondrial diseases, or even develop new interventions to prevent them completely.</p><img src="https://counter.theconversation.com/content/92794/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Arunas L. Radzvilavicius receives funding from Defense Advanced Research Projects Agency.</span></em></p>The genes in our cells’ mitochondria are passed on in a different way than the vast majority of our DNA. New studies shed light on how the unique process isn’t derailed by mutations.Arunas L. Radzvilavicius, Postdoctoral Researcher of Evolutionary Biology, University of PennsylvaniaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/811682017-07-25T00:04:18Z2017-07-25T00:04:18ZThree ways the Charlie Gard case could affect future end-of-life cases globally<p>The tragic <a href="https://www.judiciary.gov.uk/wp-content/uploads/2017/07/gosh-v-gard-24072017.pdf">case of Charlie Gard</a>, the British infant whose parents have just <a href="http://www.abc.net.au/news/2017-07-24/charlie-gard-parents-end-legal-battle-over-treatment/8739588">ended their legal fight</a> to send him to the US for experimental treatment, has captured global attention.</p>
<p>The <a href="http://www.bbc.com/news/health-40554462">case</a> is significant for a number of reasons, both in the huge amount of publicity it has attracted, its progression through several courts, and the number of influential commentators who became involved.</p>
<p>Not only does the case highlight the challenges for <a href="http://www.abc.net.au/news/2017-07-24/could-a-charlie-gard-case-happen-in-australia/8735900">parents, doctors and judges</a> in making end-of-life decisions about critically impaired infants, it is unique in another respect. It highlights the changing role of the wider public in shaping how decisions about medical treatment are made.</p>
<p>Here are three factors from the Charlie Gard case that could influence future cases around the world.</p>
<h2>1. Using social media to mobilise support</h2>
<p>More than any case of this kind, advocates for Charlie Gard have been effective in mobilising support using social media and the internet.</p>
<p>Early on, Charlie’s family set up a <a href="http://www.charliesfight.org">website</a> (with <a href="http://shop.charliesfight.org/">merchandise available</a>), as well as <a href="https://twitter.com/fight4charlie?lang=en">Twitter</a>, <a href="https://www.facebook.com/Charliegardsfight/?fref=ts">Facebook</a> and <a href="https://www.instagram.com/charliesfight/">Instagram</a> accounts to highlight how they disagreed with doctors about their son’s care. The social media campaign was further bolstered by hashtags <a href="https://twitter.com/hashtag/charliesarmy?src=hash">#charliesarmy</a> and <a href="https://twitter.com/hashtag/charliesfight?src=hash">#charliesfight</a> to keep the topic trending.</p>
<p>The campaign, which brought together supporters under the banner of “Charlie’s Army”, attracted support from <a href="https://www.theguardian.com/uk-news/2017/jul/10/charlie-gard-pope-and-trump-biggest-help-in-keeping-him-alive-says-mother">US President Donald Trump, and the Pope</a>.</p>
<p>The online campaign also raised awareness of Charlie’s rare genetic condition, <a href="http://www.telegraph.co.uk/news/0/charlie-gard-mitochondrial-disease-suffers-legal-battle/">mitochondrial DNA depletion syndrome</a>, which in his case, resulted in muscle weakness and irreversible brain damage.</p>
<p><div data-react-class="Tweet" data-react-props="{"tweetId":"886569976945156097"}"></div></p>
<p>The social media campaign helped gather support for <a href="http://www.getwestlondon.co.uk/news/west-london-news/charlie-gard-protesters-dubbed-charlies-13270232">several protests</a> about Charlie’s care. We’ve also seen <a href="http://www.smh.com.au/world/baby-charlie-gard-has-a-chance-doctor-tells-court-20170713-gxazg3.html">criticisms of</a>, and <a href="http://www.bbc.com/news/uk-england-london-40691478">death threats against</a>, Charlie’s treating doctors at <a href="http://www.gosh.nhs.uk/frequently-asked-questions-about-charlie-gard-court-case">Great Ormond Street Hospital</a> in London, again fuelled by social media.</p>
<p>Clearly, Charlie’s case has been played out both in the courts of law and the court of public opinion. The courts were asked to decide upon emotional and ethical issues. Yet, in this case, every aspect of Charlie’s life seems to have been played out through social media. </p>
<hr>
<p><em>Further reading: <a href="https://theconversation.com/charlie-gard-who-is-best-placed-to-decide-his-fate-80771">Charlie Gard: who is best placed to decide his fate?</a></em></p>
<hr>
<p>It’s time to ask ourselves whether matters that ultimately concern life and death, particularly of the most vulnerable and who cannot speak for themselves, be considered more privately. In this light, we may need to reflect on whether a social media campaign really has a place, not only now but in future cases.</p>
<p>In future cases where parents and doctors disagree on treatment decisions, will the Charlie Gard case form a template for how to rally public support? And could a similar approach influence future decisions about broader medical treatment, not just about end-of-life care?</p>
<h2>2. Crowdfunding to pay for unauthorised treatment</h2>
<p>In a novel move for cases of this kind, Charlie Gard’s supporters had <a href="https://www.gofundme.com/please-help-to-save-charlies-life">raised £1.3 million</a> via a GoFundMe <a href="https://theconversation.com/explainer-what-is-crowdfunding-9444">crowdfunding</a> initiative for him to be able to travel to the US for experimental treatment.</p>
<p>His parents and a handful of medical experts believed <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4892756/">nucleoside experimental therapy</a>, while not a cure, could provide a small chance of improving his quality of life. This is a claim Charlie’s treating doctors rejected.</p>
<p>With finite health-care resources, there’s a chance other families of critically ill infants could think of crowdfunding to fund a treatment doctors or the courts consider not in the best interest of the child.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/179369/original/file-20170724-28505-hhdtad.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/179369/original/file-20170724-28505-hhdtad.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=361&fit=crop&dpr=1 600w, https://images.theconversation.com/files/179369/original/file-20170724-28505-hhdtad.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=361&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/179369/original/file-20170724-28505-hhdtad.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=361&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/179369/original/file-20170724-28505-hhdtad.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=453&fit=crop&dpr=1 754w, https://images.theconversation.com/files/179369/original/file-20170724-28505-hhdtad.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=453&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/179369/original/file-20170724-28505-hhdtad.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=453&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">The crowdsourcing campaign raised £1.3 million to send Charlie Gard to the US for experimental treatment.</span>
<span class="attribution"><a class="source" href="https://www.gofundme.com/please-help-to-save-charlies-life">Screenshot/gofundme</a></span>
</figcaption>
</figure>
<p>Yet crowdfunding for medical expenses is <a href="https://theconversation.com/explainer-what-is-crowdfunding-9444">not as simple as setting up an account or website</a>. There are processing fees, and other tax and legal implications to consider. </p>
<p>Beyond that, we need to ask ourselves what happens when crowdfunding money runs out and how people choose which campaign to donate to. We also need to consider not only how crowdfunding affects issues of privacy, but also how it affects the wider issues of fair and appropriate access to medical treatment.</p>
<h2>3. Fuelling anti-establishment sentiment</h2>
<p>End-of-life decisions for critically ill infants have traditionally been made privately, <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4124260/">in collaboration between doctors and parents</a>. Typically these decisions require an evaluation, among other factors, of the child’s best interests and quality of life. Parents generally tend to listen to and follow the advice of the medical professionals.</p>
<p>In this case, some may see the attempts of Charlie’s parents to overrule the courts, hospital and medical advice as a departure from the traditional <a href="https://stanford.library.sydney.edu.au/entries/paternalism/">paternalistic</a> doctor-patient relationship (sometimes known as “doctor knows best”). </p>
<p>Unlike many others in this situation, Charlie’s parents <a href="http://www.independent.co.uk/news/uk/home-news/charlie-gard-army-high-court-medical-experts-great-ormond-street-hospital-murder-doctors-lying-a7840236.html">had rejected</a> not only the advice of the treating medical team, but have also repeatedly rejected the decisions of the courts, who are assumed to be fulfilling an independent and objective role.</p>
<hr>
<p><em>Further reading: <a href="https://theconversation.com/when-parents-disagree-with-doctors-on-a-childs-treatment-who-should-have-the-final-say-64813">When parents disagree with doctors on a child’s treatment, who should have the final say?</a></em></p>
<hr>
<p>Future cases will demonstrate whether the Charlie Gard case can be regarded as an indicator of a trend away from the medico-legal establishment. But, as some have indicated, “doctor knows best” <a href="http://www.bbc.com/news/uk-40600932">is shifting to</a> “parent knows best”. </p>
<p>Questions of “best interests” and “quality of life” are nuanced and difficult, but to Charlie’s vocal supporters in the court of public opinion, this case has been one of “us” and “them”.</p>
<p><div data-react-class="Tweet" data-react-props="{"tweetId":"884184391240626177"}"></div></p>
<p>We don’t yet know how this power shift will play out in future cases. But so far, public debates have been less about Charlie and his individual best interests, and more about the interests of others – be they <a href="http://www.express.co.uk/news/uk/824747/charlie-gard-terminally-ill-baby-us-hospital-free-treatment-donald-trump">political</a>, “sticking it” to the establishment or being heard on social media.</p>
<p>Perhaps, in the future, the courts may want to regain some control in end-of-life cases by enforcing suppression orders (limiting what’s made public about a case) to avoid such a media circus.</p>
<h2>Where to from here?</h2>
<p>It is likely that this will become a seminal case for some of the above reasons. The case will also be discussed to some degree in both Commonwealth and non-Commonwealth jurisdictions, as evidenced by US President Trump’s involvement. </p>
<p>In the meantime, it might be prudent to pause and reflect. Amid all the noise of clicks, hashtags, likes, tweets and protests, we need to go back to the essentials. At the heart of this frenzy is a very ill 11-month-old infant, who was unable to express his wishes. Yet there were millions who thought they could do just that.</p><img src="https://counter.theconversation.com/content/81168/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Neera Bhatia does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>The high-profile Charlie Gard case could change the way end-of-life decisions play out around the world.Neera Bhatia, Senior Lecturer in Law, Deakin UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/671322016-11-18T03:34:09Z2016-11-18T03:34:09ZThe next frontier in reproductive tourism? Genetic modification<figure><img src="https://images.theconversation.com/files/144124/original/image-20161101-24460-1pylff6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Human oocyte in vitro fertilization.</span> <span class="attribution"><a class="source" href="https://www.flickr.com/photos/zeissmicro/27771482282">Ziess Microscopy/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span></figcaption></figure><p>The birth of the first baby born using a technique <a href="https://www.newscientist.com/article/2107219-exclusive-worlds-first-baby-born-with-new-3-parent-technique">called mitochondrial replacement, which uses DNA from three people</a> to “correct” an inherited genetic mutation, was announced in September 2016. </p>
<p>Mitochondrial replacement or donation allows women who carry mitochondrial diseases to avoid passing them on to their child. These diseases can range from mild to life-threatening. No therapies exist and only a few drugs are available to treat them.</p>
<p>There are no international rules regulating this technique. Just one country, the United Kingdom, explicitly <a href="http://www.legislation.gov.uk/uksi/2015/572/contents/made">regulates the procedure</a>. It’s a similar situation with other assisted reproductive techniques. Some countries permit these techniques and others don’t. </p>
<p>I study the intended and unintended consequences of regulating, prohibiting or authorizing the use of new technologies. One of these unintended consequences is “medical tourism,” where people travel from their home countries to places where practices such as commercial surrogacy or embryo selection are allowed. </p>
<p>Medical tourism for assisted reproductive technologies raises a host of legal and ethical questions. While new reproductive technologies, like mitochondrial replacement, promise to bring significant benefits, the absence of regulations means that some of these questions, including those related to safety and risks are unanswered, even as people are starting to use them. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/144123/original/image-20161101-14771-1fuj1bn.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/144123/original/image-20161101-14771-1fuj1bn.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=600&fit=crop&dpr=1 600w, https://images.theconversation.com/files/144123/original/image-20161101-14771-1fuj1bn.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=600&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/144123/original/image-20161101-14771-1fuj1bn.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=600&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/144123/original/image-20161101-14771-1fuj1bn.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=754&fit=crop&dpr=1 754w, https://images.theconversation.com/files/144123/original/image-20161101-14771-1fuj1bn.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=754&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/144123/original/image-20161101-14771-1fuj1bn.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=754&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Mitochondria power our cells.</span>
<span class="attribution"><a class="source" href="http://www.shutterstock.com/pic-425512399/stock-photo-mitochondrium-3d-rendering-microbiology-illustration.html?src=TrjF1GC8FGuEZ0mQ-utOwA-3-61">Mitochondrium image via www.shutterstock.com.</a></span>
</figcaption>
</figure>
<h2>How does mitochondrial replacement work?</h2>
<p>We each inherit our mitochondria, which provide the energy that our cells need to function and the tiny fraction of DNA contained in it, only from our mothers. Some of that mitochondrial DNA might be defective, carrying mutations or errors that might lead to mitochondrial diseases.</p>
<p>The mother of the baby born using this technique carried one of these diseases. The disease, known as <a href="https://ghr.nlm.nih.gov/condition/leigh-syndrome#genes">Leigh Syndrome</a>, is a neurological disorder that typically leads to death during childhood. Before having this baby, the couple had two children who died as a result of the disease. </p>
<p>Mitochondrial replacement is done in a lab, as part of in vitro fertilization. It works by “substituting” the defective mitochondria of the mother’s egg with healthy mitochondria obtained from a donor. The child is genetically related to the mother, but has the donor’s mitochondrial DNA. </p>
<p>It involves three germ cells: an egg from the mother, an egg from a healthy donor and the sperm from the father. While the term “three-parent” child is often used in news <a href="http://www.nytimes.com/2016/09/28/health/birth-of-3-parent-baby-a-success-for-controversial-procedure.html?_r=0">stories</a>, it is a highly controversial one. </p>
<p>To some, the tiny fraction of DNA contained in a mitochondria provided by a donor is not sufficient to make the donor a “second mother.” The U.K., the only country that has regulated the technique, takes this position. Ultimately, the DNA replaced is a tiny fraction of a person’s genes, and it is unrelated to the characteristics that we associate with genetic kinship.</p>
<p>There is some discussion as to whether mitochondrial replacement is a so-called “germ line modification,” a genetic modification that can be inherited. Many <a href="http://www.nature.com/news/where-in-the-world-could-the-first-crispr-baby-be-born-1.18542">countries</a>, including the U.K., have either banned or taken a serious stance on technologies that could alter germ cells and cause inherited changes that can affect future generations. But a great number of countries, including Japan and India, have ambiguous or unenforceable regulations about germline modification.</p>
<p>Mitochondrial replacement results in a germline change, but that change is passed to future generations only if the child is a girl. She would pass the donor’s mitochondrial DNA to her offspring, and in turn her female descendants will pass it to their children. If the child is a boy, he wouldn’t pass the mitochondrial DNA on to his offspring. </p>
<p>Because the mitochondrial modification is only heritable in girls, the U.S. National Academies of Science recently recommended that use of this technique be <a href="https://www.nationalacademies.org/hmd/Reports/2016/Mitochondrial-Replacement-Techniques.aspx">limited to male embryos</a>, in which the change is not inheritable. The U.K. considered but then rejected this approach.</p>
<h2>A thorny ethical and regulatory debate</h2>
<p>In the U.S., the FDA claimed jurisdiction to regulate mitochondrial replacement but then halted further discussions. A rider included in the <a href="https://www.congress.gov/bill/114th-congress/house-bill/2029/text">2016 Congressional Appropriations Act</a> precludes the FDA from considering mitochondrial replacement.</p>
<p>While the technique has been given the green light in the U.K., the nation’s Human Fertilisation and Embryology Authority is gathering more <a href="http://www.hfea.gov.uk/10363.html">safety-related information</a> before granting the first licenses for mitochondrial replacement to clinics.</p>
<p>Experts have predicted that once the authority starts granting authorization, people seeking mitochondrial replacement would go to the U.K. </p>
<p>At the moment, with no global standard dictating the use of mitochondrial replacement, couples (and experts willing to use these technologies) are going to countries where the procedure is allowed. </p>
<p>This has happened with other technologies such as embryo selection and commercial surrogacy, with patients traveling abroad to seek out assisted reproduction services or technologies that are either prohibited, unavailable, of lower quality or more expensive in their own countries.</p>
<p>The <a href="https://www.newscientist.com/article/2107219-exclusive-worlds-first-baby-born-with-new-3-parent-technique/">first documented case</a> of successful mitochondrial replacement involved U.S. physicians assisting a Jordanian couple in Mexico. Further reports of the use of mitochondrial replacement in <a href="https://www.newscientist.com/article/2108549-exclusive-3-parent-baby-method-already-used-for-infertility/">Ukraine</a> and <a href="http://www.nature.com/news/reports-of-three-parent-babies-multiply-1.20849">China</a> have followed. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/146461/original/image-20161117-18108-1di8hjo.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/146461/original/image-20161117-18108-1di8hjo.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/146461/original/image-20161117-18108-1di8hjo.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/146461/original/image-20161117-18108-1di8hjo.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/146461/original/image-20161117-18108-1di8hjo.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/146461/original/image-20161117-18108-1di8hjo.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/146461/original/image-20161117-18108-1di8hjo.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">In this Nov. 3, 2015 photo, a newborn baby is transferred to an ambulance at the Akanksha Clinic, one of the most organized clinics in the surrogacy business, in Anand, India.</span>
<span class="attribution"><span class="source">Allison Joyce/AP</span></span>
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<p>The increasing trend of medical tourism has been followed by sporadic <a href="http://www.telegraph.co.uk/news/2016/04/14/baby-gammy-was-not-abandoned-in-thailand-court-rules/">scandals</a> and waves of tighter regulations in countries such as <a href="http://www.cnn.com/2016/09/08/asia/india-surrogacy-laws/">India</a>, <a href="http://www.nytimes.com/2016/05/03/world/asia/nepal-bans-surrogacy-leaving-couples-with-few-low-cost-options.html?_r=0">Nepal</a> and <a href="http://www.bbc.com/news/world-asia-31546717">Thailand</a>, which have been leading destinations of couples seeking assisted reproduction services.</p>
<p>Intended parents and children born with the help of assisted reproduction outside of their home countries have faced problems related to family ties, citizenship and their relationship with donors – especially with the use of <a href="http://scholarship.law.berkeley.edu/cgi/viewcontent.cgi?article=1420&context=bjil">commercial surrogacy</a>.</p>
<p>Mitochondrial replacement and new gene editing technologies add further questions related to the safety and long-term effects of these procedures.</p>
<h2>Gene modification complicates reproductive tourism</h2>
<p>Mitochondrial replacement and technologies such as gene-editing with the use of <a href="http://www.nytimes.com/2015/12/18/opinion/a-pause-to-weigh-risks-of-gene-editing.html">CRISPR-CAS9</a> that create germline modifications are relatively new. Many of the legal and ethical questions they raise have yet to be answered.</p>
<p>What if the children born as a result of these techniques suffer unknown adverse effects? And could these technologies affect the way in which we think about identity, kinship and family ties in general? One technique to replace mutated mitochondria involves the creation of embryos that will be later disposed. How should the use and disposal of embryos be regulated? What about the interests of the egg donors? Should they be paid? </p>
<p>Some of these problems could be avoided through a solid regulatory system in the U.S. and other countries. But as long as patients continue to seek medical treatments in “havens” for ethically dubious or risky procedures, many of these problems will persist. </p>
<p>Regulatory authorities around the world are <a href="http://nationalacademies.org/gene-editing/consensus-study/index.htm">debating</a> how to better regulate these genetic modification technologies. Governments need to start considering not only the ethical and safety effects of their choices but also how these choices drive medical tourism.</p><img src="https://counter.theconversation.com/content/67132/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Rosa Castro does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Medical tourism for assisted reproductive technologies raises a host of legal and ethical questions.Rosa Castro, Postdoctoral Associate in Science and Society, Duke UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/661892016-09-28T13:11:49Z2016-09-28T13:11:49ZWorld’s first three-parent baby raises questions about long-term health risks<figure><img src="https://images.theconversation.com/files/139563/original/image-20160928-537-ypf3v5.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="http://www.shutterstock.com/pic-258833957/stock-photo-family-walk-on-long-straight-road-way-towards-sunset-sun-mother-father-and-child-parenthood-concepts.html?src=kA6AKRMlvlRHyxgWUv8sZg-1-66">PHOTOCREO Michal Bednarek/Shutterstock.com</a></span></figcaption></figure><p>A baby boy, the first child to be born using a new technique that incorporates <a href="https://www.newscientist.com/article/2107219-exclusive-worlds-first-baby-born-with-new-3-parent-technique/">DNA from three people</a>, is now five months old. It is great news – the birth of a healthy baby conceived by this new procedure is a major step forward and will lead to a new way of preventing the inheritance of mitochondrial diseases.</p>
<p>Mitochondria are the powerhouses of cells. They generate energy for all life processes. One in 400 people has a maternally-inherited <a href="https://blog.wellcome.ac.uk/2013/09/11/recharging-the-batteries-treating-mitochondrial-disease/">mutation in mitochondrial DNA (mtDNA)</a>, the blueprint for some vital mitochondrial components. MtDNA mutations can cause a range of illnesses, including deafness, blindness, diabetes, and heart and liver failure. People with these disorders usually have both normal and damaged mtDNA, the symptoms being generally worse the higher the dose of damaged mtDNA. Sadly, there are no cures.</p>
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<img alt="" src="https://images.theconversation.com/files/139562/original/image-20160928-576-s2fzt3.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/139562/original/image-20160928-576-s2fzt3.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=600&fit=crop&dpr=1 600w, https://images.theconversation.com/files/139562/original/image-20160928-576-s2fzt3.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=600&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/139562/original/image-20160928-576-s2fzt3.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=600&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/139562/original/image-20160928-576-s2fzt3.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=754&fit=crop&dpr=1 754w, https://images.theconversation.com/files/139562/original/image-20160928-576-s2fzt3.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=754&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/139562/original/image-20160928-576-s2fzt3.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=754&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<span class="caption">Mitochondria: the part of the cell that generates energy.</span>
<span class="attribution"><a class="source" href="http://www.shutterstock.com/pic-425227336/stock-photo-mitochondria-on-a-dark-blue-background-3d-illustration.html?src=sIkaPgcz9fc99wEiASRVaw-1-11">Wire_man/Shutterstock.com</a></span>
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<p>In Mitochondrial replacement therapy (MRT), embryos of the couple at risk of having an affected child are generated in a test tube. In this case, the nucleus that contains all of the genetic material apart from the mitochondria was removed from the mother’s egg and placed into an egg with healthy mitochondria, from which the nucleus had been removed. The egg was then fertilised with the father’s sperm and the resulting embryo was placed in the mother’s womb where it developed into the baby. </p>
<p>This means the baby has three genetic parents: the father who supplied the sperm, the mother who supplied both womb and the egg nucleus, and an anonymous donor who supplied healthy mitochondria. Of these, the mitochondrial DNA is by far the smallest contribution. This type of three-parent baby is new, although other types have existed for many years.</p>
<p>MRT is being developed by groups in the UK and US to help the families of patients who have mitochondrial disease with a high recurrence risk in future children.</p>
<h2>Unknown long-term effects</h2>
<p>While experiments on monkeys and mice suggested that such babies would probably be healthy, this procedure hadn’t been used in humans until now. Eggs are highly organised cells. Replacing the nucleus does not prevent development into a baby, but it causes damage to the cell that probably requires radical re-organisation. So, the effects of such manipulations are still unknown and could cause problems later in life, such as an increased chance of diabetes.</p>
<p>According to a <a href="https://www.newscientist.com/article/2107219-exclusive-worlds-first-baby-born-with-new-3-parent-technique/">New Scientist report</a>, the mother of the child, a Jordanian woman, had been trying for a family for 20 years. Her two children both died of Leigh syndrome – aged eight months, and six. The woman had a high risk of having further affected children.</p>
<p>In many countries, the mother would have been given other choices before MRT was offered. First, she would have been offered eggs from an unrelated healthy donor. These could be fertilised with her partner’s sperm and put into her womb, preventing transmission of the mitochondrial disease completely. The woman with mtDNA disease is then the biological but not the genetic mother. Being born to a woman who is not your genetic parent may be acceptable to some people, given that perhaps up to one in 10 people in the UK <a href="https://www.theguardian.com/society/2005/aug/11/childrensservices.uknews">do not identify their genetic fathers correctly</a> – but it may have been unacceptable to this family.</p>
<p>She would have also been offered pre-implantation genetic diagnosis whereby several embryos can be tested at an early stage and the best one selected to be placed in the mother’s womb. However, this was reportedly not ethically acceptable to this family.</p>
<p>The birth of a healthy baby after this technique is a big step forward. In the past related manipulations to improve “oocyte mitochondrial quality” have been carried out – so called “ooplasm donation” which involves donor mitochondria that are injected into a germ cell in the ovary (an oocyte). But this procedure <a href="http://humrep.oxfordjournals.org/content/17/8/1954">reportedly caused genetic defects</a> and perhaps autism in one case. </p>
<p>While it is not yet possible to give the latest baby a decisive “all clear”, he carries a low level of the damaging mutation, making it highly unlikely that he will develop Leigh syndrome.</p>
<h2>The known unknowns</h2>
<p>However, there are two more details of the story that could affect what happens next. First, the procedure could be termed “medical tourism”: it was done in Mexico by a team based in New York City, so it was not covered by US regulations, which do not permit the procedure. The Institute of Medicine’s Committee on the Ethical and Social Policy Considerations of Novel Techniques for Prevention of Maternal Transmission of Mitochondrial DNA Diseases declined to give regulatory approval for clinical use of the procedure until research to answer critical safety and efficacy questions has been done.</p>
<p>Another problem is that we are not told how high the level of damaging mtDNA was in the mother’s egg before the procedure was carried out – a detail that indicates how likely the child was to be severely affected at the outset. If the level and hence the risk was high, this is a laudable technical advance that has massively reduced the child’s chance of suffering a severe illness. If the level was low and compatible with a healthy life, then a procedure with significant unknowns might have been done unnecessarily – illustrating how much we need regulation to protect the rights of the future child. Reports do not clarify these vital details.</p>
<p>This story is the beginning of a new treatment with massive potential for good. However, rigorous regulation and checks on the unknowns of this new and controversial technology are needed.</p><img src="https://counter.theconversation.com/content/66189/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Joanna Poulton is affiliated with the University of Oxford. She has received funding from MRC.</span></em></p>It’s a landmark case but there are many unknowns.Joanna Poulton, Professor, University of OxfordLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/371922015-02-04T16:36:55Z2015-02-04T16:36:55ZDecision to allow ‘three-person IVF’ should be welcomed<figure><img src="https://images.theconversation.com/files/71101/original/image-20150204-28608-hia2kw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Mitochondrial replacement is different to changing DNA.</span> <span class="attribution"><a class="source" href="http://www.shutterstock.com/pic-165823247/stock-photo-babies-group-wearing-diapers-kids-are-crawling-on-floor.html?src=sT7mXBsQZp6m7cD1tTgTHg-1-7">Babies by Shutterstock</a></span></figcaption></figure><p>The <a href="http://www.bbc.co.uk/news/health-31069173">decision by British MPs</a> to allow the Human Fertilisation and Embryology Authority to license mitochondrial replacement therapies, popularly known as “three-parent” or “three-person” IVF, should be welcomed.</p>
<p>Mitochondrial disease can have devastating effects on children and their families, causing premature death and severe disability. At least one affected mother in this country has seen <a href="http://www.bbc.co.uk/news/magazine-19648992">seven of her children die</a>. Fundamentally then this decision is about giving families whose lives would otherwise be blighted by mitochondrial disease an opportunity to have healthy children.</p>
<p>When making policy decisions of this magnitude, however, it is always advisable to look beyond the immediate beneficiaries and to ask whether there are any ethical objections. Two of <a href="https://theconversation.com/the-ethics-of-three-person-ivf-29880">the main ones</a> considered yesterday and in the build-up to the debate were the suggestion that allowing mitochondrial replacement therapies would be to set out down a slippery slope to other less acceptable things such as human enhancement <a href="https://theconversation.com/three-person-ivf-has-nothing-to-do-with-eugenics-but-its-time-for-a-designer-baby-debate-23996">or “designer babies”</a>; and the argument that what’s proposed constitutes germline genetic modification (genetic modification that can be passed onto future generations).</p>
<h2>The specious slippery slope</h2>
<p>It is important to note that not all “slippery slope” arguments are specious. Sometimes what starts off as a relatively innocuous exception to an established principle leads, through a process of incremental progression, to something much more serious or dangerous. </p>
<p>Take university tuition fees, for example. When these were introduced at a low level in England in the late 1990s, some critics argued that, although £1,000 might be affordable and reasonable, the fees were bound to increase substantially over time as governments sought ways to contain spending, and so the initial £1,000 was the start of a slippery slope to <a href="http://www.theguardian.com/politics/2003/jan/23/uk.education">far higher tuition fees</a>. Therefore, these critics argued, the principle of free higher education should be maintained in order to avoid setting out down the slippery slope to high fees. Given that many students now pay £9,000, it looks as if this argument may have had some merit.</p>
<p>But does it apply to mitochondrial replacement? There are two reasons for answering no. One is that mitochondrial replacement is technically different from modifying nuclear DNA. And it is nuclear DNA that most people are thinking of when they express concerns about parents micromanaging the characteristics of their future children (height, eye colour, intelligence, musicality, and so on). Mitochondrial replacement simply won’t deliver this. All it does is allow us to avoid mitochondrial disease. </p>
<p>The other (related) reason is that if scientists wanted to create a child whose nuclear DNA had been modified they would not be able to do so under current law. This would require a separate debate in parliament and it is difficult to see any reason why future MPs would feel compelled to approve it.</p>
<p>Mitochondrial replacement will also be closely monitored by the HFEA with specific licences needed in each case. So it is not as if MPs have voted to allow clinicians and scientists to do whatever they like in this area; what each clinic does will still need to be monitored and licensed.</p>
<h2>Germline genetic modification</h2>
<p>Then there is the argument that what’s proposed constitutes germline genetic modification. A germline genetic modification is one that can be passed onto future generations. So, in the case of mitochondrial replacement, the worry is that when children created using this technique later go on to have children of their own, any unforeseen genetic abnormalities created by the technique may be passed onto the next generation, and then the next.</p>
<p>Against this, it can be argued that mitochondrial replacement isn’t genetic modification as such, but rather donation. The mitochondria are imported wholesale from an egg donor and indeed are ones that, if the egg donor were to have her own children, would be passed onto them anyway. So nothing really new is being added to the human gene pool.</p>
<p>When we consider any concerns about harm and risk, it is important also to reflect on what the alternatives are: in particular, what would happen if prospective patients tried to have children “naturally”. In many cases, if they proceed in this way, we can be confident that their children will inherit mitochondrial disease. So even if there is a small risk of passing on some unforeseen genetic problem to one’s children and grandchildren, this is surely better than a near certainty of passing on a serious mitochondrial disorder.</p>
<p>The decision in favour by MPs was, as public health minister Jane Ellison <a href="http://www.newscientist.com/article/dn26906-uk-parliament-gives-threeparent-ivf-the-goahead.html">put it</a>, a “bold step”. So it was important to consider fully the potential ethical pitfalls. There also needs to be serious ethical debate in the coming months and years, not so much about whether to use mitochondrial replacement therapies, but about how to use and regulate them. The UK bill still needs approval by the House of Lords and a further Commons vote on any amendments before becoming law. But overall the decision is good news – not only for affected families but also for British clinicians, scientists and regulators.</p><img src="https://counter.theconversation.com/content/37192/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Stephen Wilkinson holds a Wellcome Trust Senior Investigator Award</span></em></p>The decision by British MPs to allow the Human Fertilisation and Embryology Authority to license mitochondrial replacement therapies, popularly known as “three-parent” or “three-person” IVF, should be…Stephen Wilkinson, Professor of Bioethics, Lancaster UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/369922015-02-01T10:36:45Z2015-02-01T10:36:45ZThree-person IVF: science shows ethical questions remain unanswered<figure><img src="https://images.theconversation.com/files/70621/original/image-20150130-25917-bde4qg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Time for human trials?</span> <span class="attribution"><span class="source">Halfpoint</span></span></figcaption></figure><p>Diseases caused by genetic mutations in the mitochondria – the powerhouses of the cell – can be disabling, or even deadly. That is why mitochondrial replacement therapy (MRT), otherwise also known as three-person IVF (<em>in vitro</em> fertilisation), is being touted as a much-needed option for women carrying mitochondrial mutations.</p>
<p>Most genes in a cell are trapped in the nucleus, but a tiny fraction are present in the mitochondria too. When eggs are fertilised, the genes in the nucleus of the egg combine with the genes in the nucleus of the sperm to create a new cell. However, mitochondrial genes do not undergo this mixing and are passed on from mother to child.</p>
<p>The idea behind three-person IVF is to find a way of replacing the mitochondrial genes in an affected egg cell before they are passed on to the child. This is done by acquiring a donor’s egg cell and removing the nucleus from it to leave a cell with healthy mitochondria. Then the mother’s nucleus, which is unaffected, is removed and placed in the donor’s egg cell, creating an egg cell that should contain healthy genes both in the nucleus and in the mitochondria.</p>
<p>The procedure has been performed in animals with some success, and now there is a motion in the UK parliament to allow experiments to be done in humans. This may seem like a reasonable step ahead, but I feel a lot more work needs to be done before we can go to human trials.</p>
<h2>Genes are a complex beast</h2>
<p>Genes interact with one another. That’s not really surprising – the complex range of processes that cells engage in, such as respiration or cell division, are unlikely to be accomplished by single genes acting in isolation. So genes act in networks or pathways, each one contributing some particular component. </p>
<p>Genes are also variable. This means that no two individual genomes are alike. As a consequence the outcome of a particular interacting pair of genes will sometimes differ between individuals. Geneticists call this kind of effect epistasis. It is the dark side of genetics, in the sense that it is poorly studied and we know very little about how widespread it may be, but a <a href="http://www.nature.com/nature/journal/v504/n7478/full/nature12678.html">recent study</a> suggests it is important.</p>
<p>Epistasis can occur between individual genes, between sets of genes, or even between whole genomes. This latter kind of epistasis is of relevance to the discussion on the safety and ethics of MRT. This is because when a mitochondrial genome from a donor replaces the diseased mitochondria, the nuclear DNA from the parents must now converse with a completely novel genomic partner. But, although epistasis has formed part of the debate over safety, the ethical implications of changing epistasis between mitochondrial and nuclear DNA have so far been ignored.</p>
<h2>Ethics first</h2>
<p>The <a href="http://www.nuffieldbioethics.org/mitochondrial-dna-disorders">ethical review of MRT</a> within the UK was carried out by the Nuffield Council on Bioethics in 2012. Its conclusion was straightforward: provided it was safe, it was ethical. In short, if human trials showed that the treatment was safe then the council considered it to be ethical too.</p>
<p>An important part of the review revolved around whether the therapy might alter the individual’s identity in some significant way. The report cites the view of the Medical Research Council and the Wellcome Trust that:</p>
<blockquote>
<p>We do not believe the transfer of mitochondrial DNA raises issues around identity, since it does not carry any genetic data associated with the normally accepted characteristics of identity. An analogy could be drawn with replacing the battery in a camera – the brand of the battery does not affect the functioning of the camera.</p>
</blockquote>
<p>The rationale for this is that the mitochondrial genome contains only 37 genes out of the 20,000 genes in the human genome, and that these genes are involved in mitochondrial functions and nothing else. Others see things differently. For instance bioethicist Annelien Bredenoord argued that, in terms of a person’s genetic identity, the distinction between the nuclear and mitochondrial genomes is a false one: </p>
<blockquote>
<p>No matter whether one modifies a (pathogenic) nuclear gene or a (pathogenic) mitochondrial gene, the identity of the future person will be changed. </p>
</blockquote>
<p>In fact there is growing evidence that mitochondrial DNA has <a href="http://www.yalescientific.org/2015/01/reinventing-the-human-embryo/">far-reaching effects</a> on a range of traits, from the core “battery” functions, to fertility, cognitive ability, ageing and even personality. One key feature of this extensive scientific literature is that the effect of the mitochondrial genome is sometimes surpassed by the effect of it interacting with the nuclear genome. So epistasis matters, although in ways that we don’t fully understand.</p>
<p>This is a clear shortcoming of the ethical review, since it apparently did not explore in depth the substantial literature on this topic, which goes back decades. So while the battery analogy gives people a rough idea of what mitochondria do, it really is a highly simplified version of reality. It ignores the fact that batteries don’t do anything by themselves, their function only being fully evident when placed within a device.</p>
<p>This issue is likely to crop up again when other technologies that allow scientists to literally re-write the genetic code are up for ethical approval. So bioethicists, policy makers and the general public need to appreciate that genes act in networks and if pathogenic genes are edited this may have unpredictable effects on processes and traits that do not form the target of the intervention. That is the reality of biological complexity. Whether that is ethical or not is up for discussion.</p>
<hr>
<p>Next read: <a href="https://theconversation.com/meet-mama-papa-and-mama-how-three-parent-ivf-works-15725">Meet mama, papa and mama: how three-parent IVF works</a></p><img src="https://counter.theconversation.com/content/36992/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Ted Morrow receives funding from the Royal Society, the European Research Council and the Swedish Research Council.</span></em></p>Diseases caused by genetic mutations in the mitochondria – the powerhouses of the cell – can be disabling, or even deadly. That is why mitochondrial replacement therapy (MRT), otherwise also known as three-person…T Morrow, Senior Research Fellow, University of SussexLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/298802014-08-04T13:53:00Z2014-08-04T13:53:00ZThe ethics of three-person IVF<figure><img src="https://images.theconversation.com/files/55538/original/mgzqhmyh-1406906736.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Three person IVF will prevent mitochondrial disease.</span> <span class="attribution"><span class="source">Sukharevskyy Dmytro/Shutterstock</span></span></figcaption></figure><p>The UK parliament will soon consider making Britain the first country to allow three-person IVF. The <a href="https://www.gov.uk/government/consultations/serious-mitochondrial-disease-new-techniques-to-prevent-transmission">regulations</a> are yet to be approved, but the government is currently backing moves to allow the creation of babies with DNA from three people in cases where the children are at risk of inheriting mitochondrial disease. </p>
<p>Objections have been raised, however, and it’s important to consider the ethical arguments for and against allowing this new procedure.</p>
<h2>Mitochondrial disease</h2>
<p>Mitochondria generate energy for our cells and have been compared to batteries or power stations. When people suffer from mitochondrial disease, their mitochondria don’t produce enough energy to make their cells work properly. The disease takes many forms but often affects important body parts such as the brain, liver or heart. Some mitochondrial disease is fatal and, at present, there’s no effective cure.</p>
<p>Mitochondrial replacement is proposed, not as a treatment for existing sufferers, but as a way of helping “at risk” parents avoid passing it on to their children. One technique (Maternal Spindle Transfer) involves removing damaged mitochondria from the mother’s egg and replacing them with healthy mitochondria from a donated egg. </p>
<p>Another (Pronuclear Transfer) involves removing damaged mitochondria from the parents’ embryo and replacing them with healthy mitochondria from a donated embryo, or from an embryo made using the father’s sperm and a donated egg. Any child created would be genetically linked, through mitochondrial DNA, to an egg donor, as well as to his or her main genetic parents; hence the expression “three-person IVF”.</p>
<p>As with any novel treatment, there are questions about safety and efficacy, but mitochondrial replacement also raises ethical concerns that go beyond the usual assessment of risks and benefits.</p>
<h2>Three genetic parents?</h2>
<p>One such concern is that the children created will have <a href="http://www.nuffieldbioethics.org/sites/default/files/files/Mitochondrial_donation_evidence_CalumMackellar.pdf">three genetic parents</a>. However, whether mitochondrial donors should be considered biological <em>parents</em> is questionable. For while the children created will be genetically linked to the donors, it’s far from clear that that link is sufficient to constitute parenthood.</p>
<p>Only around 0.1% of our genes are contained in mitochondria (with the other 99.9% being in the cellular nuclei) and so the mitochondrial donor only provides a tiny minority of the child’s genetic material. Similarly, the <a href="http://www.nuffieldbioethics.org/sites/default/files/Novel_techniques_for_the_prevention_of_mitochondrial_DNA_disorders_compressed.pdf">scientific consensus</a> appears to be that genetic material contained in the nucleus has a much greater role in shaping each person’s unique personal characteristics than does mitochondrial DNA.</p>
<p>We can also ask whether there’s really anything troubling about children having a biological link with three people. There are already lots of families that only exist because of the biological input of a third person: for example, ones created using traditional egg donation, or surrogacy. Given these precedents, it’s not clear that “three parent IVF” is all that different from practices that we already accept.</p>
<h2>Genetic modification</h2>
<p>A second concern is that mitochondrial replacement is germ-line genetic modification – where changes affect future generations. For example, if a man’s sperm were genetically altered and that in turn affected the eggs or sperm of his children, and then of his grandchildren, and so on, that would be a germ-line modification: a potentially permanent change to the gene pool. Some people are concerned that <a href="http://www.nature.com/news/a-slippery-slope-to-human-germline-modification-1.13358">germ-line modification</a> is too dangerous because of its potential to affect future generations for evermore. Others object to it because they think it wrong to “interfere with” human nature.</p>
<p>But against this, it can be argued that mitochondrial replacement isn’t really modification. Donated mitochondria are naturally occurring (in the donor’s egg) and not engineered or manufactured. This means that we’re using genetic material that occurs in nature, not adding anything fundamentally new or artificial. On this view, mitochondrial replacement is more like transplantation than genetic engineering.</p>
<p>Another response is that even if mitochondrial replacement is an instance of germ-line modification, it should nonetheless be allowed because the alternative for these children – allowing them to be born with some pretty terrible diseases – is so bad that intervention is justified to prevent them from suffering.</p>
<p>Also, many different policy decisions have significant permanent effects on future generations: for example, decisions about the environment and climate change, nuclear power, or whether to go to war. Mitochondrial replacement is not unique in affecting the future and, given the small numbers involved (1 in 6,500 babies), its effects may be quite limited compared to the examples just mentioned.</p>
<h2>Mitochondrial replacement unnecessary?</h2>
<p>Some have argued that we shouldn’t allow mitochondrial replacement because it’s <a href="http://www.theguardian.com/science/2013/mar/15/eugenics-fear-over-gene-modification">not needed</a>. The argument here is that “at risk” parents already have other options - adoption and egg donation - and so there’s no need to develop mitochondrial replacement.</p>
<p>There’s certainly some truth in this. In principle, it’s possible for people to use an egg donor or to adopt instead. Those wanting this new treatment, however, will point out that finding a suitable egg donor or adoptive child isn’t easy and that – in common with many other families – they attach value to the genetic link between parent and child and would very much like to have children who are both genetically “theirs” and free from mitochondrial disease.</p>
<p>It’s also worth noting that this argument (the suggestion that people should settle for adoption or egg donation instead) could, if accepted, be used against a very wide range of practices, including traditional IVF and even gynaecological surgery to cure infertility. All of these interventions could be met with the question: “why should we expend resources on this when you could just adopt instead?”</p>
<p>It remains to be seen whether mitochondrial replacement therapies can be developed which are sufficiently safe and effective for widespread clinical use. And, as with any new biomedical intervention, extensive evaluation and research is needed. </p>
<p>There is, however, no decisive ethical argument against proceeding with such research. Plus, given the importance to many patients of having a child who is both genetically “theirs” and free from mitochondrial disease, there’s a strong case for allowing it to proceed, provided that careful regulation and monitoring is in place.</p><img src="https://counter.theconversation.com/content/29880/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Professor Wilkinson is presently the holder of a Wellcome Trust Senior Investigator Award. The views expressed here are his own and not necessarily those of the Wellcome Trust.</span></em></p>The UK parliament will soon consider making Britain the first country to allow three-person IVF. The regulations are yet to be approved, but the government is currently backing moves to allow the creation…Stephen Wilkinson, Professor of Bioethics, Lancaster UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/184022013-09-20T02:28:07Z2013-09-20T02:28:07ZViewpoints: the promise and perils of three-parent IVF<figure><img src="https://images.theconversation.com/files/31637/original/sn7vcgm8-1379574080.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Three-parent IVF is about allowing women who carry genetic diseases in their mitochondria to avoid passing them on to their children.</span> <span class="attribution"><span class="source">Glenn/Flickr</span></span></figcaption></figure><p><em>Far from creating designer babies, <a href="https://theconversation.com/meet-mama-papa-and-mama-how-three-parent-ivf-works-15725">three-parent IVF</a> is about allowing women who carry genetic diseases in their mitochondria to avoid passing them on to their children. The process involves replacing the mitochondria from the ovum of a woman who has a mitochondrial disease with one from a healthy donor.</em></p>
<p><em>It’s controversial because it requires a third “parent”, a woman who can donate a healthy mitochondria. The technology is currently prohibited throughout the world although the UK government has <a href="http://www.bionews.org.uk/page_318118.asp">announced its intention</a> to draft proposals allowing it.</em> </p>
<p><em>The technology could work in two ways – transferring the chromosomes from the mother into an egg from a healthy donor that has only the mitochondria (with other chromosomes removed) before fertilisation. Or we could take all the chromosomes out of a fertilised egg and put them into a donor egg that, again, has been “emptied” apart from the mitochondria.</em></p>
<p><em>An article published in the journal Science today raises some potential concerns about the technique. Here, one of the authors of the paper, Damian Dowling explains some limitations of the process. And professor of mitochondrial genetics Justin St John responds.</em></p>
<hr>
<p><strong>Damian Dowling:</strong> Our article outlines key research findings, as well as the outcome of a public consultation by the UK Human Fertilisation and Embryology Authority (HFEA) into the safety and ethics of mitochondrial replacement, which is also known as mitochondrial replacement-assisted IVF, or popularly as three-parent IVF. We believe the technique holds exciting promise for prospective mothers suffering from mitochondrial disease. </p>
<p>We talk about a body of scientific literature that is highly pertinent to the technology, but has been by-and-large overlooked in the scientific and public forums of this debate.</p>
<p>People have different nuclear genomes (genetic make-up) and different mitochondrial DNA sequences (mtDNA or haplotypes). How we make energy is determined by how these genomes work in tandem with our mitochondrial haplotypes. Indeed, experimental research on model organisms, ranging from mice to insects, indicates that how the mitochondrial DNA interacts with the genome is tightly preserved by natural selection – nature’s quality control process. </p>
<p>This interaction (mito-nuclear) is salient to life as we know it because it regulates much of our energy production. </p>
<p>When researchers have used mitochondrial replacement-type techniques to mix-and-match different combinations of putatively healthy mitochondrial haplotypes and nuclear genomes, they have typically found that new mito-nuclear combinations change how organisms function – from altering development rates to cognitive ability, reproductive success to life expectancies. Sometimes, this is for the worse.</p>
<p>Mitochondrial replacement-assisted IVF can make novel combinations of mito-nuclear interaction in ways that normal sexual reproduction cannot. </p>
<p>Under normal conception, a copy of the mother’s nuclear genome is transmitted to her children in 100% of cases, along with her mitochondrial genotype. This gives natural selection the fuel to preserve optimally functioning mito-nuclear gene combinations, perpetually across generations.</p>
<p>In public discussions of this technology, mitochondria have been likened to batteries in a camera; it doesn’t matter what brand of battery you use, the camera will function well. The body of research we bring to the table suggests this analogy needs rethinking – the brand can affect the expression of many health-related traits.</p>
<p>We don’t want to block the transition of this technique to the clinic. But, we feel it’s our obligation to bring to the discussion the research that has been overlooked. This research should be considered by the authorities involved in bringing mitochondrial replacement-assisted IVF to the clinic, who should decide how relevant the results and principles highlighted in this literature are to humans. </p>
<p>Ultimately, it will be difficult to predict how relevant this all is to the human case.</p>
<p>Women who suffer mitochondrial disease and might benefit from this technique should at least have access to the full array of evidence. They should understand its potential implications, so they can make an informed choice that is right for them and their situation.</p>
<p>While we don’t claim that this is the whole solution, perhaps matching mitochondrial haplotypes of the donor and mother would make sense and should be explored further. This option has been discussed by the HFEA.</p>
<hr>
<p><strong>Justin St John:</strong> The authors of the Science piece mention that the research they are highlighting hasn’t been included in the public debate. It’s important to note that it has not been overlooked by the scientists working on the technology or the agencies involved.</p>
<p>For quite a while now, scientists have been trying to develop approaches to prevent future generations from inheriting diseases associated with the mitochondrial genome. </p>
<p>Proposed assisted reproductive technologies offer the opportunity to prevent these diseases from being passed from one generation to the next. This is a highly worthwhile pursuit, but there are a number of safety issues that still require further explanation. </p>
<p>The most important issue that Damian Dowling raises above is that research he is drawing attention to has been considered by the Human Fertilisation and Embryology Authority (HFEA). I have also previously argued this case in the scientific literature. </p>
<p>I would even go a step further and suggest the technology needs an all-round safety assessment, which is also the view of the UK’s Nuffield Council on Bioethics and the HFEA. It’s important to note that the HFEA is the only body in the world considering proceeding with the technology.</p>
<p>I want to be sure that there’s no accompanying mutated mitochondrial DNA introduced into the egg when the chromosomes from the mother are transferred into the donor egg. Modifications to this technology could prevent that.</p>
<p>I would also want to ensure that there are no other abnormal processes resulting from the transfer. It has previously been argued that the transfer of chromosomes from one egg to another could affect chromosomal gene expression patterns through <a href="https://theconversation.com/explainer-what-is-epigenetics-13877">epigenetic factors</a>.</p>
<p>To overcome these concerns, we are currently developing technologies to prevent the transfer of accompanying mitochondrial DNA. Once we have perfected this, we will test the outcomes in model systems.</p>
<p>That data would be available to the scientific community and the regulatory authorities, and it would enable informed decisions to be made about safety. </p>
<p>Sometimes, the public debate about complex science is simplified but that doesn’t mean that the science has been simplified, careless or rushing ahead heedless of negative consequences. It’s good that as we move closer to using this technology that the public debate becomes deeper, but that doesn’t mean that this depth is new in scientific circles. </p>
<p>We all seek to ensure that this area of research doesn’t generate another problem while solving one.</p><img src="https://counter.theconversation.com/content/18402/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Damian Dowling receives funding from the ARC.</span></em></p><p class="fine-print"><em><span>Justin St. John receives funding from NHMRC, which looks at mitochondrial mutations and previously held a grant from the UK MRC, which looked at cloned embryos and mitochondrial inheritance.</span></em></p>Far from creating designer babies, three-parent IVF is about allowing women who carry genetic diseases in their mitochondria to avoid passing them on to their children. The process involves replacing the…Damian Dowling, Senior Research Fellow , Monash UniversityJustin St. John, Professor and Director, Centre for Genetic Diseases, Monash Institute of Medical Research, Monash UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/157252013-07-03T04:33:33Z2013-07-03T04:33:33ZMeet mama, papa and mama: how three-parent IVF works<figure><img src="https://images.theconversation.com/files/26761/original/ky37qp8f-1372823641.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Mitochondrial genes are inherited from our mothers’ eggs and passed on through her daughters to subsequent generations.</span> <span class="attribution"><span class="source">Shutterstock</span></span></figcaption></figure><p>The UK government has announced its <a href="http://www.bionews.org.uk/page_318118.asp">intention to draft proposals</a> allowing carriers of mitochondrial disease to have babies using a controversial IVF treatment that’s currently prohibited. The procedure is controversial because the babies will inherit DNA from three genetic parents.</p>
<p>The draft proposals will detail the regulation of the procedure and need to be endorsed by public consultation and parliament before being put into practice.</p>
<h2>The mighty mitochondria</h2>
<p>Mitochondrial DNA diseases offer distinct challenges to scientists and clinicians because we inherit our mitochondrial DNA in a different manner to our chromosomal genes. Our mitochondrial genes are passed down from our mothers’ eggs and on through her daughters to subsequent generations. </p>
<p>Mitochondrial genes are located in very small bodies called mitochondria and not with the chromosomes in the nucleus of the cell, which determine characteristics such as hair and eye colour.</p>
<p>The mitochondria are the “powerhouses” of the cell as they generate energy. Our cells use this form of energy for their everyday functions; mitochondrial genes are essential to this process. </p>
<p>If one of these genes is mutated, the individual may suffer from very debilitating diseases that affect, for example, muscle and nerve function. There are an increasing number of diseases that are associated with these mutations including diseases we hear about everyday, such as diabetes and Alzheimer’s disease. </p>
<p>The dilemma for a woman who carries mitochondrial DNA disease is that she doesn’t know how much damaged mitochondrial DNA is present in each of her eggs; each of these eggs is likely to have a different amount of mutation. Also, there’s no simple genetic test that can be used to tell the carrier whether her child would be affected. </p>
<p>So, if she and her partner choose to have a family, they will have no idea of the outcome – for them, it’s simply a matter of chance.</p>
<h2>Overcome mitochondrial disease</h2>
<p>Scientists are now developing two approaches to try and prevent children from inheriting these diseases. </p>
<p>The first of these techniques will transfer the mother’s chromosomes from one of her eggs into an egg from a donor. The donor egg would have had its chromosomes removed but retains its healthy mitochondrial DNA. </p>
<p>Then, as with normal IVF treatment, the eggs are fertilised with her partner’s sperm and the resultant embryo can develop for a few days in the lab before being transferred to the chromosomal mother to implant into her womb.</p>
<p>The second technique is similar but would first allow the partner’s sperm to fertilise the egg and then transfer the mother’s and father’s chromosomes to a healthy (empty apart from mitochondria) donor egg.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/26764/original/b5by5ywb-1372824517.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/26764/original/b5by5ywb-1372824517.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/26764/original/b5by5ywb-1372824517.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/26764/original/b5by5ywb-1372824517.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/26764/original/b5by5ywb-1372824517.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/26764/original/b5by5ywb-1372824517.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/26764/original/b5by5ywb-1372824517.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">The controversy around these approaches lies with the baby having three genetic parents.</span>
<span class="attribution"><span class="source">Shutterstock</span></span>
</figcaption>
</figure>
<p>The controversy around these approaches lies with the baby having three genetic parents. These are the chromosomes that the mother and father contribute, as is normal following fertilisation. And then there’s the “third parent” – the mitochondrial DNA mother who donated the egg.</p>
<h2>Some things to consider</h2>
<p>Some groups argue that scientists are entering the brave new world of designer babies and that these techniques are similar to cloning. For them, these procedures are unacceptable.</p>
<p>Others argue that the technologies offer significant benefits, such as the potential to eradicate mitochondrial diseases. </p>
<p>In many respects, UK scientists are at the forefront of convincing government to legalise these procedures under the control of the country’s fertility regulator, the <a href="http://www.hfea.gov.uk/index.html">Human Fertilisation and Embryology Authority</a>.</p>
<p>In the last two years, there have been two significant reports supporting these procedures but they contained important reservations. In 2012, the UK’s <a href="http://www.nuffieldbioethics.org/mitochondrial-dna-disorders">Nuffield Council on Bioethics ruled</a>: </p>
<blockquote>
<p>If further research shows these techniques to be sufficiently safe and effective, we think it would be ethical for families to use them if they wished to, provided they receive an appropriate level of information and support. </p>
</blockquote>
<p>The Human Fertilisation and Embryology Authority sought public views on behalf of the secretary of state for health and <a href="http://www.hfea.gov.uk/7796.html">reported in late March, 2013</a>. It noted: </p>
<blockquote>
<p>… there is general support for permitting mitochondria replacement in the UK, so long as it is safe enough to offer in a treatment setting and is done so within a regulatory framework.</p>
</blockquote>
<p>These reservations are important because they are directed to two key aspects of the procedures. The first is whether any of the mutant mitochondrial DNA accompanies the chromosomes as they are transferred into the donor egg. </p>
<p>This is very important as even a small amount of mutant mitochondrial DNA in the egg can become the dominant population in the baby and lead to mitochondrial disease. We are unsure why this happens but this is currently an area of intense research activity.</p>
<p>The second is whether these techniques would lead to the baby suffering from any harmful side effects.</p>
<p>While I fully embrace these new approaches to fight mitochondrial disease, we still need to make significant advances in determining their safety and effectiveness, and they require a considerable amount of validation. </p>
<p>If they pass these tests, these technologies offer ways to prevent mitochondrial genetic disease from being passed from a female to her descendants through one round of assisted reproduction.</p><img src="https://counter.theconversation.com/content/15725/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Justin St. John receives funding from NHMRC, which looks at mitochondrial mutations and previously held a grant from the UK MRC, which looked at cloned embryos and mitochondrial inheritance. </span></em></p>The UK government has announced its intention to draft proposals allowing carriers of mitochondrial disease to have babies using a controversial IVF treatment that’s currently prohibited. The procedure…Justin St. John, Professor and Director, Centre for Genetic Diseases, Monash Institute of Medical Research, Monash UniversityLicensed as Creative Commons – attribution, no derivatives.