tag:theconversation.com,2011:/africa/topics/three-person-ivf-14710/articlesThree-person IVF – The Conversation2017-09-22T03:57:55Ztag:theconversation.com,2011:article/831062017-09-22T03:57:55Z2017-09-22T03:57:55ZExplainer: what are mitochondria and how did we come to have them?<figure><img src="https://images.theconversation.com/files/186721/original/file-20170920-905-19pmmiz.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Mitochondria live inside our cells but have a different genome. Here's why. </span> <span class="attribution"><span class="source">from www.shutterstock.com.au</span></span></figcaption></figure><p>We’ve probably all heard of mitochondria, and we may even remember learning in school that they are the “powerhouses of the cell” – but what does that actually mean, and how did they evolve? To answer this question, we have to go back about two billion years to a time when none of the complexity of life as we see it today existed. </p>
<h2>Where did mitochondria come from?</h2>
<p>Our primordial ancestor was a simple single-celled creature, living in a long-term rut of evolutionary stagnation. Then something dramatic happened – an event that would literally breathe life into the eventual evolution of complex organisms. One of the cells engulfed another and enslaved it as a perpetual source of energy for its host. </p>
<p>The increase in available energy to the cell powered the formation of more complex organisms with multiple cells, eyes, and brains. Slowly, the two species became intertwined – sharing some of their DNA and delegating specific cellular tasks – until eventually they became firmly hardwired to each other to form the most intimate of biological relationships. Two separate species became one. </p>
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<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>These energy slaves are the mitochondria, and there are hundreds or even thousands of them inside every one of your cells (with the exception of red blood cells) and in every other human alive. They still resemble their bacterial origin in appearance, but we can no longer exist without them, nor they without us. The evolutionary explosion powered by mitochondria is evident by the fact they are found in every complex multicellular organism that has ever existed, from giraffes to palm trees, mushrooms and dinosaurs. </p>
<p>As vestiges of their ancient origin, mitochondria still have their own genome (although some of their DNA has been transferred to our genome). It’s alien in appearance and composition when compared with our own nuclear genome (the DNA inside each of your cell’s nuclei that contains about 20,000 genes). In fact, our nuclear genome shares more in common with that of a sea sponge than with the mitochondrial genome inside our own cells. </p>
<p>Unlike the nuclear genome, the mitochondrial genome is small (containing just 37 genes), circular, and uses a different DNA code. The mitochondrial genome slinks its way across generations by stowing away within mitochondria harboured in each egg, and as such, is passed down from the mother only. This is different to the nuclear genome, half of which is inherited from your father and the other half from your mother. </p>
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Read more:
<a href="https://theconversation.com/do-you-share-more-genes-with-your-mother-or-your-father-50076">Do you share more genes with your mother or your father?</a>
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<h2>What do the mitochondria do?</h2>
<p>The mitochondrial genome is vital for the mitochondria’s main role: burning the calories we eat with the oxygen we breathe to generate the energy to power all of our biological processes. But this amazing source of energy is not without its cost.</p>
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<a href="https://images.theconversation.com/files/186947/original/file-20170921-10635-rk7evh.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/186947/original/file-20170921-10635-rk7evh.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/186947/original/file-20170921-10635-rk7evh.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/186947/original/file-20170921-10635-rk7evh.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/186947/original/file-20170921-10635-rk7evh.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/186947/original/file-20170921-10635-rk7evh.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/186947/original/file-20170921-10635-rk7evh.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/186947/original/file-20170921-10635-rk7evh.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"></a>
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<span class="caption">The mitochondrial genome is passed down from the mother only.</span>
<span class="attribution"><span class="source">Natalya Zaritskaya/Unsplash</span>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
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<p>Like any powerhouse, mitochondria produce toxic byproducts. Free radicals (highly reactive oxygen molecules with an odd number of electrons that can cause ageing and health problems) can be created by accidents that happen during energy production. </p>
<p>So in essence, mitochondria power <em>and</em> imperil our cells.</p>
<p>Because the mitochondrial genome is in close proximity to the source of free radicals, it’s more susceptible to their damaging effects. And the mitochondrial genome undergoes replication thousands of times more than the nuclear genome, simply because you have so many in each cell. Making copies of copies introduces mistakes. </p>
<p>A combination of these two effects results in the mitochondrial genome mutating up to 50 times faster than the nuclear genome, which is meanwhile kept safely in the nucleus. These mutations can be passed down to maternal offspring, causing devastating metabolic disorders in the next generation.</p>
<h2>What happens when something goes wrong?</h2>
<p>Only as recently as 1988 was the first disease caused by such a mutation in the mitochondrial genome identified. Now, we know about many such disorders, called mitochondrial diseases, which can be traced to mutations in the mitochondrial genome. These diseases can manifest at any age and result in a wide range of symptoms including hearing loss, blindness, muscle wasting, stroke-like episodes, seizures, and organ failure.</p>
<p>These diseases are currently incurable. But <a href="https://academic.oup.com/brain/article/139/6/1633/1754057/Emerging-therapies-for-mitochondrial-disorders">multiple lines of investigation</a> are currently underway to treat and <a href="https://theconversation.com/safety-in-numbers-how-three-parents-can-beat-genetic-diseases-2524">prevent transmission to subsequent generations</a>.</p>
<p>Despite this, during life, it’s inevitable that mutations will occur in the mitochondrial genome in an individual’s neurons, muscle, and all other cells. <a href="http://www.nature.com/ng/journal/v38/n5/full/ng1769.html?foxtrotcallback=true">Compelling work</a> now <a href="https://www.ncbi.nlm.nih.gov/pubmed/26014345">suggests</a> that the accumulation of these mistakes may contribute to the progressive nature of late-onset degenerative diseases such as Alzheimer’s and Parkinson’s. </p>
<p>The health of this seemingly alien genome is inextricably linked to that of our own bodies. As we come to grips with mitochondria’s importance in disease, we continue to uncover the intimate secrets of a two-billion-year relationship that has given complex life to the planet.</p><img src="https://counter.theconversation.com/content/83106/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Steven Zuryn receives funding from the National Health and Medical Research Council and the Stafford Fox Medical Research Foundation. </span></em></p>To explain why we have a mitochondria, we have to go back about two billion years to a time when none of the complexity of life as we see it today existed.Steven Zuryn, Group Leader, The University of QueenslandLicensed 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>
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<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>
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<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>
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<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/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/371212015-02-03T14:28:32Z2015-02-03T14:28:32ZAncient Greece has something to say about the three-person baby debate<figure><img src="https://images.theconversation.com/files/70920/original/image-20150203-25516-m03s0f.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Rubens, The Discovery of the Child Erichthonius.</span> </figcaption></figure><p>The science and morality of creating a life with DNA from three different individuals is hot news. The UK parliament <a href="https://theconversation.com/three-person-ivf-science-shows-ethical-questions-remain-unanswered-36992">has voted in favour</a> of allowing trials of mitochondrial replacement therapy (MRT), otherwise also known as three-person IVF, which would allow women with mitochondrial mutations to have healthy children.</p>
<p>Of course, <a href="http://www.bbc.co.uk/news/health-31044255">commentators</a> have been keen to stress that such a child would have only two “parents” – the people raising the resulting offspring. The third person is the woman who gives the healthy mitochondrial DNA to compensate for a fault in the mother’s DNA.</p>
<p>For anyone who has studied ancient Greece, the situation of two women and one man contributing to a child will be familiar, as indeed are weird birth stories more generally. The father involved in the three-parent birth I’ll be describing here – the <a href="http://www.theoi.com/Olympios/Hephaistos.html">god Hephaistos</a> – was himself the result of a most unusual conception. </p>
<p>His mother Hera became pregnant by eating lettuce (a plant associated with semen because of the milky white fluid in its leaves). In some versions of the myth she did this to take revenge on her husband Zeus, who himself had given birth with a minimal female contribution. He had eaten another of his many loves, Metis, while she was pregnant – and so he gave birth to their daughter Athena from his own head. </p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/70922/original/image-20150203-25540-1jd1u9l.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/70922/original/image-20150203-25540-1jd1u9l.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/70922/original/image-20150203-25540-1jd1u9l.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=700&fit=crop&dpr=1 600w, https://images.theconversation.com/files/70922/original/image-20150203-25540-1jd1u9l.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=700&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/70922/original/image-20150203-25540-1jd1u9l.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=700&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/70922/original/image-20150203-25540-1jd1u9l.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=879&fit=crop&dpr=1 754w, https://images.theconversation.com/files/70922/original/image-20150203-25540-1jd1u9l.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=879&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/70922/original/image-20150203-25540-1jd1u9l.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=879&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">The birth of Athena from Zeus’s head.</span>
</figcaption>
</figure>
<p>In an alternative version, Hephaistos was born before this Athena incident. When Zeus gave birth, the midwife – wielding the axe to cure Zeus of his monster headache – was sometimes shown as being <a href="http://www.greekmythology.com/images/mythology/birth_of_athena_77.jpg">Hephaistos</a>. Many other myths of Hephaistos depicted him as a weakling, implying that someone born without a male contribution must be inadequate. Despite his many skills, in particular in metal-working, Hephaistos was represented as being lame.</p>
<h2>Erichthonios: birth from Earth</h2>
<p>It’s when we come to the conception and birth of Hephaistos’s son Erichthonios that we find a three-person conception. There are two women involved. The myth tells of how Erichthonios was born from Gaia, the goddess Earth. So she was in some ways a “parent”. </p>
<p>Hephaistos contributed the seed. But the reason that Erichthonios existed was Hephaistos’s lust for a third divine person, the goddess Athena – who had a special and obvious significance for the people of Athens.</p>
<p>Hephaistos had a strong desire for Athena, but as a virgin goddess she ran away from him. He was not able to catch her – but he ejaculated and the seed fell on her leg. She wiped it away with a piece of wool and the seed fell on Gaia, the Earth, making her pregnant. </p>
<p>So while Athena contributed no material to the child, if Hephaistos hadn’t lusted after her there would never have been an Erichthonios – and Athena is not just the object of desire, but the one who makes arrangements for bringing up the baby.</p>
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<a href="https://images.theconversation.com/files/70921/original/image-20150203-25516-auw43x.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/70921/original/image-20150203-25516-auw43x.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/70921/original/image-20150203-25516-auw43x.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=906&fit=crop&dpr=1 600w, https://images.theconversation.com/files/70921/original/image-20150203-25516-auw43x.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=906&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/70921/original/image-20150203-25516-auw43x.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=906&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/70921/original/image-20150203-25516-auw43x.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1138&fit=crop&dpr=1 754w, https://images.theconversation.com/files/70921/original/image-20150203-25516-auw43x.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1138&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/70921/original/image-20150203-25516-auw43x.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1138&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">Athena receives the baby Erichthonius from the hands of Gaia.</span>
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</figure>
<p>Erichthonios grew in the womb of Gaia and, when he was born, Gaia passed him over to Athena to care for him. In <a href="http://www.theoi.com/image/T1.2Gaia.jpg">vase paintings</a> of this scene, only the upper part of the body of the goddess Earth is shown. She keeps her connection to the soil. </p>
<p>Sometimes Zeus, the baby’s grandfather in two ways, is <a href="http://www.theoi.com/image/T1.6Gaia.jpg">there too</a>. But in other versions the scene involves Earth, Athena – and <a href="http://www.theoi.com/image/T1.3Gaia.jpg">Hephaistos</a>, standing by and watching the “birth” of his son.</p>
<h2>Nature and nurture</h2>
<p>Like us, the ancient Athenians were concerned about what “true parenthood” is. Was the biological aspect or the nurturing aspect most important? The myth of Erichthonios focuses on the contributions to the child made by Earth and by Hephaistos’s seed. Athena does not give any raw material to this child yet she is the one who looks after him when he is born, making arrangements for his care. </p>
<p>In this story of three people and one baby, it seems to me easy to answer the question: “Who are the parents?” All three divine persons. By having three people involved in his origin, Erichthonios helped Athenians think about their links to their native soil and to their chief deity Athena. </p>
<p>The myth shows awareness of how parenthood can be about nurture as well as nature. And the third person, Hephaistos, was also necessary to provide the crucial biological material. For the Greeks, it was seed: for us, it’s DNA. </p>
<p>There have been hypothetical three-parent babies for millennia. Now, we may be about to see them outside the world of mythology.</p><img src="https://counter.theconversation.com/content/37121/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Helen King 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 science and morality of creating a life with DNA from three different individuals is hot news. The UK parliament has voted in favour of allowing trials of mitochondrial replacement therapy (MRT), otherwise…Helen King, Professor of Classical Studies, The Open 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.